The internally cured material known as superabsorbent polymer (SAP) is an important innovation in concrete engineering technology. This paper investigates the effect of adding a polymer with superabsorbent capabilities on the physical and mechanical performance of concrete. The microstructure of the new hybrid concrete was also studied, and the influence of the polymer particle size and volume on the mechanical durability was evaluated. The mechanical properties of the new hybrid concrete, such as compressive strength, flexural strength, elastic modulus, and splitting tensile strength, were measured through laboratory experiments. The microstructure characteristics of the concrete were also investigated by scanning electron microscopy (SEM). The results show that shrinkage was reduced, while the volume stability of the concrete improved. Moreover, we found that cracking was reduced, while issues such as chloride penetration and freeze-thaw resistance were also improved. In addition, the SAP could effectively improve the microstructure of the concrete and refine the pore structure, as seen in the microscopic test. This paper helps to promote the development of internally cured material and improve technology for the prevention of concrete construction cracks. It is essential for sustainable development in concrete engineering to develop a resource-saving strategy. Improving the construction quality and working performance has been the core of the development of concrete engineering construction . The worIt has been suggested and demonstrated that the internally cured method can effectively improve the hydration process of concrete ,8. ReseaExtensive research on the application of SAP materials in concrete engineering has been conducted by scholars. The effects of different kinds of fiber, internal curing agents, and extra water equivalent on concrete were discussed by ,7. The iHowever, the influence of the SAP particle size, content, w/c ratio, and other factors on the mechanical properties and microstructure of concrete is vague, which needs to be determined further. Existing studies have not proposed prediction models and formulas for the SAP particle size, content, and mechanical properties under different water‒cement ratios. In addition, few quantitative studies on the degree of improvement by SAP for the dry shrinkage and durability of concrete have been conducted. The influence of SAP on the tensile strength of concrete also needs to be studied further. The range and mode of influence of the micropore structure characteristics of concrete with SAP on the compressive strength have not been determined, and need to be explored further. In addition, related literature on the importance of graded porosity is sparse. The influence mechanism of different pore classifications on the concrete strength has not been investigated in depth, and further research is needed.Therefore, the influence of the SAP in different particle size and content on the mechanical performances, volume stability, and durability of concrete under different water‒cement ratios are studied, based on laboratory experiments. The prediction equations for the SAP particle size, content and mechanical performances are given. The influence mechanism of SAP on the properties of concrete is studied from three aspects: porosity, the average radius of pores, and the average spacing coefficient of pores. This can be concluded by using SEM, combined with optical microscopic image analysis. The micropore structure characteristics of concrete and their impact on the concrete strength are analyzed. The research results provide a theoretical basis and technical support for the application of SAP in engineering. They will also lay a foundation for research on the microscopic pore structure characteristics of concrete mixed with SAP.SAP, a superfine white powder with strong and fast water absorption, was selected for this experiment. The SAP particles  used in the present study are sol-gel polymerized and irregular crushed powders. The chemistry of the 0.15 mm and 0.3 mm SAP was mainly low cross-linking acrylic acid-based sodium acrylic copolymer , while the main chemical composition of the 0.6 mm SAP was polyacrylamide of the DS series (obtained from a Shanghai company). The tea-bag method ,30 was aTo investigate the impact of SAP on the concrete performance, the effects of the SAP content, particle size, and different water‒cement ratios on the mechanical properties, volume stability, and durability of the concrete were studied. The crack prevention technology for concrete was improved, and a strong theoretical basis for the application of SAP was provided.SAP with particle sizes of 0.6 mm, 0.3 mm, and 0.15 mm was used as raw materials. The amount of SAP was 0.2%, 0.4% and 0.6% of cement, respectively. The water‒cement ratios of 0.3 and 0.37 were used for comparison, and a total of 20 control experiments were designed. The specific mixing proportions were chosen based on actual bridge engineering, and also selected according to “the specification for the mix proportion design of ordinary concrete” (JGJ55-2011). The effects of SAP are different for different w/c ratios, especially for the healing approach. Lam and Hooton  reportedThe mechanical properties such as compressive strength, flexural strength, elastic modulus, and splitting tensile strength were analyzed, refer to “the standard test method of mechanical properties on ordinary concrete” (GB/T50081-2002). And the total of 3 cubes (150 mm × 150 mm × 150 mm in size) were tested under standard conditions, and the compressive strength test was performed at 1, 7, 14, and 28 days. The standard prism of 150 mm × 150 mm × 300 mm was measured by a Tm-2 elastic modulus tester. The dry shrinkage, autogenous shrinkage, and durability of the concrete at 3, 7, 14, and 28 days were investigated by the non-contact method. Three prismatic samples (100 mm × 100 mm × 515 mm in size) were measured in each batch. When preparing the test mold in the non-contact experiment, lubricating oil and two layers of plastic film were needed to line the test mold. It was necessary to apply lubricating oil evenly on the contact surface between the film and the test mold, and fix the reflection target at both ends of the test mold. After pouring the concrete mixture into the trial mold, it needs to be vibrated and smoothed, and a plastic film should be used for securing the sample against water loss through its surfaces. Then, the specimens were positioned under constant humidity conditions of (60 ± 5)% and a temperature of (20 ± 2) °C. The initial setting time of the concrete was measured when the specimen was formed. When the concrete was initially condensed, the initial readings on both sides of the specimen were measured and read. Then, the deformation readings on both sides of the specimen were measured at intervals of 6 h. The position and direction of the specimen placed on the deformation tester always remained fixed during the whole process. In addition, a DTL-6 concrete chloride ion electric flux tester was used to carry out an anti-chloride ion penetration, and each batch was conducted in 3 groups. The frost resistance of the concrete was determined by a KDR-V9 fast freeze‒thaw cycle. Scanning electron microscopy (SEM) tests were conducted to investigate the concrete microstructure.The basic mechanical properties, volume stability, and frost resistance of concrete are included in the specific test process see .The effects of SAP content, particle size, and water‒cement ratio on the mechanical performances, volume stability, and durability of concrete were studied through laboratory tests, thus providing theoretical and technical support for practical engineering applications .The compressive strength of concrete aged for 1, 3, 7, 14, and 28 days was measured under standard conditions of curing. The compressive strength of concrete at two water‒cement ratios is shown in X-axis, Y-axis, and Z-axis, refer to The SAP particle size, content, and 28-day concrete compressive strength were, respectively, set as the The Chebyshev 2D model was adopted, and the specific equation was Formula (1):2 at the w/c ratios of 0.3 and 0.37 were 0.843 and 0.912, respectively. This indicated that the difference between the predicted and measured value was small, which further verified the rationality of the prediction equation. The standard error is abbreviated as SE in The specifically fitted constants are presented in Flexural strength is an important performance parameter of concrete, which reflects the concrete’s ability to resist failure under shear. Therefore, the influence of the SAP content and particle size on the flexural strength of concrete is discussed in this section.The 28-day flexural strength of concrete at two water‒cement ratios is shown in 2 was greater than 0.95, which indicated the rationality of the prediction equation.The Chebyshev2D, a two-dimensional nonlinear surface model, was used to fit the relationship among the particle size, the content of SAP, and flexural strength, which is shown in cE is the elastic modulus, p1 is the load at 0.5 MPa stress (N), p2 is the ultimate failure load of 40% (N), A is the area (mm2), L is the gauge length for measuring the deformation, (mm), and ∆L is the deformation value of the specimen under p1 to p2 load(mm).The elastic modulus is a necessary parameter for calculating the crack development, structure deformation, and temperature stress of concrete ,40. The The calculated elastic modulus of concrete aged for 28 days under different water‒cement ratios is plotted in 2 of the predicted and measured values are 0.956 and 0.974, respectively, under two w/c ratios, which further verifies the rationality of the fitting equation.The relationship among the SAP particle size, content, and elastic modulus under different water–cement ratios is presented in f is the splitting tensile strength, (MPa), p’ is the load, (N), and A’ is the area (mm2).It is, of course, important to know the splitting tensile strength to determine the cracking resistance of concrete in structural design. The calculation of the splitting tensile strength of the concrete cube is shown in Formula (3):The splitting tensile strength of concrete, under two water–cement ratios, is given in The fitting diagram of the SAP particle size, content, and splitting tensile strength of concrete aged for 28 days is shown in Early cracking of concrete often occurs in windy, dry, and high-temperature areas. The concrete cracking can be effectively solved by the internal curing material called SAP, which has broad application prospects . Its serThe drying shrinkage of SAP concrete at different ages is demonstrated in The autogenous shrinkage of concrete at different ages with a fixed w/c ratio of 0.37 is shown in The serviceability of concrete in a freeze-thaw environment is determined by its frost resistance. With SAP, a certain closed pore structure inside the concrete after the water release