The incidence of colorectal polyps is rising. Certain types of polyps are considered to be the precursor lesions for colorectal cancers. To investigate the prevalence and related factors of colorectal polyps in Chinese subjects, we first performed a cross-sectional study. A total of 3066 subjects were documented, and the prevalence of colorectal polyps was 18.1%. Then we evaluated the incidence and risk factors of polyps via a retrospective cohort study in the same population. 561 subjects who received at least twice surveillance colonoscopies with available reports during the study period and had no polyp at the first endoscopy were included in the retrospective cohort study, of whom 19.1% developed colorectal polyps. Regular smoking was independently associated with the presence and development of colorectal polyps. Further analyses indicated that polyps were associated with smoking status, daily cigarette consumption, and drinking habit. Moreover, smoking tends to be more relavent to rectal, small and single polyp. In conclusion, colorectal polyp is a common disease in China. Exploring the epidemiology and risk factors may improve the prevention of colorectal polyps, even colorectal cancer. Adenomatous polyps are thought to be the precursor lesions for the majority of CRCs2, developing mostly through an adenoma-carcinoma sequence3. Recent studies proposed that hyperplastic polyps also contribute to CRCs through serrated or microsatellite instable pathways5. Some polyps may cause gastrointestinal symptoms such as hematochezia, stomachache, abdominal distension, affecting health and quality of life. More seriously, other asymptomatic polyps may quietly develop into malignancies, which are more likely to be ignored. The detection and resection of precancerous polyps under colonoscopy is a critical way to reduce the incidence of CRC and its subsequent morbidity and mortality7. However, to explore the prevalence and risk factors for colorectal polyps could be a better way to prevent and manage this disease in advance.The incidence of colorectal polyp is rapidly increasing worldwide. Colorectal cancer (CRC) was found to be the third most common cancer among men and the fourth most common cancer among womenHelicobacter pylori infection, smoking, alcohol drinking, etc.10. As for CRC, a population-based colorectal cancer screening program in China suggested that age, gender, BMI, family history, meat intake and smoking were associated with colorectal neoplasms11. Smoking is proposed to be closely associated with colorectal polyps, neoplasia, and CRCs13. However, most evidence came from case-control or cross-sectional studies, and there is still no cohort study to evaluate the risk factors for colorectal polyps in China.Population characteristics, living habits, and health conditions are closely related to the presence and development of colorectal polyps and cancers. In recent studies, some risk factors for adenomatous polyps were reported, including sex, metabolic syndrome, Therefore, we first evaluated the prevalence of colorectal polyps and factors associated with the presence of this disease in a cross-sectional study. Then we investigated the incidence and risk factors for the colorectal polyps via a retrospective cohort study. Associations between the risk factors and features of colorectal polyps were further assessed.We designed two linked studies to investigate the prevalence and incidence of colorectal polyps, and risk factors for its presence and development in a Chinese population. The first was a cross-sectional study to determine the prevalence of colorectal polyps and factors associated with its presence. Then we conducted a retrospective cohort study of baseline polyp-free subjects from the first study who underwent at least twice surveillance colonoscopies to assess the incidence and risk factors for colorectal polyps.This retrospective study was performed among the employees of Zhenhai Refining & Chemical Company . All of the employees attending the health examinations and colonoscopies between January 2009 to December 2013 were screened for enrollment. Exclusion criteria were: (1) history of colorectal cancer or colectomy before the first surveillance colonoscopy; (2) history of inflammatory bowel disease; (3) incomplete colonoscopy or incomplete clinical information. A total of 3066 eligible subjects were enrolled in the cross-sectional study to investigate the prevalence of colorectal polyp and potential factors associated with its presence. Then in the same population, subjects who had at least twice surveillance colonoscopies and had no polyp at the first endoscopy were selected for the retrospective cohort study , normoweight (18.5 ≤ BMI < 25) and overweight (BMI ≥ 25). Blood samples were analysed in the same laboratories. In blood tests, following data were collected: white blood cell (WBC) count, red blood cell (RBC) count, platelet, hemoglobin, plasma viscosity, erythrocyte sedimentation rate (ESR), albumin, total cholesterol (TC), triglycerides (TG), creatinine and uric acid.Smoking and drinking habits, medical histories such as colorectal cancer, colectomy, and inflammatory bowel disease were inquired by a physician. Regular smoking (or current smoking) was defined as smoking at least one cigarette per day. Former smoking status was defined as a cessation of smoking for at least one year. Regular drinking was defined as drinking at least one alcoholic beverage per week.For each colonoscopy report, we extracted the following data: date, quality of bowel preparation, presence of polyps, diameter of the biggest polyp, position and number of the polyps. Duration of follow-up was defined as the interval time between baseline and the examination when colorectal polyps were first identified, or the last endoscopy before the end of our study period.t-test or Mann-Whitney U test. Categorical variables were expressed as frequencies with percentages and were analysed by chi-squared(χ2) test. Logistics regression was used to evaluate the factors associated with the presence of colorectal polyps in the cross-sectional study. Cox proportional hazards regression analyses were applied to assess the risk factors for the development of colorectal polyps in the retrospective cohort study. Those considerable covariates  were included in multivariate analysis. Interactions among the covariates in multivariate analyses were tested by collinearity diagnosis; no significant collinearity was found. A P value < 0.05 (two-tailed) was considered to be statistically significant.The statistical analyses were conducted using SPSS 24.0 . Continuous variables were presented as mean with standard vision or medians with interquartile range, and were compared by Student’s This study was performed according to the Declaration of Helsinki. The study protocol was approved by the Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (Reference Number: 2019648). Due to the retrospective nature of the study, informed consent was waived.A total of 3066 subjects were documented in the cross-sectional study Fig. , of whomLogistic regression analysis was applied to evaluate the factors associated with the presence of colorectal polyps Table . In the A total of 561 subjects  who had no colorectal polyps at baseline and underwent at least twice surveillance colonoscopies were included in the cohort study. The average follow-up time was 3.42 years. Baseline characteristics of 561 subjects were presented in Table P = 0.013) and lower albumin  were the independent risk factors for the development of colorectal polyps.During the 1919 person-years of follow-up, 107 (19.1%) subjects developed colorectal polyps. Cox proportional hazards regression analysis was applied to explore the factors associated with the development of colorectal polyps Table . In the P = 0.022). People who smoked more than 20 cigarettes per day were more likely to develop colorectal polyps  than those who smoked less . Since smoking and drinking are always mentioned together, we found that subjects with both smoking and drinking habits had a significantly higher risk for colorectal polyps .We further explored the association between cigarette smoking ways and colorectal polyp features in different regression models Table . After aP = 0.009) rather than colonic polyps . Besides, smoking tends to be associated with small (<1 cm) polyps  and single polyp .The relation between smoking and colorectal polyps was different in polyp position, size and number Table . RegularWe performed two linked studies to assess the prevalence and risk factors for the presence and development of colorectal polyps. In the cross-sectional study, the prevalence of colorectal polyps was 18.1% in our study population. Age, gender, TC, regular smoking and WBC count were independently associated with the presence of colorectal polyps. The retrospective cohort study revealed that the cumulative incidence of subjects developed colorectal polyps was 19.1% during their follow-up colonoscopy surveillance. Regular cigarette smoking and albumin were independent risk factors for the development of colorectal polyps. Thus the two studies have the consistent result that smoking plays an essential role in the presence and development of colorectal polyps. Further analyses showed those who were current smokers, had more daily smoking consumption, and combined with regular drinking had a higher risk of developing colorectal polyps. Moreover, regular smoking was more relevant to rectal, small (<1 cm) and single polyp.14. The incidence of colorectal polyp and CRC varies in different geographical locations and races. The highest incidence is found in western countries, while the lowest is in Africa and South-Central Asia15. A large study from the United States reported that 44.9% polypectomies were performed on 17275 patients who underwent average-risk screening colonoscopy between 2005–200616. However, endoscopy is much more accessible in western countries. Besides, interval CRC risk was found higher in blacks than in whites17. Recently, there are more Asian studies investigating prevalence and risk factors for colorectal polyps and CRC. A Korean study reported that the prevalence of colorectal adenomas was 34.5% in men and 20.0% in women among subjects at average risk, and the prevalence increased annually over the study period14. A Thai study found that in the population aged 50–65 years old, 18.2% of subjects had adenomatous polyps, of which 7% were high-risk adenoma18. In our study, the prevalence of colorectal polyp was 18.1% at baseline, while almost one-fifth subjects developed colorectal polyps in the subsequent cohort study. Therefore, it is crucial to investigate the risk factors of this disease.In recent years, the prevalence of colorectal polyps is increasing, which may be influenced by factors like changes in diet and lifestyle habits. Moreover, another important reason is that the improved equipment or colonoscopy techniques cause higher detection rates over time22. We found that regular cigarette smoking is an independent risk factor for the presence and development of colorectal polyps in Chinese population. Previous studies have revealed dose-response relations among the daily number of cigarettes smoked, the duration of smoking, the pack-years of smoking, and the risk for colorectal polyps24. The association was robust in all kinds of polyps . Reduced risk of all stages of colorectal carcinogenesis  was found in people with a healthy lifestyle, including nonsmoking25. Previous studies revealed some potential mechanisms for the association between smoking, colorectal polyps and CRN, such as the reduced methylation of relevant genes26, genetic variants in carcinogen-metabolising enzymes12, the polymorphisms in DNA repair genes EXO1 and ATM27, the mutations in mismatch repair enzymes28, and XPC polymorphisms29, etc. In a word, tobacco contains many carcinogens that are thought to create no less than irreversible genetic damage to the colorectal mucosa, initiating the formation of colorectal polyps19.Smoking is a well-known modifiable risk factor for colorectal polyps and CRC31. Recent meta-analysis showed that alcohol also linked with an increased risk of colorectal adenomas32 and serrated polyps33. However, the association appears to be more influential in European studies compared to those conducted in Asia or the US32. Our study failed to show the effect of alcohol alone on the development of colorectal polyps. Possible reasons could be genetic and lifestyle differences. Nevertheless, we found that when drinking combined with a regular smoking, the risk for colorectal polyp was doubled. This phenomenon may be due to the interactive effects of alcohol and tobacco/nicotine on cross-cue reactivity to alcohol and tobacco