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Abstract Background The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. Methods We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). Results In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. Conclusions The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.

Abstract Objective Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging‐related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera–Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM‐BAge and PhenoAge‐BAge measures based on the Levine method. The KDM‐AAge and PhenoAge‐AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results During a median follow‐up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000–1.223) for KDM‐AAge and 1.180 (95% CI, 1.068–1.303) for PhenoAge‐AAge, respectively. For PhenoAge‐AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374–2.639) in males with CAge

Objective To compare and analyze the characteristics of the teaching evaluation tools for evidence-based medicine(EBM) in recent 5 years, so as to provide suggestions for further design and optimization of curriculum evaluation methods. Methods PubMed, Web of Science, Chinese biomedical literature database, CNKI, Wanfang database were searched from January 1, 2018 to September 16, 2022. Two researchers screened the literature, extracted the objects, focused topics, psychometric indicators, item contents, etc. of the tools, and made a comprehensive analysis of the existing tools. Results 16 articles (involving 14 tools) were finally included, all of which were reliable. Among them, 11 tools focus on the mastery level of the respondents' knowledge and (or) skills related to evidence-based medicine (the number of items ranges from 6 to 24), mostly involving the comprehensive cognition of evidence-based medicine, the understanding of common terms, the judgment of key concepts, the sharing and application of evidence-based practice, etc., and the evaluation criteria are mostly the judgment of right and wrong, self-evaluation, and the objective evaluation of feedback content; 7 tools focus on the true attitude of the respondents to the evidence-based practice (the number of items ranges from 3 to 21), and the evaluation criteria are mostly subjective intention options; 4 tools are used to understand the implementation frequency, time allocation and sharing of key links of evidence-based practice by the respondents (the number of items ranges from 6 to 18). The evaluation criteria are mostly subjective choices of frequency. Conclusion The questionnaire of knowledge/skills and their attitudes and behaviors can be used as an auxiliary tool in the evaluation of EBM courses. However, it is still necessary to further optimize the content and proportion of items according to the teaching characteristics and goals of the teaching objects, and develop monitoring and evaluation tools for the teaching process of evidence-based medicine curriculum.

With the popularization and promotion of information technology, healthcare big data is growing exponentially, and clinical real-world research based on healthcare big data is receiving increasing attention. The hospital electronic medical record (EMR) records the whole process of diagnosis and treatment of patients in the "real-world", and is one of the most supportive data sources for clinical decision-making. However, the existence of a large number of unstructured text data in EMR data increases the difficulty of data processing and restricts the development of research based on EMR data. Advanced methods such as information technology and artificial intelligence need to be applied to the processing of unstructured EMR data to accelerate the transformation of data value. This paper summarizes the current common methods of unstructured medical data processing, including methods based on dictionaries and rules, methods based on traditional machine learning and deep learning, and methods based on cognitive models represented by ontology, and also discusses the problems of standardization and transparent reporting when processing unstructured EMR data and looks forward to the relevant development.

PurposeMajor depressive disorder (MDD) and venous thromboembolism (VTE) may be linked in observational studies. However, the causal association remains ambiguous. Therefore, this study investigates the causal associations between them.MethodsWe performed a two-sample univariable and multivariable bidirectional Mendelian randomization (MR) analysis to evaluate the associations between MDD and VTE. The summary genetic associations of MDD statistics were obtained from the Psychiatric Genomics Consortium and UK Biobank. Information on VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) were obtained from the FinnGen Biobank. Inverse-variance weighting was used as the main analysis method. Other methods include weighted median, MR-Egger, Simple mode, and Weighted mode.ResultsUnivariable MR analysis revealed no significant associations between MDD and VTE risk (odds ratio (OR): 0.936, 95% confidence interval (CI): 0.736–1.190, p = 0.590); however, after adjusting the potential relevant polymorphisms of body mass index and education, the multivariable MR analysis showed suggestive evidence of association between them (OR: 1.163, 95% CI: 1.004–1.346, p = 0.044). Univariable MR analysis also revealed significant associations between MDD and PE risk (OR: 1.310, 95% CI: 1.073–1.598, p = 0.008), but the association between them was no longer significant in MVMR analysis (p = 0.072). We found no significant causal effects between MDD and DVT risk in univariable or multivariable MR analyses. There was also no clear evidence showing the causal effects between VTE, PE, or DVT and MDD risk.ConclusionWe provide suggestive genetic evidence to support the causal association between MDD and VTE risk. No causal associations were observed between VTE, PE, or DVT and MDD risk. Further validation of these associations and investigations of potential mechanisms are required.