is formed, so the frost resistance of the concrete can be improved ,47.The effect of SAP on the relative dynamic elastic modulus of concrete when the water–cement ratio is 0.37 is shown in The impact of SAP on the mass loss rate of concrete when the water‒cement ratio is 0.37 is shown in Concrete foundations or enclosure structures that are exposed to chloride ion corrosion environments for a long time will affect the service life of the concrete ,21,24.The effect of SAP on the chloride resistance of concrete is presented in Concrete is a typical porous medium material with a wide pore size distribution, and a complex and diverse pore structure . The porThree main indicators were included in the stomatal structure parameters, which were the mean radius of the pore, the stomatal volume percentage, and the coefficient of average pore spacing .Porosityβ is the porosity, pS is the porosity area, and S0 is the cross-sectional area of the sample.The porosity was calculated as Formula (4):2.Equivalent pore diameterDe is the equivalent pore diameter, and S is the coefficient of average pore spacing.According to Delesse’s law, the area fraction of pores can be regarded as an unbiased expected value of bulk density. Since the pores are not perfectly round, the equivalent diameter of the pores is used to express the size of the pores, as shown in Formula (5):3.Coefficient of average pore spacingS is the coefficient of average pore spacing, F is the volume percentage of effective slurry, P is the volume percentage of cement paste, a is the specific surface area of pores, and A is the pore volume percentage.Using Emmanuel’s formula, the coefficient of average stomatal spacing was calculated as Formula (6):The SEM image and the influence of SAP on the concrete porosity under different water‒cement ratios are shown in 2 of the porosity grading at 10–200 μm, 200–1000 μm, and 1000–1600 μm were 0.413, 0.383, and 0.321, respectively. Thus, it was concluded that a porosity classification of fewer than 1000 μm had a great influence on the concrete strength. This was because the gel pores and small pores increased when SAP was added to the concrete. The size of the large and medium pores decreased, which was consistent with the results of Dang [To further study the relationship between porosity and concrete strength, the porosity was divided into 5 grades: 10–200 μm, 200–600 μm, 600–1000 μm, 1000–1400 μm, and 1400–1600 μm. The different porosity classifications are shown in The effects of the SAP content and particle size on the mean radius of concrete pores are shown in This paper studies the influence of SAP on the mechanical performances, volume stability, and durability of concrete, based on laboratory experiments, and the characteristics of the microscopic pore structure of concrete have been further explored. Some conclusions are as follows.There are inversely proportional relationships among the SAP content and the concrete mechanical performances, such as compressive strength, flexural strength, elastic modulus, and splitting tensile strength. The mechanical properties of the concrete tend to first increase and then decrease with the SAP particle size. In addition, the mechanical performances of concrete mixed with SAP can be reduced by 10% on average. The best SAP particle size and content are 0.3 mm and 0.2%, respectively, which have the most comprehensive effect to ensure the mechanical properties of concrete.Through the Chebyshev2D model adopted, the relationship among the SAP particle size, content and mechanical performances at different water‒cement ratios have been obtained. This provides great assistance with the prediction of concrete’s mechanical properties.There is an inversely proportional relationship between the SAP content and shrinkage of concrete. The volume stability of the concrete tends to first increase and then decrease with SAP particle size. The drying shrinkage and autogenous shrinkage of concrete can be best improved by 16.09% and 30.62%, respectively, and thus, the volume stability of concrete is improved.A certain closed pore structure is formed inside the concrete after the SAP releases water. Therefore, SAP can effectively improve the frost resistance of concrete by 28.3%, and the resistance to chloride ion penetration by 16.6%. Overall, the frost resistance and corrosion resistance of the concrete are improved.Through the SEM research on the microscopic pore structure characteristics of SAP concrete, it has been found that the mix proportion has a significant effect on the pore structure parameters. It is also seen that the development of concrete compressive strength is mainly affected by a pore classification of fewer than 1000 μm, and the order of importance of the graded porosity has been obtained. It is determined by the use principle for SAP, which involves a low water‒cement ratio, coarse particle size, and low content. However, the optimal use principle for SAP still needs to be determined through more experimental studies, which are necessary for future work to confirm the database.


To identify the prevalence of positive IgG4 immunostaining in orbital tissue among patients previously diagnosed with nongranulomatous idiopathic orbital inflammation (IOI) and to compare the clinical characteristics of patients with and without IgG4-positive cells.A retrospective review of all patients with a histopathologic diagnosis of IOI was performed. Immunohistochemical staining was performed to identify IgG-positive cells and IgG4-positive cells. Multivariate analysis was performed using likelihood ratio-test logistic regression on the differences between IgG4-related disease (IgG4-RD) and non-IgG4-RD.P = 0.016) and infraorbital nerve enlargement  were frequently found in IgG4-RD patients. Complete remission occurred in 23.8% of IgG4-RD patients and 41.7% of non-IgG4-RD patients. IgG4-RD patients had more frequent recurrent disease than non-IgG4-RD patients.Of the 45 patients included, 21 patients (46.7%) had IgG4-positive cells, with 52.4% being male and a mean age of 55.9 ± 13.4 years. Bilateral ocular adnexal involvement (adjusted odds ratio [aOR] = 9.45; Nearly 50% of IgG4-RD patients were previously diagnosed with biopsy-proven IOI. IgG4-RD was more frequent in patients with bilateral disease and infraorbital nerve enlargement, showing the importance of tissue biopsy in these patients. Immunohistochemistry studies of all histopathology slides showing nongranulomatous IOI are highly recommended to evaluate for IgG4-RD. Idiopathic orbital inflammation (IOI), previously named orbital pseudotumor, is a benign, noninfective, tumefactive lesion of the orbit. Inflammatory clinical syndrome is characterized by features of a nonspecific or nonidentifiable local or systemic inflammatory condition , 2. IOI The pathogenesis of IOI has remained inconclusive. Various lines of evidence point to an immune-mediated process as the main mechanism , 11. In The aim of this study was to determine the prevalence of positive immunostaining of IgG4 in patients who were previously diagnosed with biopsy-proven nongranulomatous IOI. We also compared the clinical features and treatment outcomes of patients with and without biopsy-proven IgG4-RD.The electronic medical records of the patients initially diagnosed with biopsy-proven nongranulomatous IOI and treated at Songklanagarind Hospital from October 1, 2006, to September 30, 2016, were reviewed. This study was approved by the Research Ethics Committee and was performed in full compliance with the guidelines of the Declaration of Helsinki and the International Conference on Harmonization in Good Clinical Practice Guidelines (REC number 59–040–02-1). During the study period, tissue biopsies were not the first diagnostic step for all patients with IOI in our center. The inclusion criteria included all patients aged ≥18 years with biopsy-proven IOIs. Patients with a final diagnosis of other identifiable diseases, including Graves’ autoimmune disease, granulomatosis with polyangiitis (Wegener granulomatosis), lymphoma, and orbital cellulitis, were excluded from this study. We also excluded patients who had a follow-up time of less than 6 months and poor-quality histopathologic slides.Data were reviewed, including age, sex, affected eye, visual acuity (VA), signs and symptoms, the location and extent of the disease, radiologic data, histopathologic features, and treatment outcome. Blood eosinophilia was defined as a percentage of eosinophils > 10 .Serial 3-μm-thick sections were sliced from formalin-fixed, paraffin-embedded tissue. Immunohistochemistry staining was performed using anti-IgG  and anti-IgG4  antibodies. All histopathologic specimens that revealed lymphoplasmacytic infiltrates were reviewed by an expert pathologist (KK), and additional immunohistochemical staining was performed to identify IgG4-RD according to the new diagnostic criteria for IgG4-related ophthalmic disease, reported in 2014 by Goto et al.   with the highest concentration of IgG4-positive cells and IgG-positive cells, which were evaluated and counted. The average number of IgG4-positive cells per HPF and the average ratio of IgG4-positive to IgG-positive cells were then calculated. All orbital images were reported by the neuroradiologist (NS). Infraorbital nerve enlargement was evaluated using coronal sections of orbital computed tomography or magnetic resonance imaging scans. The criteria for the diagnosis of infraorbital nerve enlargement was abnormal findings including a loss of fat planes around the infraorbital nerve, focal or diffuse alteration of the caliber, irregular course, an expansion of the infraorbital canal or foramen, an enhancing infraorbital nerve, and asymmetrical size and signal intensity .The primary outcome measure was the prevalence of IgG4-RD in the case of previously diagnosed IOI. The secondary outcome measure was the difference between histopathologically confirmed IgG4-RD and non-IgG4-RD in terms of the clinical features and treatment outcomes. The treatment outcomes were classified into three categories: complete remission, partial response, and disease recurrence. Complete remission was defined as complete clinical remission, a lack of disease activity for 90 or more days with steroid or immunosuppressant discontinuation without relapse. Partial response was defined as persistent disease with relapse within 90 days after the discontinuation of steroid or immunosuppressant treatment. Disease recurrence was defined as repeated episodes of disease separated by periods of inactivity after 90 or more days without steroid treatment.P < 0.05.Data were analyzed using Stata Statistical Software (STATA MP 14.1 StataCorp LP). Clinical characteristics between the IgG4-RD and non-IgG4-RD groups were compared using Student’s t test for continuous variables and Fisher’s exact test for categorical variables. In the analysis of histologic features, the chi-square test and Fisher’s exact test were used to compare categorical variables