craving, subjective feelings of stimulation and sedation, and alcohol and smoking self-administration34. In addition, smoking and alcohol could cause changes in the gastrointestinal microbiome35. However, specific mechanisms need to be further explored.It’s worth mentioning that drinking and smoking often together affect the prevalence, occurrence, and development of many diseases. In 2007, the International Agency for Research on Cancer (IARC) indicated that there was sufficient evidence to support the inclusion of CRC in the list of alcohol-related malignancies36. This phenomenon might be explained that distal colorectal carcinogenesis is highly associated with environmental carcinogens such as various chemicals while proximal carcinogenesis is more relevant to genetic background38. A case-control study from Germany suggested that frequent cigarette smoking was an independent risk factor for the occurrence of large (≥20 mm) colorectal polyps, but our results showed a more substantial relation to small (<10 mm) polyps, possibly due to the small number of the subjects with large polyps in our study, as well as the racial and genetic disparities39. Nevertheless, the size and number of polyps are changing with the prolonging of time. Within the time frame of our study, smoking tends to be associated with rectal, small and single polyps.The current study also demonstrated that regular tobacco consumption tends to cause rectal, small and single polyps. Consistent with our result, a stronger association between smoking and distal rather than proximal polyps was also found in another study40. Serum albumin is a recognised biomarker for assessing the nutritional condition and were considered to be an important factor to predict recovery and survival of CRC41. In our study, decreased albumin was found to be associated with the development of colorectal polyps. In a recent study, Sun F et al. found elevated FAR (FAR = 100*Fibrinogen/Albumin) in newly diagnostic CRC patients compared with the healthy or benign controls, while albumin was low in the cases42. However, the specific association between albumin and the development of colorectal polyps remains to be further studied.As is known to all, diseases would result in nutrient consumption. Meanwhile, malnutrition is also a significant problem that could cause a number of clinical consequences in turn, such as deteriorated quality of life, decreased response to treatment, and shorter survival rate18. Our results also showed increasing age associated with the presence of colorectal polyps. Most studies reported a higher prevalence in men than in women, which even can’t be explained by the influence of cardiovascular and lifestyle risk factors43. A cross-sectional analysis of the data from a large colonoscopy-based screening program showed that in each age group, the numbers needed to undergo colorectal-cancer screening for detecting advanced neoplasia was significantly lower in men than in women44. However, we didn’t find relevance between sex and colorectal polyps after adjusted for confound factors, but the trend existed in the first study.Age and gender might be unmodifiable factors for polyps. The prevalence of colorectal polyps and CRC generally increases with age46, serum lipids47 and colorectal polyps, but not all48. Mechanisms related to insulin resistance and inflammation have been postulated to be involved in colorectal carcinogenesis. In our study, TC and WBC were related to the presence of polyps, while others did not independently influence the presence and development of colorectal polyps, but modest relevance could not be excluded.Some factors were found not significantly associated with colorectal polyps in multivariable analysis, such as BMI, lipid metabolic parameters, WBC and RBC. Previous studies indicated a weak association between BMIThe present study had some limitations that should be acknowledged. First, as is a retrospective study, we failed to get sufficient polyp histopathology reports of every subject to further evaluate the risk factors for different pathological types of colorectal polyps. Second, data on smoking and drinking were self-reported, which may cause recall bias. Last, we did not explore the mechanism of how smoking and decreased albumin increases the risk of polyps. Future studies are expected to clarify the molecular mechanisms and signal pathways of these factors in the development of colorectal polyps.In summary, our study indicated that colorectal polyps are prevalent in China, and nearly one-fifth subjects developed polyps during the study period. Smoking was significantly associated with the presence and development of polyps, especially related to the rectal, small and single polyp. The incidence of colorectal polyps was also influenced by smoking status, daily tobacco consumption, and whether smoking was combined with a drinking habit. As potential precursor lesions of CRC, we should pay more attention to the risk factors for colorectal polyps, to better prevent and manage this series of disease.


The selective multi-nanosoldering leads to lowering the sheet resistance of the metal grid transparent conductors, while keeping the optical transmittance constant. Also, it reinforces the electromechanical stability of flexible metal grid transparent conductors against a small bending radius or a repeated loading. Finally, organic light-emitting diodes based on the flexible metal grid transparent conductors are demonstrated. Our approach can open a new route to enhance the functionality of metallic structures fabricated using a variety of solution-processed metal patterning methods for next-generation optoelectronic and micro/nanoelectronic applications.Solution-processed metal grid transparent conductors with low sheet resistance, high optical transmittance and good mechanical flexibility have great potential for use in flexible optoelectronic devices. However, there are still remaining challenges to improve optoelectrical properties and electromechanical stability of the metallic structures due to random loose packings of nanoparticles and the existence of many pores. Here we introduce a selective multi-nanosoldering method to generate robust metallic layers on the thin metal grid structures (< a thickness of 200  Recently, there have been increasing efforts in developing alternative nanomaterial TCs based on carbon nanotubes4, graphene5, metal nanowires6 and metal grids7 to replace indium tin oxide (ITO)-based films. Among these nanomaterial-based TCs, the metal grid TCs have been spotlighted for use in flexible optoelectronic devices due to facile control over their grid width and spacing, scalability to large-area application, uniform sheet resistance and low junction resistance11. Especially, the metal grid TCs are typically fabricated using a variety of printing technologies of metal nanoparticles (NPs), including inkjet printing11, gravure printing12, micro-contact printing13 and direct imprinting16 at low costs and in a high throughput manner.Transparent conductors (TCs) are essential components for a variety of optoelectronic devices, including organic solar cells17, photonic sintering18, laser sintering19 and chemical sintering20. They exhibited the poor electrical conductivity compared with the evaporative metal grids obtained using photo-roll lithography23 due to random loose packings of NPs, incomplete elimination of organic complexes and the existence of many pores between NPs25. Oh et al.16 carried out experiments on temperature-controlled direct imprinting of silver ionic ink, enhancing the optoelectrical properties of metal grid TCs by the porosity reduction. The unsintered metal grid structures with non-uniform shape and thickness (> μm) suffered from a local damage or a crack generation, resulting in locally unstable mechanical, electrical and optical properties during the mold detachment. Especially, these issues hindered the use of large-scale TCs.The solution-processed metal grid TCs show the electrical conductivity from merging of neighboring NPs and eliminating of insulating organic complexes by several sintering processes, including thermal sinteringet al.26 introduced the SG metal grid TCs generated using electroless plating and soft lithography on a glass substrate. After rapid thermal annealing, the SG metal grid TCs showed superior optoelectrical properties than those obtained using vacuum-based metal deposition: sheet resistance (Rs) of 3.5 Ω sq−1 vs 10.7 Ω sq−1 at transmittance (T550nm) of 76%, respectively. Jin et al.27 suggested a method for directly generating the SG metal grid TCs on polyethylene terephthalate (PET) substrates, which were coated using a poly(dopamine) to improve interfacial adhesion between the SG metal NPs and the substrate. The SG metal grid TCs exhibited Rs of 8 Ω sq−1 at T550nm of 91% and a reasonable electromechanical stability under bending stresses. Also, Khan et al.28 showed the metal grid structures that are embedded and mechanically anchored onto a flexible substrate using electroplating process. This method could provide flexible metal grid TCs with the high aspect ratio, showing Rs < 1 Ω sq−1 at T550nm = 91%. However, all of these methods suffered from a time-consuming and expensive task related to the generation of polymer masks and the need of dry (or wet) etching process.Recently, solution-grown (SG) metal grid TCs fabricated using electroless plating or electroplating have been reported to show excellent optoelectrical properties. Sciacca nm) can be fabricated using a self-pinning assisted direct inking of silver ions based on the ink capturing. When the mold is detached in a liquid state of ink, the process facilitates the prevention of unwanted structural damages from the metal grids. After the SMN treatment, the metal grid structures based on loosely packed metal NPs were transformed into compact and robust metallic structures. The effect of SMN on the optoelectrical properties of the metal grid TCs was evaluated by considering cycle number, growth time (tG), growth temperature (TG), sintering temperature (TS). Also, the effect of SMN on the electromechanical stability of flexible metal grid TCs after a transfer process was examined under static and dynamic bending stresses.Here we introduce a selective multi-nanosoldering (SMN) method for simultaneously enhancing both optoelectrical properties and electromechanical stability of solution-processed metal grid structures without polymer masks and etching process. The thin metal grid structures  to form the silver NP structures and to eliminate of larger amounts of organic insulating complexes, which cause the generation of many pores inside the metal NP structures16.The metal grid structures were fabricated on a glass substrate S) that is given by S = σsg − σsl − σlg, where σ is the interfacial tension between two different phases, including solid-gas (σsg), solid-liquid (σsl) and liquid-gas (σlg), respectively. When S < 0, an equilibrium force balance at contact lines is described by Young’s equation, given by σsg = σsl + σlgcos θE, where θE is an equilibrium contact angle. However, θE of the liquid droplet was modulated by the NPs confined at contact lines. Weon et al.29 suggested a simple model to quantitatively describe the self-pinning behavior of colloidal droplet by equating a spreading force (Fs = 2πRS) with a capillary force (Fc = 2πrNσlg (cosθ)2) at contact lines, where R is the diameter of droplet, r is the average diameter of NPs, N is the number of NPs at contact lines and θ is the contact angle, respectively. They insisted that the self-pinning behavior of the colloidal droplet should be generated at a critical value of 15° and a critical linear packing fraction of 10%, regardless of the NP size and the initial volume fraction.Figure θE of a silver ionic ink droplet was modulated from the thermally decomposed silver NPs and organic complexes confined at contact lines. Figure θE of the ink droplet after ink addition and heating. An ink volume of 5 μl was added to the ink droplet (5 μl). The measured θE of the ink droplet without heating showed similar (or slightly decreased) values due to solvent evaporation. After heating at 60 °C for 2 min, the ink droplet showed the spreading behavior at θE = 50°. The measured θE of the ink droplet increased with an addition of ink due to the thermal reduction of silver ions. The measured θE of the ink droplet slowly decreased with solvent evaporation. This self-pining behavior is important to guarantee the physical continuity and the rigorous resolution of the grid-patterned ink as well as the capture of large amounts of ink.Similar to the colloidal droplet, Rs of 20 Ω sq−1 at T550nm of 88.0%. In Fig. Rs and T550nm of the metal grid TCs for different heating times were compared. Figure