The mechanical strength and crosslinking density of the F-LSR-POSSs were determined using a universal testing machine (UTM) and dynamic mechanical analysis (DMA), respectively. Finally, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) measurements confirmed that the low-temperature thermal properties were maintained, and the heat resistance was significantly improved compared with conventional F-LSR. Eventually, the poor heat resistance of the F-LSR was overcome with three-dimensional high-density crosslinking by introducing POSS-V as a chemical crosslinking agent, thereby expanding the potential fluorosilicone applications.Fluorosilicone rubber (F-LSR) is a promising material that can be applied in various cutting-edge industries. However, the slightly lower thermal resistance of F-LSR compared with that of conventional PDMS is difficult to overcome by applying nonreactive conventional fillers that readily agglomerate owing to their incompatible structure. Polyhedral oligomeric silsesquioxane with vinyl groups (POSS-V) is a suitable material that may satisfy this requirement. Herein, F-LSR-POSS was prepared using POSS-V as a chemical crosslinking agent chemically bonded with F-LSR through hydrosilylation. All F-LSR-POSSs were successfully prepared and most of the POSS-Vs were uniformly dispersed in the F-LSR-POSSs, as confirmed by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy ( Hsilicone ,12,13,14A large amount of silica can be introduced into silicone matrices compared to other fillers owing to the similar compositions, without significantly changing the original properties and color of silicone. Nevertheless, the agglomeration of silica particles can occur inside the silicone matrix, thus resulting in some silicone property degradation ,15. To p1.5)8 comprises a robust framework and eight organic functional groups [T-8 POSS of the cage-type silsesquioxane with the general formula , NMR, scanning electron microscopy (SEM), matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-ToF MS), X-ray diffraction (XRD), UTM, differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA).4, >99%), tetramethyltetravinylcyclotetrasiloxane , divinyltetramethyldisiloxane , and hexamethyldisiloxane  were purchased from DAMI POLYCHEM . Meanwhile, 1,3,5-trimethyl-1,3,5-triscyclotrisiloxane  was purchased from the HRS Corporation . To prepare the liquid silicone, fumed silica was purchased from Grace Continental Korea .All chemicals and solvents were commercially available and used without further purification. Tetramethylammonium hydroxide  and methanol were purchased from Alfa Aesar . Octamethylcyclotetrasiloxane (D4 (261.07 g), 0.882 mol F-D3 (413.25 g), and 0.036 mol Vi-D4 (12.40 g) were charged into a flask under an argon atmosphere at 90 °C for 1 h to maintain the initiating temperature. Next, 0.3 wt% tetramethylammonium silanolate  and 0.006 mol ViVi (1.116 g) were added to the solution and stirred at 300 rpm under an argon atmosphere for 5 h. After the reaction, the product was heated to 150 °C and maintained for 24 h under vacuum to remove unreacted reactants and initiators. Finally, the products were purified with methanol to eliminate cyclic monomers. The purified F-silicone was a transparent, high-viscosity liquid obtained with a yield of 85%.Raw F-silicone was synthesized in a 1 L four-neck flask with a mechanical stirrer and reflux condenser. Before initiating polymerization, 0.882 mol D4 and F-D3 were charged into a flask under an argon atmosphere at 90 °C for 1 h to maintain the initiating temperature. The reaction was initiated by adding TMAS to the reactor under stirring at 300 rpm and 90 °C. After initiating the reaction, H-D4 was added dropwise to this solution over 0.5 h under vigorous stirring using a 250 mL dropping funnel. Subsequently, the end-blocker MM was added to the reactor, and the mixture was stirred at 90 °C for 2 h. After the reaction, the products were heated to 150 °C and maintained under vacuum for 24 h to remove unreacted reactants and initiators. Finally, the products were purified with methanol to eliminate the cyclic monomers.The F-crosslinker was synthesized in a 1 L four-neck flask with a mechanical stirrer and reflux condenser. First, Dv/v 1:3) and allowed to stand for 24 h at room temperature. The recrystallized POSS was collected by filtration using filter paper and dried overnight in an air circulation oven at 60 °C. The purified POSSs were obtained as white powders in 30–40% yields. All synthesized POSS-Vs had vinyl content of 100, 75, 50, and 0%, named POSS-V8, POSS-V6, POSS-V4, and POSS-V0, respectively.An acetone (500 g) solution containing a mixture (0.45 mol) of VTMS and MTMS was charged into a 1 L four-neck flask equipped with a mechanical stirrer. The solution was stirred at 300 rpm under an argon atmosphere at 40 °C. HCl was added dropwise to this solution over 2 h under vigorous stirring using a 250 mL dropping funnel. Next, the mixture was stirred at 40 °C for 34 h and subsequently cooled to room temperature. After the reaction, a white solid was deposited on the flask wall. The white powder was filtered and washed with copious amounts of ethanol, water, and acetone and subsequently dried in an air circulation oven at 60 °C overnight. The crude product was recrystallized from a mixture (300 mL) of dichloromethane and acetone  to ensure complete dispersion. Next, raw F-silicone and F-crosslinker were added successively to the beaker and mixed vigorously using a hand mixer. The amount of reactant was adjusted such that the ratio of Si–H/Si–Vi in the product was maintained at 1, and the total amount was 300 g. The mixture was then placed in a vacuum oven  at 100 °C for 2 h to remove residual moisture and air bubbles. Subsequently, 0.1 g of Karstedt’s catalyst was mixed using a hand mixer  at 300 rpm and directly injected into the molding cavity for hot-press molding. All the F-LSR-POSSs were compression-molded at 140 °C for 5 min and post-cured at 200 °C for 4 h in an oven. The formulations of all synthesized F-LSR-POSSs are presented in −1 by acquiring 32 scans under vacuum (pellet composed of KBr and substrate at a ratio of 100:1). The analysis was conducted within the frequency range of 4000–400 cm−1.Fourier transform infrared spectroscopy (FT-IR) was used to analyze the functional groups of the prepared POSS-Vs. FT-IR spectra were obtained using a VERTEX 80 V spectrometer  with a resolution of 1 cm1H-NMR at 400 MHz ) was performed to elucidate the detailed chemical structure and calculate the ratio of each functional group of the sample. All samples were prepared in 0.6 mL of CDCl3, and the NMR spectra were recorded.−1 by acquiring 16 scans. The analysis was performed within a frequency range of 4000–400 cm−1.Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) spectra were obtained using a Spectrum 2 spectrometer  with a resolution of 1 cmSEM  was used to observe the morphology of the POSS-Vs. Elemental mapping was performed using energy-dispersive spectroscopy .MALDI-ToF MS was performed using an Autoflex maX  instrument equipped with a 355 nm ND:YAG laser in the positive ion reflection mode, with 1,8,9-anthracenetriol as the matrix and silver trifluoroacetate (AgTFA) as the ion source. The samples were prepared by mixing dithranol (10 mg/mL in THF), the sample (1 mg/mL in THF), and AgTFA. Electrospray ionization of the samples was performed at a capillary voltage of 3 kV.The crystal structures of the F-LSR-POSSs were determined by XRD  using a Cu Kα radiation generator within the 2θ range of 5°–90°.Tensile tests of the F-LSR-POSSs were performed according to the ASTM D-412 method using a universal testing machine. All test specimens were dumbbell-type 1 at room temperature with a crosshead speed of 500 mm/min. The hardness of the F-LSR was analyzed according to ASTM D2240-15el using an ASKER Durometer type A .The storage and loss moduli of the F-LSR-POSSs were measured via DMA using a dynamic mechanical analyzer in tensile mode under an argon atmosphere. All samples were scanned from −130 to 30 °C at a heating rate using a frequency of 1 Hz.DSC  was used to investigate the thermal properties at low temperatures. DSC measurements of all samples were performed using 5–10 mg of the sample from −130 to 30 °C, at heating and cooling rates of 10 °C/min, under an argon atmosphere.TGA was carried out using a TGA 4000 instrument , wherein the samples were heated from 40 to 750 °C at 10 °C/min under a nitrogen atmosphere. The weight loss rate curves of all samples were obtained by differentiating the TGA thermograms.The entire synthetic process of F-LSR-POSS is illustrated in −1 in all spectra was attributed to the–Si–O–Si– asymmetric stretching vibration of the F-silicone and F-crosslinker. In addition, the absorption bands of –CF3 (1210 cm−1), Si–CH3 (1226 cm−1), the –CH bond in –CH3 (2960 cm−1), the −CH2−CH2− bond (1315 cm−1), and the C−H bond in −CH2− (1128 cm−1) were observed in the spectra of the F-silicone and F-crosslinker. A characteristic absorption band at 2245 cm−1 for the Si–H bond was observed in the FT-IR spectrum of the F-crosslinker [2=CH2 bond in the F-silicone FT-IR spectrum was difficult to identify because of the small amount of CH2=CH2 present. In the NMR spectra of the F-silicone and F-crosslinker, a peak corresponding to Si–CH3 at approximately 0 ppm was confirmed , loss modulus (E′), and tan δ of the F-LSR-POSSs are shown in gT was measured at approximately −81 °C, thus exhibiting similar viscoelastic behavior as fluorosilicone, as reported previously [gT. Interestingly, the tan δ value at gT decreased with increasing vinyl content of POSS-V and increasing POSS-V8 loading in the F-LSR-POSSs  is proportional to the crosslinking density [σ is the crosslinking density of the F-LSR-POSSs; R is the gas constant; T is the absolute temperature; and E′ is the elastic modulus of the F-LSR-POSSs in the rubbery plateau region. In addition, the molecular weight between the crosslinking sites can be defined using the following formula:cM is the molecular weight between the crosslinking sites of the F-LSR-POSSs; and ρ is the F-LSR-POSS density. The crosslinking densities and