across groups. One-way analysis of variance (ANOVA) was used to compare means between groups. The risks for predicting IgG4-RD was determined by calculating the odds ratio (OR). Multivariate analysis was performed using likelihood ratio-test logistic regression on the differences between the IgG4-RD and non-IgG4-RD groups. Statistical significance was defined as n = 13]; poor quality of histopathologic slides [n = 7]). Of the 45 patients who fulfilled the inclusion and exclusion criteria for this study, 21 patients (46.7%) had IgG4-positive cells, with 52.4% being male with a mean age of 55.9 ± 13.4 years, while the mean age at diagnosis of patients with IgG4-negative cells was 50.3 ± 17.1 years, and the patients were mainly female (79.2%). The mean logMAR of VA at diagnosis for IgG4-RD and non-IgG4-RD patients was 0.36 ± 0.33 and 0.39 ± 0.55, respectively. The most common presenting sign and symptom of both groups was a palpable mass or localized swelling in IgG4-RD and non-IgG4-RD patients . Of the 21 IgG4-RD patients, 4 had lymph node enlargement. Between October 1, 2006, and March 25, 2014, serum IgG4 level testing was not available in our center. Only 5 out of 65 patients were tested to determine their serum IgG4 concentration, and all 5 patients had a concentration higher than 1.35 g/L. An imaging study was available for review in the picture archiving and communication system for 37 patients (82.2%). The most common imaging was computed tomography (70.3%), followed by magnetic resonance imaging (29.7%).Sixty-five patients underwent tissue biopsy, and 20 patients were subsequently excluded (follow-up time of < 6 months [P = 0.002). The mean number of IgG4-positive cells in IgG4-RD and non-IgG4-RD patients was 138.1 ± 108.3 cells and 9.4 ± 13.2 cells, respectively (P < 0.001). The mean ratios of IgG4-positive cells to IgG-positive cells in patients with IgG4-RD and non-IgG4-RD were 56.3 ± 18.3 and 6.0 ± 8.2, respectively (P > 0.001). In the IgG4-RD group, we found that 95.2% of patients had > 50 IgG4+ cells/HPF, 81.0% of patients had an IgG4-positive cell/IgG-positive cell ratio ≥ 40, and 76.2% of patients fulfilled both criteria. Based on histopathologic criteria and limited evidence of serum IgG4 levels, only 2 patients were diagnosed with definite IgG4-RD, and 19 were diagnosed with probable IgG4-RD. Three patients who were histopathologically confirmed to have non-IgG4-RD with elevated serum IgG4 levels were diagnosed with possible IgG4-RD.The mean number of IgG-positive cells in IgG4-RD patients was 251.2 ± 172.4 cells, while the mean number of IgG-positive cells in non-IgG4-RD patients was 108.3 ± 119.6 cells (P = 0.032). The frequency of patients with bilateral ocular adnexal involvement tended to be higher in IgG4-RD patients than in non-IgG4-RD patients (P = 0.010). Twelve of the 13 IgG4-RD patients with an enlargement of the infraorbital nerve also had canal enlargement. Blood eosinophilia was found to be more common in IgG4-RD patients (P = 0.015).The results of the univariate analysis of the variables associated with IgG4-RD diagnosis are illustrated in Table P = 0.016) and an enlargement of the infraorbital nerve (P = 0.008)  Table .Table 3MP = 0.259). This study revealed that only 1 IgG4-RD patient received orbital radiation and showed a good response, and 3 non-IgG4-RD patients received orbital radiation and showed a good response. Methotrexate was used to treat 5 IgG4-RD patients and 2 non-IgG4-RD patients who had elevated serum IgG4 levels and were diagnosed with possible IgG4-RD. Observation was reported for 1 patient with IgG4-RD and 2 patients with non-IgG4-RD due to the refusal of treatment.Of the 45 patients, 41 (91.1%) patients received oral prednisolone in various doses. Oral prednisolone was given with an initial dose of 1 mg/kg/day or 60 mg/day for 2 weeks, which was then tapered by 5–10 mg every 2–4 weeks, adjusting the duration according to the patient’s response. Seven patients (15.6%) received high doses of intravenous corticosteroids due to severe visual loss associated with optic nerve involvement or severe bilateral inflammation, with a mean logMAR VA of 0.50 ± 0.55, whereas the mean logMAR VA of patients who received oral prednisolone was 0.38 ± 0.51  in the IgG4-RD group and 51.9 ± 39.3 months  in the non-IgG4-RD group. Among the 45 patients, complete resolution was reported in 15 patients (33.3%).In IgG4-RD patients, on the basis of treatment response, only 23.8% of patients had a complete resolution of their symptoms and signs with one round of treatment, 57.1% of patients had a recurrence of disease. Ten (41.7%) out of 24 non-IgG4-RD patients had a complete response. The mean age of the IgG4 patients with complete remission was 65.20 ± 8.35 years, which was slightly higher than that of the noncomplete remission group .(1 mg/kg/day) of oral prednisolone than those in the complete remission group . Seven patients (5 IgG4-RD patients and 2 non-IgG4-RD patients) were treated with methotrexate (6 with a good response and 1 being lost to follow-up). The treatment outcome in the patients with IgG4-RD tended to involve more disease recurrence or more intermittent episodes than in the non-IgG4-RD patients.Overall, patients in the incomplete remission group received higher doses This study demonstrated that IgG4-RD accounted for nearly half of the total cases previously classified as biopsy-proven nongranulomatous IOI. We observed that bilateral ocular adnexal disease and an enlargement of the infraorbital nerve were more frequent in IgG4-RD than in non-IgG4-RD patients.P = 0.016). This correlates with recent evidence suggesting that bilateral disease should be considered for IgG4-RD [In agreement with previous studies, IgG4-RD showed similarities with several of the clinical characteristics of IOI, which, in general, tends to affect men more than women , 14, 17. IgG4-RD –21. Addi IgG4-RD . We also IgG4-RD .Infraorbital nerve and canal enlargement was strong evidence for a diagnosis of orbital reactive lymphoid hyperplasia and IgG4-RD with concurrent orbital myositis, focal orbital disease, or paranasal sinus disease –26. AddiPrevious published studies on pathologic characteristics have advocated a strong relationship between IOI and IgG4-RD , 19. We We reported that IgG4-RD accounted for a high prevalence of cases originally diagnosed as IOI. The reasons for the higher frequency of probable IgG4-RD may be due to the following facts. First, the study was performed in a tertiary-care hospital; thus, more severe cases were included. Second, some patients underwent multiple incisional biopsies due to partial response to treatment or a recurrence of inflammation. We used the most severe tissue specimen as the representative specimen. Third, we tended to perform incisional biopsy in patients with atypical presentations or those who failed to respond to the initial therapy rather than in patients with classic IOI cases, which might have led to a selection bias.For the treatment of previously diagnosed IOI in the current study, most patients were treated with systemic corticosteroids, primarily at various doses. The majority of patients initially received oral prednisolone 1 mg/kg/day with a low chance of complete resolution. High doses of intravenous corticosteroids were used for patients with severe visual loss associated with optic nerve involvement and severe orbital inflammation to hasten inflammation reduction. However, there was no consensus on the treatment protocol, and the choice of therapy needs to be individualized by ophthalmologists and physicians with experience using these drugs in ocular inflammatory disease . This hiFive tissue-proven IgG4-RD and 2 possible IgG4-RD patients were treated with methotrexate. Therefore, ophthalmologists preferred prescribing steroid-sparing agents in patients with intractable orbital inflammation, including IgG4-RD, which was more prevalent in elderly patients with frequent comorbidity and polypharmacy . MethotrThe strength of the present study was its enrollment of nongranulomatous IOI patients and focus on the significant clinical differences between IgG4-RD and non-IgG4-RD, including treatment outcomes with long-term follow-up. We could determine the predictors for the diagnosis of IgG4-RD in terms of demographic data, imaging studies, and laboratory features. To the best of our knowledge, this study is the first to determine clinical differences between IgG4-RD and non-IgG4-RD using multivariate analysis. Clinical indicators of IgG4-RD were bilateral disease and an enlargement of the infraorbital nerve. The findings from our report could provide more information on IgG4-RD to clinicians in a developing country with a limited number of oculoplastic surgeons. Therefore, the clinical features could help in the formation of the diagnosis, especially in patients with suspected IgG4-RD in whom a surgeon cannot perform a tissue biopsy. Reportedly, lymphoid hyperplasia of IgG4-RD can provide a substrate for the emergence of lymphoma , 37; thuThe data of this study were reviewed between 2006 and 2016. Nearly 50% of all biopsy-proven cases were previously diagnosed as IOI. Interestingly, IgG4-RD has been underestimated until now. Furthermore, the identification of IgG4-RD using serum IgG4 levels and immunohistochemistry staining in patients with suspected IgG4-RD is beneficial for more systemic investigation, optimal treatments, and adequate follow-up time. Prospective randomized controlled trials are required to determine the pattern of tissue involvement and histopathology in IgG4-RD, in addition to the development of effective treatment.There were some limitations in our study. First, given the retrospective nature of this study, information bias arising from incomplete or missing data may be more pronounced than in a prospective study. Second, there was a lack of consistent laboratory testing for serum IgG4 levels when the patients underwent tissue biopsy, for which serum IgG4 concentration is one of the IgG4-RD diagnostic criteria. Therefore, there were few patients with definitive diagnoses of IgG4-RD in our study. If clinical features, orbital imaging, and pathologic findings met the diagnostic criteria, a probable diagnosis of IgG4-RD could be made. Last, we found that lymph node involvement was low because the lymph node status was assessed by manual palpation, which may have led to an underestimation of the rate of lymph node involvement. Additionally, we could not assess the association with extraorbital manifestations of IgG4-RD due to the low awareness of this disease in recent decades.In summary, the results of our study revealed that IgG4-RD accounted for nearly half of cases initially diagnosed as biopsy-proven IOI. The main clinical features were strong recognition of IgG4-RD, including bilateral disease and an enlargement of the infraorbital nerve. Patients presenting with orbital inflammatory lesions should have biopsies obtained whenever possible and should be evaluated for IgG4-RD.