The self-pinning of the grid-patterned ink was easily controlled by a heating time at a fixed temperature of 60 °C to minimize unwanted residual layers within grid spacings. In Fig. −7 Ω m) than that of bulk silver (1.59 × 10−8 Ω m). Especially, when the size of the metal grid structures decreases to micro/nanoscale, the resistivity can be considerably increased and locally unstable due to electron scattering at grain boundary of loosely packed NPs30. Figure tG = 1 min (SMN 1). The SG silver NPs were deposited on the metal grid TCs with minimum residual layers within grid spacings, and then were merged at 250 °C for 1 min. In Fig. As the metal grid structures include random loose packings of silver NPs with many pores, they usually have larger electrical resistivity /Rs)−2, where σOp and σDC are the optical and direct current conductivity of the nanostructure-based TCs, respectively. The term σDC/σOp is used as a figure of merit (FoM), whose larger value represents better TC performance. Figure T550nm. Figure Rs and T550nm of the SG metal grid TCs with different widths after SMN 1. When a linewidth decreased with keeping T550nm of 90% by a geometrical consideration, the metal grid TCs showed the higher sheet resistance due to electronic scattering and local defects. Especially, the metal grid TCs with a linewidth of 3 μm showed RS of ~kΩ, which lowered to few hundred Ω after SMN 1. This result means that the SMN treatment leads to enhancing optoelectrical properties of micro/nanoscale metallic structures fabricated using a variety of solution-based patterning processes.Optoelectrical properties of the SG metal grid TCs could be evaluated using the following equation; Rs of 13.1 Ω sq−1 and T550 nm of 78.8%) showed superior than those obtained using the ITO-coated PET film (Rs of 15.1 Ω sq−1 and T550 nm of 75.4%). The transmittance spectrum of the ITO-coated PET film decreased with significant fluctuations over the wavelength range of 400–1500 nm. On the other hand, the transmittance spectrum of the flexible SG metal grid TCs remained constant. The inset shows a photograph of the SG metal grids TCs attached on a test tube, demonstrating its flexibility and transparency.The electromechanical stability of metal grid structures against bending stresses is one of the most important issues for use in next-generation flexible optoelectronic devices. The SG metal grid TCs were transferred, and embedded into transparent and UV-curable polymer films of Norland Optical Adhesive 81 (NOA 81) to evaluate the electromechanical stability. In general, a transfer process of the metallic TCs leads to lowering a surface roughness, to giving a flexibility and to protecting them from mechanical stress and surface oxidation. After the transfer process, a transmittance spectrum of the flexible SG metal grid TCs was compared with those obtained from a commercially available ITO-coated PET film in Fig. R/Ro obtained from the flexible metal grid TCs  under static bending stresses. The inset shows an AFM surface profile and an AFM image of the flexible SG metal grid TCs where the metal grid structures were embedded into the NOA 81 film with a root-mean-square surface roughness of 4.3 nm and a maximum peak-to-valley value of 22.9 nm. All of the flexible metal grid TCs  showed superior electromechanical stability than the ITO-coated PET film under static bending stresses. However, R/Ro of the flexible metal grid TCs significantly increased at r ≤ 2.5 mm due to serious damage. R/Ro of the flexible metal grid TCs treated using SN decreased with increasing tG at r = 1 mm. The flexible metal grid TCs treated using SMN 1 showed lower R/Ro than those obtained using both SN 1 and SN 5. When the flexible metal grid TCs were bent up to r = 1 mm, the values of ΔR/Ro increased by 376% and 36%, respectively. Also, ∆R/Ro of the flexible metal grid TCs were evaluated under an extremely localized bending stress that is so called folding. Figure R/Ro of the flexible metal grid TCs under folding (r < 0.3 mm), respectively. The metal grid TCs underwent a ∆R/Ro of more than 1360%. The flexible metal grid TCs treated using SN 1 and SN 5 showed a considerable decrease of R/Ro with increasing tG . The flexible SG metal grid TCs treated using SMN 1 showed ∆R/Ro of less than 85%. The inset shows a photographic image of LED integrated circuit operation connected with the flexible SG metal grid TCs under folding. This result reveals that the SMN treatment leads to enhancing the electromechanical stability of the flexible metal grid TCs even under an extremely localized bending stress.Figure R/Ro obtained from the flexible metal grid TCs  under dynamic bending stresses with r = 7.5 mm. ΔR/Ro of the ITO-coated PET film was evaluated as a reference. Although all of the flexible metal grid TCs showed similar values of ∆R/Ro under static bending stresses with r = 7.5 mm, they exhibited different aspects of ∆R/Ro under dynamic bending stresses. After 1000 cycles of repeated bending/relaxation, ∆R/Ro obtained from the flexible metal grid TCs increased by more than 1000%. The flexible metal grid TCs treated using SN 1 and SN 5 showed a considerable decrease of ∆R/Ro with increasing tG . On the other hand, the flexible metal grid TCs treated using SMN 1 showed ∆R/Ro of less than 30%. The SMN treatment results in reinforcing the mechanical strength of the metallic structures, which leads to enhancing the electromechanical stability under static bending, folding and dynamic bending stresses.Figure −1) was used as a buffer transparent electrode on top of the flexible metal grid TCs. The low conductive PEDOT:PSS  and MoO3 were used as a hole injection layer31. On top of the MoO3, organic layers and metal electrode were sequentially deposited using thermal evaporator, and the detailed configuration is described in the experimental section. The flexible metal grid TCs-based OLEDs exhibited superior electro-luminous properties than those obtained using the flexible metal grid TCs due to excellent optoelectrical properties. Also, since the flexible metal grid structures is relatively compact and robust, the flexible metal grid TCs-based OLEDs showed leakage-free performances due to a minimal breakage during the transfer process. On the other hand, the flexible metal grid TCs-based OLEDs showed a large leakage current due to a breakage of the loose and weak metal grid structures during the transfer process that leads to rough bottom surface of the device  and power efficiency (ηPE) as high as 18.9%, and 47.6 lm/W at 103.7 cd/m2, while the flexible metal grid TCs-based OLEDs showed the limited performance as low as 15.2% and 33.8 lm/W at 95.0 cd/m2, as shown in Figs. 32. Moreover, the flexible OLEDs was evaluated to verify performance stability under dynamic bending tests with r = 4.3 mm. As a result, the flexible metal grid TCs-based OLEDs (tensile strain (εf) of 1.97%, dSub-NOA: 170 μm) shows relatively superior luminance characteristics even after 1000 cycles of repeated bending/relaxation, however, the devices based on the flexible metal grid TCs and ITO-coated PET exhibit degraded performances under the same conditions (r and applied voltage), as shown in Fig. Using the flexible metal grid TCs, the green phosphorescent OLEDs were fabricated as shown in Fig. Rs of the SG metal grid TCs without degrading T550nm, but also enhancing the electromechanical stability of the flexible metal grid under static bending, folding and dynamic bending stresses. SMN can be used with chemical or photonic sintering to enhance optoelectrical properties and electromechanical stability of various metallic structures fabricated on flexible substrates in roll-to-roll system. Also, SMN facilitates the reinforcement of optoelectrical properties and electromechanical stability of random loose micro/nanoscale metallic structures. This method is particularly a promising candidate for producing next-generation optoelectronic and micro/nanoelectronic devices based on advanced metallic structures with high transparency and conductivity, reinforced mechanical strength and flexibility.In summary, we introduced the fabrication of the metal grid structures based on self-pinning assisted direct inking of silver ions, and the demonstrated the SMN treatment for transforming the loose and weak NP networks of the metal grid structures to compact and robust metallic structures. SMN led to not only decreasing 33.The silver ionic ink  with a metal concentration of 12 wt%, consisted of silver ions , a base solvent (methanol and toluene), and additives. Before self-pinning assisted direct inking of silver ions, the silver ionic ink of 0.2 ml was heated at 100 °C for 5 min to evaporate the base solvent. The silver alkyl carbamate complexes were decomposed to silver NPs, carbon dioxide, and the corresponding alkyl amines by heating of 60 °C for a few minutesw) of 3, 5, 10, 15 μm and a spacing (s) by considering the geometrical shadow zone, T = s2/(s + w)2. The value of h is a half of w to prevent destruction of the silver NP structures during the detachment of PDMS mold.The PDMS solution  was formed by mixing the silicon elastomer kit and a curing agent (10:1), and this mixture was poured onto a SU-8 master. After PDMS curing at 100 °C for 1 hour, the PDMS replica of the grid-patterned mold was carefully released from the SU-8 master. The grid-patterned cavity was designed with a width (P < 120 kPa) and low temperatures (T = 60 °C). During solvent evaporation, some of the silver ions were thermally decomposed to silver NPs. Even after the mold detachment, the grid-patterned ink was maintained due to packings of silver NPs at contact lines of the meniscus. The grid-patterned ink was completely decomposed at heating of 150 °C to eliminate large amounts of organic complexes derived from the thermal decomposition and to improve the thermal decomposition rate of the silver ions. The silver NP structures were sintered at TS = 200–300 °C for 1 min.The silver ionic ink (~10 μL) was dispensed onto a glass substrate. It was squeezed and filled inside a grid-patterned mold under low pressures  containing silver nitrate (Tollen’s reagent) and a reducing sugar (glucose) at 30 °C. After the cleaning process, the SG silver NPs were merged with the metal grid structures by a thermal sintering.A glass substrate  was treated using 1 H, 1 H, 2 H, 2H-perfluorooctyl-trichlorosilane  for 20 min in a vacuum chamber. The SG metal grid TCs on the glass substrate were re-treated with the fluorinated silane for 5 min. The NOA 81 solution was poured onto the SG metal grid TCs on the glass substrate, and it was covered by another fluorinated glass substrate (borosilicate) to generate a uniform, thin and transparent NOA 81 film (below 200 μm). A thickness of the NOA 81 films was controlled using a stack of 3 M magic tape. The NOA 81 solution were cured to the NOA 81 film under UV exposure. After the glass substrate (borosilicate) was firstly detached from the NOA 81 film due to relatively weak adhesion energy, the flexible metal grid TCs were separated from the glass substrate .−6 Torr) with below configuration: MoO3 (10 nm)/4,4′-Bis(N-carbazolyl)-1,1′-biphenyl /CBP doped with bis(2-phenylpyridine)iridium(III)-acetylacetonate (Ir(ppy)2acac, 7 wt%) (20 nm)/2,2,2″--tris(1-phenyl-1-H-benzimidazole) /LiF (1 nm)/Al (100 nm).On top of the SG metal grid TCs, highly conductive PEODT:PSS (Clevios PH 1000) was spin-coated with 3000 rpm for 30 sec, and annealed them at 100 °C on the hot plate for 10 min. After coating the PH1000, the low conductive PEDOT:PSS (Clevios PVP AI4083) as a hole injection layer was coated with 2500 rpm for 30 sec on the SG metal grid TCs as well as ITO pre-coated (150 nm) PET as a control device. After coating the PEDOE:PSS, samples were loaded into a thermal evaporator to deposite the organic multilayers, inorganic buffer layers and a metal electrode under high vacuum condition . Two electrodes between the metal grids, separated by a square area (25 mm2), were fabricated using conductive pens of CW2200MTP and CW2900 (ITW Chemtronics). The electro-luminance characteristics of OLEDs were measured using a source meter , a fiber-optic spectrometer  and a calibrated Si-photodiode  in N2-filled glove box. The motorized goniometric system was used to characterize angular electroluminescence profile of OLEDs. The cyclic bending test of OLEDs was performed using a custom-made bending tester that can control the number of cycles and a bending radius.The SG metal grid TCs were imaged using field-emission SEM . Cross-sectional profiles of the SG metal grid TCs were measured using FIB-SEM , and the surface roughness of the SG metal grid TCs was measured using AFM . The transmittance spectra were measured using a UV-VIS-NIR spectrophotometer . The Supplementary information.