molecular weights of the crosslinking sites are presented in 3, which is identical to that previously reported for fluorosilicone rubber [cM of F-LSR-V0-0.5 increased from 18,841 to 33,332 g/mol compared with that of the F-LSR-raw. This indicates that POSS-V0 cannot be chemically crosslinked with silicone because it contains only methyl groups, without vinyl groups. Therefore, POSS-V0 acts as a physical filler, thereby reducing the crosslinking density and increasing the cM of the F-LSR. Conversely, at constant POSS-V loading, the increasing vinyl group content of the POSS-V increased the crosslinking density of F-LSR-POSS while decreasing cM. With the increasing vinyl content of POSS-V, the number of hydrosilylation chemical crosslinking sites with F-crosslinker increased, and the crosslinking density of F-LSR-POSS increased. Furthermore, with increasing numbers of chemical crosslinking points, the dense crosslinking points resulted in a decreased cM. cM of F-LSR-POSS with different POSS-V8 loadings. Evidently, with increasing POSS-V8 content, the crosslinking density increased significantly as cM decreased. This is consistent with the previous results that reported that the crosslinking density increases owing to an increase in vinyl group content. Therefore, with increasing POSS-V loading, the crosslinking density of the resulting F-LSR-POSSs also increases. Further, POSS-V with vinyl groups as a chemical crosslinking agent was confirmed to significantly affect the crosslinking density of the F-LSR-POSSs.However, the storage modulus value at the rubbery plateau ( density . All F-L density ,47,48.(e rubber . Figure gT of the F-LSR-raw was measured at −96.6 °C via DSC analysis (gT measured by DSC compared with DMA owing to the difference in the measurement method [gT of all F-LSR-POSSs with different POSS-V loadings was around −96 °C. Similarly, the gT of all F-LSR-POSSs measured by DMA was approximately −81 °C. Therefore, the gT values of the F-LSR-POSSs did not change significantly with varying vinyl group ratios and POSS-V loading. Thus, the introduction of POSS-V as a chemical crosslinking agent into F-LSR-POSS did not significantly change the thermal properties at low temperatures and had little effect on the cold resistance of the F-LSR-POSSs.The thermal properties of the F-LSR-POSSs at high and low temperatures were analyzed using DSC, DMA, and TGA . The Tg analysis  and −81.t method . Generalt method ,50. Therd10, Td30, and Td50, respectively, and Tdmax denotes the fastest mass loss rate in the DTG curve (d10, Td30, and Td50 of the F-LSR-raw were determined to be 448.5, 494.7, and 523.2 °C, respectively, whereas Tdmax was observed at 514.19 °C. The degradation points of all F-LSR-POSSs were confirmed to shift to higher temperatures compared with the F-LSR-raw. Two factors increased the heat resistance of F-LSR-POSSs when POSS-V was introduced. First, the high-density chemical crosslinking owing to the increased vinyl group content strengthened the bonding between silicone chains. Second, the framework structure of POSS-V, which has a higher ratio of inorganic Si–O bonds than silicone, can increase the heat resistance of the F-LSR-POSSs. Increasing the vinyl group content of POSS-V is speculated to increase the number of chemical crosslinking sites, thus resulting in improved heat resistance. Meanwhile, with increased POSS loading, the degradation of the F-LSR-POSSs shifted to considerably higher temperatures (d10, Td30, Td50, and Tdmax values of F-LSR-V8-0.5 were 454.00, 500.94, 530.76, and 530.27 °C, respectively; these are significantly higher than those of the F-LSR-raw. Remarkably, Td50 increased by >90 °C when only 5 wt% POSS-V8 was added, thus indicating that the heat resistance was considerably improved with POSS loading. Interestingly, with further increasing POSS-V8 content, the amount of residue >700 °C increased. Generally, silicone rubber can be converted to silica at high temperatures and chemically crosslinked POSS can accelerate this phenomenon [TGA was performed to determine the effect of POSS-V on the thermal properties at high temperatures, and TG curve . As showeratures b. In pargT values were identified through DSC and DMA analyses, and the cold resistances of the prepared F-LSR-POSSs were verified. Although all gT values of the F-LSR-POSSs were slightly changed upon POSS introduction, the fluctuation range was within 2 °C and it did not significantly affect the cold resistance. However, the heat resistance of the F-LSR was dramatically changed upon POSS introduction and the Td50 was improved by >90 °C when only 5 wt% of POSS-V8 was added. This indicated that POSS with various vinyl groups could be introduced into F-LSR as a crosslinking agent and successfully crosslinked in the LSR matrix. The low mechanical strength and heat resistance of fluorosilicone could be improved by POSS introduction. This study clearly established strategies to increase the operating temperature of fluorosilicone and expand its application potential to harsh conditions.F-LSR-POSSs were prepared by introducing POSS-V with vinyl groups as a chemical crosslinking agent to improve the heat resistance of fluorosilicone, which has excellent cold resistance but poor heat resistance compared with general PDMS. First, F-silicone, F-crosslinker, and various POSSs required for the fabrication of F-LSR-POSS were successfully synthesized and characterized. Most POSSs were well dispersed within the F-LSR via chemical crosslinking. When the loading of POSS-V8 exceeded 5 wt%, phase separation occurred between F-LSR and POSS owing to the large amount of trifluoropropyl groups in F-LSR, as confirmed by XRD and SEM. In terms of mechanical properties, the elongation and hardness consistently exhibited opposite trends with varying POSS loadings or types of POSS. Although the mechanical properties improved upon POSS introduction, no defined correlation between the tear and tensile strengths and the type or loading of POSS-V could be established. DMA analysis confirmed the storage modulus, loss modulus, and tan δ of POSS-V with different vinyl content. In addition, higher ratios of vinyl groups in POSS-V and higher POSS-V8 loadings increased the crosslinking density of the resulting F-LSR-POSSs.


In this study, full iron tailings concrete (FITC) was created using iron tailings from a tailings pond in Qian’an, China. Iron tailings account for 86.8% of the total mass of solid raw materials in the FITC. To enable large-scale use of FITC, a comprehensive investigation of the structural behaviour of full-iron tailing-reinforced concrete (FITRC) specimens is warranted. Therefore, eight rectangular reinforced concrete (RC) columns with conventional reinforced concrete (CRC) as a control were tested to investigate the effects of section dimensions, initial eccentricities, and concrete strengths, on the structural behaviour of FITRC columns under large eccentric short-term loading. The experimental and analytical results indicated that the sectional strain of the FITRC columns satisfied the plane-section assumption under short-term loading, and the lateral deflection curve agreed well with the half-sinusoidal curve. In addition, the FITRC columns exhibited a slightly lower cracking load and lower ultimate load capacity than the CRC columns, and the crack widths were larger than those of the CRC columns. The reduction in the load capacity observed in the FITRC was within the permissible range stated in the design code, thereby satisfying the code requirements. The deformation coefficients of the FITRC and CRC columns were identical, and the cracking and ultimate loads calculated according to the current code and theories were in good agreement with the measured results. Tailings are a major source of solid waste generated by the separation of valuable fractions from ore during mining operations ,2. ImproConcrete is a leading construction material, with an annual global consumption of approximately 25 billion tonnes . The conIron tailings are inert at room temperature ,27. PrevTo enable the extensive application of iron tailings in reinforced concrete, it is imperative to validate the structural behaviour of reinforced concrete samples containing iron tailings compared with plain concrete. A study was conducted to compare the flexural behaviour of iron tailings sand concrete beams and conventional concrete (CC) beams . The resThese studies show that the mechanical behaviour of reinforced concrete (RC) specimens made from iron tailings sand replacing fine aggregates is marginally different from that of conventional reinforced concrete (CRC) specimens. However, very few studies have been conducted on the mechanical behaviour of full iron tailings reinforced concrete (FITRC) specimens. The novelty of this study is the use of full iron tailings concrete (FITC), which was produced using iron tailings powder as an admixture, iron tailings gravel as a coarse aggregate, and iron tailings sand as a fine aggregate. To the best of our knowledge, this is the first investigation of the structural behaviour of FITRC columns under large eccentric loads. We aimed to comprehensively evaluate the characteristics and limitations of FITRC columns to provide a theoretical basis for the large-scale use of iron tailings. We believe that this study will be of practical significance to structural engineers in China. Previous dam failures in tailings ponds have caused significant casualties and property losses and have adversely affected the environment. Therefore, large-scale use of iron tailings in RC can effectively dispose of iron tailings, reduce the consumption of resources needed for cement production and sand mining, and ensure sustainable development.All the samples were in powder form (<50 μm). The mineral composition of the raw materials was determined using X-ray diffraction (XRD). Quartz is the primary mineral in iron tailings, with trace amounts of anorthite, haematite, and microcline , all of Ordinary Portland cement (P.O 42.5) was selected, and its primary indices are listed in −3 and bulk density of 1666 kg·m−3. River sand has a fineness modulus of 2.6, apparent density of 