Collectively, our results establish a novel molecular mechanism for the USP37–BLM axis in regulating DSB repair with an important role in chemotherapy and radiotherapy response in human cancers.The human RecQ helicase BLM is involved in the DNA damage response, DNA metabolism, and genetic stability. Loss of function mutations in BLM cause the genetic instability/cancer predisposition syndrome Bloom syndrome. However, the molecular mechanism underlying the regulation of BLM in cancers remains largely elusive. Here, we demonstrate that the deubiquitinating enzyme USP37 interacts with BLM and that USP37 deubiquitinates and stabilizes BLM, thereby sustaining the DNA damage response (DDR). Mechanistically, DNA double-strand breaks (DSB) promotes ATM phosphorylation of USP37 and enhances the binding between USP37 and BLM. Moreover, knockdown of USP37 increases BLM polyubiquitination, accelerates its proteolysis, and impairs its function in DNA damage response. This leads to enhanced DNA damage and sensitizes breast cancer cells to DNA-damaging agents in both cell culture and  Maintaining genome stability is essential for the health of organisms ,2. The gRecQ helicases are a highly conserved family of DNA processing enzymes. There are five RecQ helicases including RecQ1, BLM, WRN, RecQ4 and RecQ5 in humans . These mIn this study, we found that ubiquitin specific peptidase 37 (USP37) functions as the deubiquitinase of BLM and regulates the DDR. Mechanistically, USP37 is phosphorylated by ATM following DNA damage, which increases the binding between USP37 and BLM and leads to BLM deubiquitylation. Knockdown of USP37 impairs the DDR through BLM and results in increased sensitivity to cisplatin or IR treatment in breast cancer cells. In addition, we found that USP37 expression is up-regulated in breast cancer tissue arrays. In addition, GEO database showed that high expression of USP37 is significantly correlated with poor survival in breast cancer patients. Furthermore, USP37 knockdown sensitizes cancer cells to DNA-damaging agents in xenograft models, suggesting that the USP37–BLM axis may provide new therapeutic targets for overcoming chemo or radiotherapy resistance in breast cancer.HEK293T, GP293, U-2OS, BT-549, T47D, MDA-MB-436, MDA-MB-468, MDA-MB-231, MCF7, Hela, ER-AsiSI U2OS and MCF10A cell lines were cultured in DMEM, RPMI-1640, McCoy's 5A or Ham's F-12 supplemented with 10% FBS, 100 U of penicillin, and 100 μg/ml streptomycin. These cells were originally from ATCC.Wild-type HA-FLAG-USP37 plasmid was purchased from Addgene (plasmid #22602), generated by Dr Wade Harper from Harvard University. HA-FLAG-USP37 and MYC-BLM were subcloned into 3*FLAG-Plvx3 vector. All site mutants were constructed using the site-directed mutagenesis Kit (Stratagene) and verifified by DNA sequencing. MYC-tagged BLM was a gift from Junjie Chen in the University of Texas MD Anderson Cancer Center. The sequences of shRNAs from Sigma are listed below: USP37 shRNA#1: CCGGATTTGCAGAAGATGATA, USP37 shRNA#2: CCCTAACTTCTCTGGCCTATT, BLM shRNA: GCCTTTATTCAATACCCATTT. RAP80 shRNA: TGAGAAGGAAGTAGCTATTTC. The siRNAs sequences are as follows: USP37 siRNA#1: CAAAAGAGCUACCGAGUUA. USP37 siRNA#2: GCAUACACUUGCCCUGUUA. BLM siRNA: CAGGAUGGCUGUCAGGUUA.® 488-AffiniPure Goat Anti-Mouse IgG (H + L) (115-545-062), Alexa Fluor® 488-AffiniPure Goat Anti-Rabbit IgG (H + L) (111-545-045), Rhodamine Red-X-AffiniPure Goat Anti-Mouse IgG (H + L) (115-295-146) and Rhodamine Red-X-AffiniPure Goat Anti-Rabbit IgG (H + L) (111-295-144) were purchased from Jackson Lab.Anti-USP37 antibodies were purchased from Proteintech (18465-1-AP) and Bethyl Laboratories (A300-927A). Anti-RAP80 (A303-763A) and anti-Phospho RPA32 (A300-245A) antibodies from Bethyl Laboratories. Anti-BLM antibodies were obtained from Abcam  and Santa Cruz Biotechnology (sc-376237). Anti-Myc (9E10) antibody was purchased from Covance. Anti-HA (H3663), anti-Flag (m2), and anti-β-actin (A1978) antibodies were obtained from Sigma. Anti-His (sc-8036), anti-Ubiquitin (sc-8017), anti-RPA32 (sc-56770) and anti- cyclin A (sc-239) antibodies were purchased from Santa Cruz Biotechnology. Anti-pT68-CHK2 (#2661), anti-CHK2 (#3440), anti–γH2AX (#9718) and anti-pS/TQ-ATM/ATR (#6966s) antibodies were obtained from Cell Signaling Technology. Anti-Histone H3(ab1791) and anti-ATM(ab32420) antibodies were purchased from Abcam. Anti-γH2AX antibody(05-636) was obtained from Millipore. Alexa FluorPackaging of lentivirus and retrovirus as well as subsequent infection of various cells were performed according to our previously described experimental procedures .For protein turnover analysis in cells, a CHX (cycloheximide)-based assays were carried out according to our previously described experimental procedures .in vivo and in vitro deubiquitination assays were performed as described previously -USP37, CA mutant-USP37 and Myc-ub in HEK293T cells. After transfection 48h later, cells were treated with MG132 for 4 h before being harvested and the cells were lysed in the SDS buffer and boiled. Once diluted (1:10 ratio) with NETN buffer containing 1 mM iodoacetamide and 20 mM NEM, the lysates were immunoprecipitated with the indicated antibodies for 8 h (4°C). After NETN buffer washing, the immunocomplexes were subjected to western blot.The eviously . Brieflyin vitro assays, we purified His-Ub conjugated Myc-BLM from HEK293T cells through multiple steps as described previously (For the eviously . The pur3 cells/well) per well were plated in 96-well plates and treated with cisplatin or IR. After incubated with drugs for 48h, the survival cells were detected by Cell Counting Kit-8 (CCK8) assay according to the manufacturer's instructions .For cell survival assays, infected cells (5 × 10Colony formation assays were performed as described previously . Breifly6 cells in 140 μl of 1× PBS and 60 μl of Matrigel). When the mean size of tumor volume in each randomized group reached ∼100 mm3, the mice were randomly treated with cisplatin (20 mg/kg) every other day. Tumor volumes were measured every 7 days using calipers, and tumor volumes were calculated using the formula length × (width)2. Mice were sacrificed for tumor dissection on day 28 of treatment. All experimental procedures were performed under the approval of the Medical Ethics Committee of Shanghai East Hospital .The nude mice were maintained in specific pathogen-free environments. USP37 knockdown MDA-MB-231 cells stably expressing USP37 WT, S114A or EV were subcutaneously injected into the 6-week-old female BALB/C nude mice using 18-gauge needles. Each mouse received two injections of 200 μl mixture (3 × 10www.Alenabio.com) (BRN801b and BC081120e) and the detailed information including stage, age, and classification and so on in the 2χ test and the Pearson correlation coefficient were used for statistical analysis of the correlation between USP37 and BLM.The tissue microarray of breast cancer samples were purchased from Alenabio ] for in vitro kinase assay,In vitro kinase assays were performed as described previously . BreiflyThe percentage of single-stranded DNA (ssDNA%) generated by resection was measured as previously described ,35. BrieU-2OS cells were seeded on coverslips for 24 h before experiments. Cells were permeabilized for 10min at room temperature with 0.1% Triton X-100 and then fixed by 3% paraformaldehyde for 10min. And then, coverslips were washed twice with PBS. Following this, cells were blocked with 5% goat serum for 30 min and then washed one time with PBS. And incubated with primary antibodies, diluted in 3% BSA in PBS, at 4°C overnight. The following day, after washing with PBS for three times, secondary antibodies diluted in 3% BSA in PBS for 1 h at room temperature.Finally, the coverslips were washed three times with PBS and then mounted with Prolong Diamond antifade mountant (Thermo Fisher). The foci intensity was quantified with ImageJ software.2, 10 mM EGTA and 4% paraformaldehyde) for 15min, and then permeabilized with 0.2% Triton X-100 in PBS for 5 min. Next, cells were blocked with 3% BSA dissolve in PBS for 30 min. Following this, cells were incubated with BLM antibody , diluted in 3% BSA in PBS, at 4°C overnight. The following day, after washing with PBS, secondary antibodies diluted in 3% BSA in PBS for 1 h at room temperature. The coverslips were washed three times with PBS and then mounted with Prolong Diamond antifade mountant (Thermo Fisher).The detection of UFBs was performed as described previously . Briefly2PO4 (pH 8.0)], rinsed in distilled water, and stained with 5% Giemsa for 8 min. Finally,slides were then rinsed and air-dried.Sister chromatid exchange assays (SCE) were performed as previously described ,38. Brien = 6). Statistical significance was assessed by two-way ANOVA with Tukey's multiple comparisons test in cell survival assays.All data are based on experiments performed at least in triplicate for cell survival and data are presented as the mean ± SD . In the figures, statistical significance is presented by: n.s.: not significant,*In order to identify the potential deubiquitinase(s) that regulate(s) BLM, we transfected HEK293T cells with a panel of HA-tagged deubiquitinases individually and immunoprecipitated with HA antibody-conjugated beads. We found that only HA-tagged USP37 bound with endogenous BLM Figure . FurtherWe next sought to determine whether USP37 regulates BLM protein level as USP37 is a deubiquitinase. As shown in Figure To further explore whether USP37 stabilizes BLM, we used cycloheximide (CHX) to inhibit protein synthesis and determined the half-life of BLM. The half-life of BLM protein dramatically decreased in USP37 knockdown cells Figure , G. On tin vitro  upon cisplatin treatment Figure –F. MoreoIt is well known that the status of the DDR pathway has an effect on cancer cell response to chemotherapy or radiotherapy, and loss of DDR elements induces sensitivity to DNA-damaging agents . We nextin vivo. As shown in in vitro . Moreover, clinical data from the GEO database indicated that increased expression of USP37 was markedly correlated with poor survival of breast cancer patients  was observed in these breast carcinomas , which can result in immunodeficiency, dwarfism, sterility, premature aging, and multiple cancers, such as breast cancer . BLM unwPost-translational modification (PTM) of BLM is important for its function in DNA repair and tumor radiosensitivity. Phosphorylation, SUMOylation, and ubiquitination of BLM have been reported, in turn regulating its subcellular localization, protein/protein interactions, and protein stability . For exaPrevious studies showed that USP37 regulates diverse cellular events by mediating the deubiquitination of various target proteins. For example, USP37-mediated deubiquitinaition of Wings Apart-Like (WAPL) affected chromosomal cohesion and mitotic progression . Other win vivo.In this study, we carried out a screen for potential BLM DUBs and found that USP37 interacts with BLM, leading to deubiquitination and stabilization of BLM, which in turn regulates the DNA Damage Response (DDR) in the BLM-dependent manner. Future studies will be needed to investigate the physiological significance of USP37 stabilization of BLM et al. (Previous study showed that depletion of USP37 reduces homologous recombination (HR) efficiency by promoting excessive spreading of Ub-K63 signal that promotes sequestration of BRCA1 by RAP80 . As showet al.  suggesteet al.  and USP1et al.  also deuIn addition, USP37 is overexpressed in breast cancer samples and GEO database showed that high expression of USP37 is related to poor survival in breast cancers. Moreover, a positive correlation between BLM and USP37 protein levels was observed in the breast carcinomas supporting a role for the activity of the USP37–BLM axis in human breast cancer cells. It will be interesting to further investigate the molecular mechanisms underlying the overexpression of the USP37–BLM axis in breast cancer. Nevertheless, our results reveal that USP37 regulates the stability, ubiquitination and thus the function of BLM, providing a mechanistic link between the deubiquitinase USP37 and the BLM-mediated DDR. Our findings indicate that the USP37–BLM axis plays a critical role in the cellular response to cisplatin or IR treatment in breast cancer, supporting the pursuit of molecules targeting this pathway in breast cancer intervention. Therefore, targeting USP37 in the breast cancer may sensitize cancer to cisplatin or IR treatment. Finally, considering that USP37 is overexpressed in breast cancer, small molecules that inhibit USP37 have broad development prospects and a combination of USP37 inhibitor with platinum-based therapy or IR may provide a novel approach for breast cancer therapy.gkab842_Supplemental_FilesClick here for additional data file.