Abstract Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Objective To systematically review the effectiveness and safety of cathe-ter-directed thrombolytic therapy (CDT) using alteplase and urokinase in the treatment of deep vein thrombosis (DVT) in the lower extremities.Method PubMed, The Cochrane Library, Web of Science, Embase, WanFang Data, CNKI and SinoMed databases were searched electronically to collect randomized clinical trials and cohort sudies on CDT using alteplase and urokinase in the treatment of DVT in the lower extremities from inception of the databases to December 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias in included studies, a Meta-analysis was performed using RevMan 5.4 software.Result A total of 7 cohort studies involving 598 patients were included. The results of the Meta-analysis showed that there was no sta-tistically significant difference between alteplase and urokinase in the clinical effectiveness rate [RR=1.07, 95%CI(0.91, 1.25), P=0.43] and thrombolysis rate [RR=1.08, 95%CI(0.99, 1.16), P=0.07]; the thrombolytic time of alteplase was shorter than that of urokinase [MD=-1.12, 95%CI(-1.93, -0.31), P=0.007]; there were no statistically sig-nificant differences between alteplase and urokinase in the incidence of minor bleed-ing[RR=1.19，95%CI(0.70, 2.00), P=0.52] and major bleeding[RR=0.73, 95%CI(0.27, 1.98), P=0.54]. Conclusion The effectiveness and safety of CDT of alteplase and urokinase in the treatment of DVT in the lower extremities and the risk of bleeding are comparable, but alteplase achieved thrombolysis in a shorter time than urokinase. The above conclusions are limited by the quantity and quality of included studies and need to be verified by more high-quality research.

The real-world data comes from the real medical environment, which can reflect the med-ical process and the patient's health status under real clinical conditions, and can be used as an important source of evidence and knowledge. As a semantic network, knowledge map can be used to organize, pre-sent and reason medical knowledge. The combination of real-world data and knowledge map can better supplement, display and use medical knowledge. At present, using real-world data to build a medical knowledge map or using real-world data to complete the medical knowledge map are the main ways of combining the two applications. When carrying out the application research on the combination of re-al-world data and medical knowledge map, attention should be paid to the issues about the multidiscipli-nary team collaboration, patient privacy protection and data standardization.

There are many shortcomings in the readability and applicability of current clinical practice guidelines used both in the computer-aided clinical decision making process and in clinical practice. We have explored the framework of the universality of guidelines by standardizing the representation of their structure and knowledge; and the relationship between this and the guideline knowledge. Promoting the standardization and standardized expression of guideline knowledge and constructing a standardized easily shareable guideline knowledge base that is transplantable through modeling and demonstration, is conducive to meeting the needs for the development of a clinical decision support system promoting the implementation of clinical practice guidelines and the improvement of clinical diagnosis and treatment service quality. The introduction of knowledge graphs provides a solid foundation for digital intelligentization of guidelines. However, there is little methodological content available for guideline knowledge graph construction. This study used the construction of a knowledge graph for Evidence-based clinical practice guidelines for the treatment and monitoring of non-muscular invasive bladder cancer in China (2018 Standard Edition) as an example. We identified the guideline module, analyzed its basic information, background and the scope of its methodological content, then set out the hierarchical relationship between concepts in combination with expert opinions, designed the concept structure table according to multi-level concept layers and concept examples, adjusted the relationship structure between concepts, and improved the relationship between the different entities. This article discusses and summarizes the modeling and representation methods of the basic information, background and methods of the guidelines, thus providing a reference for the construction of knowledge maps for other clinical practice guidelines in the future.

Abstract Background Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. Methods We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P

Objective To systematically evaluate the prognostic value of circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC).Methods We electronically searched CNIK, WanFang Data, CBM, VIP, PubMed, Web of Science, The Cochrane Library, and Embase database for literature regarding detection of baseline levels of CTCs and survival in NSCLC patients from inception to 28 September 2021. After screening for inclusion criteria, data extraction and quality assessment were performed followed by Meta-analysis using the RevMan 5.3 and Stata 15.0 software.Results 19 studies were included in this Meta-analysis with a total of 1,853 NSCLC patients. Meta-analysis revealed that NSCLC patients with high levels of CTCs had poorer progression-free survival (PFS) than those with low levels of CTCs [HR=2.49, 95% CI(1.50, 4.13), P=0.0004], but levels of CTCs had no significant predictive effect on overall survival (OS) [HR=1.18, 95%CI(0.70, 1.99), P=0.54].Conclusions Baseline CTCs levels have a significant predictive effect on PFS in NSCLC patients, but have no significant predictive ability on OS. This is an area which requires further study in the future.

