Poly (PEDOT:PSS) water and toluene solutions were investigated in detail, taking into consideration their stability, wettability, transparency, and electrochemical properties, along with change polarity caused by dopant. As dopant, methanol, ethanol, and isopropanol were used with different dipole moments  and dielectric constants . Three techniques, i.e., spin coating, doctor blade coating, and spray coating, were employed to created PEDOT:PSS layers on glass, glass/indium tin oxide (ITO), and glass/fluorine-doped tin oxide (FTO) substrates with optimized technical parameters for each used equipment. All used PEDOT:PSS water and toluene solutions demonstrated good wetting properties with angles below 30° for all used surfaces. Values of the energy bandgap (Eg) of PEDOT:PSS investigated by cyclic voltammetry (CV) in solution showed increase energy Eg along with addition of alcohol to the mixture, and they were found in the range of 1.20 eV to 2.85 eV. The opposite tendency was found for the Eg value of the PEDOT:PSS layer created from water solution. The storage effect on PEDOT:PSS layers detected by CV affected only the lowest unoccupied molecular orbital (LUMO) level, thereby causing changes in the energy bandgap. Finally, simple devices were constructed and investigated by infrared (IR) thermographic camera to investigate the surface defects on the created PEDOT:PSS layers. Our study showed that a more stable PEDOT:PSS layer without pin-holes and defects can be obtained from water and toluene solutions with isopropanol via the spin coating technique with an optimal speed of 3000 rpm and time of 90 s. In recent years, increased interest in organic devices, such as solar cells (SCs), was observed in both academia and industry, focusing on high efficiency and solution-based fabrication ,2,3. ComFlexible and low-temperature processes are needed to create transparent electrodes, which are important for many optoelectronic devices, i.e., touch screens, organic light-emitting diodes, and solar cells . A trans(1)conducting polymers  (PEDOT:PSS), polyaniline (PANI), polypyrrole (PPy)) ,11,12;(2)inorganic nanostructures  ,14,15,16(3)l,d-PLA, PANI nanowire/nylon nanofiber) [hybrid materials  ,18.Generally, strategies for the preparation of flexible transparent electrodes can be classified as follows:In organic devices, other layers in addition to the electrodes should also possess good flexibility and transparency. It is well known that PEDOT:PSS can act as a transparent electrode in devices, while it can also play the role of a hole transporting layer (HTL) in organic solar cells, taking into consideration its high work function, high transparency, and good conductivity. Unfortunately, PEDOT:PSS in organic solar cells exhibits various disadvantages when it comes to HTL formation, with a consequent decrease in the long-term stability and performance of devices . The mai2O5, WO3, NiO, and MoO3 were proposed instead of PEDOT:PSS applied in organic solar cells [g-PANI) [3 moieties (PC-P) [To solve these difficulties, various inorganic compounds such as Var cells . Organic[g-PANI) , polypyr[g-PANI) , PEDOT:P[g-PANI) , PEDOT:P[g-PANI) , or a nes (PC-P) .In recent years, poly (PEDOT:PSS), especially with regard to its use in electronic devices including photovoltaics, received interest on account of its relatively simple processability at low temperature, antireflecting properties, and water-based dispersion ,25,26,27PEDOT:PSS can be also used as a hybrid electrode over ITO or fluorine-doped tin oxide (FTO) giving improved electrical properties and mechanical support ,32,33, oPEDOT:PSS was investigated in the past taking into consideration both molecular and supramolecular engineering concepts. In this study, we would like to present a technical approach in the preparation of PEDOT:PSS layers for organic devices via an investigation of layer formation via spin coating, doctor blade coating, and spray coating techniques. Our main focus was on the comparison of different PEDOT:PSS solutions based on pure solvents like water or toluene and their mixtures with different alcohols such as methanol, ethanol, and isopropanol. In this article, we evaluate the electrical, thermal, and electrochemical properties of thin PEDOT:PSS layers over three different substrates  in order to assess the influence of alcohol adjuncts on conductive polymers. As a substrate, we tested glass with ITO or FTO, taking into consideration the fact that, depending on the type of organic solar cells, ITO or FTO substrate is mainly used. In organic/polymer solar cells, ITO substrate is mainly used. In DSSCs, FTO substrate is mainly used, while, in perovskite solar cells, both ITO and FTO were tested to find the best conductive substrate.In our work, for the first time, a thermographic camera was used to detect the location of defects in the created devices, as well as to determine the electrical behavior of PEDOT:PSS and its mixture with alcohols.In this work, we tested commercially available PEDOT:PSS in water or toluene solution. Our aim was to investigate how three alcohols with different polarity can influence the selected properties of PEDOT:PSS, taking into consideration a ternary component solution. As alcohols, methanol, ethanol, and isopropanol were used with different dipole moments  and dielectric constants . Our study showed that the presence of isopropanol with a lower dipole moment and lower dielectric constant in PEDOT:PSS solution used for layer preparation caused an almost two-fold increase in the electrical resistance and a 30 °C decrease in the thermal response.All chemical reagents and substrates were purchased from a commercial source. The mainly used components were a PEDOT:PSS (0.5:0.8 weight ratio) aqueous dispersion with a solid content of 1.3 wt.% , PEDOT:PSS dispersion in toluene with a solid content of 1.5 to 2.5 wt.% , and high-purity alcohols, such as methanol, ethanol, and isopropanol. To study PEDOT:PSS layers, we used the following substrates: glass, FTO- and ITO-coated glass. Microscope slides  were used for UV–Vis spectrometry. For FTO , we used cyclic voltammetry for the electrochemical study with an IR thermographic camera ITO .PEDOT:PSS solutions dispersed in water or toluene were mixed with three different alcohols, methanol, ethanol, or isopropanol with volume ratio of 1:0.5. All mixtures were ultrasonicated for 1 h at room temperature. PEDOT:PSS mixtures in toluene with methanol and ethanol were unstable after 30 min, at which point they stratified A. For thPEDOT:PSS films were prepared by spin coating, doctor blade coating, and spray coating techniques. All substrates  were cleaned alternately with isopropanol and acetone, three times, prior to use. Additionally, all substrates were placed in UV Ozone Cleaner for 10 min. The layers for each mixtures were prepared with the same set of parameters as for pristine PEDOT:PSS solutions. Films deposited by spin coater were prepared at 3000 rpm for 90 s. Layers made using the doctor blade device were applied at a speed of 50 mm/s, and the casting knife was set at 10 µm. In the case of samples prepared by spray coater, the solution was sprayed on the substrate from a height of 10 cm with air pressure of 2 bar. All prepared films were annealed on a hot plate at 30 °C for 20 min.A contact angle goniometer  coupled with a computer system served as the basic diagnostic tool that enabled contact angle measurements via drop shape analysis after wetting the surface with aqueous or toluene solutions. The drop images were recorded up to 5 s counting from the moment the drop touched the surface. The volume of a drop dosed with a syringe was on the order of 7 μL. As the contact angle, we used the angle between the tangent to the surface of the drop placed on the solid at the point of contact of three phases: solid, liquid, and gas.The transmission UV–Vis spectra were acquired using an A360 UV–Vis spectrophotometer  with an interval of 0.2 nm and medium scan speed.4NPF6  was used as the supporting electrolyte. The concentration of compounds was equal to 1.0 × 10−6 mol/dm3. The deaeration of the solution was achieved by argon bubbling through the solution for about 15 min prior to the measurement. All electrochemical experiments were carried out at ambient temperature and pressure.Electrochemical measurements were carried out as described in our previous work , using aThermal behavior was observed according to our standard protocol described elsewhere , using aIn this study, we investigated in detail a technical approach in the preparation of PEDOT:PSS layers for organic devices and their influence on optical and electrochemical properties. Our main focus was on the comparison of different PEDOT:PSS solutions based on pure solvents like water or toluene and their mixtures with three different alcohols. We performed an assessment of the wettability of different surfaces with selected solutions and their impact on the preparation of thin layers via spin coating, spray coating, or doctor blade techniques. Moreover, an evaluation of the electrochemical behavior of PEDOT:PSS in solution or in a layer was also performed.One of the most crucial factors to be taken into account when spreading a solution is the wettability of solid substrates. The contact angle is one of the commonly used methods to assess the wettability of a surface or material. Obtained results give a direct answer of whether a liquid applied over a solid surface has the tendency to exhibit good wetting properties. Usually, in this case, the contact angle is smaller than 90°. In the opposite situation, for non-wetting liquids, the