After provision of hearing aids, median household income improved among cases (p = 0.03). In the comparison group, median individual income (p = 0.01) and PCE (p = 0.03) fell between baseline at follow-up. At follow-up, there were also improvements in productive time use, quality of life, and depressive symptoms among cases, but these were less apparent in the comparison group. In conclusion, this study has demonstrated a positive effect of hearing aids in improving quality of life, economic circumstances and mental health among Guatemalan adults.There are 466 million people globally with disabling hearing loss, many of whom can benefit from hearing aids. The aim of the study was to assess the impact of providing hearing aids on poverty, mental health, quality of life, and activities, among adults in Guatemala. A nonrandomised before and after study was conducted, with a comparison group to assess for secular trends. Adult cases with bilateral hearing impairment were identified within 150 km of Guatemala City, as well as age- and sex-matched comparison subjects without disabling hearing loss. All participants were interviewed with a semistructured questionnaire, and cases were offered hearing aids. Participants were reinterviewed 6–9 months later. We interviewed 135 cases and 89 comparison subjects at baseline and follow-up. At baseline, cases were poorer than comparison subjects with respect to individual income ( Hearing loss is very common; an estimated 466 million people globally live with disabling hearing loss, defined as >40 dBHL average at frequencies 0.5, 1, 2, and 4 kHz in the better hearing ear in adults (15 years or older) or >30 dBHL in the better hearing ear in children (0 to 14 years) [Disabling hearing loss has wide-ranging impacts. It diminishes the capacity to detect and localise sounds and recognize speech, and thereby adversely affects communication. As a consequence, people with hearing loss may find it difficult to participate in different activities, particularly those that require social interaction and communication ,4. For iMany people with disabling hearing loss can benefit from provision of hearing aids. A hearing aid does not restore normal hearing or repair the underlying damage that has caused the hearing loss. However, the aid can help to improve sound detection and speech understanding, and thereby improve a person’s ability to take part in everyday life. Evidence from high-income countries shows that provision of hearing aids has benefits , includiThe aim of this study was to assess the impact of hearing aid provision on multidimensional outcomes, including poverty, mental health, quality of life and activity participation, among adults living in Guatemala. Guatemala is a lower middle-income country in Central America. A nonrandomised before and after study with a comparison group was conducted to assess the impact of hearing aids provision on poverty, quality of life, depression, functional activity and participation, among adults with disabling hearing loss compared to comparison subjects without disabling loss. The study participants were selected from adults living in Guatemala, and the follow-up period was 6–9 months.Ethical approval for the study was granted from the ethics committees of the London School of Hygiene and Tropical Medicine and the Zugueme Comite Etica Independiente, based in Guatemala City. All research participants gave written informed consent to take part in the study. People identified as having hearing loss were referred to services for diagnosis and, where appropriate, provision of hearing aids.We aimed to identify 200 cases with disabling hearing loss and 200 comparison subjects without disabling hearing loss. This sample size was appropriate to detect a 30% improvement in quality of life after provision of hearing aids, with 80% power and 95% confidence .http://sonrisasqueescuchan.org.gt/), based in Guatemala City in 2015. An experienced audiologist screened potential cases through pure-tone audiology, using calibrated, portable equipment. Cases were eligible for inclusion if they were aged ≥15 years, their bilateral hearing loss was classified as “disabling” (measured as 41 dB and above in the better ear), and they lived within 150 km of Guatemala City. Furthermore, cases were only included if they were judged to be eligible for subsidized hearing aid provision, as they were unable to finance the service independently, and so would be from relatively poor households.We identified adult cases who had disabling hearing loss through the community outreach, ear-health screening activities of the Sonrisas que Escuchan Foundation (We asked each case to identify three neighbors or nonrelated people living in their community of a similar age (+/− 5 years) and of the same sex to identify a matched comparison group. All potential comparison subjects were visited in their homes and underwent an auditory screening test by a trained fieldworker using a portable, electronic-tablet-based ‘’Shoe-Box Application’’ audiometer. Participants who presented with disabling hearing loss were excluded from the comparison group and offered a referral and follow-up assessment at the Sonrisas que Escuchan Foundation. Initially, eligible comparison subjects were restricted to those with normal hearing, but after difficulties identifying eligible subjects, the eligibility criteria for comparison subjects were extended so that those with mild hearing loss (26–40 db) were included.All cases and comparison subjects were interviewed at baseline (October 2015–January 2016), with a semistructured questionnaire, including the following items:Poverty was measured through assessing assets, income and per capita expenditure (PCE), based on previous approaches  and deveActivities data was collected using an activity list , based uWe assessed depressive symptoms using the Patient Health Questionnaire . This toQuality of life was measured using the WHOQOL-BREF, a person-centered tool for assessing subjective well-being, which has been translated into many languages and has good psychometric properties . It inclSociodemographic data was also collected, including marital status, education level and literacy level .A pair of trained fieldworkers administered the questionnaire in Spanish, in the participant’s home, using a mobile data collection tool (the “KoBo Toolbox”).The Sonrisas que Escuchan Foundation contacted all cases after baseline data collection, and cases were given a clinic appointment for fitting with hearing aids. World Wide Hearing donated behind-the-ear devices, which were brand-new and made by Phonak (Baseo Q15 Model). These instruments are considered to be reliable and quality devices, which provide effective sound quality. They are suitable for people with mild–profound hearing loss.All cases and comparison subjects were revisited in their homes and reinterviewed in July–August 2016 (6–9 months later) using the structured questionnaire, with some additional components . We measured actual hearing aid usage data, which was electronically downloaded from the device during a follow-up clinic appointment, as well as self-reported hearing aid use from the interview data.At baseline, we compared the demographic characteristics and outcome variables between cases and comparison subjects using logistic regression, adjusting for the matching variables of age and sex. Our hypothesis was that we would observe an improvement in outcomes for cases between baseline and follow-up, but no change for comparison subjects. We did not adjust for other variables, such as SES, as these may have been on the causal pathway between hearing loss and the outcomes .t-test was used to compare the mean quality of life scores before and after the intervention. These analyses were repeated for comparison subjects, to assess whether there had been secular trends in these variables during the follow-up time period that needed to be taken into account in interpretation of data. A difference-of-difference comparison was not undertaken, as the study was not adequately powered for this test.We reported the median income and expenditure at baseline and follow up. A comparison between baseline and follow-up was performed within the cases using a Wilcoxon sign rank test, to account for the paired data. A similar test was performed within the comparison subjects to identify if the secular trends could explain the changes, or lack of changes, observed in the cases. A similar approach was applied to the depression, but Mcnemar’s test was performed as the outcome—depression—was a binary variable. A paired We identified 201 cases with moderate-profound hearing loss, of whom 21 (10%) were excluded as they had unilateral hearing loss. The remaining 180 cases had bilateral, disabling hearing impairment, including 49% with moderate impairment, 39% severe impairment and 12% profound hearing loss. We identified 263 potential comparison subjects, of whom 120 (46%) were excluded because they had disabling hearing loss (98%) or an inconclusive test result (2%), leaving 143 in the comparison group for inclusion in the study. After follow-up, we reinterviewed 135 cases (75%), with the remainder lost to follow-up (96%) or who had lost or suffered theft of their hearing aid (4%). Among the comparison group, 89 (62%) were reinterviewed, and the remainder were lost to follow-up (89%) or refused to be reinterviewed (11%). Data were restricted to cases and comparison subjects who completed both baseline and follow-up questionnaires.p = 0.01), as were older people (p = 0.003), but there was no difference in follow-up by gender or category of PCE (as proxy for socio-economic status—SES). Most (71%) of the cases reported that they used their hearing aids every day, of whom 93% stated that they used them at least four hours each day, and 69% for 8–16 h daily. Self-report data were very similar to actual hearing aid usage data, which showed that 98% of cases wore their hearing aids for at least 1–4 h per day, and 53% wore them for 8–16 h each day.Cases were more likely to be followed-up than comparison subjects , and case households had lower annual household income than comparison households (p = 0.02) (p = 0.003). After provision of hearing aids, there was an improvement in median household income among cases (p = 0.03). In the comparison group, there was a fall in median individual income (p = 0.01) and PCE (p = 0.03) during this time period. Allocation of PCE  did not change after follow-up among cases or comparison subjects (data not shown).At baseline, amongst those who were receiving income, individual income was significantly lower among the cases than the comparison subjects ( = 0.02) . Similarp < 0.001) and more time on paid tasks or self-employment (p = 0.05). No changes in time allocation were observed in the comparison group after follow-up.At baseline, cases spent more time on household tasks than people in the comparison group . After hp = 0.05). At follow-up, there were significant improvements in depression (p = 0.03), depressive symptoms (p = 0.02) and severity of depressive symptoms (p < 0.01), among cases compared with baseline. Similarly, in the comparison group there were improvements in depressive symptoms (p = 0.01) and