Abstract Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued “Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline”. Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette–Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

Benign prostatic hyperplasia is the most common benign disease that causes urination dysfunction in middle-aged and elderly men, and is also the main cause of lower urinary tract symptoms. Transurethral plasmakinetic resection of prostate has been widely used in clinical practice for its good efficacy and safety. In order to further standardize the clinical application of this surgery, the National Health Commission published the initial Clinical Pathway Interpretation of Transurethral Plasmakinetic Resection of Prostate for Benign Prostatic Hyperplasia in 2019. In view of the limited content of this clinical pathway, using it as a blueprint, we have interpreted it and applied the ideas and methods of evidence-based medicine, aiming to provide a more detailed evidence supplement to help medical staff and managers better understand, grasp and correctly use this clinical pathway.

Bladder cancer is the tenth most frequently diagnosed cancer in the world, and is more common among men. Transurethral resection of bladder tumor is not only an important diagnostic method for bladder tumors, but also a major treatment for non-muscle invasive bladder cancer. Com-pared with traditional unipolar electrotomy, plasma bipolar electrotomy has the advantages of good surgical results and fewer complications, and its clinical application is becoming more and more exten-sive. In order to standardize the diagnosis and treatment of common diseases, the National Health Commission continues to issue relevant clinical pathways; however, the content of a clinical pathway is limited, and its interpretation can help it be better disseminated and used. This interpretation is based on the latest "clinical pathway for transurethral plasma resection of bladder tumor (2019 edition)". It uses the method of evidence-based medicine to make a detailed and necessary supplementary descrip-tion of the pathway, and gives a detailed interpretation of the drug delivery scheme involved, so as to provide reference for medical staff and managers to better understand, grasp and correctly use it.

In this study, based on the characteristics of Traditional Chinese Medicine (TCM) diagnosis and treatment and TCM clinical guidelines, knowledge extraction and knowledge storage were carried out to construct a knowledge graph depicting Traditional Chinese Medicine/Integrated Traditional Chi-nese and Western Medicine (IM) clinical guidelines using the "Guidelines of the Traditonal Chinese Medicine management of stable angina pectoris in coronary artery disease" as an example. This enabled us to further test the operability and rationality of the application of knowledge graph technology to the field of TCM/IM guidelines. The graph was constructed using the design of the concept layer and the da-ta layer, extracting entities and relationships from the guidelines, sorting them into the entity database and triple relationship databases for knowledge importation, using neo4j for knowledge storage, re-trieving and verifying the correctness of the knowledge graph, and completing the visual display. The methods used in constructing the knowledge graph for this clinical guideline also provides a template for the construction of knowledge graphs for TCM/IM clinical guidelines for other diseases.

With the application of hybrid wheat, lodging is becoming one of the major factors limiting high yield in its production. However, few studies have focused on combining ability and heterosis analysis of stem-related traits. In this study, 24 crosses were made according to NCII genetic design, using the three (photo-sensitive male sterile lines)×eight (restorer lines) incomplete diallel crosses. The length of basal second internode (LBSI) and breaking strength of basal second internode (BSBSI) as well as other stem-related traits were used to perform the principal component analysis (PCA), combining ability and heterosis analysis. The PCA results showed that the variables could be classified into two main factors, which were named as the positive factor (factor 1) and the negative factor (factor 2), and accounted for 52.3 and 33.2%, respectively, of the total variance in different variables, combined with the analysis for index weight indicated that the factor 1-related traits play positive roles in lodging resistance formation of hybrids. Combining ability variance analysis indicated that its genetic performance was mainly dominated by additive gene effects, and the hybrid combinations with higher lodging resistance can be selected by using of 14GF6085 (R1), 14GF6343-2 (R4), 14GF6937 (R6), 14GF7433-1 (R7), and BS1086 (M3), which are with the features with lower general combining ability (GCA) effects of factor 2-related traits whereas higher GCA effects of factor 1-related traits. The heterosis analysis showed that the wide range of heterosis varied with the traits and combinations, and GCA or specific combining ability (SCA) effects of factor 1-related traits except wall thickness of basal second internode (WTBSI) were positively and closely related to the heterosis of lodging resistance. Generally, the correlation coefficients of heterosis to GCA effects of sterile lines (GCAm) of factor 1-related traits are significantly higher than that to GCA of restorer lines (GCAr) and SCA, combined with the higher GCAm variance values of factor 1-related traits compared to GCAr, the GCAm of factor 1-related traits should be particularly considered when breeding hybrid combinations. The heritability analysis showed that the narrow-sense heritability of the diameter of basal second internode (DBSI) and the center of gravity height (TCGH) were obviously lower (

BackgroundInterleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them.MethodsWe conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively.ResultsThe odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; P=1.58×10-05) and 1.12 (95% CI, 1.07, 1.17; P=6.61×10-07) for one standard deviation increase in genetically predicted IL-1ra and IL-6 levels, respectively. Genetically predicted levels of IL-1ß, IL-2a, IL-6ra, IL-8, IL-16, IL-17, IL-18, and IL-27 were not associated with the risk of prostate cancer. Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (β, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (β, 0.002; 95% CI, -0.011, 0.014; P=0.755).ConclusionThis MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.