Antibiotics are amongst the more frequently prescribed medicines in pregnant women and the use of antibiotics is increasing. However, with limited studies available in this population, the safe use of antibiotics in pregnancy remains a concern.To evaluate the use of antibiotics amongst pregnant women attending a public health care facility. The main objective of this study was to quantify the types of antibiotics used in pregnant women.A public hospital classified as a referral hospital located in Durban, KwaZulu-Natal.Demographic and treatment information of women were collected retrospectively from January 2019 to July 2019. A total of 184 pregnant patients, who received antibiotic therapy, were included in this study. Descriptive and analytical measures were used to analyse both patient demographics and treatment variables.A total of 416 antibiotic prescriptions, issued to 184 patients, were reviewed. Penicillins (39.7%), macrolides (13.0%) and combination penicillin- and beta-lactam inhibitors (12.3%) were reported as the most commonly prescribed antibiotics. Rifamycin (2.9%), hydrazides (2.2%) and aminoglycosides (1.9%) were less frequently prescribed. Most antibiotics were prescribed for diseases of the circulatory system (36.1%).Several classes of antibiotics were used in pregnancy despite the lack of available safety data and clinical evidence. Informing women of the potential side effects and keeping abreast with new information played an important role in the safe, rational and effective use of medicines that contributed to improving maternal health. Antibiotic use in pregnancy is increasing . The epidemic of AMR is changing the way antibiotics are used, increasing mortality and morbidity and greatly increasing the cost of healthcare. The management and use of antibiotics have clinical, economic and environmental implications.The primary aim of this study was to evaluate the use of antibiotics amongst pregnant women attending a public healthcare facility. The main objective of this study was to quantify the types of antibiotics used in pregnant women. The secondary objectives were to comment on the trends, rationale and safety profile of the prescribed antibiotics.This retrospective study was conducted over 7 months (from January 2019 to July 2019) at a tertiary and quaternary public hospital, centrally located in Durban, KwaZulu-Natal .The selected population consisted of both inpatients and outpatients. Participants included in this study met the following eligibility criteria:18 years of age or abovefemale and pregnanttreated with an antibiotic as an inpatient or outpatient.Details around antibiotic use, diagnosis, patient demographic information and human immunodeficiency virus (HIV) status were recorded. A probability sampling method was adopted, which included every potential participant who visited the hospital from January 2019 to July 2019 and met the eligibility criteria, yielding a sample size of 184 participants. This sample size was large enough to allow for a detailed analysis of antibiotic usage as each patient received an average of two to three prescriptions, yielding a total of 416 prescriptions.Data were obtained from a software programme called MediTech®. MediTech® electronically stores patient files and treatment information. A pre-designed data collection tool was used to record available demographic and treatment information from patient files . The temdemographics antibiotic namedoseroute of administrationfrequency of administrationduration of treatment.All information collected was kept confidential. Patient names were coded and records were kept in a password protected device. Individual patients’ written informed consent for the data collection was not needed, as only anonymised, retrospective data were extracted.Descriptive and analytical measures were used to describe both patient demographics and treatment variables. Measures of central tendency such as the frequency, mean and median were calculated. Antibiotic usage patterns amongst the participants were then identified. The quantitative data values are represented in frequency distribution tables by grouping them into categories and in a frequency distribution bar chart.The linear relationship between the patient demographics and treatment variables was established using correlation analysis. The relationship between treatment duration, age, HIV co-infection and the number of prescriptions was investigated using the Chi-square test. The level of significance was set at α = 0.05.Firstly, the probability for biased selection was eliminated as a probability sampling method was adopted, which included every pregnant woman who visited the hospital from January 2019 to July 2019 and who met the criteria. Secondly, data were collected using a pre-designed tool, and the extraction of data was not performed by medical staff who prescribed or dispensed the antibiotics.Ethical approval was sought from the relevant bodies; the Biomedical Research and Ethics Committee (BREC) at the University of KwaZulu-Natal (UKZN) (BE330/19), KZN Department of Health (KZN-DoH) and the Head of Department and Chief Executive Officer (CEO) at the study site.Patient demographic data for 184 pregnant women are shown in Demographic variables correlated with the duration of antibiotic treatment included the following:p = 0.0009, 20–29, p = 0.017, 30–42, p = 0.03)age group gestational week (p = 0.9)HIV co-infection (p = 0.9).high-risk pregnancy (A description of the different antibiotic classes and their prescribed frequencies are shown in Whilst the Pregnancy and Lactation Labelling Rule (PLLR) has come into effect for all new drugs registered in the United States of America and is being phased in for older drugs, medication use in this study was classed according to the ‘A to X’ categories of the FDA Feibus , 2019. APenicillins were the most frequent class (39.7%) of antibiotics prescribed to pregnant women followed by the macrolides (category B) (13.0%) and combination penicillin- and beta-lactam inhibitors (category B) (12.3%). Nitrofurantoin (8.1%) and carbapenems (6.3%) were also amongst the commonly used antibiotics, although they were slightly less prescribed in comparison to macrolides and beta-lactams. Other antibiotics such as rifamycin, hydrazides, aminoglycosides, fluoroquinolones and trimethoprim-sulphonamide combinations were sparingly prescribed.The five most frequently prescribed category B antibiotic classes  and their respective dosing characteristics, including the route of administration and indication, are described in The strength, dosing frequency and average duration varied amongst the different classes with most women receiving oral or intravenous (IV) doses of administration, whilst a few received treatment intramuscularly (IM).Most antibiotics were given for 7 days or less. Phenoxymethylpenicillin was an exception as the average duration for this antibiotic was 9 days. The remaining penicillin classes, nitrofurantoin and carbapenems were commonly used for 4–7 days. Macrolides were frequently prescribed for less than or equal to 3 days.More than 67% of the antimycobacterial agents (rifamycins and hydrazides) were dispensed for periods longer than 8 days. Half of the women who were treated with aminoglycosides received the drug for 3 days or less, whilst the other half received it for 4–7 days. Fluoroquinolones were mostly prescribed for a short period of fewer than 5 days. Trimethoprim-sulphonamide combinations were dispensed to seven patients, with most patients receiving treatment for approximately 20 days.The primary aim of this study was to evaluate the use of antibiotics amongst pregnant women attending a public healthcare facility.Safety and efficacy information of antibiotics is usually very limited in pregnancy because of ethical implications around clinical testing in pregnant females. This study classifies the safe use of antibiotics according to the FDA safety categories.p = 0.0009, 20–29, p = 0.017, 30–42, p = 0.03). No previous studies have investigated this relationship. It is possible that with increased age, the change in pregnancy hormone levels and the patients’ immune response may contribute to a longer recovery and hence the longer duration of treatment. However, this may differ amongst individuals and various studies . This might indicate the positive impact of antiretroviral (ARV) therapy on decreasing the possible risk of infection in HIV-positive individuals. Similarly, these results were found in KwaZulu-Natal and Nigeria, although this explanation cannot be extrapolated to the general population and is limited to this study , used most commonly because of its longstanding safety record. These antibiotics remain widely prescribed in pregnancy , an antibiotic specific for the urinary system, was also commonly prescribed. Some studies reported no severe malformation during pregnancy, whilst others found conflicting evidence , were used in this study. Carbapenems are broad-spectrum beta-lactams and are typically reserved for infections that are resistant to penicillin and cephalosporin antibiotic therapy   is one of the few antibiotics that is completely avoided in pregnancy because of the risk of neonatal toxicity, particularly grey baby syndrome Amstey . It was According to several studies, the majority of antibiotics are used to treat genitourinary infections in pregnancy . The long-term reliance on antibiotics that are considered safe to use has led to emerging resistance resulting in the use of broad-spectrum or alternative agents where safety has not yet been established. Patients should be educated and encouraged to be a part of the decision-making process. The role of healthcare professionals in risk assessment and evaluation of available evidence for optimal antibiotic selection, dosing, duration of therapy and monitoring is pertinent to improving maternal health.