severity of depressive symptoms (p = 0.03).At baseline, few participants reached the diagnostic threshold for depression, whether they were cases (4%) or in the comparison group (1%) . We alsoAt baseline, cases had poorer quality of life than comparison subjects, across all domains excepting psychological quality of life and overall quality of life, where the differences were not statistically significant . After hWe found that at baseline, adults with disabling hearing loss living around Guatemala City were poorer than the comparison group without disabling hearing loss in terms of individual and household income and PCE. Furthermore, cases spent more time on household tasks, were more likely to experience depressive symptoms and had poorer quality of life than the comparison group. After receipt of hearing aids, cases spent more time on paid work or self-employment, and experienced improvements in household income. At the same time, the comparison group suffered a fall in individual income and PCE, as well as in the social relationships score, which was not apparent in the cases. These data are consistent with a worsening in economic conditions in the comparison group, with provision of hearing aids buffering cases from these impacts. Both cases and comparison subjects reported improvements in mental health at follow-up. Cases showed more substantial gains in quality of life than the comparison group during follow-up, and these were most pronounced in the domains of psychological, social relationships and environmental, and so are plausibly attributable to improved ability to communicate.These findings are consistent with the existing literature, in terms of the broad impact of hearing impairment. A systematic review investigating the association between poverty and disability in LMICs included 150 studies and showed strong evidence for this relationship, including for people with sensory impairment . Data frThe findings also support the existing literature in terms of finding a positive impact of hearing aids, although almost all existing data are from high-income settings. A systematic review of 16 studies concluded that hearing aids improve adults’ health-related quality of life by reducing psychological, social and emotional effects of sensorineural hearing loss . A seconThe literature from LMICs is far sparser, and includes mostly small-scale impact studies. However, these have also shown that hearing aid usage contributes towards better quality of life and mental health. For instance, one study from Turkey with a relatively small sample size (including only 37 participants) demonstrated that depressive signs reduced and psychological state and mental function improved within 3 months of hearing aid use in an elderly population . SimilarThere are a number of strengths and limitations that must be taken into account when interpreting the findings of the study. Unexpectedly, we detected mild–severe hearing loss among 66% of potential comparison participants. Consequently, we extended the eligible age range from 5 to 10 years in order to reach the necessary sample size of the comparison group. However, this meant that on average cases were older than comparison subjects, with the increased possibility of residual confounding by age. Additionally, the eligibility criteria for comparison subjects was extended so that those with mild hearing loss (26–40 db) were included. This change could mean that cases and comparison group would be more similar in key outcomes, so that as a result the study could have been under-powered to detect differences between the two groups. The study population consisted of adults living within a 150 km radius of Guatemala City, making generalisability to other settings uncertain. The cases were selected from a low socio-economic status group, who could not afford hearing aids and so were eligible for subsidized hearing aid provision, and this may have over-estimated differences in poverty at baseline between cases and comparison groups, although comparison subjects were selected from the same communities. A drop in the median income for the comparison subjects was observed between baseline and follow-up, making it more complex to make inferences on the impact of hearing aids. However, population-based economic data were not available for this time period in this region of Guatemala, making it difficult to understand the fall in the income in the comparison group, and the implications for the study findings. Follow-up was also relatively short, at just 6–9 months. In terms of strengths, multidimensional outcomes were measured using validated tools, and a comparison group was included to adjust for secular trends.This study has filled an important evidence gap by demonstrating a positive effect of hearing aids in improving quality of life and mental health among Guatemalan adults. There is also evidence that hearing aid provision may have buffered cases from the economic downturn experienced by comparison subjects during the follow-up period. It is well known that there are currently large gaps in coverage and accessibility of hearing aids, despite their potential positive impacts, as the international production and supply of hearing aids meets less than 10% of the global need . This si


South Africans have an increasing burden of hearing loss, especially in low-income rural areas. Limited information is available regarding caregivers’ knowledge and views regarding infant hearing loss, which is essential for the successful implementation of early hearing detection and intervention (EHDI) programmes.The main aim of the study was to describe the knowledge and views of mothers with children aged between 0 and 5 years old regarding hearing screening, risk factors, symptoms of hearing loss, and intervention options for hearing loss.A survey was employed at a primary care clinic to gain insight into the maternal views on hearing loss and early intervention services for children aged 0–5 years old.The majority (83.2%) of the mothers believed that hearing can be tested at birth, 90.7% believed in the biomedical model of intervention which is based on cure, prevention, and pathology as opposed to traditional or alternative medicinal beliefs, and 95.3% indicated that they would seek medical attention if they noticed symptoms of hearing loss. Consequences of hearing loss, such as academic, communication and social problems, were indicated by 65.4% of mothers.The findings demonstrated that although cultural beliefs regarding superstitious causes of hearing loss and use of traditional medicine exist, satisfactory maternal knowledge regarding detection and intervention for hearing loss is present. Maternal views are favourable and a general willingness to participate in EHDI programmes was present. This study advocates for the implementation of EHDI programmes at all primary healthcare clinics across South Africa. Roughly 141 million live births occurred in the world in 2012, approximately 127 million of which occurred in developing countries  if the mothers are aware that hearing could be tested and/or screened at birth, (2) what mothers do when they first suspect that their children have a hearing loss, (3) maternal knowledge regarding the consequences and recognition of unidentified and untreated hearing loss, and (4) whether mothers believe in the biomedical model or traditional medicine regarding intervention for hearing loss.Inclusion criteria were mothers with children aged 0–5 years, who who were either English, Setswana, Isizulu and Xitsonga proficient, and who were 18 years and older. Exclusion criteria were mothers who had children older than 5 years, who were not literate (unable to read or write), who did not understand English, Setswana, IsiZulu and Xitsonga, and who were younger than 18 years of age.Purposive sampling was used because this method is based on the judgement of researchers regarding the characteristics of a representative sample  was used to conduct the descriptive study.The study was conducted at a primary healthcare clinic in the north of Pretoria, South Africa, that provides EHDI services. The clinic services a large population in the north of Pretoria and provides all primary healthcare services. Although selection of a single clinic may influence the generalisation of results, this clinic services populations from various African backgrounds, as described in Speech-Language Pathology and Audiology students have community outreach programmes at the clinic where they educate mothers about the cause, prevention and treatment of hearing loss. There are also audiology services provided at the clinic and the audiologist does biweekly home visits in the community.A structured questionnaire with open- and closed-ended questions was used. The questionnaire was adapted from focus group questions used in a study in India . Consent was obtained from the Gauteng Department of Health, as well as from the clinic manager before commencement of data collection. For the purpose of the current study, confidentiality and anonymity of respondents were maintained by ensuring that no names appeared on the completed questionnaires.n = 102, 95.3%) lived in Soshanguve, 1 (0.9%) came from Hammanskraal and 3.7% (n = 4) did not provide a home address.The self-administered survey was completed by 107 mothers attending a semi-urban primary healthcare clinic in Tshwane. The minimum age of the mothers in years was 18, and the maximum age was 47. Most mothers (The majority (83.2%) of the mothers reported that hearing can be tested between the ages of 0 and 5 years, whilst 9.3% reported that hearing can be tested at any age.n = 102) would take their child to the clinic, doctor or audiologist.When mothers were asked what they would do if they suspected that their child has a hearing loss, the overwhelming majority of the participants  indicated that their child should be taken to the traditional healer and 2.8% (n = 3) did not give a response, which could indicate a lack of knowledge or uncertainty in understanding the question even though literacy was an inclusion criterion for this study.A limited number of participants  indicated that, should a child have normal hearing, the child will look at you when spoken to and 23.4% (n = 25) mentioned that the child will startle when hearing a loud sound. Results revealed that most  mothers believed that children will not respond to speech if they have a sign of hearing loss. A few reported that blood or discharge coming out of the ear could indicate hearing loss. A large number of participants  reported that hearing loss can cause communication, academic and social problems and 13.1% (n = 14) stated that hearing loss could lead to emotional problems. Only 2.8% (n = 3) of the participants indicated that hearing loss can be identified by doing a hearing test.The knowledge of mothers regarding the consequences and recognition of unidentified and untreated hearing loss revealed that the majority of the mothers , infant jaundice and oxygen after birth  and maternal high blood pressure . Only five participants  indicated complications during pregnancy such as bleeding, anaemia, fibroids, placenta praevia and thrombocytopoenia. The remainder of the participants  