Drug abuse remains a global problem; nonetheless, its mechanism has not yet been fully understood. Recent studies have reported on the non-motor functions of the cerebellum, and evidence from neuroimaging and behavioral studies has suggested the role of cerebellum in drug reward, which has received increasing attention. Furthermore, emerging technological developments have aided in clarifying the various circuits and functions of the cerebellum. Exploring the role of the cerebellum in drug reward can improve our understanding of the mechanism underlying addiction and facilitate the development of new treatment schemes. This review summarizes the anatomy of the cerebellum and its connections to brain regions considered important in addiction. Subsequently, we investigate the neurological reasons elucidating why the cerebellum is a potential target for drug reward. Additionally, we expound the molecular targets of addictive drugs in the cerebellum, mainly glutamate and endocannabinoids. Unlike previous studies, this article focuses on the influence of alcohol, nicotine, morphine, cannabis, and cocaine on the cerebellum from multiple viewpoints, including imaging and behavioral changes, molecular signals, neurotransmitters, and synaptic transmission. We aim to clarify some drug-induced cerebellar changes to supplement the previous research regarding the relationship between addiction and the cerebellum. Finally, we discuss the limitations and prospects of drug reward research on the cerebellum to provide novel insights into studying the cerebellum and its role in addiction. We recommend that future addiction network models should include the cerebellum to provide new therapeutic targets for treating addiction.

The transformation and application of the guidelines is a crucial link in the transformation of medical science achievements and technology. However, there are still many problems with the op-erability of the current guidelines in clinical decision-making and practice. The knowledge graph has provided a solid foundation for the intelligentization of the guidelines and a good method for solving the problems of the implementation of the guidelines. Non-muscle invasive bladder cancer (NMIBC) is a common malignant tumor of the urinary system, and new diagnosis and treatment methods for NMIBC are emerging. In view of the time-consuming and frequent update of clinical guidelines for NMIBC, as well as the urgent need for clinicians to learn, use, and sort out the updated content of the guidelines, this study is based on the disease characteristics of NMIBC and the clinical guidelines to propose and construct a knowledge graph framework for clinical guidelines of NMIBC, which mainly starts from ana-lyzing the scope of the guideline, combing the guideline content modules, summarizing the guideline knowledge structure. Then, we referred to the OMAHA Schema, and designed the concept structure ta-ble according to the secondary concept layer and concept instances. Thereafter, we designed and ad-justed the relationship structure between concepts, improved the relationship between entities, and finally reviewed and evaluated the scientific and method validity of the knowledge graph through ex-perts. The design of the knowledge graph construction framework based on the guideline for NMIBC proposed in this paper provides a basis for the digitization and intelligence of the guideline, which is conducive to the implementation and dissemination of the guideline.

The implementation of clinical practice guidelines is an important form of evidence transformation and a main way to narrow the gap between research results and clinical practice. Af-fected by factors such as low operability, single form of dissemination and application, not timely update, and lack of implementation tools and implementation evaluation tools, the implementation of clinical practice guidelines is still insufficient. Combining the evidence ecosystem framework, constructing guideline implementation evaluation tools, and using knowledge graph and other artificial intelligence technologies to provide theoretical support, effect evaluation tools, and technical paths for the imple-mentation of the guidelines are effective methods to promote the implementation of clinical practice guidelines.

Abstract Background Known as the prerequisite component for the heterosis breeding system, the male sterile line determines the hybrid yield and seed purity. Therefore, a deep understanding of the mechanism and gene network that leads to male sterility is crucial. BS366, a temperature-sensitive genic male sterile (TGMS) line, is male sterile under cold conditions (12 °C with 12 h of daylight) but fertile under normal temperature (20 °C with 12 h of daylight). Results During meiosis, BS366 was defective in forming tetrads and dyads due to the abnormal cell plate. During pollen development, unusual vacuolated pollen that could not accumulate starch grains at the binucleate stage was also observed. Transcriptome analysis revealed that genes involved in the meiotic process, such as sister chromatid segregation and microtubule-based movement, were repressed, while genes involved in DNA and histone methylation were induced in BS366 under cold conditions. MethylRAD was used for reduced DNA methylation sequencing of BS366 spikes under both cold and control conditions. The differentially methylated sites (DMSs) located in the gene region were mainly involved in carbohydrate and fatty acid metabolism, lipid metabolism, and transport. Differentially expressed and methylated genes were mainly involved in cell division. Conclusions These results indicated that the methylation of genes involved in carbon metabolism or fatty acid metabolism might contribute to male sterility in BS366 spikes, providing novel insight into the molecular mechanism of wheat male sterility.

