The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To explore the expression of lncRNA ARHGAP5-AS1 in renal cancer tissues and cell lines, and the effect of ARHGAP5-AS1 on the proliferation and invasion of renal cancer cell lines and its molecular mechanism.Methods:The GEPIA database was used to analyze the expression of ARHGAP5-AS1 in renal cancer tissues, and its relationship with clinical stage, overall survival and disease-free survival of renal cancer patients was analyzed. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of ARHGAP5-AS1 in renal cancer cells (786-O, Caki-1, OS-RC-2, ACHN, A-498). Renal carcinoma OS-RC-2 cells were transfected with pcDNA3.1-ARHGAP5-AS1 plasmid or pcDNA3.1 plasmid, denoted as ARHGAP5-AS1 group and control group. Colony formation assay and Transwell assay were used to detect changes in the proliferation and invasion ability of OS-RC-2 cells. Dual-luciferase reporter gene experiment was used to verify the targeting relationship between ARHGAP5-AS1 and miR-155-5p. The Starbase v3.0 online database was used to analyze the correlation between the expression of ARHGAP5-AS1 and miR-155-5p in renal cancer tissues. RT-qPCR was used to detect the expression level changes of miR-155-5p. Western blotting was used to detect the expression changes of Raf/MEK/ERK molecular pathway proteins p-Raf, p-MEK, p-ERK, p-FBW7, and c-MYC. The measurement data were expressed as mean ± standard deviation ( ± s), the independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:ARHGAP5-AS1 was lowly expressed in renal cancer tissues ( P<0.01), and its expression level was related to the clinical stage, overall survival and disease-free survival of patients with renal cancer ( P<0.01). ARHGAP5-AS1 showed low expression in renal cancer cell lines (786-O, Caki-1, OS-RC-2, ACHN, A-498) ( P<0.01). Compared with the control group, the proliferation and invasion abilities of OS-RC-2 cells in ARHGAP5-AS1 group were significantly reduced ( P<0.01). Dual-luciferase reporter gene experiment confirmed that ARHGAP5-AS1 targets and binds to miR-155-5p ( P<0.01). The expression of ARHGAP5-AS1 and miR-155-5p in renal cancer tissues was negatively correlated ( P<0.01). Compared with the control group, the expression of miR-155-5p in OS-RC-2 cells in the ARHGAP5-AS1 group was significantly reduced ( P<0.01). Compared with the control group, the expression levels of Raf/MEK/ERK molecular pathway proteins p-Raf, p-MEK, p-ERK, p-FBW7, and c-MYC in OS-RC-2 cells in the ARHGAP5-AS1 group were reduced. Conclusions:lncRNA ARHGAP5-AS1 is lowly expressed in renal cancer tissues and is related to the clinical stage and survival of renal cancer patients. ARHGAP5-AS1 inhibits the proliferation and invasion of renal cancer cells by targeting the expression of miR-155-5p.

Objective:To collect data on urinary flow rate in the elderly female population across the country and to analyze the range of reference values.Methods:This study enrolled 333 subjects from July 2020 to June 2022.The study implementation process was divided into two steps.In the first step, subjects completed an electronic questionnaire, which included basic information about the subject, a short form for urinary incontinence, and a scoring form for the symptoms of overactive bladder syndrome.In the second step, the staff introduced the use of a mobile uroflowmetric device and distributed the instrument and materials.Uroflow rate data were automatically uploaded to a cloud database via the mobile phone.Subsequently, two or more physicians specializing in urinary control performed Uroflow rate-qualifying screenings and conducted statistical analyses.Results:A total of 333 subjects were enrolled in the study, and the researchers collected 1375 qualified urine flow rate records using a mobile urine flow rate instrument.The age of the subjects ranged from 60 to 84 years, with a mean age of 69 years.The reference ranges for urinary flow rate were found to be 24.8-26.2 s, with a mean urinary flow rate of 12.2-12.9 ml/s, a maximum urinary flow rate of 22.2-23.4 ml/s, and a time to peak of 8.5-9.7 s. The study observed a tendency for both maximal and mean urinary flow rates to decrease in older women as their age increased(Pearson correlation coefficient: -0.1, P<0.001). Conclusions:The uroflow rate of older women decreases with aging.Specifically, the average uroflow rate of women over 80 years old is lower than that of other age groups.This study aims to establish normal uroflow parameters for uroflowmetry in healthy older women in China.