Studies have shown significant variability in antibiotic trough concentrations in critically ill patients receiving renal replacement therapy (RRT). The purpose of this study was to assess whether adding beta-lactam antibiotics to dialysate solution can maintain stable antibiotic concentrations during RRT in experimental conditions. A single compartment model reflecting the patient was constructed and connected to the RRT machine. Dialysate fluid was prepared in three different concentrations of meropenem . For each dialysate concentration various combinations of dialysate and blood flow rates were tested by taking different samples. Meropenem concentration in all samples was calculated using spectrophotometry method. Constructed experimental model results suggest that decrease in blood meropenem concentration can be up to 35.6%. Moreover, experimental data showed that antibiotic loss during RRT can be minimized and stable plasma antibiotic concentration can be achieved with the use of a 16 mg/L Meropenem dialysate solution. Furthermore, increasing meropenem concentration up to 64 mg/L is associated with an increase antibiotic concentration up to 18.7–78.8%. Administration of antibiotics to dialysate solutions may be an effective method of ensuring a constant concentration of antibiotics in the blood of critically ill patients receiving RRT. The cause of AKI is often multifactorial; however, sepsis, septic shock and concomitant systemic inflammatory response syndrome are the most common causes of AKI in the critically ill, accounting for over 60% of cases13. Furthermore, mortality in this subgroup of patients is considerably higher, reaching up to 50%13.Acute kidney injury (AKI) is a common syndrome in patients admitted to the intensive care unit (ICU). The incidence of AKI in ICU patients varies widely from 3 to 33% with mortality ranging from 26 to 90%16. This unintended under-dosing leads to increased resistance of the microflora and sub-optimal effect, prolonged hospitalization and worse clinical outcome19.Irremissible treatment for these patients includes broad spectrum antibiotics and, in more severe cases, renal replacement therapy (RRT). A critical state and a diminished kidney function leads to altered distribution and elimination of the antibiotics. Upon starting the RRT these alterations are further exacerbated by introducing a machine generated clearance of drugs. Therefore, the antibiotic dosing during continuous RRT is particularly complex. Studies have shown that there is a significant variability in antibiotic trough concentrations in critically ill patients receiving RRT, revealing that empirical dosing failed to achieve the target in 25–60% of patients receiving continuous RRT24. Beta-lactam antibiotics are small and hydrophilic molecules, presenting with low to moderate distribution volumes, low protein binding and are mainly excreted by the kidneys25. Therefore, after initiation of the CRRT the clearance of these antibiotics is unpredictable, effected by constitution of the dialysate, blood and dialysate flow rates across the filtration membrane. The estimated clearance of beta-lactams during CRRT up to 30%26. Various dosing modifications are routinely applied to prevent inadequate antibiotic concentrations, leading to higher exposure to the drug, higher incidence of adverse effects and higher costs of the treatment27.Beta-lactam antibiotics are used commonly in the management of critically ill patients with sepsis in ICU. Based on numerous in vitro and in vivo experimental data, the most significant parameter that influence their efficacy is the duration of the effective antibiotic exposure, i.e. time when antibiotic concentration in blood is higher than minimal inhibitory concentration (MIC) of the bacteria, in contrast to other possible pharmacokinetic targetsThe aim of the study was to assess whether adding beta-lactam antibiotics to dialysate solution can maintain stable antibiotic concentrations during CRRT in experimental conditions.A single compartment model was constructed from the glass container of 25 L. The volume of the patient was imitated with a dialysate fluid with a fixed concentration of the drug Table . This co28. However, the actual estimated sieving coefficient in our model was nearly 1.0 due to unobstructed movement of the drug and no clotting or clogging in the filter. The concentration of the meropenem set in the container was 16 mg/L, representing both recommended dosage for continuous infusion and the four-fold higher concentration than reported MIC of the most common microflora in the intensive care units29.The beta-lactam antibiotic chosen for the study was meropenem , due to its clinical indications and suitable pharmokinetic profile making it susceptible to elimination during CVVHD: volume of distribution of 21 L, 2% protein bound, molecular size of 383.5 Da, sieving coefficient of 0.93 and estimated removal of around 30% during the therapyTo determine whether adding meropenem into the dialysate fluid will remove the concentration gradient and equilibrate antibiotic concentrations during CVVHD the dialysate fluid was prepared in three different concentrations . The maximum concentration we used was 64 mg/L, which is 2 times lower than concentration achieved after bolus injection of meropenem, therefore, in the safe range. Furthermore, the amount of meropenem used to achieve 64 mg/L in the dialysis bag was less than 1 g. Thus, we do comply with safety recommendations of European Medical Agency. The drug was injected into dialysate bags via a sterile accessory spike using a sterile plastic syringe. Each bag was then gently shaken to ensure proper mixing.To determine the effect of blood flow (Qb) and dialysate flow (Qd) three different sets of samples were generated, providing nine combinations of blood and dialysate flow rates. For each dialysate concentration  various combinations of dialysate and blood flow were tested Table . Samples30.Meropenem concentration in all samples was calculated using spectrophotometry method at a wavelength of 300 nm using extinction coefficient. The natural degradation of the meropenem in the container was estimated by taking control samples on 0 time, 2 and 4 h later All of Meropenem containing solutions were clear in appearance and no color change or precipitation was observed throughout the experiment period. Spectrophotometric testing of control samples from the container collected on 0 time, 2 and 4 h later  showed no significant changes in Meropenem concentration. The absorption spectra of Meropenem in controls are shown in Fig. In the present model, a standard CVVHD procedure was associated with a decrease in blood meropenem concentration ranging from 8.8 to 35.6%, according to the flow rates of blood and dialysate. This loss was eliminated with the use of a 16 mg/L meropenem dialysate solution. Increasing meropenem concentration up to 64 mg/L in the dialysate solution revealed that this approach may raise antibiotic concentration up to 18.7–78.8%  parameters vary widely during critical conditions. Studies have shown that the apparent plasma concentrations of bound and free Beta-lactam antibiotics are not in line with the expected values and a correlation with albumin concentration exists only in special conditions making it challenging to represent the system in a fully mechanistic fashion and thus underestimate the effect33. However, an increase in cytokine clearance result in decreased filter membrane permeability. Our model represented a ~ 0% reduction in permeability during CVVHD procedure. Changes in membrane permeability may lead to significant inadequacy between experimental design and clinical application.Another limitation of the study is the permeability of the filter. During CRRT in vivo, blood is conducted through an extracorporeal circuit, activating coagulation by a complex interplay of patient blood and the circuit. Furthermore, critically ill patients may develop a procoagulant state due to multiple mechanisms including sepsis and SIRS related pro-inflammatory cytokine increase. High flux membranes with a cut-off of 30-40kD should be capable of eliminating significant amounts of inflammatory mediators including chemokines and cytokines by convection or by direct absorption on the filter. This advantage of RRT technique is effectively used in the management of sepsis related cytokinemia


The effects of pore structure changes on concrete frost resistance, durability, and compressive strength mechanical properties after freezing and thawing cycles in different salt solution environments are analyzed. This paper provides new means and ideas for the study of concrete pores. The results show that with the increase in the freezing and thawing times, the concrete porosity, two-dimensional pore area, three-dimensional pore volume, and pore number generally increase in any solution environment, resulting in the loss of concrete compressive strength, mortar spalling, and the decrease in the relative dynamic elastic modulus. Among them, the CH3COOK solution has the least influence on the concrete pore changes; the NaCl solution has the greatest influence on the change in the concrete internal porosity. The damage of CaCl2 solution to concrete is second only to the NaCl solution, followed by clean water. The increase in the concrete internal porosity from high to low is NaCl, CaCl2, clean water, and CH3COOK. The change in the pore volume of 0.1 to 1 mm3 after the freeze–thaw cycle is the main factor for reducing concrete strength. The test results have certain guiding value for the selection of deicing salt in engineering.The macroscopic mechanical properties and frost resistance durability of concrete are closely related to the changes in the internal pore structure. In this study, the two-dimensional and three-dimensional ICT  pore characteristics of C30 concrete specimens before and after freezing and thawing in clean water, 5 wt.% NaCl, 5 wt.