contact angle is between 90 and 180° . In thisThe results of static contact angle measurements for aqueous PEDOT:PSS solutions with and without the addition of alcohols are summarized in A similar experiment was also performed for toluene-based PEDOT:PSS solutions with and without the addition of alcohol. In these cases, the solutions demonstrated good wetting properties with angles below 30° for all used surfaces, as expected. It was noticed that solutions containing methanol and ethanol formed emulsions and suffered from low stability, resulting in separation over time. The separation was relatively fast and occurred in the syringe used for contact angle measurements; therefore, contact angle measurements for PEDOT:PSS in toluene:methanol and toluene:ethanol were not recorded. The results of wettability are presented in In this section, PEDOT:PSS layers were prepared via three techniques, namely, spin coating, doctor blade, and spray coating. The application parameters for individual devices were selected during the initial optimization process. The focus of this section was on the evaluation of three different film-forming techniques in order to select the best one that gives reproducible results using PEDOT:PSS water- or toluene-based solutions with or without the addition of alcohol.As the first step of this work, selected parameters were changed to optimize the spin coating technique. We changed the speed value from 2000 to 4000 rpm and time from 30 to 90 s until we found the best technical parameters for the PEDOT:PSS solutions A. Detail3H groups of the PSS polymer. Moreover, H–H interactions cannot be excluded. In the case of the toluene solution of PEDOT:PSS, these reactions did not take place. In both solutions of PEDOT:PSS, interactions between the alcohol and OH or SO3H groups are possible, as schematically presented in In our case, for the spin coater, the optimal speed value was found to be 3000 rpm for 90 s. The layer obtained in such conditions was estimated to have 80 nm thickness, based on the spin speed to thickness correlation provided by Ossila. Due to the specific limitations of this technique, it was possible to obtain repeatable samples for both water- and toluene-based solutions. Layers of PEDOT:PSS with and without alcohols obtained via spin coating were more homogeneous see B. In FigSelected parameters were also changed to optimized the process of layer formation for the doctor blade technique. We changed the gap value as 10, 25, and 50 µm and speed rate as 20, 50, and 80 mm/s to find the best technical parameters for PEDOT:PSS solutions. Details of the optimization of the doctor blade technique for PEDOT:PSS in water and toluene are presented in PEDOT:PSS layers were applied with a doctor blade device with a gap set at the 10-µm layer with 50 mm/s film developing speed A. FormatIn the case of toluene-based solutions after annealing, a visually more homogenous layer was formed , which would hinder the application of these samples. The agglomerate formation is related to the mechanism of layer formation using this technique; during dispersion of the polymeric solution, before the solution gets into contact with the solid surface, it loses solvent via partial evaporation. Due to this fact, in some parts of the formed layer, there were small droplets containing undissolved polymeric material . This efIn order to study electrochemical properties of different PEDOT:PSS solutions, cyclic voltammetry (CV) was employed. The first step was to record voltammetry curves for solutions and solvent to identify characteristic signals for single components. The second step involved the electrochemical study of layers on FTO-coated glass, while the third step elucidated the aging process and its influences on the electrochemical response.g), and, in this case, the gap was smaller for the toluene-based solution than for the water-based solution by about 0.19 eV. The addition of alcohol to PEDOT:PSS in water resulted in an extension of over 1 eV compared to the starting solution. The best result from the electrochemical point of view was achieved for the water:isopropanol mixture giving an Eg value equal to 2.85 eV. The electrochemical series in terms of solvent-containing water based on decreasing Eg value was water:isopropanol > water:methanol > water:ethanol > water.The first step involved aqueous and toluene-based PEDOT:PSS solutions, as well as their mixtures with methanol, ethanol, and isopropanol and pure solvents. The cyclic voltammetry response was very stable in the measured range from −2.37 to 0.70 V see . In all g; however, the values shifted by approximately 0.30 eV toward more negative potentials.In the case of PEDOT:PSS in toluene, the addition of alcohol also expanded the electrochemical window, giving the highest value for the toluene:isopropanol mixture at 2.54 eV. The results for the mixture with methanol and ethanol gave similar nominal EFor all samples, additional oxidation maxima at approximately 1.5 V were observed, which can be a consequence of reversible oxidation of some –OH alcohol groups at the platinum electrode . This waWe based our investigation on commercially available homogenous solutions of PEDOT:PSS in water or in toluene. As a dopant, we used methanol, ethanol, or isopropanol with various dipole moments, as presented in In the second step, layers based on PEDOT:PSS solutions in different solvents were prepared via the spin coating method over FTO-coated glass substrate due to the better quality of redox signals registered in the CV curve compared to samples prepared on ITO. In this evaluation, toluene:methanol and toluene:ethanol were not examined due to the instability of solutions. The experimental values of HOMO, LUMO, and energy bandgap are shown in g value as follows: toluene:isopropanol > water > toluene > water:isopropanol > water:methanol > water:ethanol. The values of energy gap for starting solutions were very similar to those obtained for solutions, where the aqueous solution had a higher value. In the case of layers, the signals for the presence of alcohol in the structure were not observed. In g by 0.22 eV, 0.26 eV, and 0.31 eV for isopropanol, methanol, and ethanol, respectively.Generally, upon comparing obtained results for all created layers, it can be easy noted that the HOMO–LUMO limit values were very similar to each other unlike the electrochemical response in solution. This might be an effect of concentration. In solution, the PEDOT:PSS was diluted, whereas, in the form of a thin layer, it was more concentrated. The series of PEDOT:PSS layers depending on used solvent can be organized in terms of decreasing EIn order to evaluate the stability of prepared PEDOT:PSS layers, we carried out short-term storage up to three days in a dark box and argon atmosphere. After each day, the electrochemical performance of the new sample was tested in order to detect any changes in the CV curve. The storage in the abovementioned conditions affected only the LUMO level, thereby causing changes in the energy bandgap . It was The hole transport layer (HTL) in organic solar cells such as PEDOT:PSS should be as transparent as possible. We investigated the influence of the addition of alcohols on the transmittance of PEDOT:PSS films. The UV–Vis measurements were carried out for layers made with a spin coater  on a thin glass substrate to avoid the additional influence coming from the thickness of the glass or deposed conductive layers of ITO or FTO. Details on the influence of technical parameters of spin coating on the transmittance spectra are presented in As shown in ITO/PEDOT:PSS(water)/Ag/ITO;ITO/PEDOT:PSS(water:isopropanol)/Ag/ITO;ITO/PEDOT:PSS(toluene)/Ag/ITO;ITO/PEDOT:PSS(toluene:isopropanol)/Ag/ITO.For thermal imaging, four samples  were selected. These four samples showed the best electrochemical behavior from the whole series. Thermal imaging was used to observe overall behavior of the sample device during application of an external potential. For this experiment, the active layers were prepared using the spin coating technique over ITO-coated glass support. The architecture of the devices was as follows:In The analysis of electrical conductivity for all tested samples revealed the behavior of electric conductors correlated with the applied voltage . The resThe presence of alcohol did not have a significant influence on the wetting abilities of the prepared solutions for all three tested surfaces ;In our study, the spin coating technique showed the best reproducibility and homogeneity of prepared samples compared to other techniques on a laboratory scale;The preparation of thick layers promotes the crystallization of PEDOT:PSS in the layer;g of layers (mainly in terms of LUMO levels) decreased the starting value in the presence of alcohol;The adjustability of EThe presence of isopropanol in PEDOT:PSS solutions used for layer preparation caused an almost two-fold increase in electrical resistance, as well as a decrease in thermal response by 30 °C.To summarize, in our study we presented a technical approach for the preparation of PEDOT:PSS layers for organic devices. Our main focus was on the comparison of different PEDOT:PSS solutions based on pure solvents like water or toluene and their mixtures with three different alcohols. The results of our study demonstrated the following:We can conclude that, for laboratory-scale or small-scale preparation of organic devices, the best technique would be spin coating, which allows the greatest precision in adjusting the parameters. Moreover, the addition of isopropanol allows changing the original behavior of PEDOT:PSS.