Objective To comprehensively evaluate the quality of the non-randomized studies on the effects of published interventions into the Chemoprophylaxis, diagnosis, treatments, and dis-charge management of COVID-19: an evidence-based clinical practice guideline (updated version).Methods The well-established guideline search strategy was used in this study. An electronic litera-ture search was conducted using PubMed, Embase, the Cochrane Library, CNKI, Wanfang Database and major medical journals which included the topics of infection or respiration, preprint platforms and clinical trial registries from December 1, 2019, to July 8, 2020. The language was limited to Chi-nese and English. Non-randomized intervention studies of pharmacotherapies for the prevention and treatment of COVID-19 were sought and included, and methodological quality assessment was con-ducted using the f ROBINS-I tool.Results A total of 40 non-randomized intervention studies were retrieved, including 20 antiviral drug intervention studies, 16 immunotherapy intervention studies and 4 traditional Chinese medicine intervention studies. Our evaluation showed that the overall risk of bias in all 40 studies was moderate to serious, and 15 of them had a "serious" overall risk of bias. Two domains (bias due to confounding and bias due to deviations from intended interventions) had a high risk of bias, mainly because of the poor control of baseline confounding factors, time-varying confounding factors and important intergroup variations of intervention measures.Conclusions The overall quality of existing non-randomized intervention studies on pharmacotherapy for the preven-tion and treatment of COVID-19 is poor, and some recommendations are inconclusive. Large, pro-spective studies and randomized controlled trials with a rigorous design are needed to improve the quality of evidence.

Objective To evaluate complications related to transurethral plasmakinetic prostatectomy (TUPKP) in the treatment of benign prostatic hyperplasia (BPH).Methods CNKI, Wanfang database, VIP Chinese journal service platform, CBM, PubMed, Embase, Web of Science and The Cochrane Library were searched for cross-sectional studies on the incidence of complications of TUPKP in the treatment of BPH from January 1st, 2018 till to September 15th, 2020. Two researchers independently screened the literature, extracted data and evaluated the risk of bias in the included studies, the R software meta package was used for meta-analysis.Results Twenty-seven studies were finally included, reporting on 5,247 patients with 31 complications described. Meta-analysis showed that the incidence of 6-month abnormal ejaculation rate is 75.15% [95%CI (68.25%, 81.47%)]; the incidence of retrograde ejaculation is 24.77% [95%CI (0.00%, 73.81%)]; the incidence of irritating symptoms was 17.15% [95%CI (9.61%, 26.22%)]. The incidence of other complications was less than 10%, and 21 of them had an incidence of less than 3%. The incidence of transurethral resection syndrome in 15 studies was 0.Conclusion There are many types of complications after TUPKP treatment for BPH, and the incidence rate varies greatly.

Objective To systematically evaluate the efficacy and safety of transurethral plasmakinetic prostatectomy (TUPKP) and trans urethral resection of prostate (TURP) in the treatment of benign prostatic hyperplasia (BPH).Methods We searched the databases of PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Weipu, China Biomedical Literature Database and Wanfang Database, and collected relevant randomized controlled trials (RCTs) from their inception to September 15, 2020. Data extraction and assessment of risk of bias were performed by two reviewers independently. Meta-analysis was performed using Stata 16.0 software.Results A total of 45 RCTs involving 6 490 subjects were included. The results of Meta-analysis showed that, in patients with normal volume of prostate (

Objective To evaluate the efficacy and safety of transurethral plasmakinetic prostatectomy (TUPKP) versus transurethral plasmakinetic enucleation of prostate (TUPEP) in treating benign prostate hyperplasia (BPH).Methods PubMed, EMBASE, the Cochrane Library, CNKI, VIP, CBM database and Wanfang database were searched for relevant randomized controlled trials from January 1st, 2018until September 15, 2021, and references were manually searched. Two researchers independently conducted literature screening, data extraction and quality evaluation. Stata13.0 software was used for Meta-analysis.Results A total of 30 studies were included, reporting on 3,218 BPH patients, of whom 1,626 received TUPKP and 1,592 received TUPEP. Meta-analysis of results show that: for effectiveness, when treating a normal volume (