2650 kg·m−3 and bulk density of 1623 kg·m−3.The concrete mix proportions were designed according to the JGJ55-2011 specification in China . In totaThe mechanical behaviour of the concrete, including cubic and prismatic compressive strength, splitting tensile strength, modulus of elasticity, and Poisson’s ratio, was tested according to GB/T 50081-2019 . The tesAn HRB400 grade rebar was selected, consisting of 14 mm and 16 mm diameter longitudinal bars and 8 mm diameter stirrups. L/h) should not exceed 5. The 1200 mm high specimen had 150 mm × 250 mm sectional dimensions and symmetrical reinforcement of two 14 mm rebars in tension and two 14 mm rebars in compression made of C45 strength concrete. The 1500 mm-high specimen had a 200 mm × 300 mm section and asymmetric reinforcement with three 16 mm rebars in tension and two 16 mm rebars in compression made from C35 concrete. To ensure that the specimens could withstand a large eccentric load, cow legs were placed at the top and bottom of the specimen. The concrete was poured into three FITRC columns and one CRC column.To mitigate the effect of an additional bending moment on an eccentrically pressurised column specimen, the span-depth ratio , which is known as the second-order effect of eccentrically loaded columns [Considering the axial and flexural deformations that occurred in the RC columns under large eccentric loads during the experiment, the axial capacity, moment, and crack resistance should be calculated across the section at the mid-span of the column depth.  columns ,60. Duri columns .pφ and Δp of RC columns can be expressed as:According to , the relThis equation is valid only if the first- and second-order deformations of a column can be expressed as sinusoidal shapes.η can be expressed as:Therefore, the moment augmentation factor ae is introduced because of uncertain load locations, uneven concrete quality, and construction variations, and a value of 20 mm is considered with an eccentricity of ie = e0 + ae.In the design code, an additional eccentricity In general, the bearing capacity under eccentric compression is calculated using the equivalent rectangular stress diagram , assuminThe compressive stress curve of the concrete in the compression zone was replaced with an equivalent rectangular diagram. According to the equilibrium conditions of the forces, the following formula was obtained.α1 is the equivalent rectangular stress block coefficient of concrete in the compression zone, defined as 1.0; b and h are the sectional dimensions of the RC columns; ytf and ycf are the yield strengths of the tensile and compressive longitudinal bars, respectively; stA and scA are the sectional areas of the tensile and compressive longitudinal bars, respectively. According to the resultant point of various forces on the tensile specimens in e is the distance from the point of axial force to the resultant point of stA of tensile longitudinal bars, h0 is the distance from the resultant point of stA of tensile longitudinal bars to the edge of the compressive concrete, x is the depth of concrete in the compression zone, sta is the distance from the resultant point of stA of tensile longitudinal bars to the edge of the tensile concrete, and sca is the distance from the resultant point of scA of compressive longitudinal bars to the edge of the compressive concrete.Here, mγ is the plastic section modulus, with the rectangular section set to 1.55; ctα is the tensile stress limit coefficient of concrete, offset to 0.85; A0 is the area of the transformed section; and W0 is the elastic section modulus of the tensile edge of the transformed section, calculated as:I0 is the moment of inertia of the column section, y0 is the distance from the axis of gravity of the transformed section to the compression edge, and ρ is the reinforcement ratio of the tensile longitudinal bars.According to the SL191-2008 standard in China , the craAccording to the aforementioned formulae, the moment augmentation factor and bearing capacity of the RC columns were calculated using the measured mechanical parameters of the rebar and concrete, respectively, and compared with the experimental results. As shown in η should be 1.0 when L/h ratios do not exceed 5.0. Furthermore, the moment augmentation factor of the FITRC columns is greater than that of the CRC columns in the control group. The measured moment augmentation factors of the six FITRC columns are close to each other, with a maximum value of 1.079, whereas the η value of the FITRC columns increases by a maximum of 1.5% compared to the CRC columns. This is because the L/h ratios of the RC columns in this study do not exceed 5.0 and the impact of the second-order effects is marginal.η of the FITRC columns should be 1.15 for safety reasons.In addition, Under large eccentric short-term loads, the failure modes of the FITRC and CRC columns were found to be similar, and the failures were manifested by the yielding of the tensile and compressive rebars and concrete crushing in the compression zone. The long-term behaviour of FITRC (creep and shrinkage) requires further investigation.As the prismatic compressive and tensile strengths of the FITRC columns were slightly lower than those of the CRC columns, the ultimate load capacity of the FITRC columns was slightly lower than that of the CRC columns, and the crack widths of the FITRC columns were greater than those of the CRC columns.The sectional strain of the FITRC columns, which was similar to that of the CRC columns, satisfied the planar section assumption, and the lateral deflection curve agreed well with the half-sinusoidal assumption, which is consistent with the CRC column assumption in the current specifications.Compared with the CRC45 and CRC35 columns, the ductility factors of the FITRC45 and FITRC35 columns were 36.6% and 19.5% lower, respectively. The underlying cause of this phenomenon was the comparatively low modulus of elasticity of FITC, which resulted in a more pronounced lateral deformation of the FITRC columns when subjected to eccentric loading than the CRC columns under equivalent conditions.Based on the current Chinese standards, the theoretical calculations for the cracking load and ultimate load capacity of FITRC columns are relatively accurate. The calculation results indicate that FITRC columns have a certain safety reserve, and that FITC has the potential for practical application in the construction sector.L/h ratios should be investigated further.Because the lateral deflection of the FITC columns was greater than that of the CRC columns, the second-order moments of the FITC columns were greater than those of the CRC columns. If the second-order effect is considered in the structural design, the moment augmentation factor of the FITRC columns should be 1.15 for safety reasons. Therefore, FITRC columns with high This study investigated the structural behaviour of FITRC columns under large eccentric loading. Six FITRC columns and two CRC column specimens were examined to investigate the effect of different raw materials, section dimensions, and eccentricities, on the mechanical behaviour of RC columns under large eccentric compression. The following conclusions were drawn from this study:The ductility factor of FITRC columns is much lower than that of CRC columns, so the ductility of FITRC columns can theoretically be improved by stirrup reinforcement. However, this hypothesis requires further investigation.


Teaching Point: Multiple micronodular pneumocyte hyperplasia (MMPH) is a less-known presentation of tuberous sclerosis complex (TSC) associated lung disease that usually requires no treatment or follow-up imaging. Tuberous sclerosis complex (TSC) is a genetic systemic disorder characterized by the formation of widespread hamartomas and other dysplastic lesions in various organs. The typically affected organs are the brain, kidneys, lungs, skin, and heart.Pulmonary involvement is frequent in patients with TSC, most typically lymphangioleiomyomatosis (LAM). LAM is characterized by multiple cystic lung lesions, which can lead to pneumothorax or chylous pleural collection and ultimately can cause progressive pulmonary failure. Multiple micronodular pneumocyte hyperplasia (MMPH) is a second and lesser-known presentation of lung disease associated with TSC. Early diagnosis of MMPH on computed tomography is critical to prevent unnecessary treatment or follow-up, since MMPH is not progressive and is asymptomatic.In this case report, we will discuss a patient with TSC and signs of MMPH on a screening computed tomography scan of the chest.We present a case of a 37-year-old woman with a history of tuberous sclerosis without any respiratory complaints.A computed tomography scan was ordered to examine lung involvement secondary to TSC. Multiple scattered nodules, both solid and ground glass, were noted in a random distribution pattern , 2. The Lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH) are both classic manifestations of lung involvement in TSC. The prevalence of LAM is estimated at around 40% of female patients with TSC and increases with age up to around 80% prevalence in patients above 40 years old.LAM presents typically with progressive cystic lesions in the lungs which can cause recurrent pneumothorax, chylous pleural collection and can lead to progressive pulmonary failure. A lesser-known presentation of pulmonary involvement of TSC is multiple micronodular pneumocyte hyperplasia (MMPH). MMPH is characterized by the proliferation of type II pneumocytes along the alveolar septa combined with an increase in alveolar macrophages, fibrotic interstitial thickening, and possible lymphocytic infiltration . MMPH afMMPH typically presents multiple pure ground glass nodules in a random distribution pattern , 2, 3. TMultiple micronodular pneumocyte hyperplasia is a less-known presentation of TSC associated lung disease compared to lymphangioleiomyomatosis. It presents as multiple pure ground glass nodules with a random distribution pattern on computed tomography. Patients with MMPH are typically asymptomatic and lung lesions are not progressive. Treatment or follow-up imaging are therefore unnecessary.