Background and Objectives: Rugby players engage in demanding, high loading muscular activity in the spine. Study of the abdominal wall architecture in female rugby athletes is relevant to the possible muscular asymmetry secondary to sport practice and the relationship between the abdominal wall and the pelvic floor muscles. Activation of the transversus abdominis (TrAb) generates an increase in the bladder neck muscle. Moreover, an increased interrecti distance (IRD) is related to urinary incontinence and has a higher prevalence in athletic women. The aim of the present study was to compare and quantify, with ultrasound imaging (USI), the thickness of the transversus abdominis (TrAb), external oblique (EO), internal oblique (IO), rectus abdominis (RA), and interrecti distance (IRD) in female rugby players versus non-athletic women in order to improve upon existing knowledge about abdominal wall configuration in female athletes. Materials and Methods: A sample of 32 women was recruited at the Universidad Europea Research Lab and divided in two groups: a rugby group (n = 16) and a non-athletic women group (n = 16). The thickness of the TrAb, EO, IO, RA, and IRD were assessed by USI in both groups. Results: There were statistically significant differences for the ultrasound evaluation thickness of the right TrAb , EO , IO , and RA  showing a thickness increase for the rugby group with respect to the control group. For the IRD thickness, there were no significant differences (p > 0.05) between groups. Conclusions: An increased TrAb, IO, EO, and RA thickness may be shown in female rugby players versus non-athletic women. Nevertheless, statistically relevant differences were not found for the IRD between both groups. The structural integrity of the abdominal wall is provided by the muscular, fascial, and connective tissue layers, ensuring the protection of the abdominal viscera and spine ,2. In adThe use of ultrasound imaging (USI) has been exponentially increasing and was described as a non-invasive, safe, and non-time-consuming tool to assess soft tissue features, such as thickness, length, cross-sectional area (CSA), and morphology ,7. In adComputerized axial tomography  and magnUSI assessment of the abdominal wall has shown excellent intra- (ICC 0.92–0.99)  and inteThe USI examination of the abdominal wall muscles has been previously carried out in healthy populations ,29, postRegarding the abdominal wall muscle activity implications in sports training and competition, rugby players engage in demanding, high-loading muscular activity in the spine during the launching, reception, and blocking movements . SeveralThe execution of asymmetric repeated actions in the rugby context could influence the morphology of the abdominal muscles . TherefoSeveral studies have evaluated the IRD in women by USI evaluations ,42, due To date, no previous studies have examined the features of abdominal wall muscle morphology in female rugby players. The purpose of the present study was to compare and quantify with USI the thickness of the TrAb, EO, IO, RA, and IRD in female rugby players versus non-athletic women. We hypothesized that abdominal wall muscles thickness was increased in the rugby players secondary to the prolonged mechanical loads exposure during training and competition.A case–control study was developed from February to July 2019, following the guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology Statement (STROBE) guidelines .The study was approved by the Intervention Clinical Committee of the European University of Madrid, Spain . The present study was adhered to the ethical standards of the Declaration of Helsinki. In addition, the consent inform form was obtained from all subjects before the beginning of the study.n = 16, aged 24.73 ± 4.90 years) and healthy women who do not practice any sport activity for the non-athletic women group . The inclusion criteria were subjects from 18 to 45 years [2 [A total sample of 32 women was recruited at the Universidad Europea Research Lab and divided into two groups: semi-professional players from an entertainment Spanish division for the rugby group , divided into eight individuals for the rugby group (0.45 ± 0.11) and eight individuals for the control group (0.33 ± 0.09). A power of 0.80, an α error of 0.05 and an effect size of 1.19 with two-tailed hypotheses were used. To conclude, a sample of 26 participants was estimated. Considering a possible 20% loss to follow-up, we recruited a sample of 32 participants.For the sample size calculation G*Power software for iOS was used with the difference between two independent means based on the difference between rugby and control groups using the TrA thickness (mm) variable of a pilot study (All measures were carried out by the same therapist (P.B.M) with USI experience. An ultrasound system  with a 10–13 MHz range linear transducer (with 55 mm footprint) was used in B mode for ultrasound imaging measurements. All participants were placed in supine position for the ultrasound data collection. Following the Whittaker et al.  guidelinThe mean of three repeated values was recorded for each measurement at the end of expiration, maintaining the transducer at the same place and with the same pressure (pressure generated by the weight of the transducer). All the measurements were evaluated at the right side. ImageJ software  was employed to measure all the images offline . The opet-test for independent samples were used for data analysis. In addition, Levene’s test was utilized to check the equality of variances. The median, interquartile range (IR), and Mann–Whitney U test were applied for non-parametric data analysis. The effect size between groups was estimated through the use of Cohens’s d. To interpret the effect size results, Cohen suggested that d = 0.02 was considered “small”, d = 0.5 was considered “medium” and a d = 0.08 was considered a “large” effect size [Statistical analysis was performed with the Statistical Package for Social Sciences (SPSS) for iOS . First, the Shapiro–Wilk test was employed to assess the normality. Second, the descriptive analysis for the total sample was carried out. Finally, a comparative analysis for both groups was performed. For parametric data, the mean, standard deviation (SD), and Student’s ect size . For allp = 0.011; d = 0.10), EO , IO , and RA  showing a thickness increase for the rugby group with respect to the control group. For the IRD thickness, there was no significant differences (p > 0.05) between groups (The age, weight, height, and BMI of the sample were homogeneous between the rugby and control groups . There wn groups .To our knowledge, this is the first study performing a comparison of the abdominal wall muscles between female rugby players and non-athletic women. Previous studies explored muscle thickness measures at rest in order to establish reference values ,29. The Several authors have shown differences in the muscle thickness in basketball  and baseRegarding the muscular asymmetries between dominant and non-dominant sides, several authors reported differences in the abdominal wall complex. For example, Jones et al.  observedWhittaker et al. showed significant changes in RA thickness in patients with lumbar pain, with wider IRD and changes in the perimuscular connective tissue . This maIRD showed no statistically relevant differences in both groups in this study. An increased IRD distance is related to pelvic floor disorders and urinary incontinence , which hMoreover, the increased TrAb thickness found in this study may be considered as a sign of continuous activation of this muscle during training and practice of this sport. There is also a close relationship between the musculature of the pelvic floor and the abdominal musculature . An actiThe findings of the present study did not provide a cause or explanation about the pelvic floor disorders in female athletes populations. We suggest that the examination of the abdominal wall muscles by USI could help to develop a complete evaluation for the prevention and managing the lumbopelvic disturbances that occur in female athlete populations. The direct relationship between core muscles and pelvic floor muscles and the good reliability for assessing the abdominal muscle thickness by USI present an interesting evaluation approach for researchers and clinicians.Several limitations in this study should be considered. First, all assessments have been carried out only at rest. It is possible that changes during specific muscle actions could provide information of interest for sports training . In addiIn conclusion, an increased TrAb, IO, EO, and RA thickness may be shown in female rugby players versus non-athletic women. However, statistically relevant differences were not found for the IRD between both groups.


Oligoasthenotspermia is a condition in which the number and motility of sperm in the semen of fertile men are lower than the normal level. Oligoasthenotspermia not only causes damage to the reproductive system, but also causes infertility in severe cases. Compound Xuanju capsule is a kind of Chinese patent medicine. Traditional medicine believes that compound Xuanju capsule can nourish kidney Yang, benefit kidney essence, improve semen quality, and treat infertility caused by oligoasthenotspermia. Clinical practice shows that compound Xuanju capsule combined with western medicine has a good therapeutic effect on male oligoasthenotspermia, but there is no evidence of evidence-based medicine. The purpose of this study is to systematically evaluate the efficacy and safety of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia, and to improve the evidence-based basis for the clinical application of compound Xuanju capsule in the treatment of male oligoasthenotspermia.A systematic search was performed by retrieving on English database  and Chinese database , CBM). Besides, manually search for Google and Baidu academic of compound XuanJu capsule combined western medicine in the treatment of male oligoasthenotspermia in randomized controlled clinical research. The retrieval time limit was from the establishment of the database to July 2020. Two researchers independently extracted and evaluated the quality of the data in the included study. A meta-analysis was performed using RevMan5.3 software, no language restrictions.In this study, the efficacy and safety of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia were evaluated by the total effective rate, semen parameters and other indexes.This study will provide reliable evidence-based evidence for the clinical application of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia.Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF Registration number: DOI 10.17605/OSF.IO/2PM8T. Routine semen examination was performed on male patients for 2 consecutive times. The results of the 2 examinations indicated that sperm density was less than 20 × 106/ml, and the sum of the forward motile A-grade sperm and B-grade sperm, namely A-grade + B-grade sperm <50% or A-grade sperm <25%, could be diagnosed as oligoasthenotspermia. According to western medicine, its pathogenesis is related to testicular dysfunction, varicocele, excessive oxidative stress, environment, diet, genetic genes, stressful life and work, sexually transmitted diseases and other factors. For the time being, there is no specific drug for the treatment of male spermatogenic disorders in modern medicine. Although the existing surgical and hormone drugs are effective, they have a narrow range of adaptation. Assisted reproductive technology has solved the problem of reproductive difficulties to a great extent, however, there are many disadvantages, such as low live birth rate, huge cost, many side effects and ethical risks.According to the statistics of the World Health Organization (WHO), the incidence of infertility among married couples of childbearing age is about 15%, while the male factor accounts for about 40%. According to traditional medicine, compound Xuanju capsule has the effects on warming kidney, invigorating Yang, benefiting kidney essence and dispelling rheumatism, and can be used to treat oligoasthenotspermia in male infertility. Traditional Chinese medicine has accumulated rich experience in the treatment of male infertility and oligoasthenotspermia, and the curative effect has been proved. Individualized treatment can be provided according to the patient's condition. Compound Xuanju capsule can improve male semen quality and male reproductive function by adjusting human Yin and Yang, Qi and blood, and it is simple, safe and effective, with few adverse reactions and no drug dependence.,11Compound Xuanju capsule is a kind of Chinese patent medicine, which is mainly composed of black ants, plus Herba Epimedii, Fructus Lycii, and Fructus Cnidii. It is reasonably compatible according to the theory of traditional Chinese medicine.At present, many clinical studies have shown that compound Xuanju capsule combined with western medicine is effective in the treatment of male oligoasthenotspermia with high cure rate, low recurrence rate and few adverse reactions, but the number of clinical trials is less, and also there are differences in research design and efficacy, which affect the promotion of this therapy to a certain extent. Therefore, in this study, we conducted a meta-analysis to explore the effects of compound Xuanju capsule combined with western medicine on the reproductive ability and quality of life of patients with oligoasthenotspermia, so as to provide a reliable evidence-based basis for the treatment of male oligoasthenotspermia by compound Xuanju capsule combined with western medicine.22.1This protocol of systematic review and meta-analysis has been drafted under the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Moreover, it has been registered on the open science framework (OSF) on September 10, 2020. (Registration number: DOI 10.17605/OSF.IO/2PM8T).2.2Since this is a protocol with no patient recruitment and personal information collection, the approval of the ethics committee is not required.2.32.3.1We collected all available randomized controlled trails (RCTs) on compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia, regardless of blinding, publication status, region, but Language will be restricted to Chinese and English.2.3.2Patients with oligoasthenotspermia were clearly diagnosed according to the WHO, Standard Diagnostic Manual for Infertile Couples, and The Chinese Guidelines for Clinical Research on New Chinese Medicines. There were no other complications. There were no restrictions on nationality, race, age, gender, course of disease and location of the included samples.2.3.3The treatment group: use compound Xuanju capsule only or combined with western medicine.The control group: western medicine intervention or placebo.2.3.41.Main outcome: Effective rate, Pregnancy rate;2.Secondary outcome: Sperm density, sperm motility, number of Grade A sperm, percentage of normal sperm morphology.2.41.Studies published repeatedly;2.Studies whose literature are abstract and conference papers, in which the original data cannot be obtained;3.Studies whose data are incomplete or where there are obvious errors that cannot be handled after contacting the author;4.Studies with wrong random method;5.Studies in which subjects with infertility caused by uncured genital infection, sex hormone disorder and other reasons.6.Studies in which subjects were given drugs that inhibit sperm production and sperm motility.2.5“Oligospermia”(shao jing zheng), “ asthenotspermia”(ruo jing zheng), “male infertility”, “compound Xuanju capsule”(fu fang xuan ju jiao nang) and other Chinese search terms were used for retrieval in Chinese databases, including CNKI, Wanfang Data Knowledge Service Platform, VIP Information Chinese Journal Service Platform, and China Biomedical Database. English retrieval words such as “ oligoasthenotspermia”, “oligospermia”, ;2.Intervention measures: The dosage, frequency and course of treatment of compound Xuanju capsule, the name, frequency and course of treatment of western medicine used in the treatment group, the name, administration mode, frequency and course of treatment of western medicine used in the control group;3.Evaluation factors of risk bias in randomized controlled studies;4.Observation indicators.The literature screening process is shown in Figure 2.7Built-in Risk bias evaluation tool of Review Manager 5.3 Software (the Cochrane collaborations tool for assessing risk of bias) was used to assess the risk bias in the included studies. Two researchers determined the literatures from 3 levels, including low-risk, unclear, and high-risk based on the performance of the included literature in the above evaluation items. After completion, they would recheck. In case of a disagreement, they would discuss. If no agreement could be reached, a decision would be made in consultation with researchers from the third party.2.82.8.1The RevMan 5.3 software provided by the Cochrane Collaboration was used for statistical analysis.1.For dichotomous variables, relative risk (RR) was used for statistics. For continuous variables, weighted mean difference (WMD) was selected when the tools and units of measurement indicators are the same, standardized mean difference (SMD) was selected with different tools or units of measurement, and all the above were represented by effect value and 95% confidence interval (CI).2.Heterogeneity test: Q test was used to qualitatively determine inter-study heterogeneity.P ≥ .1, there was no inter-study heterogeneity, if P < .1, it indicated inter-study heterogeneity. At the same time, I2 value was used to quantitatively evaluate the inter-study heterogeneity. If I2 ≤ 50%, the heterogeneity was considered to be good, and the fixed-effect model was adopted. If I2 > 50%, it was considered to have significant heterogeneity, the source of heterogeneity would be explored through subgroup analysis or sensitivity analysis. If there was no obvious clinical or methodological heterogeneity, it would be considered as statistical heterogeneity, and the random-effect model would be used for analysis. Descriptive analysis was used if there was significant clinical heterogeneity between the 2 groups and subgroup analysis was not available.If 2.8.2If data is missing or incomplete, we will contact the corresponding author to obtain the missing data. If not, this study will be removed.2.8.3Subgroup analysis was carried out according to the treatment group of compound Xuanju capsule combined with western medicine and Chinese herbal compound treatment only. Subgroup analysis was carried out according to the age of the patients, which can be divided into 2 subgroups: young people and middle-aged people. Subgroup analysis was carried out according to the disease, which can be divided into 2 subgroups: male oligospermia and male asthenospermia. Subgroup analysis can also be performed according to the course of treatment.2.8.4In order to test the stability of meta-analysis results of outcomes, a one-by-one elimination method will be adopted for sensitivity analysis.2.8.5For the major outcome indicators, if the included study was ≥10, funnel plot was used to qualitatively detect publication bias. Eggers and Beggs test are used to quantitatively assess potential publication bias.2.8.6The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used to assess the quality of evidence. It contains 5 domains . And the quality of evidence will be rated as high, moderate, low, and very low.3 Traditional Chinese medicine believes that the kidney stores essence and dominates reproduction, and the production of spermatozoa is directly related to the kidney. If the kidney is deficient in producing nutrients, sperm production will be inadequate; the spleen is the acquired foundation and the source of Qi and blood, and also can transport nutrient substance in the body to nourish the kidney essence so as to transform into reproductive essence. Lack of congenital endowment and nurturing, sexual immoderation, irregular diet, emotional discomfort and other factors will consume kidney essence and cause kidney essence deficiency. Then sperm becomes scarce, semen becomes thin, resulting in male oligospermia and oligoasthenotspermia. Modern studies have also shown that oligoasthenotspermia patients with kidney deficiency infertility are different from normal men in plasma metabolic pathway and biomolecule level, which may be the cause of oligoasthenotspermia.The understanding of male infertility in traditional Chinese medicine has a history of more than 2000 years, and there are many related discussions in ancient books of traditional Chinese medicine. Using Fructus Lycii and Fructus Cnidii to warm the kidney, tonify essence, strengthen tendons and tonify Yang, can significantly improve the symptoms such as deficiency of kidney Yang, lethargy, fatigue, cold sperm and night emission, low sexual desire and so on. Modern medical research has found that Black Ants, Epimedium and other drugs are rich in amino acids, vitamins, coenzymes, flavonoids and other ingredients,which can significantly increase the content of various nutrients in the human body. Clinical studies have shown that compound Xuanju capsule can effectively improve semen quality and reduce sperm chromatin damage in infertile men with oligoasthenotspermia; increase the level of sex hormone, promote semen secretion, improve the function of sexual organs; significantly increase the concentration and total number of sperm, increase sperm motility; effectively improve the semen quality and sperm morphology of infertile male smokers; reduce genital inflammation and regulate sexual dysfunction. However, the intervention of Chinese patent medicine lacks the process of syndrome differentiation and treatment in traditional Chinese medicine, it is difficult to give full play to the best effect of traditional Chinese medicine treatment. Moreover, the deficiency syndrome of traditional Chinese medicine pays attention to slow conditioning and the treatment usually requires a long course of treatment.Compound Xuanju capsule mainly contains Black Ants, Herba Epimedii, Fructus Cnidii, and Fructus Lycii. In the compound Xuanju capsule, the major medicine is the Black Ant, assisted by Herba Epimedii, both of which belong to the liver and kidney meridians. The capsule has the effect of tonifying the kidney essence and activating collaterals.At present, many trials of compound Xuanju capsule in the treatment of male oligoasthenotspermia have been widely reported, but there is a lack of systematic evaluation. Therefore, it is necessary to objectively evaluate the effect of compound Xuanju capsule on patients with oligoasthenotspermia through evidence-based medicine, promote the treatment of compound Xuanju capsule, and provide scientific and evidence-based prescription of traditional Chinese medicine for clinic. However, this study also has some limitations, such as the lack of large samples and high-quality randomized controlled trials. What's more, it is difficult to evaluate the long-term efficacy of drugs caused by short follow-up time. At the same time, due to the limitation of language ability, only English and Chinese literature are searched, the research in other languages may be ignored. And there also may exist some publication bias.Data collection: Lili Chen, Hongyi Lan.Funding support: Yu Liu.Literature retrieval: Lili Chen, Hongyi Lan.Software operating: Yuyan Zhang, Xiaoyan Zhang.Supervision: Yu Liu.Writing – original draft: Lili Chen, Hongyi Lan.Writing – review & editing: Lili Chen, Yu Liu.