% CaCl Deicing salt can effectively reduce the freezing point and realize the effect of melting ice and snow to alleviate the traffic pressure caused by snow in winter. However, winter significantly impacts concrete with the melted ice and snow entering the concrete. In Northern China, several deicing salts are used to ensure traffic because the temperature is lower than 0 °C in winter, resulting in peeling and cracks in concrete structures, such as in roads and bridges, which affect their frost resistance durability. Additionally, the concrete strength of some foundation concrete structures, such as dams and bridge foundations, has been greatly affected ,2,3,4,5.Currently, there is no unified academic recognition for the salt freezing failure mechanism of concrete. Recently, hydrostatic pressure, osmotic pressure, and temperature stress hypothesis have been more common ,7,8. Thu2, CaAc2, and CaFm2 solutions on the durability of concrete by the freezing and thawing cycle. The test results show that the mechanical properties of concrete significantly decrease with the increase in the freezing and thawing cycle. They believed that the change in the micro-structure of the salt freezing environment is the main factor for the decrease in the mechanical properties of concrete. Lai Y. [3COOK) on the salt-freezing resistance of airport runway concrete. They discussed the influence of freezing–thawing cycles in the water and runway deicing salt environment on the apparent morphology, mass loss rate, and relative dynamic elastic modulus of concrete. It is considered that the presence of deicing salts negatively affects the frost resistance of concrete. Cao R.S. [2 in a freeze–thaw environment. With the increase in the number of freezing and thawing, the block surface strip material corrosion becomes severe, the dynamic elastic modulus falls, the mechanical properties deteriorate, and the compressive strength decreases. Among them, the test block with a low concentration salt freeze is the most severely damaged. Related personnel [Harnik A.B.  believed. Lai Y.  investigCao R.S. , employiersonnel ,18,19,20ersonnel ,22. Howeersonnel .2, and CH3COOK, in the market for durability tests. Additionally, the internal pore characteristics of concrete under different salt freezing environments based on ICT scanning technology are extracted and analyzed. Furthermore, the relationship between pore characteristics and concrete working performance under different salt freezing environments is investigated to further study concrete damage mechanisms by salt freezing.Several studies on concrete damaged by salt freeze mainly focus on durability life predictions of concrete and mechanical performance and the influence of different mineral contents on concrete frost resistance ,30,31,32The cement used is conch brand P·O 42.5 ordinary Portland cement.The Grade I fly ash is produced by Shaanxi Bahe Power Plant.3 and a bulk density of 1720 kg/m3.Coarse aggregate is the nominal size of 5 to 20 mm limestone, with an apparent density of 2835 kg/m3, and a bulk density of 1480 kg/m3.Fine aggregate is the Ba River sand in Xi’an, with a fineness modulus of 2.8, an apparent density of 2630 kg/mThe admixture is a polycarboxylic acid water-reducing agent.Ordinary Xi’an tap water is used to prepare the sample. Distilled water is used to prepare the salt solution and soaking.2, and 5% CH3COOK solution. The preparation of the solution is carried out at room temperature.The salt solutions are 5% NaCl, 5% CaClInstruments and equipment: TDR-28 concrete rapid freezing-thawing testing machine , MultiScalevoxel-450 Industrial CT , microcomputer-controlled electro-hydraulic servo universal testing machine , DT-20 dynamometer , as shown in The freeze–thaw cycle test was conducted according to the quick freezing method in Chinese standard specification GB/T50082-2009 . The conThe time of each freezing and thawing cycle is 2–4 h, and the time for thawing is not less than one-fourth of the entire freezing and thawing time. During the freeze–thaw cycle, the lowest and highest temperature of the specimen center is (−18 ± 2) °C and (5 ± 2) °C respectively.The fabrication design strength is C30, and the test cube concrete specimen size is 100 mm × 100 mm × 100 mm. 2 solution, and 5 wt.% CH3COOK solution for the freeze–thaw cycle test. After every 25 freeze–thaw cycles, the corresponding specimens are taken out for compressive strength, mass loss rate, and relative dynamic elastic modulus tests.Concrete specimens are divided into ordinary and ICT groups, a total of 81 pieces. A compressive strength test is conducted for the ordinary group after curing. Additionally, its quality and transverse base frequency data are measured at room temperature after soaking in clean water for 4 d. Then, it is placed in clear water, 5 wt.% NaCl solution, 5 wt.% CaClBy detecting the transverse fundamental frequency of concrete, the relative dynamic elastic modulus can be calculated according to the following formula:Pi (%) is the relative dynamic elastic modulus of the i-th concrete specimen after n freeze–thaw cycles, nif (Hz) is Transverse fundamental frequency of the i-th concrete specimen after n freeze–thaw cycles, and fi0 (Hz) is initial value of transverse fundamental frequency of the i-th concrete before the freeze-thaw cycle.In Formula (1), P takes the arithmetic average of the test results of three specimens as the measured value. When the difference between the maximum value, the minimum value, and the median value exceeds 15% of the median value, this value is invalid, and the remaining data are calculated and averaged. The value is used as the measured value.The relative dynamic elastic modulus The mass loss rate of concrete specimens is calculated by the following formulas:i-th concrete specimen after N freeze–thaw cycles. i-th concrete specimen before the freeze–thaw cycle test, i-th concrete specimen after n freeze–thaw cycles. In Formulas (2) and (3), The mass loss rate is based on the arithmetic average of three data as the measured value. When the difference between the maximum value, the minimum value and the median value exceeds 1% of the median value, the value is invalid, and the arithmetic average of the remaining data is taken as the measured value.The ICT group underwent CT scanning before freezing and thawing after soaking in the corresponding solution after maintenance, followed by the freeze–thaw cycle test and ICT scanning immediately after 25 cycles of freezing and thawing and 50 cycles of freezing and thawing. Then, continued the freeze–thaw cycle test to reduce the residence time of the specimen at room temperature and reduce the experimental error. Since the concrete specimen is severely damaged after 75 freeze–thaw cycles and cannot support its subsequent scanning, the ICT scanning data are recorded to the 50th freeze–thaw cycle.ICT data processing software is 2 Avizo (2019.1) of ThermoFisher Scientific, Shanghai, China, and the data processing process is shown in The essential parameters are the compressive strength, mass loss rate, and relative dynamic elastic modulus of concrete to measure its frost resistance durability. Among them, the changes in the mass loss rate and the relative dynamic elastic modulus reflect the intuitive state of concrete, and the change in the compressive strength reflects the strength loss of concrete after the freeze-thaw cycles.2 solution was reduced by 28.1%. The value was 23.9% in a clear water environment. The CH3COOK solution environment has little effect on the compressive strength of concrete, and the compressive strength decreases by 21.4% after 75 freeze-thaw cycles.2 solution environment, the mass loss rate of concrete after 75 freeze–thaw cycles was 8.47%. The water and CH3COOK solutions have minor effects on the mass loss rate of concrete. After 75 freeze-thaw cycles, the mass loss rates of the water and CH3COOK solutions were 4.08% and 3.88%, respectively.The dynamic elastic modulus is one of the important indices of material mechanical properties. It shows the difficulty of elastic deformation of the concrete test block. The lower the relative dynamic elastic modulus of the concrete test block, the worse its strength, the more severe the damage, and the greater the impact of the freeze–thaw cycle. The durability of concrete is related to the resilience index to some extent. When the concrete is affected by the external environment, it is bound to affect its durability. The worse the durability, the lower the expected resilience . Figure 2 solutions started decreasing rapidly. Among them, the relative dynamic elastic modulus of concrete specimens in the NaCl solution environment decreased significantly faster than that of other specimens, and the attenuation rate continued to accelerate. During the first 50 freeze-thaw cycles, the attenuation of the relative dynamic elastic modulus of the test block in the clean water and CH3COOK solutions was the same. However, with the progress of the freeze-thaw cycle, the attenuation rate of the relative dynamic elastic modulus of the test block in the clean water environment begins to be significantly higher than that in the CH3COOK solution. After 75 freeze-thaw cycles, the relative dynamic elastic modulus of concrete specimens in clean water, the NaCl solution, the CaCl2 solution, and the CH3COOK solution were 57.08%, 20.06%, 43.36%, and 68.32%, respectively. Therefore, the attenuation rate of relative dynamic elastic modulus of concrete under four different freeze-thaw cycle media is as follows: CH3COOK < Clean water < CaCl2 < NaCl.After 50 freeze–thaw cycles, the relative dynamic elastic modulus of concrete under the freeze-thaw cycles of NaCl and CaCl2, and 5 wt.% CH3COOK solutions were analyzed. It is consistent with the expected results. In the NaCl solution environment, the concrete quality loss is the most, and mortar peeling is the most severe. After 75 freeze–thaw cycles, the relative dynamic elastic modulus decreased by 79.94%, lower than the limit of 60% in the specification. Additionally, the compressive strength decreased by 36.1% compared with that before freezing and thawing. It can be considered that the freeze-thaw failure has been reached due to the increase in water saturation and the water absorption rate of capillary in concrete because of the existence of the salt solution. The ice pressure generated when the solution freezes will cause more severe damage to the concrete than in the clean water environment [2 solution is acidic, and it has a certain chemical erosion on concrete. In freezing–thawing cycles, it can promote the dissolution of Ca(OH)2 in concrete and [2 solution environment is lighter than that in the 5 wt.% NaCl environment. However, the influence of salt freezing damage on coagulation soil cannot be ignored. After 75 freeze-thaw cycles, the mass loss rate reaches 8.47%. The strength decreased by 28.1%, reaching the failure standard. Compared with chloride deicing salts, the CH3COOK solution is alkaline while reducing the freezing point, indicating less chemical erosion on concrete. After 75 freeze-thaw cycles, all standards fail to meet the damage conditions in the specification, and it has less impact on the salt freeze–thaw damage of concrete [Through the concrete quality loss tests, the relative dynamic elastic modulus, mechanical properties, and freeze–thaw damage degree of concrete in the clean water environment and 5 wt.