Although IgG4-related disease (IgG4-RD) can affect various organs, its association with a cardiac mass is exceptionally rare. Here, we report a case of a woman with IgG4-RD and a cardiac mass and discuss 10 similar cases reported previously.A 65-year-old woman was referred to our hospital for chest discomfort and back pain.In accordance with the 2019 ACR/EULAR diagnostic criteria for IgG4-RD, she was diagnosed with IgG4-RD based on dense lymphocytic infiltration on histopathology, IgG/IgG4-positive cell ratio <40%, >10/hpf IgG4-positive cells on immunostaining, and paraspinal zone soft tissue lesions in the chest.An external pacemaker was implanted for the complete atrioventricular block on the electrocardiogram. After the diagnosis of IgG4-RD, she was treated with glucocorticoids and rituximab.She remains under observation without disease recurrence.IgG4-RD are usually treated with glucocorticoids; however, in cases of a cardiac mass, life-threatening complications may occur and surgery is often needed. Combination therapy with glucocorticoids and rituximab may be effective even in patients with IgG4-RD and cardiac mass, which may avoid the need of invasive treatments, such as surgery. Most patients are men and aged > 50 years.,3 Glucocorticoids are the treatment of choice. Several disease-modifying antirheumatic drugs, such as methotrexate and azathioprine, have been used as steroid-sparing treatment of IgG4-RD, although studies confirming their efficacy are lacking. International consensus guidance statement suggest that patients should be treated initially with 0.6 kg/day of prednisolone for 2 to 4 weeks. In 2001, Hamano et al first reported that patients with sclerosing pancreatitis have high serum IgG4 levels and diffuse infiltration of IgG4-positive plasma cells in the pancreas; since then, abundant infiltration of IgG4-positive plasma cells has been demonstrated in many extra-pancreatic sclerosing lesions.,6 IgG4-RD can affect almost all organ systems, but rarely affects the heart.,7 We report a case of serum IgG4-negative IgG4-RD with a cardiac mass, which responded well to glucocorticoids and rituximab.IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disease characterized by tumefactive lesions, dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells, storiform fibrosis, and, often, elevated serum IgG4 levels.18F-fluorodeoxyglucose positron emission tomography/CT showed uptake in the cardiac mass , anterior mass of the twelfth thoracic vertebra (SUVmax = 4.5), and both lung apices (SUVmax = 2.6)  Fig. A. IgG4-R.6) Fig. B. Based ,9–17 Among these cases, the mean patient age was 62 years. In a previous study of 493 patients, the mean ages at symptom onset for patients from Asian and non-Asian countries were 57.7 and 59.5 years, respectively. The location of the cardiac masses was variable; however, the salivary glands were the most common site of extracardiac lesions. Serum IgG4 levels were measured in 6 patients, with a mean value of 800 mg/dL. The pretreatment serum IgG4 level was normal in only a single patient. In a cross-sectional study, serum IgG4 levels were elevated in 86% of 114 patients. Among patients with IgG4-RD and a cardiac mass, the proportion of patients with normal serum IgG4 level was similar to that among patients with typical IgG4-RD. IgG4-RD is usually treated with glucocorticoids; however, the association of IgG4-RD with a cardiac mass may lead to life-threatening complications and surgery is often required. Nevertheless, some such patients have been treated with only internal therapy. Matsumura et al reported a case in which the cardiac mass decreased after administration of 0.6 mg/kg/d of prednisolone, and the patient remained stable for 12 months. Carbajal et al reported a case in which the cardiac mass decreased in size in response to treatment with high-dose steroids. The combination of rituximab and glucocorticoids is particularly useful in patients who have steroid-resistant disease or are unsuitable for steroid use. Carruthers performed an open-label study of 30 patients with IgG4-RD who were treated with rituximab, most without glucocorticoids; 97% of patients had improved disease, and 40% maintained complete disease remission after 12 months. In our patient, rituximab was added to prednisolone when the latter was ineffective; the cardiac mass decreased in size in response to rituximab and prednisolone treatment. Our case suggests that combination therapy with glucocorticoids and rituximab may be effective even in patients with IgG4-RD and cardiac mass, which may avoid the need of invasive treatments, such as surgery.IgG4-RD was initially identified in patients with autoimmune pancreatitis and an elevated serum IgG4 level. It is characterized by extensive infiltration of IgG4-positive plasma cells and T lymphocyte in various organs and storiform fibrosis. IgG4-RD rarely affects the heart. To the best of our knowledge, there have been 10 previous reports on IgG4-RD affecting the heart Table .Conceptualization: Kaichi Kaneko.Writing – original draft: Kensuke Namba, Kaichi Kaneko.Writing – review & editing: Daiki Sakai, Hiroshi Mikamo, Yuta Sugizaki, Yoshiya Sugiura, Nobuyuki Hiruta, Yasuo Matsuzawa.


The increase in antibiotic resistance has been linked to antibiotic exposure. However, initiatives of antibiotic stewardship programs have been associated with decrease in antibiotic utilization but without a clear decrease in antibiotic resistance. We hypothesized that outpatient antibiotic exposure in communities geographically close to hospitals contribute to their incidence of ESBL producing Enterobacteriaceae (ESBL-PE).Outpatient antibiotic prescriptions per 1000 population by zip codeTotal antibiotic prescriptions per zip codeFrom March 2022 to March 2023 we evaluated antibiotic utilization in the inpatient and outpatient setting of a healthcare system in central Georgia. Outpatient settings included urgent cares, emergency rooms, and primary care clinics. The incidence of ESBL-PE was obtained from each hospital’s antibiogram. We calculated the number of outpatient prescriptions per zip code. Nearest neighbor analysis was used to determine the closest hospital for each zip code, with each zip code having a unique "nearest" hospital. The number of antibiotic prescriptions for those zip codes were assigned to that hospital. To estimate the antibiotic “burden” for each hospital, we used days of therapy (DOT) per 1000 days present of inpatient antibiotic use, plus antibiotic prescriptions per zip code population. Percentage of ESBL-PE for each hospital was the independent variable. QGIS v3.8 was used for spatial analysis.Inpatient antibiotic use and ESBL-PE percentageOutpatient antibiotic useThere were 61 070 outpatient antibiotic prescriptions and 500 092 DOT. Prescriptions were given to residents of over 1000 different zip codes of nearly 20 states. 60% of the prescriptions were from urgent care centers, 1 for every 2 encounters. Inpatient antibiotic use varied among hospitals, with no correlation between antibiotic use and percentage of ESBL-PE. Linear regression model had an R2 of over 0.8 although with a p-value of 0.8.The geographic reach of outpatient antibiotic prescriptions is of concern. The burden in their surrounding communities could be contributing to antibiotic resistance in hospitals, explaining the discrepancy of inpatient antibiotic use and antibiograms. Efforts to decrease antibiotic resistance should also include interventions in outpatient facilities. Our model didn’t reach statistical significance, likely due to the small hospital sample size, which we are currently evaluating.All Authors: No reported disclosures


BackgroundThe processes involving resistance development against antibiotics have historically been part of the Darwinian evolution. However, the increasing use of antibiotics in modern medicine has intensified the selection pressures with an acute gear-up, rather than as part of this very slow evolutionary process that selects for enhanced fitness for survival. Two major recommendations have been made in the past to tackle this challenge: (1) incentivizing the pharmaceutical industry to invest more in research and development endeavors so that they come up with new antibiotics, and (2) implementing antimicrobial stewardship programs in healthcare systems.MethodologyIn this study, the third and emerging approach, namely, documenting antibiotic footprint, was employed as a communication tool that targets individual consumers of antibiotics. Data obtained from the Ethiopian Pharmaceutical Supply Agency were curated to systematically compile antibiotic consumption at each of the agency’s regional hubs. The exact geospatial locations of the hubs were generated and synchronized to depict the size of the antibiotic footprint infograph as proportional to the antibiotic consumption data at each hub. Moreover, the cumulative and per-capita consumption of these antibiotics at the country level  were calculated by including estimated data for the livestock sector.ResultsA total of 698.2 tons of antibiotics were used in Ethiopia in 2018, and the per-capita consumption of antibiotics was 5.8 g per person. Extended-spectrum (J01CA) and beta-lactamase-resistant penicillins (J01CF) were the most commonly utilized classes of antibiotics which accounted for, respectively, 38.3% and 20.8% of all antibiotics used in the country’s public health sector. Hubs in Addis Ababa (14%) and Hawassa (12%) topped the overall antibiotic consumption in the country. Contrarily, hubs in Gambella and Semera received relatively smaller quantities of antibiotics, with totals of 4.8 tons (0.9%) and 10.2 tons (1.9%), respectively.ConclusionsThis study shows that the newly emerging concept of the antibiotic footprint is a simple and suitable tool for public health policy communications targeting individual consumers of antibiotics. If implemented judicially, the concept of the antibiotic footprint has a huge potential to support global scientific efforts and collaborations in setting standards that help to reduce the overuse and misuse of antibiotics in the future. Streptomyces bacteria in beer fermentation was used for the treatment of infectious diseases [Historical records on man’s understanding of infectious diseases and their causative agents are centuries old. In the 14th century for instance, two notable Persian scholars, Ibn Khatima and Ibn-al-Khotib, proposed that infectious diseases were caused by what they called “contagious entities” [diseases .Fast forward, particularly since the period commonly called “the scientific revolution” (ca 1500-1800) marked by the emergence of modern science, sustained efforts had been underway to discover cures for infectious diseases. Several chemical entities were synthesized in laboratories as part of such scientific endeavors. The major limitations of the chemical entities synthesized in laboratories had not, however, been efficacy, but safety. For example, Salvarsan, an anti-syphilis agent synthesized in 1910 by Ehrlich and, in fact, the first antibiotic ever made by man in a laboratory was too toxic to make it to the clinical catalog. Penicillin was the first safe and efficacious antibiotic discovered in the laboratory by the Scottish scientist Alexander Fleming and his co-workers in 1928 and came to clinical use during the Second World War  and in fThe series of outbreaks of infectious diseases in Europe during and right after the end of the Second World War, the primary victims of which were wounded soldiers during the war, further boosted the scientific endeavors made to synthesize more effective antibiotics in laboratories. In fact, all of the scientific investigations that ultimately brought penicillin, hitherto forgotten on the Petri dishes of Alexander Fleming’s lab for over a decade, were centrally coordinated and funded by government research agencies and scientific wings of army departments which were in desperate need for anti-infectives for soldiers who sustained wounds in the war . Over thOver the last seven decades, antimicrobial chemotherapy constituted man’s