indicated no pre-, peri- or post-natal risk factors or problems.The reported pre- and post-natal risk factors were prematurity (n = 70) indicated that hearing loss can result from ear malformations or infections, 15.9% (n = 17) indicated that it could result from loud noise. Eight (7.5%) of the participants indicated that hearing loss may be a result of punishment from gods or a curse . Furthermore, 2.8% (n = 3) indicated both ear malformations or infections and noise as a possible cause of hearing loss. A few  indicated a blocked ear, 0.9% (n = 1) indicated putting objects in the ear, and 6.5% (n = 7) didn’t respond, which could indicate a lack of knowledge or understanding of the question. When asked if they believe that hearing loss can be a curse, most  indicated no, 22.4% (n = 24) indicated yes and 8.4% (n = 9) were unsure and indicated maybe; 4.7% (n = 5) indicated that they did not know. Almost all participants  indicated that children can be taken to the doctor if they have hearing loss. This supports the notion that most mothers believe in the biomedical model of health as opposed to traditional medicine.More than half of the participants  were of the opinion that hearing aids would be an effective treatment option. The second most common treatment option (9.3% (n = 10) was aural rehabilitation. The least common treatment option was the use of herbs from a traditional healer . A single participant (0.9%) indicated that all three treatment options could be consulted. Thirteen of the participants (12.1%) indicated that they didn’t know of any treatment options. Most parents  indicated that special schools would be the educational option for a hearing-impaired child. Eighteen participants (16.8%) indicated inclusive schools and 11.2% (n = 12) indicated mainstream schools.With regard to treatment of hearing loss, most of the participants  of the mothers indicated that they would regularly visit a doctor or audiologist, followed by avoiding noise exposure , however, it is significant from the results that some  mothers believe that hearing loss can be avoided by praying or giving an offering to the gods and/or ancestors.In terms of the prevention of hearing loss, the results obtained indicated that the majority  exhibit substantial and often similar challenges when it comes to the healthcare system and attaining universal health coverage  have been identified  required assistance when completing the questionnaire, even though they reported being literate. Assistance with completion of the questionnaire could introduce social desirability bias (the desire of respondents to present themselves in the best possible light), however, some research has reported no differences between interviewer versus self-completion modes and type of response Bowling, . The widThis study was representative of a semi-urban population and results from rural and/or urban populations may be different. Further research is required to determine the readiness of mothers to receive EHDI services in urban, semi-urban and rural primary healthcare clinics across South Africa.This study was conducted to gain insight into the knowledge and views of mothers regarding hearing loss, as mothers play a very important role in the health of their children. The results indicated that the majority of the mothers believed that hearing can be tested at birth. An overwhelming number of mothers indicated that they would seek medical attention if they noticed symptoms of hearing loss in their children. A large number of mothers indicated academic, communication and social problems as possible consequences of hearing loss. Most mothers believed in the biomedical model. These results indicate that the mothers have appropriate awareness regarding hearing loss and its management. This could be attributed to the active audiological services in the community regarding prevention, diagnosis, and intervention of hearing loss.In order for the mothers to make correct and appropriate health decisions for their children, they need to have knowledge about health disorders in their childhood years. Hearing loss is one of the childhood disorders that both mothers and caregivers need to be aware of in light of the high prevalence rates. The current study demonstrated that although cultural beliefs regarding superstitious causes of hearing loss and use of traditional medicine exist, satisfactory maternal knowledge regarding detection and intervention for hearing loss is present. Maternal views are favourable and a general willingness to participate in EHDI programmes was present. This study advocates for the implementation of EHDI programmes at all primary healthcare clinics across South Africa.


Age-related hearing impairment (ARHI), also referred to as presbycusis, is the most common sensory impairment seen in the elderly. As our cochlea, the peripheral organ of hearing, ages, we tend to experience a decline in hearing and are at greater risk of cochlear sensory-neural cell degeneration and exacerbated age-related hearing impairments, e.g., gradual hearing loss, deterioration in speech comprehension , difficulty in the localization sound sources, and ringing sensations in the ears. However, the aging process does not affect people uniformly; nor, in fact, does the aging process appear to be uniform even within an individual. Here, we outline recent research into chronological cochlear age in healthy people, and exacerbated hearing impairments during aging due to both extrinsic factors including noise and ototoxic medication, and intrinsic factors such as genetic predisposition, epigenetic factors, and aging. We review our current understanding of molecular pathways mediating ARHL and discuss recent discoveries in experimental hearing restoration and future prospects. Aging is a progressive decline or loss of tissue and organ function over time due to the gradual accumulation of deleterious biological changes. The aging process has three distinct components: biological degeneration, extrinsic damage, and intrinsic damage. These factors are superimposed on a genetic substrate and can be overshadowed by the general age-related susceptibility to diseases. Age-related diseases are those that are observed with increasing frequency with increasing age, such as atherosclerosis, cardiovascular disease, cancer, arthritis, cataracts, Alzheimer’s disease, presbyopia, and presbycusis. Whereas all adult humans or animals become old, not all suffer from age-related diseases. Age-related diseases can be conceptualized as accelerated aging resulting from the genetic background interacting throughout life with environmental and lifestyle factors .Presbycusis, or age-related hearing loss (ARHL), is the loss of hearing that gradually occurs in most people as they grow older. According to the World Health Organization , approxiEpidemiologic studies in large populations of unscreened elderly adults show that the decline in hearing sensitivity accelerates above the age of 20 to 30 in men, and above age 50 in women ,5. The aBased on temporal bone analyses correlating the patterns of hearing loss with defect location, Schuknecht  proposedThis review recapitulates our current understanding of biological cochlear aging on hearing, extrinsic and intrinsic risk factors that exacerbate age-related hearing function decline in animal models and in humans, the molecular pathways mediating cochlear cell senescence and degeneration as a consequence of aging, injury , and genetic predisposition. We discuss also the recent discoveries in experimental hearing restoration.The clinical presentation of presbycusis, the rate of the progression, age at onset, and ultimate severity of hearing loss varies from patient to patient. Whereas the majority of elderly patients present clear hearing losses, a significant fraction of the geriatric population has almost normal hearing. This is due to intrinsic , and extrinsic factors  that are either the sole etiology for hearing loss, or several work in synergy with the physiopathology of presbycusis .The clinical diagnosis of presbycusis is based on bilateral progressive loss of hearing starting from a high-frequency region of the hearing spectrum. Loss of hearing can begin in young adulthood, but is initially evident at 60 years for most people . Over tiTo study the impact of cochlear aging on hearing, animal models are a useful tool due to their short lifespan, controlled environments and diet composition, and limited genetic heterogeneity. Gerbils that grew up in quiet environments  showed vGSTM1 and the GSTT1 null genotypes) and N-acetyltransferase 2 (NAT2*6A) [UCP2 Ala55Val polymorphisms exhibited a significant association with ARHL [Presbycusis shows a clear familial association. Heritability studies of presbycusis in humans have estimated that 25% to 75% of the variance in this pathology has a genetic component ,27,28. GNAT2*6A) ,30,31 weNAT2*6A) . The maiNAT2*6A) . In a Jaith ARHL .GRHL2), nonsyndromic sensorineural deafness type 5 (DFNA5) and potassium voltage-gated channel subfamily q Member 4 (KCNQ4) genes, whose mutations are responsible for DFNA28, DFNA2, and DFNA5, respectively [GRM7, e.g., OMIM ID: 604101) [An increased individual susceptibility to ARHL may rely on single nucleotide polymorphisms in the grainyhead-like 2 gene  ,39. Fina 604101) .age-related hearing loss gene 1 (Ahl1), localized in chromosome 10, Ahl2 [Ahl1 locus), and Ahl3 on chromosome 17 [Some genes associated with ARHL have also been identified in mice, including 10, Ahl2  on chromosome 17 . The AhlTraditionally, genetics and adult lifestyle factors are considered to be among the main determinants of aging-associated pathological conditions. Accumulating evidence, however, suggests that epigenetic factors may contribute to these conditions ,43. The SLC26A4, DFNB4) and purinergic receptor P2X 2  resulted in an increased risk for presbycusis in men. In addition, reduced expression of P2RX2, KCNQ5, ERBB3, and SOCS3 genes through DNA hypermethylation in elderly women was associated with presbycusis [CDH23) gene is likely to be associated with presbycusis in elderly women [Age-related changes in DNA methylation include global hypomethylation and region-specific hypermethylation . In the sbycusis . More rely women . These rHistone proteins including H1/H5, H2A, H2B, H3, and H4 are the chief proteins of chromatin and play an important role in maintaining the shape and structure of a nucleosome. In the last few years, the role of histone modifications in aging and age-related diseases has emerged. Watanabe and Bloch  investigThe complexity of etiological factors for presbycusis begins with the number of environmental risk factors, such as occupational or leisure noise, ototoxic medication , cigarette smoking, and alcohol abuse . HoweverA retrospective clinical study from a large cohort of men in the Framingham Heart Study observed that in ears with presumed cochlear damage from previous noise exposure, subsequent progression of ARHL was exacerbated at frequencies outside the original noise-induced hearing loss . These oIncreasing evidence from animal aging models indicates that early noise exposure renders the inner ears significantly more vulnerable to aging and may have an impact on the onset