OBJECTIVE To explore the current status and challenges of informatization construction for clinical trial centralized pharmacy based on the relevant experience of The First Affiliated Hospital, Zhejiang University School of Medicine. METHODS Review the development of clinical trial drug management and informatization process, along with the management experience of the hospital where the author works, and then introduce the framework and specific operation details of the informatization system when conducting centralized management method, summarize the problems encountered at present and propose future prospects. RESULTS Informatization construction played a significant role in the management of central pharmacies in clinical trial, enabling them to adapt to the complex management needs of investigational products and meet the high standards and strict requirements of Good Clinical Practice(GCP) and related regulations. However, the development of the current information system was still not perfect, and there were problems that need to be solved. CONCLUSION Each hospital needs to pay attention to the informatization construction of the central pharmacy of the clinical trial, improve and perfect the centralized management method of the investigational products, and explore modern technologies and equipments, which are of immense importance for the construction of the clinical trial pharmacy management that conforms to the development trend of drug clinical trials and GCP.

In recent years, many scholars have explored the clinical application value of a number of peripheral hematology indexes in tumor patients. The significant correlation of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio with the prognosis in various tumors has also been confirmed. At present, more peripheral blood indexes have been gradually applied to the evaluation of the prognosis in patients with malignant tumors. Small cell lung cancer (SCLC) is a type of highly malignant tumor and most patients are in advanced stage at the time of diagnosis. The evaluation value of tumor stage for survival is extremely limited. Therefore, this review intends to explain the relationship between various peripheral hematology indexes and the prognosis of SCLC patients, so as to provide some academic evidence for the clinical assessment of the survival of SCLC patients and formulation of appropriate treatment strategy, which may contribute to the improvement of the prognosis.

Clinical trial management system is independently developed by our hospital, which basically realized the whole process management and data collection of clinical trials. Based on the platform, the functional architecture of data remote monitoring and auditing was established. By desensitizing and encrypting of data, the project and subject hologram were visualized to facilitate to review of data. The data remote monitoring and auditing cloud platform adopts the B/S architecture pattern. Users register to apply for an account through the cloud platform, and access to the account via HTTPS security protocol. The authorized users were able to view the relevant items online to ensure the secure data transmission and easy operating. The electronic management of data is the direction of future efforts. By compliance with laws and regulations, the remote monitoring/auditing can be realized, and the data security and personal privacy can be ensured with the application of information technology. In this paper, the feasibility of remote monitoring/auditing mode is explored, specific technical schemes and system functions are suggested, and the realization scenarios are conceived in case of major public health emergencies.

Objective To analyze the clinocopathological characteristics of infectious granulomas.Methods The clinical features,histopathological manifestations of 39 patients with infectious granulomas were analyzed retrospectively.Results Among 39 cases of infectious granulomas,there were 15 males and 24 females,and 17 cases of fungal granuloma and 22 cases of tuberculous granuloma.There was no statistically significant difference in gender and age between fungal granulomas and tuberculous granulomas.The mean course of tuberculous granuloma aud tuberculous granuloma was (0.88 ± 0.67) years and (5.54 ± 3.49) years,respectively (t =4.51,P =0.00);there was no significant difference in mean age of onset in fungal granuloma patients and tuberculous granuloma patients [(54.6 ± 19.6) vs.(47.6 ± 18.1) years,P ＞0.05)].There were 4 and 18 cases of fungal and tuberculous granulomatosis at the face,and 13 and 3 cases at the extremities (all P =0.00);the lesions occurred in the trunk in one case of tuberculous granuloma.The clinical manifestations of fungal and tuberculous granulomas as plaques/nodules were in 14 cases aud 22 cases (P =0.08);as ulcers and pus exudates were in 10 and 2 cases,respectively (P =0.00).The histopathological features showed epidermal hyperplasia in 12 and 4 cases,infiltrative patterns in 4 and 21 cases,infiltration of neutrophils in 14 and 3 cases,infiltration of plasma cells in 15 and 5 cases,infiltration of eosinophils in 10 and 0 cases,necrosis in 1 and 10 cases in fungal granulomas and tuberculous granulomas,respectively (P =0.00,0.00,0.00,0.00,0.00,0.01).Conclusion Fungal granuloma and tuberculous granuloma are different in the lesion sites,clinical manifestations and histopathological features.

Bypass surgery ( BSX ) and endovascular therapy ( EVT ) are the most important therapeutic method to critical limb ischemia?EVT has potential advantages in reducing surgical trauma and early postoperative complications, shortening hospital stay and so on? Concerning long?term results, BSX is better in reducing long?term mortality and improving long?term patency than EVT group? Therefore, control indications reasonably and select individualized methods, avoid the abuse of EVT are more meaningful for patients.