effective strategy to fight infectious diseases with remarkable gains that significantly improved life expectancies in different parts of the world . A reporHowever, evolution is challenging these gains of the antibiotic revolution in modern medicine. The processes involving resistance development against antibiotics have historically been part of the Darwinian evolution. However, in the backdrop of this evolutionary reality, the ever-increasing use of antibiotics in modern medicine, particularly in the post-penicillin era, has intensified the selection pressures with an acute gear-up rather than as part of the slow and natural evolutionary process that selects for enhanced fitness for survival -11.Two major recommendations were made in the past to tackle this challenge. One is incentivizing the pharmaceutical industry to invest more in research and development endeavors so that they come up with new and novel antibiotics ,13. The Moreover, these two recommended strategies are absolutely important. However, as much important is also the third one, the active engagement of individual consumers of antibiotics in society through organized campaigns in tackling the problems of misuse and overuse of antibiotics. And for such public awareness campaigns to become effective, generic measurements for antibiotic consumption as well as simple communication tools are key. Currently, available measurement systems for quantifying consumption of antibiotics such as defined daily doses (DDDs), or its derivative DDD per a thousand inhabitants per day (DID), are meant for healthcare professionals and they are technically too complex to understand for nonprofessionals and to the wider public at large.With this understanding of the existing gap in effectively engaging individual consumers in public campaigns aiming to reduce the misuse and overuse of antibiotics in the community, the concept of the “antibiotic footprint” was recently recommended by researchers as a global communication tool ,17.The concept envisages to stimulating behavioral changes practically needed to reduce individuals’ direct and indirect consumption of antibiotics in communities. Adopted from the already established innovative concept of “carbon footprint” and aspiring to build on its successes, antibiotic footprint quantifies the consumption of antibiotics in human health, in animals/livestock, and in agriculture/aquaculture as measured in simpler and generic terms such as the total mass of antibiotics used or per-capita of a population. As carbon footprint captures the mass of greenhouse gases such as carbon dioxide emitted to the environment by every individual, antibiotic footprint quantifies the mass of antibiotics consumed by each individual in the population.The goal of carbon footprint is to reduce the use of energy generated from fossil fuels and hence emissions of greenhouse gases to a minimum . LikewisThis study, which was previously posted on Research Square pre-print server on October 24, 2022, aims to employ this newly emerging concept of antibiotic footprint to estimate the gross and per-capita consumption of antibiotics in Ethiopia for the year 2018.Disaggregated data depicting the utilization of antibiotics at all the regional hubs of Ethiopia’s public health sector pharmaceutical supply chain monopoly, the Ethiopian Pharmaceutical Supply Agency (EPSA), for the year 2018 were used in this study.Data obtained from the central EPSA’s excel spreadsheets on demand quantification and delivery of all medicines, medical equipment, healthcare technologies, medical supplies, and laboratory reagents, all of which constitute “Pharmaceuticals” as per the Ethiopian law, to the regional hubs were curated to systematically compile the consumption of all antibiotics.These compiled data were used to compute antibiotic consumption at each of the 17 regional hubs of EPSA in human health. QGIS, version 3.4.4, Madeira 2018  was employed to generate the exact geospatial locations of the hubs, synchronized to depict the size of the antibiotic footprint infograph as proportional to the antibiotic consumption data at each hub. The percentages of different classes of antibiotics, at the fourth level of the ATC classification index , consumeMoreover, percentage expenditures on all antibiotics were calculated from EPSA’s registers compared to that of the total expenditures on all medications. Results are presented as text, figures, and infographics.Per-capita consumption of antibiotics for Ethiopia in 2018 was 5.8 g per person. In the public sector, which accounts for about three-quarters of healthcare service delivery, percentage expenditure on antibiotics  accounted for 37.3% of the expenditures on all medications.Penicillins with extended-spectrum J01CA) and beta-lactamase-resistant penicillins (J01CF) were the most commonly utilized classes of antibiotics in 2018 which accounted for, respectively, 38.3% and 20.8% of all antibiotics used in the country’s public health sector in 2018  and Hawassa (12%) topped in terms of the quantities of antibiotics they received. Contrarily, hubs in Gambella and Semera received relatively smaller quantities of antibiotics, with totals of 4.8 tons (0.9%) and 10.2 tons (1.9%), respectively Figure .In this study, the newly emerging digital concept of the antibiotic footprint was employed to estimate the cumulative and per-capita consumption of antibiotics in Ethiopia for the year 2018, which is a holistic estimate for the human and livestock health sectors. The concept is termed digital because, like carbon footprint, it is powered by a digitized and generic platform on the world wide web. Consumers are no doubt in a strong position to influence antibiotic misuse and overuse. The concept, therefore, envisages to reinvigorating the role of individual consumers of antibiotics in society in tackling the challenges of antibiotic resistance by stimulating positive behavioral changes needed to reduce the overuse and misuse of antibiotics. This concept is gaining traction among policymakers worldwide, much like the hitherto established concept of the carbon footprint from which it was adopted, and an online interactive database pulling official data on antibiotic consumption in human health, livestock, and agricultural sectors from various countries have been established. The online interactive database for antibiotic footprint was launched quite recently, but it has already stored data since the year 2010 for many countries. Figure The concept of antibiotic footprint also complements the other newly emerging concept called the “One Health Concept”  because Comparing the findings of the current study with antibiotic footprints for two African countries (Sudan and Tanzania) whose official data have been published in the online interactive database  may helpNevertheless, differences in the antibiotic footprints among countries could be attributed to various factors such as healthcare-seeking behaviors of the population, socioeconomic differences, variations in the epidemiological distributions of infectious diseases, and differences in agricultural practices in different countries, among others. Furthermore, importantly, comparison of such data can influence peoples’ curiosity, thereby helping bring practical behavioral changes which can positively contribute to efforts made to reduce individual antibiotic consumption such as keeping environmental sanitation, taking vaccinations, keeping personal hygiene, considering food choices, and avoiding self-medication practices or over the counter use of antibiotics .Ethiopia is a very vast country with multiple physical features of geography and ecological systems ranging from arid lowland areas to scorching-sun deserts, to tropical highland plateaus, and all the way to wet mountainous hinterlands. Such ecological variants are obviously important determinants for the differential distribution of diseases, and, hence, the use of a longer list of antibiotics and other medications in the country seems to be a logical consequence of that. Particularly outstanding data in this study was that cloxacillin was the sole antibiotic product that did exclusively account for the level of consumption (20.8%) constituted by beta-lactamase-resistant penicillin (J01CF) whose total consumption came second only to extended-spectrum penicillin (J01CA). On the other hand, ampicillin and amoxicillin were the two products added up to constitute 38.3% of consumption accounted by extended-spectrum penicillin (J01CA).A countrywide comprehensive study on the prevalence of resistance against antibiotics has yet to be undertaken in Ethiopia, but a few studies conducted at the level of healthcare institutions reported a high percentage of resistance against some of these commonly used antibiotics as ampicillin and amoxicillin ,24. The Moreover, the distributions of disaggregated data for antibiotic consumption at Ethiopia’s regional hubs  appear to draw parallels with the patterns of population settlement density in Ethiopia, and, hence, the subsequent pressure on the demands for healthcare service provisions. See Figure This is to say, hubs situated in densely populated parts of the country and hence serve healthcare facilities within such catchment areas such as in central , south/south-west , north/north-west , and in eastern parts  have a relatively higher consumption of antibiotics. On the contrary, lowland areas where we have healthcare facilities that serve sparsely populated parts of the country such as in the western lowland frontiers  and eastern lowland areas  got relatively lower consumption of antibiotics. Antibiotic consumption in the remaining hubs falls far in between, and that too corresponds well with the population density within the catchment areas of their services. In addition to that, differences in the epidemiological distribution of infectious diseases, determined by the ecological variations as discussed above, must have also played their part.The strength of this study is that it employed the newly emerging digital concept of antibiotic footprint to estimate the total, as well as the per-capita annual consumption of antibiotics in Ethiopia for the year 2018. The study can, therefore, offer important and countrywide refined input of datasets to the initiative now underway in Ethiopia to institutionalize the antimicrobial stewardship system through the sentinel-based resistance surveillance program established in 2017.The study is not, however, without its limitations. First, the data for the consumption of antibiotics in the livestock sector used in the current study are not primary data as were the case for those in the human health sector, which is due to the lack of complete and compiled data availability for the former in Ethiopia’s official registers. For the data in the livestock sector, we had to rely on documented scientific projections, i.e., secondary data, offered by expert consultants at Precise Consult International in which they estimated the annual consumption of antibiotics in Ethiopia for the year 2018 based on the 2012 data. This means that the quality of our data on antibiotic consumption for the livestock sector are only as good as secondary data could be. Second, our data for annual antibiotic consumption in the human health sector did not include antibiotics used within the private health sector in Ethiopia due to a lack of complete and compiled official data. Official reports show that the private health sector in Ethiopia accounts for some 27% of the total number of healthcare facilities available in the country . Hence, This study shows that the newly emerging concept of the antibiotic footprint is a simple and suitable tool for public health policy communications targeting individual consumers of antibiotics in the community. The data and our interpretation of them in this study suggest that if implemented judicially, the digital concept of antibiotic footprint has a huge potential to support global scientific efforts and collaborations in setting standards that help to reduce the overuse and misuse of antibiotics in the future.