Glycine max (L.) Merr.] have characteristics of larger seeds, less beany flavor, tender texture, and green-colored pods and seeds. Rich in nutrients, vegetable soybeans are conducive to preventing neurological disease. Due to the change of dietary habits and increasing health awareness, the demand for vegetable soybeans has increased. To conserve vegetable soybean germplasms in Taiwan, we built a core collection of vegetable soybeans, with minimum accessions, minimum redundancy, and maximum representation. Initially, a total of 213 vegetable soybean germplasms and 29 morphological traits were used to construct the core collection. After redundant accessions were removed, 200 accessions were retained as the entire collection, which was grouped into nine clusters. Here, we developed a modified Roger’s distance for mixed quantitative–qualitative phenotypes to select 30 accessions (denoted as the core collection) that had a maximum pairwise genetic distance. No significant differences were observed in all phenotypic traits  between the entire and the core collections, except plant height. Compared to the entire collection, we found that most traits retained diversities, but seven traits were slightly lost (ranged from 2 to 9%) in the core collection. The core collection demonstrated a small percentage of significant mean difference (3.45%) and a large coincidence rate (97.70%), indicating representativeness of the entire collection. Furthermore, large values in variable rate (149.80%) and coverage (92.5%) were in line with high diversity retained in the core collection. The results suggested that phenotype-based core collection can retain diversity and genetic variability of vegetable soybeans, providing a basis for further research and breeding programs.Vegetable soybeans [ Glycine max (L.) Merr.] is a legume crop that is rich in protein, oil, and other nutrients such as lecithin and isoflavones. It is one of the most important economic crops worldwide , smooth texture, less beany flavor, and higher contents of vitamin A, vitamin C, sucrose, and starch . The demSoybeans are rich in isoflavones and anthocyanins, which prevent or inhibit the progression of cancer and other chronic diseases . EvidencApart from the amount of nutrient composition in vegetable soybeans, the quality of vegetable soybeans depends on the external appearance . To markThe concept of a CC, defined as a limited set of accessions, was first introduced by Euclidean distance and Manhattan distance, which are well-defined  in Taiwan. The countries of origin of the accessions were grouped into Taiwan, Japan, United States, China, Hong Kong, and Philippines. Phenotypic traits were investigated and recorded in the field at Kaohsiung District Agricultural Research and Extension Station, COA, and followed the guidelines of distinctness, uniformity, and stability (DUS) test for vegetable soybean in four consecutive seasons (1995–1998 autumn). Each accession was characterized for 47 phenotypic traits in relation to morphology (38 traits), growth (5 traits), phenology (2 traits), and production (2 traits). For detailed agronomic descriptors, please refer to t-test only when ANOVA p-value reached significant difference. The results suggested that no significantly environmental effects were observed on the phenotypes investigated in the field at Kaohsiung District Agricultural Research and Extension Station , humidity (%), duration of sunshine (hours), precipitation (mm), and days with precipitation (days), were collected daily during 1995–1998 from the Kaohsiung District Agricultural Research and Extension Station and the Kaohsiung Weather Station of the Central Weather Bureau in Taiwan. One-way ANOVA was conducted to test for differences among four autumn seasons (October–November) and among 4 years, followed by paired samples  Station .Multiple imputation is a mathematically computational method to deal with missing values in phenotypes . There wputation .k-means approach by kamila package in R  is calculated asTo examine the diversity of vegetable soybean germplasms, weighted age in R  was usedail is an n×k assignment matrix, which subjects towhere ail = 1⇔xi belongs to the lth clusterwj is the weight parameter, which is defined byw is an adjustable parameter, and we selected weight as 0.5 by default. d represents the distance between xij and clj. Let xij be the value of the jth phenotype in the ith accession, and cljbe the centroid of the lth cluster in the jth phenotype. The distance of the quantitative trait is measured by Euclidean distance dwhere Y = {Y1,Y2,…,Yn} with p different trait levels is expanded to p indicator variables, denotedasIA(y)The qualitative trait is converted to dummy variable (0 or 1). For instance, a qualitative phenotype P during the procedure of iteration. To select the optimal number of clusters, we set criteria as follows: Shannon diversity index is above 90%, Nei’s diversity index is above 85%, and the proportion of variance explained is at least 70%.Thus, Euclidean distance can be applied to measure the distance. The aim is to minimize the objective function j (∈ C)can be expressed asWe proposed modified Roger’s distance to construct a CC, which is a small collection with minimal redundancy and maximal representative of the ES. The modified Roger’s distance is a suitable algorithm for mixed quantitative–qualitative phenotypes. The distance  is defined as,where Q is the qualitative phenotype, and fij and fi^*j represent the frequency of ith and i∗th accession in jth trait, respectively. Thus, the modified Roger’s distance can be of the form Where H′) and Nei’s diversity index (H′) is defined asPhenotypic diversity is calculated using the Shannon–Weaver diversity index  MD% is small and the percentage of significant mean difference (α = 0.05) between the CC and the EC in all 29 phenotypic traits is no more than 20%, and (2) the CR% is greater than 80%  the mean difference percentage .Levene’s test was conducted, with 1,000 bootstrap iterations, to check homogeneity of variance among groups . After ts t-test . For quas t-test  .p-values > 0.05) among observed and imputed phenotypic traits, suggesting reliable and accurate imputed values.Our data suffered, to a certain extent, from missing rates, ranging from 0.5 to 26.5% . These menotypes . Tables k-means clustering method, using completed phenotypes , to search for the population structure of the whole picture on the EC. k-means clustering algorithm for 29 mixed-type phenotypic traits. We calculated modified Roger’s distance for mixed quantitative–qualitative phenotypic traits to capture pairwise genetic distance among accessions in the EC. The larger genetic distance, the much dissimilar. As a result, 30 accessions  was observed between the CC and the EC in all traits, except plant height , an intermediate value of VD% (52.90%), a large value of CR% (97.70%), a very high value of VR% (149.80%), and a very high percentage of coverage  . These pTo the best of our knowledge, our vegetable soybean germplasms consisted of 213 accessions, which are the largest collection worldwide. Vegetable soybean becomes popular just for more than one decade and mostly in East Asia, e.g., Japan, Taiwan, China, and South Korea; therefore, other countries take merely a small amount of production; the majority of vegetable soybeans are imported from Asia . This isIn this study, a total of 29 traits  were selected from 47 phenotypic traits, based on at most 30% threshold of missing rate. Among them, 5 traits had no missing rates, 10 traits had low missing rates (0.5–11.5%), and the remaining traits had moderate missing rates (25.5–26.5%) . GeneralPhenotype completeness is the key to access in developing a core set of germplasm for efficient exploration and effective utilization in breeding programs. In fact, the impact of missing data on phenotypic traits research can be serious, and the utilization of phenotypes is often limited by incomplete phenotypes of interest . In partthan 1.1 , suggestthan 1.1 . Multiplthan 1.1 . TherefoThe selection of sampling strategies does affect the results of the selection of the CC, as well as its diversity. To have a better illustration, we compared the proposed modified Roger’s distance algorithm with other sampling schemes, including stratified proportional sampling (SPS), simple random sampling (SRS), and advanced M strategy (using PowerCore software). As the difference test, there were only two traits, seed width by advanced M strategy and number of branches by SRS, showing significant mean difference between the EC and the CC . Most ofThe CC collected from distinct sampling strategies was evaluated. We evaluated the percentage of the trait differences between the CC and the EC, using PowerCore, SPS, and SRS methods, compared to our developed modified Roger’s distance  affect our trait values measured during 1995–1998 autumn seasons  of the entire collection. Moreover, the high diversity of the CC indicated that the germplasms were simplified without losing information. The result showed that the modified Roger’s distance algorithm was a good approach to construct the CC. This study provides a detailed list of the CC, which can be a basis for future research of vegetable soybeans and breeding practices.To the best of our knowledge, this study reported results of the first CC for vegetable soybean (or edamame) worldwide. This study consisted of the largest vegetable soybean germplasms worldwide at present, which provided valuable and/or special information on Taiwanese vegetable soybean germplasms. We proposed a modified Roger’s distance algorithm, which is a mixed-type sampling strategy, to construct a CC composed of a total of 30 accessions based on morphological traits. It was evident that the properties of the CC constructed by the modified Roger’s distance algorithm were reliable, stable, and feasible. With the representativeness of the whole germplasms, the high-quality CC possessed small mean difference, high coincidence rate, variable rate, and high coverage. The CC preserved the high phenotypic diversity in germplasms of vegetable soybean. The removal of redundancy enables us to make full use of the vegetable soybean germplasms for overall phenotype clustering. With the support of the material, the CC can be helpful for further breeding of commercial varieties.The original contributions generated for this study are included in the article/C-FK: study conception and design and acquisition and analysis of data. C-FK, S-SH, C-SW, D-GL, and SC: interpretation of data. C-FK and S-SH: drafting the manuscript. C-FK and Z-YL: manuscript revision. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The R software and Meta package were used for data analysis. After removing duplicates, 5431 studies were submitted to the steps of the systematic review, and 21 articles were included in the data analysis. In total, 3,504,303 patients, 521,216 with obesity, and an average follow-up time of 9.86 years were included. The relative risk of obese people for developing CKD in the random effects model was 1.81 (95%CI: 1.52-2.16). The evidence found in this meta-analysis confirmed that obese people are at higher risk of developing CKD that the non-obese population (1.81 times higher), with obesity being a priority risk factor in preventive actions.Chronic kidney disease (CKD) is one of the main chronic diseases affecting the world population due to its high prevalence and increasing morbidity. Similarly, obesity gained the interest of the scientific community as it directly or indirectly increases mortality from cardiovascular causes, and its prevalence characterizes a pandemic. The objective of this study was to investigate obesity measured by body mass index as a predictor for end-stage renal disease in the general adult population. A systematic review and meta-analysis was carried out by searching 10 databases for prospective or retrospective cohort studies, with no restrictions on the language of publication, including adults with obesity without previous renal disease and who evolved to CKD (diagnosed by estimated glomerular filtration rate below 60 mL&mac_middot;min Chronic kidney disease (CKD) is one of the main chronic diseases that affects the world population. In the United States, according to the National Health and Nutrition Examination Survey, new cases of CKD doubled in individuals over 65 years old from 2000 to 2008 and the prevalence of CKD in the population over 60 years of age went from 18.8% in 2003 to 24.5% in 2006.Based on the 2018 census of the Brazilian Nephrology Society, 133,464 patients were estimated to be under treatment in 781 dialysis units in Brazil, with 80% of dialysis treatments being funded by the Public Health System  - calculated as: weight in kilograms divided by the square of the height in meters . AccordiDifferent mechanisms are involved in the relationship between obesity and CKD. Indirectly, obesity can mediate the onset and worsening of diabetes mellitus and systemic arterial hypertension, and directly, it can lead to structural and inflammatory changes .vs overnutrition), optimizing clinical performance  , an inflProspective or retrospective observational studies assessing the association between obesity and CKD were included without limitations on the publication date. The target population was obese adults with normal renal function at the beginning of the follow-up, with a minimum follow-up of 3 years, who progressed to CKD stages 3 to 5 at the end of the research. Studies that included patients undergoing renal replacement therapy, that evaluated bariatric surgery as obesity treatment in parallel with CKD, and that included patients with kidney transplant as past medical history at baseline were not included in the meta-analysis. The studies that included patients who underwent bariatric surgery during the study were excluded from the final analysis.Obesity, defined as a BMI above 30 or above 27.5 (for Asian studies), was the study predictor. The classification adopted in this study was in accordance with that recommended by the World Health Organization -1 or need for renal replacement therapy .Glomerular filtration rate (GFR) is a measure of the flow rate of the fluid filtered by the glomeruli that is not reabsorbed or secreted while in the tubules. GFR is considered the gold standard for assessing renal function . The esthttp://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018091865. The study received ethics approval with the code CAAE 81020017.2.0000.5327 and title “Obesity as a predictor of chronic kidney disease: systematic review and meta-analysis” and was approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre .This review was registered in the PROSPERO database with the code PROSPERO 2018 CRD42018091865; the study protocol and methodology can be accessed at The search terms used in the study prioritized sensitivity over specificity, with the aim to include any and all available evidence.http://www.teses.usp.br) were also searched.A search was conducted in 10 databases that contained studies in the health field: PubMed Medline, Virtual Health Library (VHL), LILACS, Web of Science, Google Academics, Scopus, The Cochrane Library, Ovid, Scielo, and ProQuest. Hard data sources, such as bibliographic references of studies and the Thesis Bank of the São Paulo University , Chronic Kidney Disease, Chronic Kidney Failure, Chronic Kidney Insufficiency, Chronic Renal Insufficiency, Falência Renal Crônica, Fallo Renal Crónico, ĺndice de Masa Corporal, ĺndice de Massa Corporal, Insuficiencia Renal Crónica, Insuficiência Renal Crônica, Obesidade, Obesidad, Obesity, Overweight, Quetelet’s Index, and Sobrepeso.The terms Quetelet’s Index, Chronic Kidney Disease, CKD, Chronic Kidney Insufficiency, End-Stage Kidney Disease, ESRD, Chronic Renal Disease, Chronic Renal Failure, Chronic Renal Insufficiency, Renal Impairment, and Kidney Injury were also searched as descriptors but were not registered as keywords or were used as synonyms in the databases.The terms were searched for in the title, summary, and keywords with no filters for language and study dates, making it possible to include articles published in any past time.The factors related to exposure and those related to the outcome were connected by “OR”, generating two search phrases - exposure and outcome. The phrases originated were then connected to each other with “AND”, maintaining the objective of establishing a causal relationship.The search strategies for each database are shown in Supplementary Table S1.A paired review was conducted by the researchers K.R.D. Pinto and C.M. Ferkinghaus. The studies were classified according to the quality parameters of the AMSTAR scale  in the fThe AMSTAR scale  assessesArticles that had statements about which the researchers disagreed were classified as potentially eligible and selected for full-text reading.After excluding experimental studies, editorials, and review articles, studies were assessed for design and eligibility criteria. Finally, articles were included for quality analysis and data extraction.The included articles were submitted to quality assessment using the Newcastle-Ottawa scale (NOS). This scale was developed by the collaboration between the Universities of Newcastle  and Ottawa (Canada) to analyze the quality of non-randomized studies. A “star system” judges three perspectives: the selection of the study groups, the comparability of the groups, and the ascertainment of either the exposure or outcome of interest for the study, respectively .The data about year, country and continent of publication, design, age at baseline, age group, length of follow-up, obesity criterion, sample size, BMI classification, number of individuals who progressed to CKD, and quality classification were extracted from the selected studies.2 was calculated for heterogeneity verification. Due to heterogeneity, regressions were performed with the following variables: 1) years of follow-up; 2) baseline mean age; 3) cohort design; 4) quality score (NOS); 5) continent of study publication; 6) obesity criteria; and 7) GFR formula used. Subgroup analyses were done to interpret the heterogeneity. The Meta command of the R software  and the Meta package  were used for data analysis and the significance level was 0.05.A meta-analysis of risk ratio (RR) for the development of CKD was carried out. The IThe publication bias analysis is presented in a Funnel plot in Supplementary Figure S1.The search in the 10 databases retrieved 12,215 articles. The number of articles returned in each database is described in Supplementary Table S1.After removing duplicates, 5,431 studies were screened by titles and abstracts and 141 studies underwent full-text evaluation. The Kappa coefficient  for the Supplementary Table S3 shows the characteristics of the 21 studies included in the meta-analysis –36.2=97%).In two studies ,33, 2=0.4719) of the variation.Considering the 97% heterogeneity, the sensitivity assessment was done by subgroup analyses. The mean age at baseline was the variable with the strongest relationship with heterogeneity, being responsible for explaining 47.19%  and for retrospective cohorts (I2=97%), showing that heterogeneity was not due to study designs. A higher relative risk was found in retrospective studies  than in the global analysis.Another sensitivity assessment was related to study design (prospective and retrospective cohorts) . Heterog2 of 75% was found for the over-55-year-old subgroup and it was the lowest heterogeneity index present when comparing the three age groups.Analysis was carried out by age subgroups: i) up to 45 years; ii) from 46 to 55 years; and iii), above 55 years . An I2 o-1․(1.73 m2)-1.Complementary sensitivity analysis  demonstrThe 21 studies included in the meta-analysis were published between 2003 and 2018, showing that obesity as a risk factor for CKD is a relatively recent subject. Other systematic reviews and meta-analyzes also included recent studies ,38.This study also had differential points in comparison with other meta-analyzes: articles from Asia were included, the outcome of interest of the present study was CKD stages 3 to 5 and not necessarily associated with the criteria of albuminuria, studies in languages other than English were searched, and metabolic syndrome was not used as a synonym for obesity.The relationship between obesity and CKD found in this study is in accordance with the existing literature .In only two studies ,33, no sThe presence of several studies from Asia indicates the interest on this theme by that population. In addition, numerous studies from Asian countries also have cross-sectional designs for epidemiological purposes .The studies included in meta-analysis articles were submitted to quality assessment  and wereAmong the potential study limitations, our meta-analysis did not include studies carried out in Brazil or Latin America because none could be found through our search strategy; this limits the reproducibility of the results and medical recommendations for that population. In addition, the clinical heterogeneity of the included patients can be a source of inconsistency between the findings of observational studies.On the other hand, we can list several limitations observed in individual studies. First, detailed information on use of medications was not collected in some studies because of the nature of community-based health research . Second,Such limitations can be overcome by selecting studies with similar methodologies in the systematic review , which wThis meta-analysis supports the hypothesis that obesity might be a risk factor to CKD and must be a priority in preventive actions. Public health measures targeting body weight control in the general population may contribute for preventing the increasing of CKD.