Abstract Background DNA methyltransferase (DMT) genes contribute to plant stress responses and development by de novo establishment and subsequent maintenance of DNA methylation during replication. The photoperiod and/or temperature-sensitive genic male sterile (P/TGMS) lines play an important role in hybrid seed production of wheat. However, only a few studies have reported on the effect of DMT genes on temperature-sensitive male sterility of wheat. Although DMT genes have been investigated in some plant species, the identification and analysis of DMT genes in wheat (Triticum aestivum L.) based on genome-wide levels have not been reported. Results In this study, a detailed overview of phylogeny of 52 wheat DMT (TaDMT) genes was presented. Homoeolog retention for TaDMT genes was significantly above the average retention rate for whole-wheat genes, indicating the functional importance of many DMT homoeologs. We found that the strikingly high number of TaDMT genes resulted mainly from the significant expansion of the TaDRM subfamily. Intriguingly, all 5 paralogs belonged to the wheat DRM subfamily, and we speculated that tandem duplications might play a crucial role in the TaDRM subfamily expansion. Through the transcriptional analysis of TaDMT genes in a TGMS line BS366 and its hybrids with the other six fertile lines under sterile and fertile conditions, we concluded that TaCMT-D2, TaMET1-B1, and TaDRM-U6 might be involved in male sterility in BS366. Furthermore, a correlation analysis showed that TaMET1-B1 might negatively regulate the expression of TaRAFTIN1A, an important gene for pollen development, so we speculated regarding an epigenetic regulatory mechanism underlying the male sterility of BS366 via the interaction between TaMET1-B1 and TaRAFTIN1A. Conclusions Our findings presented a detailed phylogenic overview of the DMT genes and could provide novel insights into the effects of DMT genes on TGMS wheat.

BackgroundThe association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association.Materials and methodsIn this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10–8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources.ResultsThe genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512–1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10–8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676–1.125, p = 0.292).ConclusionOur MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.

Because of the yield increase of 3.5–15% compared to conventional wheat, hybrid wheat is considered to be one of the main ways to greatly improve the wheat yield in the future. In this study, we performed a principal component analysis (PCA) on two-line hybrids wheat and their parents using the grain weight (GW), the length of spike (LS), the kernel number of spike (KSN), and spike number (SPN) as variables. The results showed that the variables could be classified into three main factors, the weight factor (factor 1), the quantity factor 1 (factor 2) and the quantity factor 2 (factor 3), which accounted for 37.1, 22.6 and 18.5%, respectively of the total variance in different agronomic variables, suggesting that the GW is an important indicator for evaluating hybrid combinations, and the grain weight of restorer line (RGW) could be used as a reference for parents selection. The hybrid combination with a higher score in factor 1 direction and larger mid-parent heterosis (MPH) of the GW and its parents were used to carry out the analysis of grain filling, 1-aminocylopropane-1-carboxylicacid (ACC) and polyamine synthesis related genes. The results suggested that the GW of superior grain was significantly higher than that of inferior grains in BS1453×JS1 (H) and its parents. Both grain types showed a weight of H between BS1453 (M) and JS1(R), and a larger MPH, which may be caused by their differences in the active filling stage and the grain filling rate. The ADP-glucose pyrophosphorylase (AGPase), granule bound starch synthase I (GBSSI), starch synthase III (SSS), and starch branching enzyme-I (SBE-I) expression levels of H were intermediated between M and R, which might be closely related to MPH formation of the GW. Compared with R and H, the GW of M at maturity was the lowest. The expression levels of spermidine synthase 2 (Spd2), ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) had significantly positive correlations with the grain filling rate (r=0.77*, 0.51*, 0.59*), suggesting their major roles in the grain filling and heterosis formation. These provide a theoretical basis for improving the GW of photo-thermo-sensitive male sterile lines (PTSMSL) by changing the endogenous polyamine synthesis in commercial applications.