This is a review that provides an overview of neoadjuvant therapy, landmark clinical trials, and further prospective management options which can be considered for adenocarcinoma of the oesophagus and gastro-oesophageal junction.Historically, oesophageal and gastro-oesophageal junction adenocarcinomas were associated with a poor prognosis. The advent of neoadjuvant therapy has transformed the management of oesophageal and gastro-oesophageal junction adenocarcinomas further and offers the possibility to reverse disease progression, eliminate micrometastasis, and offer potentially better outcomes for these patients. This review provides an overview of landmark clinical trials in this area, with different treatment regimens considered over the years as well as potential therapeutic agents on the horizon that may transform the management of oesophageal and gastro-oesophageal junction adenocarcinomas further. Traditionally oesophageal and gastro-oesophageal junction adenocarcinomas were associated with poor prognosis due to their insidious onset and advanced nature at the time of diagnosis . The advThe origins of neoadjuvant chemotherapy trace back to the 1980s and early 1990s, when multiple small clinical trials were underway to investigate the potential therapeutic benefits of neoadjuvant therapy. The majority of these trials were largely based on cisplatin or Carboplatin regimens often using a 5-fluorauracil infusion as dual or triple therapy ,7. Indee2) with fluorouracil (1000 mg/m2) as a neoadjuvant regimen prior to surgical intervention versus surgical resection alone. Median follow-up for the neo-adjuvant group was 36.9 months versus 37.9 months for the comparator. Their findings identified an improved R0 rate in the neoadjuvant chemotherapy group , as well as improved 2-year survival  ) with surgery alone for managing oesophageal adenocarcinoma  vs. 198 [68%]) did not differ between groups. Finally, combination therapy with two immunological agents may be considered. Further studies, such as the KEYNOTE118 and the TRAP trial are ongoing to evaluate a combination of trastuzumab and another immunological agent in gastric cancer, the latter of which has shown promising results in an initial phase II trial for HER2-positive patients [Trastuzumab is a monoclonal antibody that has a mechanism of action where it binds to and inhibits the Human Epidermal growth factor Receptor 2 (HER2/neu), which is responsible for the proliferation and inhibition of apoptosis of the cell . In patipatients ,46.p = 0.017) [p = 0.055) [Cetuximab is another monoclonal antibody, which binds and inhibits the Epidermal Growth Factor Receptor (EGFR) which has similar properties to HER2/neu. The Swiss Group for Clinical Cancer Research (SAKK) has performed trials using cetuximab in oesophageal cancer treatment. Firstly, the phase Ib/II-SAKK 75/06 trial indicated that the addition of cetuximab to induction chemotherapy followed by neoadjuvant chemoradiotherapy demonstrated high pathological complete response rates (68%) and no increase in toxicity . Subsequ= 0.017) . Median = 0.055) . These fThe programmed death factor receptor-1 (PD-1) is a regulatory immune checkpoint discovered in 1992 that is expressed in T, B, and NK cells and consists of two ligands, PD-L1 and PD-L2, which combine to downregulate a local immune response and can therefore promote carcinogenesis . ToripalThe synergistic effects between immunotherapy, chemotherapy, and radiation have been reported in the literature. Chemotherapy can lead to immunosuppression through its effects on rapidly diving cells in the immune system; however, in noncytotoxic doses, it is hypothesised that immune activation can occur, which is likely as a result of changes in the composition of the tumour microenvironment through inhibiting the expression of certain immunosuppressor genes and expression of immunogenic antigens. An example is the case of increased HSP90 found in myeloma cells with the use of the proteasome inhibitor bortezomib . It is tThis review has highlighted the different forms of neoadjuvant therapy that have been used for oesophageal and gastro-oesophageal junction adenocarcinomas in recent years. The most efficacious regimen still remains contentious in clinical practice and further high-powered randomised control trials are necessary to establish the optimal chemotherapy and radiation regimen, as well as the potential for immunotherapy to augment the neoadjuvant response in this patient cohort.


Indoor localization is one of the key techniques for location-based services (LBSs), which play a significant role in applications in confined spaces, such as tunnels and mines. To achieve indoor localization in confined spaces, the channel state information (CSI) of WiFi can be selected as a feature to distinguish locations due to its fine-grained characteristics compared with the received signal strength (RSS). In this paper, two indoor localization approaches based on CSI fingerprinting were designed: amplitude-of-CSI-based indoor fingerprinting localization (AmpFi) and full-dimensional CSI-based indoor fingerprinting localization (FuFi). AmpFi adopts the amplitude of the CSI as the localization fingerprint in the offline phase, and in the online phase, the improved weighted K-nearest neighbor (IWKNN) is proposed to estimate the unknown locations. Based on AmpFi, FuFi is proposed, which considers all of the subcarriers in the MIMO system as the independent features and adopts the normalized amplitudes of the full-dimensional subcarriers as the fingerprint. AmpFi and FuFi were implemented on a commercial network interface card (NIC), where FuFi outperformed several other typical fingerprinting-based indoor localization approaches. Location information is indispensable in the age of the Internet of Things (IoT) ,7,8,9,10In the literature, many different wireless communication standards have been applied for indoor localization, such as WiFi , RFID 1, ZigBee The approaches using WiFi for localization can be classified into two categories: link-based and fingerprinting-based. Link-based approaches estimate the location of the target by constructing a model of the WiFi signal transmission. The commonly used models are the time of arrival (ToA) , round tOn the other hand, fingerprinting-based localization approaches that do not require mathematical model are less affected by multipath and can achieve good indoor localization results. The fingerprinting-based approaches consist of two phases: the offline phase and the online phase. In the offline phase, the locations and their associated features are correlated to construct a fingerprint database. In the online phase, the features of the target are mapped to the fingerprint database to estimate its location.Fingerprinting-based indoor localization systems using WiFi typically collect received signal strength (RSS) or channel state information (CSI) as the features to construct the fingerprint database. The RSS has been widely used in fingerprinting-based localization approaches for more than a decade. Radar  and HoruIn IEEE 802.11n, where the orthogonal frequency division multiplexing (OFDM) and multiple input multiple output (MIMO) technologies are applied, the wireless communication link between the transmitter and the receiver can be quantified and evaluated using the CSI. The CSI can fully reflect the multipath effect of the physical environment, which is more fine-grained than the RSS. In addition, mainstream vendors of commercial WiFi such as Intel have gradually opened up the physical layer information, making it convenient to obtain the CSI of WiFi with open-source tools. FILA  claimed In this paper, based on the CSI, two fingerprinting-based indoor localization approaches are proposed, namely AmpFi and FuFi. AmpFi uses the amplitudes of the collected subcarriers as the features to construct the fingerprint database in the offline phase. In the online phase, to mitigate the effect of outliers in reference points on localization, an improved weighted K-nearest neighbor (IWKNN) algorithm is proposed to estimate the location of the target. To improve the performance, based on AmpFi, FuFi makes full use of the rich information in the MIMO system and creatively uses the full-dimensional subcarriers as independent variables to achieve high-precision localization.A fingerprinting-based localization method, AmpFi, is proposed, which uses the amplitude as the fingerprint and estimates the locations of the target using IWKNN.Based on AmpFi, FuFi is proposed, which fully takes into account the variability of subcarriers among multiple antennas in the MIMO system and adopts the normalized amplitudes of full-dimensional subcarriers as the fingerprint.Both AmpFi and FuFi were implemented in a commercial network interface card (NIC), and their performances were evaluated in two different environments, a living room and a conference room. The experimental results showed that FuFi outperformed AmpFi and several other typical fingerprinting-based indoor localization approaches.The main contributions of this paper are the following:The rest of this paper is organized as follows. The Linux 802.11n CSI Tool , which aAs research progressed, deep learning was applied to indoor localization. Wang et al.  proposedIn addition to the above, there are some interesting studies on indoor localization with WiFi. The goal of Chen et al.  was to sThe previous works did not pay attention to the variability between different antenna pairs in MIMO systems. In this paper, we took full advantage of this variability to achieve highly accurate indoor localization. The CSI of all antenna pairs was treated as independent features, and the full-dimensional CSI was normalized as the location fingerprint. A new fingerprint database was constructed, and eventually, excellent localization results were achieved.In this section, we first introduce the OFDM and MIMO techniques, which are widely used. After that, the CSI and its characteristics are described.OFDM is a multi-carrier digital modulation technology, which splits the high-rate information data stream into multiple low-rate parallel data streams through serial/parallel (S/P) conversion. OFDM modulates each low-rate data stream using the independent carrier and superimposes them together to form a transmitting signal.The working process of the OFDM system is shown in In signal propagation, different subcarriers will have different attenuations due to interference, resulting in unique amplitude and phase information for each subcarrier. The amplitudes and phases of these subcarriers can be used for indoor localization.MIMO technology refers to the use of multiple transmitting and receiving antennas to transmit and receive signals, respectively, thus improving communication quality. MIMO systems multiply the system channel capacity without increasing the spectrum resources and antenna transmission power, showing obvious advantages.MIMO is widely used in WLAN, and there are many types of network equipment with 2 × 2, 3 × 3, and even more antennas, greatly improving the efficiency of data transmission.Y is the set of received