Objective: Metabolic syndrome (MetS), a common disease that affects many people around the world, has been hypothesized to be associated with human cancers, including prostate cancer (PCa), but the association has not been consistent. The aim of the current study was to evaluate whether MetS and its components are risk factors for PCa biochemical recurrence (BCR) among a cohort of postoperative patients at our hospital in China.Materials and Methods: This retrospective study included 214 patients with PCa who received radical prostatectomy. Differences between groups were estimated using the χ2 test or Student's t-test. BCR rates were calculated according to the Kaplan-Meier method with the log-rank test. A Cox regression analysis was conducted for the multivariate analyses to identify significant predictors of BCR.Results: Of the 214 eligible men, 55 experienced BCR and 24 met the MetS diagnostic criteria. Multivariate Cox model analysis showed that patients with BCR had a higher Gleason score  and positive nerve invasion . MetS was not associated with BCR .Conclusion: BCR is not associated with MetS but is associated with a higher Gleason score and positive nerve invasion. Prostate cancer (PCa) has been rated as the most commonly diagnosed cancer in men in the United States according to a report published in 2019 .Metabolic syndrome (MetS), including central obesity, raised blood pressure, elevated fasting glucose and dyslipidemia (low high-density lipoprotein cholesterol and elevated triglycerides), is a cluster of metabolic abnormalities related to insulin resistance . MetS anGiven the unclear association between PCa BCR and MetS and the increasing prevalence of MetS, we hypothesized that MetS or its components might be associated with an increased risk for PCa BCR. Therefore, in the present study, we investigated a range of preoperative MetS components, including body mass index (BMI), blood pressure, fasting glucose, high-density lipoprotein cholesterol (HDL) and triglycerides (TGs), as well as the preoperative serum PSA levels of patients with clinically localized PCa who received RP, particularly with respect to the link between these indicators and BCR after surgery. The aim of the current study was to evaluate whether MetS and its components are risk factors for PCa BCR among a cohort of postoperative patients at our hospital in China to prevent increased prostate cancer mortality associated with MetS.Men with clinically localized PCa undergoing radical prostatectomy at the Department of Urology at the First Affiliated Hospital of Zhejiang University from January 2013 to December 2015 were, respectively, included in this study. Exclusion criteria: patients who received neoadjuvant hormonal therapy; components of MetS were not completed; PSA levels did not reach a nadir ≤0.2 ng/mL after surgery; loss to follow-up. A total of 214 patients were finally included in our study. Clinicopathological information, including age, height, weight, history of hypertension and diabetes, lipid profiles, preoperative prostate—specific antigen (PSA) levels, prostatectomy GS, and pathological characteristics, was gathered from medical records and analyzed. BCR was defined as two consecutive rising detectable PSA concentrations of >0.2 ng/mL or the administration of adjuvant therapy during the postoperative follow-up period. Higher GS was defined as GS ≥8. The study protocol was approved by the Institutional Research Review Boards of the First Affiliated Hospital of Zhejiang University. Due to the retrospective nature of the study, informed consent was waived. All methods were performed in accordance with the relevant guidelines and regulations.MetS was defined according to the criteria recommended by the Chinese Diabetes Society , which rt-test. BCR rates were calculated according to the Kaplan-Meier method with log-rank test. A Cox regression analysis  was conducted for the multivariate analyses to identify significant predictors of BCR. All analyses were performed using SPSS16.0 software  and a two-tailed value of P < 0.05 was considered to be statistically significant.Differences between groups were estimated using the χ2 test or Student's 2/kg. The patients with MetS showed no difference in the age and the level of PSA when compared to the Non-MetS group  as shown in P > 0.05).P < 0.01, P = 0.03, P < 0.01, and P < 0.01, respectively). Unexpectedly, P > 0.05).P = 0.147), hypertension (P = 0.785), BMI (P = 0.525), diabetes (P = 0.964), low (HDL) (P = 0.581) and hypertriglyceridemia level (P = 0.510) (P < 0.001), positive prostate capsule invasion (P = 0.001), positive nerve invasion (P < 0.001) and positive seminal vesicle invasion (P = 0.012). However, in the multivariate Cox model analysis  . To bettanalysis , only thProstate cancer is the most common carcinoma in men with nearly 174,650 new cases annually in US  and weight change were not associated with an increased risk of BCR, weight gain might early influence prostatic carcinogenesis and might play a part in the development of cancers more likely to progress . A previThe natural history of BCR after RP could be long but variable. Better risk assessment models were merited to recognize patients who were at high risk for prostate cancer-specific death early and may benefit from aggressive salvage treatment and to realize patients who were at greater odds for prostate cancer-specific survival and could be safely observed. Existing data in our study signed that BCR was associated with adverse clinicopathological features, including increased GS and positive nerve invasion. It meant patients with adverse clinicopathological features was associated with a more aggressive tumor phenotype, could be regarded as the poor prognosis indicators for BCR in patients with PCa and might need adjuvant radiation therapy or androgen deprivation treatment.Of note, the present findings have following limitations that merit mentioning. First and foremost, retrospective design is the primary limitation, which only allowed us to evaluate the temporal link between BCR and MetS, thereby causal inference is restricted, and the data we analyzed retrospectively, carries a potential selection bias for this study. Second, comorbidities of enrolled patients may not be precisely reported in the electronic medical record. Take an example, we were unable to make clear patients who didn't report the history of diabetes or hypertension to their medical providers. In this respect, we depended on self-reported information, leading to the possibility of misclassification bias. Also, some important information, such as diet, and physical activity, family history, and drug usage, including statins anti-diabetes drugs, was not collected. These latent confounders could limit the statistical power of the study. Third, the evaluation of obesity was carried out only by BMI in our study, rather than waist circumstance to define overweight, which might cause misclassification. Fourth, this study was a single-center study only in China, and the number of subjects was a small volume, which may not apply to all centers. Fifth, information pertaining to the duration of MetS and its components, which may theoretically influence BCR, was also deficient. Finally, the data of collected were fully based on Chinese men and thereby the results would not be generalized to other ethnic populations.In conclusion, the presence of BCR was associated with an increased risk of higher GS and positive nerve invasion. MetS and its components were not associated with BCR among the cohort of postoperative patients of our hospital in China. Prospective study using large multicentric patient groups with a long follow-up are warranted to more accurate verify the possible implication of MetS prevention on PCa recurrence.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by First Affiliated Hospital of Zhejiang University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.XX and XW contributed to the conception or design of the work. QL, CC, and LX contributed to the acquisition, analysis, or interpretation of data for the work. XX drafted the manuscript. XW and QL critically revised the manuscript. All authors gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: This study analyzes the current and evolving physical rehabilitation needs of BRICS nations , a coalition of large emergent economies increasingly important for global health. Methods: Secondary, cross-national analyses of data on Years Lived with Disability (YLDs) were extracted from the Global Burden of Disease Study 2017. Total physical rehabilitation needs, and those stratified per major condition groups are analyzed for the year 2017 (current needs), and for every year since 1990 (evolution over time). ANOVAs are used to detect significant yearly changes. Results: Total physical rehabilitation needs have increased significantly from 1990 to 2017 in each of the BRICS nations, in every metric analyzed . Musculoskeletal & pain conditions were leading cause of physical rehabilitation needs across the BRICS nations but to varying degrees: from 36% in South Africa to 60% in Brazil. Country-specific trends include: 25% of South African needs were from HIV-related conditions (no other BRICS nation had more than 1%); India had both absolute and relative growths of pediatric rehabilitation needs (p < 0.01); China had an exponential growth in the per-capita needs from neurological and neoplastic conditions ; Brazil had a both absolute and relative growth of needs coming from musculoskeletal & pain conditions (p < 0.01); and the Russian Federation had the highest neurological rehabilitation needs per capita in 2017 . Conclusions: total physical rehabilitation needs have been increasing in each of the BRICS nations, both in absolute and relative values. Apart from the common growing trend, each of the BRICS nations had own patterns for the amount, typology, and evolution of their physical rehabilitation needs, which must be taken into account while planning for health and physical rehabilitation programs, policies and resources. The BRICS countries  are increasingly recognized as important players in global health and development ,6,7,8,9.The BRICS countries, which formalized their coalition in 2006, generate 25% of the world’s gross national income, have approximately 40% of the world’s population, approximately 50% of the world’s poor, and represent 40% of the global burden of disease ,10,11. TDespite their economic developments and coalition, the BRICS countries face themselves a shortage of key health resources  for their growing and complex health needs, in the context of many other societal demands ,22. ThesWorldwide and especially in emerging economies, increasing numbers of people now live with functional limitations ,12,26. TIn line with increasing disability prevalence, a recent study using data from Global Burden of Disease Study 2017 found a 17% increase in the world’s physical rehabilitation needs per capita since 1990, and an almost twofold greater increase (29.9%) in upper-middle-income countries (UMICs), which include four of the BRICS countries (except India) . The Wor(1)How large are the physical rehabilitation needs in 2017 for each BRICS country , and how have those values evolved since 1990?