and/or progression of ARHL ,52,53. ITo date, the influence of other environmental risk factors such as ototoxic medications, cigarette smoking, or alcohol abuse on ARHL is less clear and often controversial. Recently, a large longitudinal cohort study (n = 3753) aimed at elucidating the association of ototoxic medications exposure with the risk of developing hearing loss during the 10-year follow-up period demonstrated that ototoxicity-age interactions may also exacerbate age-related hearing loss in older adults .Our understanding of the molecular mechanisms associated with age-related cochlear cell degeneration and hearing loss has advanced in recent years. There are a number of pathophysiological processes that were reported to be associated with age-related changes to functional components in the inner ear. Here, we highlight recent advances in identifying various mechanisms involved in the “pro-, or anti-aging process” of the cochlea .The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of reactive oxygen (ROS)- and nitrogen species (RNS)-induced DNA, lipid, and/or protein damage. ROS and RNS are generated by several biochemical and physiological processes of cellular metabolism. ROS and RNS are mainly generated by the mitochondria, endoplasmic reticulum, and peroxisomes under both physiological and pathological conditions. Fortunately, cells are able to counteract excessive ROS/RNS production via the activity of antioxidant enzymes such as superoxide dismutases (SODs), copper/zinc superoxide dismutase (Cu/Zn SOD), catalase, GPX (glutathione peroxidase), and GSR (glutathione reductase), as well as a variety of small-molecule antioxidants such as glutathione (GSH) and thioredoxin .Increasing evidence links oxidative stress to ARHL ,59. Low 2O2) was able to induce a premature senescence phenotype in House Ear Institute-Organ of Corti 1 (HEI-OC1) mouse auditory cells. These displayed mitochondrial morphology damage, reduced mitochondrial membrane potentials, an imbalance of mitochondrial fusion/fission, and an impaired mitochondrial respiratory capacity [2O2 exposed cochlear explant in culture and adult SAMP8 mice in vivo, we demonstrated that ROS-induced DNA damage responses drive cochlear cell senescence and contribute to accelerated ARHL [Oxidative stress may cause irreversible DNA damage , includicapacity . Furtherted ARHL .The incidence and frequency of mtDNA point mutations and deletions increase exponentially with age and contribute to cellular senescence in humans, monkeys, and rodents, thus providing a causative link between mtDNA mutations and aging phenotypes in mammals . In the POLG-encoding DNA polymerase γ that maintains mtDNA replication fidelity [OPA1 encoding the mitochondrial dynamin-like GTPase impact mtDNA genomic stability. These mutations are also known to cause premature hearing loss in patients and mice [Mutations in fidelity  or OPA1 and mice . Mice exand mice . These Pand mice . Finallyand mice . Thus, aMitochondrial biogenesis is the process by which cells increase their individual mitochondrial mass and copy number to increase the production of ATP as a response to greater energy expenditure, or during times of cellular stress . We show2O2)-exposure initiated a DNA damage response together with increased levels of key hallmarks of senescent cells, including increased expression levels of p21, and positive senescence-associated β-galactosidase labeling cells in cochlear explants in culture, together with increased inflammatory markers such as p38 and p-p38. Furthermore, high amounts of DNA damage and senescence-like features were observed in the cochlear tissues of SAMP8 mice during aging and were correlated with the accelerated ARHL observed in SAMP8 mice [In mitotic cells, cellular senescence is a permanent G1 arrest that is elicited in response to different stresses . The perMP8 mice . In addiMP8 mice . TogetheIt is now recognized that low-level chronic inflammation is correlated with the major degenerative diseases of the elderly . Even thBak prevented age-related loss of spiral ganglion neurons and hair cells, but also ARHL in c57BL/6J mice [BAK1/anti-apoptotic gene BCL2 was significantly upregulated in peripheral blood samples under ARHL and was also positively correlated with the results of the audiometric tests [Apoptosis may play critical roles in cochlear aging and ARHL. Several apoptosis-related genes change their expression with age and with hearing loss in the CBA mouse cochlear-aging model . Apoptos/6J mice . Consist/6J mice . Finallyic tests .Mitochondrial quality control and turnover is of particular importance to cochlear sensory and neural cells because of their constant need for high levels of energy supply. Mitochondrial functionality and integrity is achieved by the quality control mechanisms of mitochondrial dynamics (fission and fusion events) and mitochondrial autophagy (mitophagy) .Autophagy is a self-degradative process that plays a housekeeping role in removing misfolded or aggregated proteins and damaged organelles, as well as intracellular pathogens. The autophatic proteins Atg5, Atg4b, Atg9a, Beclin-1, and LC3B are expressed in the mouse and chicken cochlea from developmental stages through to adulthood . In the Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems . It has Our knowledge regarding the mechanisms of cell death provides deeper insight into various cochlear diseases and thus supports the development of pharmacological therapies. This section aims to emphasize the potential importance of antioxidants, mitochondrial metabolic regulators, apoptosis inhibitors, and neurotrophins to protect cochlear cells against age-related hearing loss .Ginkgo biloba leaves  prevented aging-related caspase-mediated apoptosis in rat cochleae [Given the role of oxidative damage in the pathogenesis of presbycusis, antioxidants may prevent the onset or progression of ARHL. Alpha-lipoic acid is an endogenous disulfide compound synthesized de novo in mitochondria, where it is an essential enzymatic cofactor and a powerful antioxidant molecule. Alpha-lipoic acid has successfully prevented ARHL in rats . Controvcochleae . Finallycochleae  , a derivative of salicylic acid, is one of the most widely used drugs worldwide. Aspirin displays anti-inflammatory and antioxidant properties . A randoSIRT3 gene, which, in turn, promotes the glutathione-mediated mitochondrial antioxidant defense system and delays the onset of ARHL in mice [The sirtuin family has seven members (SIRT1–7) which are implicated in delaying cellular senescence and extending the organismal lifespan through the regulation of diverse cellular processes, including suppression of cellular senescence and promotion of DNA damage repair . Resvera in mice . A numbeA number of specific and broad-spectrum peptide caspase inhibitors have been developed to elucidate the role of each specific caspase in cell death. Intraperitoneal injection of the pan-caspase-inhibitor z-VAD-FMK Z-VAD-FMK for eight weeks, starting at one week of age in DBA/2J and A/J mice, preserved hearing by more than 10 dB SPL in the ABR thresholds and significantly reduced OHC loss in the basal turns of the cochleae ,121. EveRecent findings from temporal bones of patients aged 54 to 89 years and without an otologic disease history indicated that the degeneration of cochlear nerve peripheral axons, despite a near-normal hair-cell population, may be an important component of human presbycusis . These dIndividual genetic predisposition and the physiological state of the subjects are confounding factors that are capable of influencing the success of therapeutic interventions. Of course, avoiding noise and other risk factors such as ototoxic drugs, diabetes, high blood pressure, and heart diseases can help prevent damage to cochlear hair cells which can minimize the effects of presbycusis later in life. However, this is not always possible, and treatments against presbyacusis are not still available. The complexity of the mechanisms underlying the various forms of sensory, neural, and/or striatal presbyacusis escape simple audiometric tests, underlying the need for more sophisticated tests to identify defects of cochlear functions, such as sound detection in noise. Another challenge is the need for the targeted delivery of drugs such as nanocarriers to improve the efficacy of drugs in cochlear therapies. The development of multifunction nanoparticles with a porous matrix, allowing encapsulation of a large range of molecules including chemicals, proteins, or gene products, is a promising perspective for future cochlear treatments . FinallyDuring the past decade, numerous efforts have been made to attempt to regrow functional hair cells or spiral ganglion neurons using adult stem cells, embryonic stem cells, and induced pluripotent stem cells in the aged inner ear. Intracerebral neural stem cell transplantation in C57BL/6J mice with presbycusis decreased apoptosis levels in the auditory cortex slightly restored auditory function and prevented further impairment of auditory function . ExogenoIn a recent pioneering study, Davidsohn et al.  showed iIn addition to pharmacological, gene, and cell therapies, progress in the technological management of presbycusis is also ongoing. Up until now, elderly individuals managed their hearing loss with hearing aids associated with listening device technologies such as frequency modulation, audio-induction loop systems, and other accessories, to coupling hearing aids with media such as phones, music players, computers, and tablet devices. However, when the hearing loss is too severe, hearing aids cannot amplify sound sufficiently, especially at the high frequencies, and this greatly compromises speech intelligibility. The remarkably improved speech discrimination observed in patients who have residual low-frequency hearing has led to the idea of extending the implantation selection criteria to patients displaying such hearing. In this context, patients with early and accelerate presbycusis may benefit from hybrid cochlear implants that combine electrical stimulation for the high-frequency loss and acoustic hearing-aid technology for the stimulation of any residual low-frequency hearing. Unfortunately, an unsolved clinical problem is the progressive loss of a patient’s residual hearing that can occur within months following cochlear implantation. Efforts to ensure the preservation of residual hearing rely on the use of soft-surgery techniques and the implantation of shorter electrode arrays to minimize the trauma caused during the process of electrode insertion ,134. CoaModern medicine is affording people longer and healthier lives. The world of artificial intelligence is quickly expanding, and hearing devices able to “learn” from our experience to address complex situations will soon be forthcoming. Moreover, the accumulation of genetic and biological biomarkers, together with classical clinical data, generates an unprecedented volume of data. These new avenues in the domain of Big Data will undoubtedly change our understanding of presbycusis, leading to molecular, individualized, patient-oriented treatments, replacing the traditional approach based on clinical symptoms and restricted laboratory or imaging markers.