vectors, X is the set of sent vectors, and H and In wireless communication, the CSI represents the channel quality of the communication link. It describes the attenuating factors on each communication link, such as scattering, distance, and interference from other signals. Thus, the CSI is more fine-grained than the RSS. In a narrowband flat-fading channel, the CSI can be represented in the frequency domain as follows:H is composed of the physical layer information of the N subcarriers and can be expressed as follows:The channel matrix For a single-input single-output (SISO) system, For a MIMO system with p transmitting antennas and q receiving antennas, H has a N × p × q dimension, where i-th subcarrier between the p-th transmitting antenna and the q-th receiving antenna. Each In the above system, the channel matrix Equation .In this section, the working processes of AmpFi and FuFi are presented, and they both use IWKNN to estimate the location of the target. IWKNN is an improved algorithm based on the weighted K-nearest neighbor (WKNN) . WKNN usThe system overview for these two approaches is shown in FuFi and AmpFi are composed of four parts: data collection, data processing, establishment of the fingerprint database, and location estimation. They are different only in the last two parts, and these four parts will be detailed below.Collecting stable and reliable data is the first step in a fingerprinting-based approach, and both the offline and online phases start with data collection. In our FuFi and AmpFi, the mobile device was placed in a fixed location, and the user stood in different locations, with changes in the location of the user resulting in the different CSI received by the mobile device. In the offline phase, the user was asked to stand at different locations known to us, which we call reference points (RPs). The CSI was recorded when the user stood at the RP, along with the location of the RP. In most cases, only information about the location in a two-dimensional plane was required, so only two-dimensional information of the location was recorded. Thus, the location of an RP Direct use of the raw CSI can lead to an error in localization due to the effect of interference, so the data must be processed. In our approaches, the data processing consisted of two parts: amplitude calculation and outlier rejection.Some reasons make the original phase of the CSI subject to error and cannot be used as the feature to distinguish locations, such as the lack of clock synchronization between the transmitter and receiver, the mismatch between transmitter and receiver frequencies, and the noise interference. The amplitude of the CSI is more stable than the phase in a stationary environment, so the amplitude was chosen as the key feature to distinguish locations. The CSI that is usually collected directly does not consist of the amplitude and phase as shown in Equation , but is Equation .(5)h=a2Outliers are values that significantly differ from other values in the dataset. Inevitably, our measurement process was subject to human or environmental interference, which could lead to outliers. The introduction of outliers had an adverse effect on our subsequent localization, so the outliers needed to be removed to reduce the localization error. The PauTa criterion can eliminate outliers and reduce gross error in the measurement process.The PauTa criterion assumes that a set of test data contains only random error, and the data that differ from the mean by more than three-times the standard deviation are considered to contain gross error, so these data should be rejected.During our data collection process, the CSI of each location was measured several times, and using this criterion, highly abnormal outliers could be removed, after which, the average of the data needed to be calculated again to obtain the true amplitude.Data collection and data processing are parts of both the offline and online phases, and the establishment of the fingerprint database was one of the parts in the offline phase. In this part, a correspondence between the CSI and the location needed to be established so that the locations of the test points could be located based on the fingerprint database during the online phase. It was also in this part that AmpFi and FuFi were different, and the differences will be described in detail below.p transmitting antennas and q receiving antennas, p × q antenna pairs can be formed. In the above system, the amplitude of i-th subcarrier after data processing is a matrix of p × q as follows:In a MIMO system with i-th subcarrier and In AmpFi, N + 2.Using A and Antenna Pair B were very different, so it was not reasonable to average the values of multiple antenna pairs when calculating the amplitudes of the subcarriers. Therefore, FuFi treated the subcarriers of all antenna pairs as independent features, which can fully utilize the full-dimensional CSI of the MIMO system to improve the localization accuracy.Unlike AmpFi, FuFi focuses on the differences in the same subcarrier between multiple antennas in the MIMO system. The Linux 802.11n CSI Tool was used to collect the CSI, which was based on the Intel WiFi Wireless Link 5300 802.11n MIMO radios and can read 30 subcarriers. From the data collected, we found that the CSI amplitudes differed considerably between multiple antenna pairs for the same subcarrier. As shown in In addition, we found that the range of amplitude transformation that resulted from the location changing significantly differed between different antenna pairs. When the user stood at two locations i-th subcarrier in the antenna pair being normalized, i-th subcarrier in all reference points in this antenna pair, and similarly, i-th subcarrier in this antenna pair after being normalized. Normalization was performed for each subcarrier of each antenna pair individually. FuFi maps the amplitudes to a value between 0 and 1, and each antenna pair can participate fairly in the location estimation.In order to make full use of the amplitude of each antenna pair, FuFi normalizes the measured amplitude using Equation  as folloSimilar to AmpFi, in FuFi, N × p × q + 2. For systems with more than one AP, the fingerprint database for all APs needs to be constructed separately.The fingerprint of FuFi at the location of Equation , but theIn the online phase, the different online CSI matrix needs to be formed to fit different approaches. The data collected in the online phase undergoes the same processing as in the offline phase, during which the online CSI matrix as shown in Equation  will be Equation  for AmpFEquation  for FuFiIn particular, during the amplitude normalization in FuFi, the amplitude of a test point was set to 1 if it was greater than the amplitudes of all the reference points in the same subcarrier of the same antenna pair, and it was set to 0 if it was smaller than the amplitudes of all the reference points.After obtaining the online CSI matrix, both AmpFi and FuFi use the IWKNN algorithm for location estimation. The steps of IWKNN are as follows.i-th subcarrier when the target is located at The Euclidean distance was used to express the difference between the amplitudes of the test point and the reference point. The calculation of the Euclidean distance is illustrated using reference point i-th subcarrier between the j-th transmitting antenna and the k-th receiving antenna when the target is located at For FuFi, the Euclidean distance is calculated as follows:If there is more than one AP in the system, the distance between these two points for each AP needs to be calculated separately and then summed up as the final result.K reference points with the smallest Euclidean distance to the test point were selected as K nearest neighbors. Then, the average coordinates of these K nearest neighbors were calculated and denoted as After obtaining all the Euclidean distances between the reference points and test point, the The distances from the K nearest neighbors to This step was repeated until there were no outliers in the K nearest neighbors.k-th nearest neighbor and the test point,  was used as a criterion to evaluate the superiority of localization approaches. First, the MDEs of FuFi and AmpFi with four other fingerprinting-based localization approaches were evaluated in the single-AP case, including FIFS , CSI-MIMThe results of the experiment conducted in the conference room are shown in The cumulative distribution function (CDF) of the distance error is also a measure to compare the performances of localization approaches. To further show the distribution of the distance errors for each localization method, we plot the respective box plots for the experimental results. In addition, the effect of the number of reference points on the localization performance was explored in the same experimental region. In the conference room, the number of reference points in the region was modified to 28 and 16. Correspondingly, The experimental results are shown in The same comparison experiment was performed in the living room. The number of reference points was modified to 18 when After that, our conclusions were verified using the CDF of the distance error. FuFi was selected to compare with the previously most-prominent approach K-means, and the experimental results in the conference room and living room are presented in Therefore, in the same area, the localization performance can be improved by setting more reference points, but it will also greatly increase the workload of the fingerprint database construction and the computational complexity of the online phase. Thus, in practical applications, a trade-off should be made to achieve a balance between the workload and localization accuracy.n to represent the number of APs used in a single experiment. Since K-means and FUSELOC do not provide localization strategies when there are multiple APs, the K-means and FUSELOC were not included in this experiment. Finally, the effect of the number of APs on the localization accuracy was explored. In the conference room, both In this paper, an online localization algorithm, IWKNN, was designed, which can reject outliers in K nearest neighbors and achieve effective localization. Then, AmpFi was proposed, which uses the amplitude of the CSI as the fingerprint and IWKNN to estimate the location of the target. After that, based on AmpFi, FuFi was proposed by using the normalized amplitudes of full-dimensional subcarriers as the fingerprint. Finally, FuFi and AmpFi were implemented using a commercial NIC. To demonstrate the advantages of our approaches, experiments were conducted in a conference room and a living room, respectively, and the results showed that FuFi outperformed AmpFi and four other fingerprinting-based location approaches. In addition, the experimental results showed that the number of APs did not significantly affect the localization accuracy when the WiFi signal was strong enough in the localization area; the larger the intervals between adjacent reference points were, the worse the localization performance was. In the experiments, FuFi achieved the best localization performance under difference scenarios.