Objective To formulate the 2019 novel coronavirus (2019-nCoV) nosocomial infection research and analysis tools.Methods Based on the questionnaire for infection process and prevention of 2019-nCoV infection in medical staffs, we developed the new questionnaire by means of three procedures including refining the purpose of the questionnaire, establishing the item pool, and evaluating the content validity of the questionnaire.Results We formulated three questionnaires for 2019-nCoV releated nosocomial infection including questionnaires for staff in administrative and logistics departments, the non-infected health care staff, and non-infected staff in administrative and logistics departments. The content of the questionnaires were consistent with the research objectives. The questionnaire for COVID-19 among staff in administrative and logistics departments included two aspects of investigation before and after diagnosis, "before diagnosis" involved infection cause, plan of prevention and control, knowledge of prevention and control, and psychological symptoms, there were 16 items in total; "after diagnosis" included 5 parts, including symptoms after diagnosis, treatment after diagnosis, impact on the surrounding environment and people after infection, psychology symptoms, awareness of protection, there were 21 items in total. The questionnaire for COVID-19 among non-infected health care staff included analysis of causes of infection in work and life, relevant prevention and control behaviors, infection prevention and control knowledge and psychological response to the epidemic, there were 29 items in total; the questionnaire for COVID-19 among non-infected staff in administrative and logistics departments included same aspects as questionnaire for COVID-19 among non-infected health care staff, and also 20 items.Conclusions We developed questionnaires for 2019-nCoV releated nosocomial infection including a study on infection processes and prevention measures for COVID-19 among staff in administrative and logistics departments, a study on infection processes and prevention measures for COVID-19 among non-infected healthcare staff, and a study on infection processes and prevention measures for COVID-19 among non-infected staff in administrative and logistics departments. The reliability, validity, and practicability of these questionnaires are all acceptable.

Background: Previous observational studies have reported a bidirectional association between periodontitis and type 2 diabetes, but the causality of these relationships remains unestablished. We clarified the bidirectional causal association through two-sample Mendelian randomization (MR).Methods: We obtained summary-level data for periodontitis and type 2 diabetes from several published large-scale genome-wide association studies (GWAS) of individuals of European ancestry. For the casual effect of periodontitis on type 2 diabetes, we used five independent single-nucleotide polymorphisms (SNPs) specific to periodontitis from three GWAS. The summary statistics for the associations of exposure-related SNPs with type 2 diabetes were drawn from the GWAS in the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) consortium and the FinnGen consortium R5 release, respectively. For the reversed causal inference, 132 and 49 SNPs associated with type 2 diabetes from the DIAGRAM consortium and the FinnGen consortium R5 release were included, and the summary-level statistics were obtained from the Gene-Lifestyle Interactions in Dental Endpoints consortium. Multiple approaches of MR were carried out.Results: Periodontitis was not causally related with the risk of type 2 diabetes (all p > 0.05). No causal effect of type 2 diabetes on periodontitis was found (all p > 0.05). Estimates were consistent across multiple MR analyses.Conclusion: This study based on genetic data does not support a bidirectional causal association between periodontitis and type 2 diabetes.

The objective of this study was to compare the efficacy and safety of 10 different surgical treatments for benign prostatic hyperplasia (BPH) with volume >60 mL. A systematic literature review and network meta-analysis of randomized controlled trials (RCTs) within a Bayesian framework was performed. A total of 52 parallel-group RCTs included, reporting on 6,947 participants, comparing open prostatectomy (OP), monopolar/bipolar transurethral resection of prostate (monopolar/ bipolar TURP), thulium, holmium and diode laser enucleation of prostate (LEP), bipolar enucleation of prostate, potassium titanyl phosphate laser vaporization of prostate (KTP LVP), bipolar vaporization of prostate (bipolar VP), and laparoscopic simple prostatectomy (laparoscope SP). Compared with OP, laparoscope SP identified better maximal flow rate (Qmax; mean differences [MDs] = 2.89 mL/s) at the 24th month, but bipolar VP demonstrated worse Qmax (MD = −3.20 mL/s) and International Prostate Symptom Score (IPSS; MD = 2.60) at the 12th month. Holmium LEP (MD = 1.37) demonstrated better International Index of Erectile Function–5 at the 12th month compared with OP. However, compared with OP, KTP LVP demonstrated worse postvoid residual volume (PVR) at the sixth (MD = 10.42 mL) and 12th month (MD = 5.89 mL) and monopolar TURP (MD = 6.9 mL) demonstrated worse PVR at the 12th month. Eight new surgical methods for BPH with volume >60 mL appeared to be superior in safety compared with OP and monopolar TURP due to fewer complications. Bipolar VP and KTP LVP maybe not suitable for prostates more than 60 mL due to short- and middle-term worse Qmax, IPSS, and PVR than OP.