Sulindac has been used for treating colorectal polyps widely. However, the efficacy and safety of sulindac for colorectal polyps are unclear. This study aims to evaluate the efficacy and safety of sulindac for colorectal polyps.Randomized controlled trials of sulindac in the treatment of colorectal polyps will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science, and Technology Periodical Database, and China biomedical literature database (CBM) from inception to August, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3.This study will summarize the present evidence by exploring the efficacy and safety of sulindac in the treatment of colorectal polyps.The findings of the study will provide helpful evidence for the efficacy and safety of sulindac in the treatment of colorectal polyps, facilitating clinical practice and further scientific studies.The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.DOI 10.17605/OSF.IO/N5GDH It may be associated with a high-fat, high-protein diet and lack of physical activity. A number of studies have also shown that metabolic syndrome-related indicators such as blood lipid, blood glucose, and body mass index are correlated with colorectal polyps.,4The colorectal polyp is a mass protruded from the surface of the colorectal. It may be an adenoma or a hypertrophy of the intestinal mucosa, collectively known as a polyp until its pathological nature is determined. Polyps are solitary or multiple, and hereditary or nonhereditary. Depending on the severity of symptoms, polyps can be treated with Chinese and Western medicine, colonoscopy, laser, freezing, ligation, and transabdominal or transanal methods. A number of current epidemiological and laboratory studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit or even reverse precancerous lesions in colorectal cancer, and some prospective studies have shown that sulindac reduces the number and size of colorectal polyps in patients with colorectal cancer, especially familial adenomatous polyposis (FAP).,8 However, there is no systematic review and meta-analysis regarding the efficacy and safety of sulindac for colorectal polyps. Thus, this study will assess the efficacy and safety of sulindac for colorectal polyps.The formation mechanism of colorectal polyps is complex and affected by a variety of factors. Over a long period of time, various pathogenic factors may act independently or synergistically at different stages, eventually causing cell canceration. Some polyps can develop into colorectal cancer, and colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Early detection and treatment are the key to improve prognosis. Resection or chemotherapy of colorectal polyps is particularly important.22.1This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P). Moreover, it has been registered on open science framework (OSF) on August 26, 2020. (Registration number: DOI 10.17605/OSF.IO/N5GDH)2.2Ethical approval is not required as there is no patient recruitment and personal information collection, and the data included in our study are from published literature.2.32.3.1Randomized controlled trials (RCTs) including sulindac for colorectal polyps will be included. The language will be limited to Chinese and English.2.3.2 regardless of nationality, race, age, sex, and source of cases.All the included cases conform to the “guidelines for management of colorectal polyps,”2.3.3The control group was treated with placebo or no medication; the treatment group was treated with sulindac. The duration of treatment in both groups was not limited.2.3.4The main outcome measures were clinical efficacy and polyp disappearance rate. Invalid: the patient's condition was not improved or even aggravated. Effective: the clinical symptoms and signs such as diarrhea or increased frequency of defecation, abdominal tenderness, and other clinical symptoms and signs were alleviated, and the scores of clinical indicators were improved by 50% ∼ 79%; Significant effect: the clinical symptoms and signs such as diarrhea or defecation frequency increased, abdominal tenderness and other clinical symptoms and signs were significantly reduced, and the scores of clinical indicators were improved by >80%. Total effective = significant effective + effective.Secondary outcome measures were adenoma diameter change and adverse reactions. ① Polyp characteristics: the pathological type of polyps, the number and size of colorectal polyps, the degree of atypical hyperplasia of colorectal polyps. According to the World Health Organization (WHO) classification, the degree of atypical hyperplasia is divided into mild and severe. The adverse pathological features were defined as intraepithelial neoplasia with a diameter of >1 cm or a high degree of atypia. ② Drug safety and adverse reactions: the adverse drug reactions of sulindac in the study group were monitored by outpatient review and emergency telephone emergency system every 6 months.2.4The treatment group used other drugs, such as aspirin, ibuprofen, naproxen, and so on;The outcome indicators of the original study did not meet the requirements;As for duplicate published literature, select the literature with the most complete data;Literature with incorrect or incomplete research data that cannot be obtained after contacting the author.2.5PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) were searched by computer to collect RCTs of sulindac for colorectal polyps, and the retrieval time was from the establishment of each database to August 2020. At the same time, search Baidu, Google Scholar, International Clinical Trials Registry Platform (ICTRP), and Chinese Clinical Trials Registry (ChiCTR) to get more comprehensive data. Keywords were “intestinal polyps,” “colorectal polyps,” “familial adenomatous polyposis,” “sporadic colorectal polyps,” “sulindac,” and so on. PubMed retrieval strategies are shown in Table 2.6Endnote X7 was used for literature management. Two researchers independently screened the literature, extracted the data, and cross-checked them. In case of disagreement, the third researcher was consulted to assist in judgment, and the lack of data was contacted with the author as much as possible to supplement. In the process of literature screening, first read the title and abstract, and then read the full text after excluding the obviously unrelated literature to determine whether it is included. Excel 2019 was used to set up a data extraction table to extract data.The extraction contents were as follows: ① included basic research information ; ② information about intervention measures ; ③ risk evaluation items of bias in RCTs; ④ Related outcome indicators. The literature screening process is shown in Figure 2.7Two researchers independently evaluated the risk of bias in RCTs in accordance with the Cochrane Handbook of Systematic Reviewers, including the following items: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. The quality of studies was classified as being at of high, unclear, or low risk of bias. In case of disagreement, a third researcher decided.2.82.8.1Q test was used to qualitatively determine inter-study heterogeneity. If P ≥ .1, there was no inter-study heterogeneity, If P < .1, it indicated inter-study heterogeneity. At the same time, I2 value was used to quantitatively evaluate the inter-study heterogeneity. If I2 ≤50%, the heterogeneity was considered to be good, and the fixed-effect model was adopted. If I2 > 50%, it was considered to have significant heterogeneity, the source of heterogeneity would be explored through subgroup analysis or sensitivity analysis. If there was no obvious clinical or methodological heterogeneity, it would be considered as statistical heterogeneity, and the random-effect model would be used for analysis. Descriptive analysis was used if there was significant clinical heterogeneity between the 2 groups and subgroup analysis was not available.The RevMan 5.3 software provided by the Cochrane Collaboration was used for statistical analysis. ① For dichotomous variables, relative risk (RR) was used for statistics. For continuous variables, weighted mean difference was selected when the tools and units of measurement indicators are the same, and standardized mean difference was selected with different tools or units of measurement, and all the above were represented by effect value and 95% confidence interval. ② Heterogeneity test: 2.8.2If data are missing or incomplete, we will contact the relevant authors to obtain the data. If not, this study will be removed.2.8.3To reduce the clinical heterogeneity between studies, subgroup analysis was conducted according to the age, which was divided into minors, adults, and the elderly. Subgroup analysis was carried out for the included studies according to the types of colorectal polyps.2.8.4To test the stability of meta-analysis results of indicators, a one-by-one elimination method will be adopted for sensitivity analysis.2.8.5For the major outcome indicators, if the included study was ≥10, funnel plot was used to qualitatively detect publication bias. Egger and Begg test are used to quantitatively assess potential publication bias.2.8.6 And the quality of evidence will be rated as high, moderate, low, and very low.The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used to assess the quality of evidence. It contains 5 domains .3Colorectal polyp is a common disease of digestive tract, which can be divided into non-neoplastic and neoplastic. Non-neoplastic polyps mainly include inflammatory polyps, proliferative polyps, and juvenile polyps. The etiology of colorectal polyp mostly comes from gene mutation, gene suppression, and family inheritance. For example, familial adenomatous polyposis and Gardner syndrome are caused by gene mutation; the pathogenic gene of Peutz-Jeghers syndrome may be a tumor suppressor gene; Turcot syndrome and juvenile polyp are familial genetic diseases. Neoplastic polyps mainly refer to adenomatous polyps, with a high probability of canceration, which is the most important precancerous disease of colorectal cancer and has a rising trend in recent years.,13 Studies have confirmed that NSAIDs have a very significant protective effect on intestinal polyps, colon cancer, and rectal cancer, which can reduce the risk of intestinal polyps by 78%, colon cancer by 87%, and rectal cancer by 85%. However, smoking and drinking are also risk factors, whereas eating bean products and vegetables are protective factors. Therefore, when using such drugs to prevent the above diseases, we should pay attention to personal life and behavior habits. If we can cooperate with abstinence, quit smoking, and eat bean products and vegetables properly, we should also pay attention to the protection factors. In vitro studies also showed that NSAIDs and cyclooxygenase-2 (COX-2) inhibitors could inhibit the formation of colorectal tumors by inhibiting cell proliferation, inducing apoptosis, inducing cell cycle arrest, and interfering with tumor angiogenesis through cox-dependent and nondependent mechanisms.,15Clinical studies have shown that long-term use of natural or synthetic drugs, such as NSAIDs, may prevent polyps from developing in the colon, this effect known as chemoprophylaxis. reported that sulindac had a regression effect on FAP patients. Researchers have found that the effect of sulindac in FAP patients act after 3 months. Polyps were significantly subsided in all patients after taking sulindac for 12 months, regardless of whether they had undergone surgery. Long-term maintenance therapy with sulindac can reduce the number of residual colorectal adenomas, the degree of heteromorphism and the proportion of villous tubular adenoma in patients, which may delay or prevent the occurrence of colon cancer. Piazza found that sulindac derivatives did not promote the differentiation of adenoma cells during cell culture, and induction of apoptosis was one of the main mechanisms. It was further speculated that sulindac may reduce the degree of adenoma atypia by inducing apoptosis of adenoma cells. So far, although sulindac is not enough to replace surgery, patients still need to regularly review colonoscopy, but it can be used as a beneficial supplement to surgical treatment.Sulindac is a precursor drug with minimal activity, which can be metabolized into active sulfide after entering the human body. It can inhibit cyclooxygenase and reduce the synthesis of prostaglandins, thus has analgesic, anti-inflammatory, and antipyretic effects. As early as 1983, Waddell and LoughryHowever, there is no systematic review and meta-analysis assessing the efficacy and safety of sulindac for colorectal polyps. This is the first protocol for systematic review and meta-analysis evaluating the efficacy and safety of sulindac for colorectal polyps. This systematic evaluation and meta-analysis can provide evidence-based evidence for clinicians to use sulindac in the treatment of colorectal polyps. However, the study has some limitations. Due to different dose and course of sulindac for colorectal polyps, the results were affected and the bias was caused. In addition, we only search for articles in Chinese and English, which may cause certain publication bias.Data collection: Qing Long and Liang Ao.Data curation: Qing Long, Liang Ao.Formal analysis: Qing Long.Funding acquisition: Yan Li.Funding support: Yan Li.Literature retrieval: Liang Ao and Kuo Li.Resources: Liang Ao, Kuo Li.Software: Liang Ao.Supervision: Yan Li.Writing – original draft: Qing Long and Liang Ao.Writing – review & editing: Qing Long and Yan Li.