Neoadjuvant immunochemotherapy may benefit patients with non-small cell lung cancer (NSCLC), but its impact requires further investigation.A meta-analysis was conducted. PubMed, Embase, Web of Science, and the Cochrane Library were searched. The study was registered in PROSPERO (registration no. CRD42022360893).2 = 52%), and longer 1-year and 2-year OS, without affecting TRAEs. For neoadjuvant immunochemotherapy in NSCLC, the pooled pCR rate was 0.35 , MPR was 0.59 , and ORR was 0.71 . The pooled incidence of all grade TRAEs was 0.70 , and that of >= grade 3 TRAEs was 0.24 . The surgical complications rate was 0.13  and R0 resection rate was 0.98 . The pooled 1-year OS was 0.97 , and 2-year OS was 0.89 . Patients with squamous cell carcinoma, stage III or higher PD-L1 performed better. Notably, no significant differences were observed in pCR, MPR, and ORR between 2 or more treatment cycles. Pembrolizumab-, or toripalimab-based neoadjuvant immunochemotherapy demonstrated superior efficacy and tolerable toxicity.60 studies of 3,632 patients were included. Comparing with neoadjuvant chemotherapy, neoadjuvant immunochemotherapy showed higher pCR , MPR , and ORR , fewer surgical complications , higher R0 resection rate (RR: 1.06, 95%CI: 1.03, 1.10, IAccording to our analysis, reliable efficacy, safety, and survival of neoadjuvant immunochemotherapy for operable NSCLC were demonstrated.https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022360893, identifier CRD42022360893. Of patiImmune checkpoint inhibitor (ICI) plays an important role in the first-line and second-line therapy of patients with NSCLC, showing a better survival benefit than chemotherapy –12. A grvs. 8.9%) and pCR (24% vs. 2.2%) were significantly improved (vs. 6.9%), MPR (52.6% vs. 13.8%), and ORR (75.4% vs. 48.2%), and help patients obtain better survival in locally advanced IIIA-IIIB resectable NSCLC , and ICI type. Our goal was to provide guidance for the clinical treatment of NSCLC.2https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022360893).To ensure the accuracy and transparency of our study, we followed the PRISMA  and AMSTAR  guidelines , 27. Thi2.1We searched PubMed, Embase, Web of Science, and Cochrane Library, using keywords such as “neoadjuvant”, “immunotherapy”, “chemotherapy”, and “non-small cell lung cancer”. The search was conducted independently by two authors and included papers updated until July 2023. Language restrictions were not applied.2.2To be eligible for our study, trials were required to have administered neoadjuvant immunochemotherapy to patients diagnosed with operable NSCLC and acquired radiological or pathological response data. Enrolled patients should not have received any prior systemic anti-neoplastic treatment for NSCLC, must have had no history of lung radiotherapy, and should have undergone surgical resection for NSCLC. Excluded were trials involving patients with concurrent progressive or actively treated additional malignancies, those who had received previous systemic antineoplastic therapy for NSCLC, or those with a history of lung radiotherapy. Studies falling into categories such as reviews, comments, case reports, trial protocols, or animal experiments were also eliminated. In the context of randomized controlled trials (RCTs), preference was given to those that compared non-combination therapy with combination therapy, establishing a basis for a comparison group. In cases where multiple publications reported results from the same study population across different journals, the most comprehensive or most current study was selected for inclusion.2.3We screened these literatures based on pre-determined inclusion and exclusion criteria. Two authors independently screened the records, read the full-text papers, and extracted details from the included studies. The primary endpoints were pCR , major pathologic response , the incidence of grade 3 or higher treatment-related adverse events (TRAEs), and 1-year and 2-year OS (the duration from randomization to death from any reason). The secondary endpoints were objective response rate , total grade TRAEs, R0 resection rate, and the incidence of surgical complications. We assessed the quality of RCTs using the Cochrane Collaboration’s tool . For dua2.42 test to determine statistical heterogeneity. If I2 > 50% or p < 0.05, we used the random effects model. If I2 < 50% or p > 0.05, we used the fixed effects model. We carried out subgroup analysis according to age, gender, smoking history, histology, stage, treatment cycles, pretreatment PD-L1, and ICI type. The sensitivity analysis evaluated the stability of the results by ruling out each trial separately. We evaluated publication bias using funnel plots. We used R 4.3.1 software and the meta_v6.2-1 package for the analysis.For single-arm studies, we combined the proportion of each endpoint with a 95% confidence interval (95% CI) to draw forest plots. For dual-arm studies, we calculated the risk ratio (RR) and 95% CI. We used the Cochrane Q test and I33.1Totally, 1,601 studies were screened. After eliminating duplicates and irrelevant studies based on their titles and abstracts, 1,416 were excluded, and the remaining 185 studies were reviewed in detail. Out of these, 125 studies were further excluded due to reasons such as incorrect study type, insufficient data, non-targeted outcomes, duplicated cohorts, trial protocol, and treatment combined with radiotherapy. Ultimately, 60 studies comprising 4 RCTs, 13 dual-arm cohorts, and 43 single-arm studies were selected for analysis, with a total of 3,632 eligible patients included. 3.22 = 0%) for pCR, 3.20  for MPR, and 1.46  for ORR (2 = 78%), the MPR rate was 0.59 , and the ORR rate was 0.71   Figure 33.32 = 21%) (2 = 19%), suggesting no significant difference (2 = 0%) and higher R0 resection rate  (2 = 96%)(2 = 97%) and that of surgical complications was 0.13 , and the R0 resection rate was 0.98   for 1-year OS, and 1.08  for 2-year OS (2 = 46%) for 1-year OS, and 0.89  for 2-year OS .Among the included patients, the histology subtypes were divided into squamous and non-squamous. Neoadjuvant immunochemotherapy treatment in patients with squamous lung cancer performed significantly higher rates of MPR (p = 0.03) and ORR (p < 0.01), and a tendency towards better pCR without reaching statistical significance (p = 0.09). Stage is also a key factor of heterogeneity, so we further explored subgroups based on stage . We found that patients with stage II NSCLC experienced less benefit in terms of pCR (p < 0.01) and ORR (p = 0.05) than those with advanced stage.vs. >2 cycles) and found no significant discrepancies in pCR (p = 0.92), MPR (p = 0.80), or ORR (p = 0.61) between these subgroups. We also examined the effect of pretreatment PD-L1 expression and found that patients with higher PD-L1 (TPS ≥ 50% or TPS = 1-49%) had significantly improved pCR, MPR, and ORR compared to those with lower PD-L1 (TPS < 1%). Patients who achieved partial response (PR) or complete response (CR) had higher MPR rates than those with stable disease (SD) (p < 0.01).The optimal treatment cycle for neoadjuvant immunochemotherapy remains uncertain, with no clear evidence indicating whether 2 or more cycles are superior. To investigate this, we conducted a subgroup analysis of treatment cycles . Pembrolizumab-based neoadjuvant immunochemotherapy demonstrated higher pCR , MPR , and ORR  rates. Toripalimab-based neoadjuvant immunochemotherapy showed higher pCR  and MPR  rates. Nivolumab-based neoadjuvant immunochemotherapy had higher pCR  and ORR  rates. In contrast, avelumab-based neoadjuvant immunochemotherapy demonstrated relatively lower pCR , MPR , and ORR  rates. Pembrolizumab-  and toripalimab-based  neoadjuvant immunochemotherapy had significantly lower incidence of 3 or higher grade TRAEs than other ICIs (p < 0.01).4ICIs plus chemotherapy have emerged in the neoadjuvant therapy of NSCLC. This approach has demonstrated good therapeutic effects and safety, offering new hope for the prolonged survival of patients with NSCLC . It reprOur study investigated the efficacy of neoadjuvant immunochemotherapy for NSCLC, and the results showed that the pooled pCR was 0.35 , MPR was 0.59 , and ORR was 0.71 . These rates were significantly higher than those for neoadjuvant chemotherapy (pooled pCR of 0.04) and neoadjuvant immunotherapy (pCR of no more than 0.10) reported in previous studies , 16. ComIn neoadjuvant immunochemotherapy for NSCLC, the pooled 1-year OS was 0.97 , and 2-year OS was 0.89 . The benefit of neoadjuvant chemotherapy of OS, compared to operation, is only 5%-6%. The CheckMate 816 trial showed that preoperative nivolumab in combination with chemotherapy resulted in a 37% lower risk of disease recurrence, progression, or death than chemotherapy . The SAKOur study suggested that neoadjuvant immunochemotherapy did not increase TRAEs compared with neoadjuvant chemotherapy and may lead to fewer surgical complications, fully confirming its safety. The pooled rate of all grade TRAEs was 0.60 , and that of grade 3 or higher TRAEs was 0.24 . In NSCLC, immune-related adverse events, including pneumonitis, thyroid dysfunction, and skin rash, are the most common types of TRAEs associated with ICIs used in neoadjuvant immunochemotherapy. The pooled rate of surgical complications of neoadjuvant immunochemotherapy was 0.13 , and the pooled R0 resection rate of neoadjuvant immunochemotherapy was 0.98 . Although these adverse events could be serious and potentially life-threatening, they are relatively rare and can usually be managed effectively if detected and treated early. Close monitoring and prompt reporting of any symptoms to the healthcare provider are essential for ensuring the safety of neoadjuvant immunochemotherapy in patients with NSCLC.Accurately identifying the population for neoadjuvant immunotherapy is critical. Our data show that higher PD-L1 expression (TPS >= 50% or TPS = 1-49%) performed better in neoadjuvant immunochemotherapy (p < 0.01). In the published NADIM trial, pCR patients had a higher proportion of PD-L1 positive tumors, but PD-L1 expression was not related to patient survival . The resMoreover, no significant differences were observed in pCR (p = 0.92), MPR (p = 0.80), and ORR (p = 0.61) between 2 or more treatment cycles, suggesting that increasing cycles of therapy may not increase efficacy. Patients who were PR or CR were related to a higher MPR rate than those in SD (p < 0.01). We also found that pembrolizumab- or toripalimab-based neoadjuvant immunochemotherapy performed better in efficacy without affecting >= 3 grade TRAEs. In most included studies, neoadjuvant immunotherapy combined with chemotherapy was used for 2-4 cycles, and operation was performed 4–6 weeks after neoadjuvant immunotherapy .Our study has some limitations. Firstly, the follow-up time of some trials was not long enough to adequately report on long-term survival. Additionally, existing studies are still limited regarding the selection of effective predictors such as ctDNA and the timing of neoadjuvant immunotherapy or adjuvant therapy, making it difficult to obtain more novel results. Thirdly, the study outcomes were non-uniform, making it difficult to pool the survival results of EFS. Therefore, more innovative long-term RCTs are needed to overcome the above obstacles, and the internal mechanism of neoadjuvant immunochemotherapy needs to be further explored. Despite these limitations, this meta-analysis provides objective information on the efficacy, safety, and survival of neoadjuvant immunochemotherapy in operable NSCLC.5Our study demonstrates the reliable efficacy, safety, and survival of neoadjuvant immunochemotherapy for operable NSCLC, making it a promising direction for neoadjuvant treatment in the future.The original contributions presented in the study are included in the article/YZ: Conceptualization, Data curation, Formal analysis, Methodology, Software, Writing – original draft, Writing – review & editing. BF: Formal analysis, Methodology, Writing – original draft. JC: Formal analysis, Project administration, Writing – review & editing, Funding acquisition. LY: Conceptualization, Funding acquisition, Supervision, Investigation, Resources, Writing – review & editing.