(2)Which condition groups  account for the highest rates of physical rehabilitation need for each of the BRICS countries in 2017, and how have those values evolved since 1990?This paper aims to analyze the current and evolving physical rehabilitation needs of the BRICS countries. The specific study questions are:This paper refers to a secondary, cross-national comparative analysis of global epidemiological data in the public domain. To estimate the physical rehabilitation needs for each of the BRICS nations, we use data from the 2017 Global Burden of Disease Study (GBD) . Specifihttp://ghdx.healthdata.org/gbd-results-tool).To determine the physical rehabilitation needs for the BRICS nations, we apply and combine the abovementioned standard methods as follows: In April 2019, public-domain data from the GBD 2017 were systematically extracted from a freely-available web platform: the Global Health Data Exchange tool , due its exclusive focus on non-fatal health losses. YLDs consist of the years lived with any short-term or long-term health loss weighted for severity by disability weights. For stroke, for example, disability weights vary from 0.019 for mild consequences to 0.588 for severe consequences plus cognition problems. Details on how YLDs and disability weights are determined, and the disability weights for all conditions, are available elsewhere ,50.For “years”, data were extracted for every year between 1990 and 2017, for a more precise determination of the evolving trend. For “location”, YLDs were extracted at the national level for each of the BRICS. No sub-national data were extracted, as we focused on nation-wide and cross-national analyses.number , rate , and percentage .As for “metrics”, we extracted YLDs data for prevalent all ages and age-standardized rates, the latter used to determine age-standardized YLD Rates .Regarding “age”, we extracted YLDs both for All the selected data were imported from the webtool to Excel spreadsheets for data storage, management, and analysis.r2 values for that. Given negligible differences in r2 values (<0.02 between the models), we retained the linear regression option.In the Excel spreadsheets, we summed YLDs within each of the five “locations”, four “metrics”, and 28 “years”, computed any percent changes from 1990 to 2017, plotted the entire time series [1990–2017] of the combined YLD values, and then determined which type of simple regression model  best fit the plotted data. We used visualization and p = 0.05 and p = 0.01, the latter accounts for a Bonferroni correction (0.05/5 = 0.01) considering the analyses are made for five countries within each item/metric under study. The respective confidence intervals (CIs) in turn were used to analyze whether yearly changes for each BRICS nation significantly differed  from those of the 4 other BRICS countries or from the global benchmarks that we extracted from the literature–as the same methods were used [To assess yearly changes of YLDs between 1990 and 2017, ANOVA was applied. This test considers the data on every year between 1990 and 2017, which increases preciseness. The significance level for the analysis was set at two subsequent levels: ere used ,49.YLD Rates as a metric, either through actual YLD Rates or through those transformed into percent values, e.g., percentage of the YLD Rates related to physical rehabilitation that came specifically from neurological conditions.Finally, using the analytical procedures above, we performed a subgroup analysis on the physical rehabilitation needs, stratified per six major groups of conditions–detailed in the We provide below the results for the two study questions:p < 0.01); the exception being Age-Standardized YLD Rates for both India and Russia, with no significant changes since 1990 (p > 0.05). Per metric, In YLD Counts , South Africa more than doubled their physical rehabilitation needs from 1990 to 2017 , similarly to low-income countries . India, Brazil, and China had a 91.6%, 82.6%, and 68.1% growth, respectively. Russia, in turn, had the lowest percentage growth in YLD counts (7.6%), substantially lower than any global benchmark: i.e., the lowest being 37.4% for high-income countries.In YLD Rates , Russia had the highest value in 2017 (6393), but South Africa and China had the highest yearly growths , each of them significantly higher  than those of the 3 other BRICS nations or any global benchmark.In Age-standardized YLD Rates, , South Africa had the highest value in 2017 (5131), and significantly greater yearly increases  than all comparators; for example high-income countries had a significant decrease. Russia and India had non-significant yearly changes in this metric.Finally, in the percentage of YLDs likely benefiting from physical rehabilitation among total YLDs, Brazil stands out with nearly two-thirds of their YLDs coming from rehabilitation-sensitive conditions in 2017 (66.2%). For the other BRICS countries or global benchmarks, values were all below 50%; in India little more than one-third (35.9%). In South Africa, the yearly growths in the YLDs percentage were significantly greater while in Russia significantly lower than in any other BRICS nations. Indeed, the 99% CIs of the Russia’s yearly growth was rather aligned  with that of high-income nations. YLD Rates from 1990 to 2017 across the BRICS countries, for all the condition groups (p < 0.01). The exceptions are the South African’s YLD rates coming from pediatric and from neoplasm conditions , although the latter had a significant increase within the 95% CI (0.03−0.53). YLD Rates came from: (1) HIV-related conditions in South Africa (b = 63.8), yet with a logarithmic growth ; (2) musculoskeletal & pain conditions in both Brazil and China ; (3) neurological conditions in China (b = 15.6), within exponential type of growth , and (4) pediatric conditions in India (b = 7.18). In each of these cases, the growths were significantly greater  than those of any comparators for the same condition group. Finally, Russia stands out with the highest YLD Rates for neurological conditions in 2017, e.g., over than 3 times that of Brazil, India, or South Africa.The highest yearly increases in p < 0.01). In China, the percentage of physical rehabilitation needs coming from both neurological conditions and neoplasms increased significantly , both with an exponential type of growth. In India, the percentage of physical rehabilitation needs coming from pediatric conditions increased significantly (from 15.7% to 17.8%: p < 0.01). In Russia, the percentage of physical rehabilitation needs that came from neoplasms has grown by 47% (p < 0.01). Finally, only in Brazil did the percentage of physical rehabilitation needs coming from musculoskeletal & pain conditions increased significantly , becoming greater than that in high-income countries (57.7% in 2017).Finally, In each of the BRICS countries, total physical rehabilitation needs have increased significantly from 1990 to 2017 in absolute values, per-capita, and in percentage of all YLDs. This means that, in each of these countries, physical rehabilitation needs have increased beyond the population growth, and that physical rehabilitation could be helpful for a greater portion of non-fatal health losses. Apart from common trends across the BRICS nations , we found important country-specific differences across the BRICS countries in the amount, typology, and evolution of their physical rehabilitation needs.For the overall age-standardized YLD Rates germane to physical rehabilitation, we did not observe significant changes for India and Russia. This means that for these countries the aging of the population  hChina stood out with the greatest amount and an exponential type of growth in the physical rehabilitation needs from neurological and neoplasm conditions. The population ageing, derived from the previous one-child policy, increased life expectancy , increasIn India, another highly populated and emerging economy in Asia, the typology of physical rehabilitation needs was different than for the other BRICS nations and, in some respects, closer to that of lower income countries. One such example is the absolute and relative growth of physical rehabilitation needs arising from pediatric conditions. This pattern may reflect different economic status from the other BRICS: i.e., although an emergent economy, India is still a lower-middle income nation per the World Bank classification while the BRICS counterparts are UMICs. Alternatively, the findings may reflect a different population ageing structure and higher fertility rates . In addiSouth Africa, a leading UMIC within the African continent, more than doubled their absolute physical rehabilitation needs, mimicking the trend in low-income countries. This increase in need for rehabilitation is partly driven by the HIV/AIDS endemic. HIV-related conditions accounted for one-quarter of South African’s physical rehabilitation needs in 2017, compared to 1% in any of the four other BRICS countries. South Africa’s successful roll-out of highly active antiretroviral therapy (HAART) has transformed HIV into a chronic disease, and people with HIV can now achieve normal life-expectancy . An incrRussia had the highest rate of physical rehabilitation needs in 2017 , but the lowest percent change since 1990; a pattern closest to that of high-income countries more than other BRICS nations. Similarly, we found that Russia had the highest rates, although not the highest growth, in physical rehabilitation needs from neurological conditions, including about the triple of those from Brazil, India and South Africa. The persistently high burden of rehabilitation-sensitive conditions in Russia may be a result of several factors. First, the incidence of major chronic non-communicable diseases remains high; national statistics have shown, for example, that the incidence of coronary heart disease has increased substantially from 495 to 701 per 100,000 inhabitants from 2010 to 2016 . That acFinally, for Brazil, we found that conditions responsive to physical rehabilitation currently account for about two-thirds of the nation’s YLD (no other BRICS nation came close to 50%). This means that physical rehabilitation can address a larger portion of the country’s non-fatal health losses when compared to the BRICS counterparts. Brazil also stood out with the highest portion of physical rehabilitation needs coming from musculoskeletal & pain conditions (60%), and with substantial growth in this percent value over time. Key explanations for that finding may include the prevalence of interpersonal violence in Brazil , and theFirst, YLDs from selected health conditions are but proxy indicators of physical rehabilitation needs, i.e., not a direct functional or impairments-based measure. Nonetheless, YLDs is the aggregative measure of non-fatal health loss from the prominent GBD study and includes variables such as the prevalence of conditions, the time lived with sequalae from the respective conditions, and weighted for the appraised severity of those sequelae.Second, the set of conditions whose YLDs likely benefit from rehabilitation were replicated from a previous study which systematically reviewed evidence linking those conditions to rehabilitation needs;  nonethelThird, YLD values (extracted from the GBD 2017) are only estimates based on the best-available evidence, not actual YLDs. The GBD 2017 is the most comprehensive epidemiological study to date, and the amount of data used to create those estimates is unprecedented ,48. EvenFourth, most data obtained for the GBD study  are from self-reports and hence many undiagnosed conditions might not be included within this data to represent the true picture. Hence results of this study could be a gross under-estimation of the problem, at least in the absolute values.Fifth, we did not extract or analyze sub-national data , although data are available for that from the GBD 2017 and some important differences exist in both economic and epidemiological profiles across regions or states of the analyzed countries ,16,39.Sixth, we do not supplement our analyses of physical rehabilitation ‘needs’ with indicators of physical rehabilitation ‘supply’ across nations, the other key element in the resources planning equation. In part, this follows the lack of available data. For example, the World Confederation of Physical Therapy reports data on the amount of practicing physical therapists per nations, as locally collected from authoritative sources or estimated by national associations  for a total of 89 countries, but unfortunately not from 3 of the analyzed countries  .This study has the following limitations:Physical rehabilitation needs have increased significantly from 1990 to 2017 in each of the BRICS nations, both in absolute and relative values. However, apart from the common trend in overall growth, each of the BRICS nations had own patterns for the amount, typology, and evolution of their physical rehabilitation needs. The BRICS nations and coalition need to address the common challenge of planning for and deploying the required resources for meeting the growing physical rehabilitation needs of their population, at the same time they look at country-specific challenges such as the physical rehabilitation needs coming from HIV/AIDs-related conditions in South Africa, pediatric conditions in India, musculoskeletal conditions in Brazil, and neurological conditions in Russia and China. This study shows that physical rehabilitation needs can be determined and compared across nations, and hence can be used to inform rehabilitation resources and service planning. Most importantly, this study makes clear that physical rehabilitation needs and growth patterns may not be assumed equal across nations, irrespective of similarities in income or emerging development.