% NaCl, 5 wt.% CaClironment ,43. The rete and ,45 the dconcrete .ICT scanning data reconstruction was performed every 25 freeze-thaw cycles to obtain 1000 cross-sectional slices. By comparing the slicing data, the concrete in different freezing and thawing environments along the direction of the casting surface height of each pore distribution of the calculated porosity of variance was obtained, and the average porosity change was further determined to influence the degree of the solution of the concrete’s internal porosity change.3COOK solution environments, the surface of the test piece is still relatively complete after 50 freeze-thaw cycles; only part of the mortar is peeled off, in a dispersed state, and the aggregate is slightly exposed. After 50 freeze-thaw cycles in the CaCl2 solution, although passivation occurs at the edges and corners, its shape is relatively regular. A small amount of aggregate is exposed, and the mortar peeling phenomenon is severe. In the NaCl solution environment, the surface mortar peeling and roughness of the test piece occurred after 25 freeze–thaw cycles. The closed hole in the lower surface of the test piece forms an opening due to mortar peeling. After 50 freeze-thaw cycles, the surface has severe mortar peeling; many aggregates are exposed and severely deteriorate.Considering the 500th slice of the intermediate layer as an example , the con3COOK solution environment changes more evenly. The variance changes slightly, indicating that the pore change trend of each layer of the specimen is relatively stable in the freeze–thaw cycle. In the NaCl solution environment, the 2D porosity of the specimen changes along the pouring depth direction. The porosity significantly fluctuates when it is close to the upper and lower surfaces and the middle of the specimen. The variance change is greater than that of the other three solutions. The greater the variance, the greater the dispersion of the porosity, the uneven porosity of each layer on the pouring surface, and the most obvious deterioration effect on the specimen. The change in the 2D porosity of the specimen in the CaCl2 solution environment is mainly concentrated in the lower half. The variance is the second only to the NaCl group, indicating that the deterioration of the specimen is concentrated in the lower half, with the largest change occurring between 80 and 90 mm. The NaCl solution has the greatest impact on concrete deterioration, followed by CaCl2. The clean water solution is similar to the CH3COOK solution and has little impact on concrete deterioration. This result is consistent with the results of the concrete frost resistance durability test, which further verifies that the change in concrete porosity will affect its performance.2 solution are more severely damaged than those in the clean water and CH3COOK solution. The reason for this is that the freezing expansion rate of the NaCl solution is larger than that of the aqueous solution, and the internal pores are more frozen and expanded. The salt freezing damage of concrete frozen and thawed in the CaCl2 solution is due to the formation of compound salt, CaCl2·Ca(OH2)·H2O, significantly reducing the frost resistance of concrete, thus causing erosion damage of the concrete [3COOK solution is much smaller than that of the chloride solution. Additionally, the degree of freeze–thaw damage is similar to that of the clean water environment, indicating that the existence of Cl− is the main reason for reducing the frost resistance of concrete.The samples frozen and thawed in the NaCl and CaClconcrete . The fre3 are small pores, 0.1 mm3 ≤ V ≤ 1 mm3 are medium pores, and V greater than 1.0 mm3 are large pores.Avizo software is used for threshold segmentation of 2D section data. The pores of each layer of the concrete slice are extracted using different gray levels for 3D reconstruction to obtain the 3D model of internal pores and analyze the influence characteristics of the freeze–thaw environment on concrete pores from the 3D pore distribution. Different pores are classified into large, medium, and small according to the pore volume. Among them, pores with volume V less than 0.1 mmBy analyzing the changes of large, medium, and small holes in concrete, the influence laws of the freeze–thaw environment and cycle on the internal pore structure of concrete are obtained. 2 solution environment, when the concrete specimen is frozen and thawed zero times, the volume proportion primarily comprised large pores; the volume proportion of small pores is relatively low. Additionally, most of the pores are concentrated in the middle and lower part of the specimen. After 25 freeze-thaw cycles, many pores were generated on the left side of the specimen. The change in the number of pores is similar to that of other solutions. They increase exponentially, mainly medium and small pores. The change in the proportion of pore volume is small; the proportion of large pores decreases; the increase in the proportion of medium pores is small; the proportion of small pores increases more, mainly small pores; and the porosity increases by 0.14%. After 50 freeze–thaw cycles, the number of medium and small holes increases. The proportion of pore volume changes due to the growth of medium holes, and there is a small decrease in large holes, a small increase in small holes, and the porosity increases by 0.13% compared with 25 freeze–thaw cycles.In the CaCl3COOK solution environment, when the concrete is frozen and thawed zero times, the proportion of pore volume is mainly macropores, and most of the pores are concentrated in the lower part of the specimen. After 25 freeze–thaw cycles, the growth rate of the pore number is smaller than that of the other three solutions; the total number is less than 20,000; the proportion of macropore volume decreases more; the proportion of mesopore volume increases exponentially; the proportion of small pore volume also increases slightly; and the porosity increases by 0.11% compared with that of zero freeze–thaw cycles. After 50 freeze–thaw cycles, the total number of pores increased by 2059. From the change in the pore volume proportion, the proportion of large pores further decreased; the proportion of medium pores increased more; the proportion of small pore volume increased slightly; and the porosity changed slightly, increasing by 0.07% compared with 25 freeze-thaw cycles.In the CH3 ≤ V ≤ 1 mm3 increases greatly from 20.6% in the initial state to 52.5%. However, the proportion of pore volume V greater than 1 mm3 decreases gradually from 67.1 to 26.7%. This shows that it is mainly dominated by the growth of mesopores during the freezing and thawing of the NaCl solution. The pore growth trend in the CaCl2 solution environment is similar to that in the NaCl solution  is the cube compressive strength of concrete, a and b are constants , and the value is determined by the test, where R2 is the error.In relations (4) and (5), The fitting curve shows that the porosity is negatively correlated with the compressive strength of concrete. As the porosity increases, the compressive strength of concrete decreases. Based on ICT scanning technology, this paper analyzes the frost resistance durability and pore characteristics of concrete in the salt freezing environment. The following conclusions are obtained through concrete durability and compressive strength tests.2 solution have the greatest impact on the frost resistance durability and mechanical properties of concrete. The impact of non-chloride deicing salt 5% CH3COOK on concrete is similar to that of the clean water solution. It has little impact on the frost resistance durability and mechanical properties of concrete. It means that the freeze–thaw damage of concrete in the chloride deicing salt environment is more severe than that in the non-chloride deicing salt and clean water environments. Therefore, when deicing ordinary concrete, it is recommended to give priority to non-chloride deicing salts.In any solution environment, with the increase in freeze-thaw cycles, the concrete will have a loss in compressive strength, an increase in mass loss rate, and a decrease in the relative dynamic elastic modulus. Chloride deicing salt 5% NaCl and 5% CaCl2, clean water, and 5% CH3COOK. In any solution environment, the compressive strength of concrete is negatively correlated with porosity. It means that the greater the porosity, the lower the compressive strength of the concrete. The test is aimed at ordinary concrete, and the use of concrete with special functions needs to be studied, such as the use of an air entraining agent to improve the thermal insulation function of concrete.With an increase in freeze–thaw cycles, the porosity of concrete in different environments shows an upward trend. After the freeze–thaw cycles, the increase in the internal porosity of concrete from high to low is 5% NaCl, 5% CaCl2, clean water, and 5% CH3COOK. The use of non-chlorine salt deicing agents can reduce the impact of freezing damage on concrete to a certain extent.The influence of different salt solutions on concrete stays on the surface and has a certain impact on the internal pores of the concrete. The internal pores of chloride concrete change significantly, which is reflected in the variance of 2D porosity. The larger the variance, the greater the influence of salt solution on the 2D pore characteristics of concrete. The influence of the salt solution on the 2D pore characteristics of concrete from largest to smallest is 5% NaCl, 5% CaCl2, and 5% CH3COOK. It is consistent with the experimental results of durability and mechanical properties. This test analyzes the internal pore changes of concrete and obtains the pore change trend of different salt solutions. This change is the same as the change trend of the durability test. It aims to study the change law of the internal pores. There are certain limitations, but the pore pair can be changed for further research. The impact of concrete performance provides a research basis.Under the salt solution environment, freezing and thawing greatly influence the internal pores of the concrete. The proportion of large pore volume decreases, and the proportion of medium and small pore volumes increase. Among them, the faster the growth rate of the proportion of the medium pore volume, the greater the impact on the frost resistance durability and mechanical properties of concrete. The increase in the proportion of the medium pore volume from the largest to smallest increase is 5% NaCl, 5% CaCl