Objective: This study aimed to systematically review the status and trends of Chinese clinical practice guidelines (CPGs) during the time period 2010–2020 and explore their methodological characteristics. Then, based on the strengths and weaknesses in development, offer several recommendations for the quality improvement which will serve as a reference for the users and developers of CPG.Introduction: With the development of evidence-based medicine (EBM), the CPGs play an increasingly important role in healthcare decision-making both in China and worldwide.Inclusion criteria: The CPGs that have been used to help the health professionals in the healthcare decision-making were included.Methodology: The China National Knowledge Infrastructure (CNKI) and WanFang databases were searched from 2010 to 2020 for the studies describing the general and methodological characteristics of Chinese CPGs. Comparisons of the methodological characteristics between the groups were conducted using the chi-square test or Fisher's exact test. The M-K test was adopted to identify the monotonically increasing or decreasing trends of methodological characteristics over the timespan.Results: A total of 2,654 CPGs fulfilled the inclusion criteria. The quantity and quality of the guidelines developed in China have improved over the time span. From 2010 to 2020,the guidelines had differing characteristics and covered a wide range of subjects. In total, 2,318(87.34%) guidelines focused on Western Medicine. Eight (0.30%) had been developed for patient versions of guidelines, 10(0.38%) were tentative guidelines, and 16(0.60%) were rapid advice guidelines. Medical specialty societies (including their branches) (71.1%) were the main guideline makers. The most addressed diseases were neoplasms (14.43%). The target population is mainly adults (84.97%). The methodological quality of consensus-based (CB)-CPGs was obviously lower than evidence-based (EB)-CPGs. Except for the item, “recommendations were based on evidence of systematic reviews,” there were statistical differences in all other methodological items between the EB-CPGS and CB-CPGS (P < 0.01). Higher methodological quality has been observed in EB-CPGs. All the data relating to the methodological characteristics indicated that higher methodological quality was present in the guidelines using GRADE (P < 0.01).Conclusion: The quantity and quality of the guidelines developed in China have improved between 2010 and 2020. CB-CPGs have also paid attention to the methodology quality, but obviously, this is lower than that in the EB-CPGs.

Abstract Backgrounds Glioma is the most fatal primary brain glioma in central nervous system mainly attributed to its high invasion. Prucalopride, a Serotonin-4 (5-HT4) receptor agonist, has been reported to regulate neurodevelopment. This study aimed to investigate the influence of the Prucalopride on glioma cells and unveil underlying mechanism. Methods In this study, glioma cells proliferation was evaluated by Cell counting kit-8 (CCK8). Wound healing and transwell assay were used to test cellular migration and invasion. Flow cytometry was utilized to determine cellular apoptosis rate. Apoptosis related markers, autophagy markers, and protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway key molecules were detected using western blot assay. Results As a result, the proliferation, migration and invasiveness of glioma cells were impaired by Prucalopride treatment, the apoptosis rate of glioma cells was enhanced by Prucalopride stimulation, accompanied by the increased pro-apoptosis proteins Bax and Cleaved caspase-3 and decreased anti-apoptosis protein Bcl-2. Prucalopride significantly promoted autophagy by increased expression level of Beclin 1 and LC3-II, while decreased expression level of p62. Prucalopride administration resulted in obvious inhibitions of key molecules of AKT-mTOR pathway, including phosphorylated- (p-) AKT, p-mTOR and phosphorylated-ribosomal p70S6 kinase (p-P70S6K). Conclusions Taking together, these results indicate that Prucalopride may be likely to play an anti-tumor role in glioma cells, which suggests potential implications for glioma promising therapy alternation in the further clinics.

In this paper, the evolution dynamics of astigmatic four-petal Gaussian beams in isotropic nonlocal nonlinear media is investigated. A series of analytical expressions are derived to describe the beam evolution, the beam width, and the critical power. The anomalous transverse transformation is presented, i.e., an astigmatic four-petal Gaussian beam is compressed in one transverse direction and it is broadened in the other transverse direction. These evolution characteristics of astigmatic four-petal Gaussian beams are illustrated through some numerical simulations. Keywords: Isotropic nonlocal media, Astigmatic four-petal Gaussian beam, Anomalous transverse transformation

In this paper, we mainly investigate the propagation properties of shape-variable four-petal Gaussian vortex breathers in strongly nonlocal nonlinear media. The analytical expression of the shape-variable four-petal Gaussian vortex breather is derived in Cartesian coordinate system by means of mathematical integral method. A series of evolution properties are described analytically and numerically, such as the transverse intensity pattern, the phase distribution, the variation of the second-order moment beam width, and the on-axis light intensity. It is found that the topological charge number and the beam order of the shape-variable four-petal Gaussian vortex breather play important roles in the propagation process, and their effects on the propagation properties of the shape-variable four-petal Gaussian vortex breather are discussed graphically. Keywords: Nonlocal nonlinear media, Four-petal Gaussian vortex breather, Topological charge