ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

OBJECTIVE To comprehensively evaluate the efficacy， safety and cost-effectiveness of insulin icodec in treating type 2 diabetes mellitus （T2DM）， providing evidence-based guidance for new drug selection in hospital and clinical medication decision-making. METHODS PubMed， Cochrane Library， Embase， CNKI， Wanfang， VIP and foreign health technology assessment （HTA） websites were searched by using rapid health technology assessment from inception to 15 July 2025 for systematic reviews/meta-analyses， pharmacoeconomic studies， and HTA reports on insulin icodec in the treatment of T2DM. After data extraction and quality assessment， the findings of the included studies were analyzed descriptively. RESULTS Ten systematic reviews/meta-analyses and three pharmacoeconomic studies were included. Among them， 4 systematic reviews/meta-analyses were of high quality； the overall quality of the 3 pharmacoeconomic studies was relatively good. Regarding efficacy， insulin icodec was superior to once-daily basal insulin in reducing glycated hemoglobin （HbA1c） and in achieving the target of HbA1c＜7% （P＜0.05）. No significant differences were observed between icodec insulin and comparators in lowering fasting plasma glucose （P＞0.05）. For safety， insulin icodec did not increase the incidence of any adverse events （AEs）， serious AEs， clinically significant hypoglycemia （random glucose＜3 mmol/L）， injection-site reactions， or allergic reactions， compared with once-daily basal insulin overall （P＞ 0.05）； however， insulin icodec was associated with a significant increase in body weight （P＜0.05）. Domestic economic evaluations indicated that insulin icodec was more cost-effective than insulin glargine and insulin degludec when its annual costs were in the range of 784.90-1 145.96 and 597.66-736.34 US dollars， respectively. CONCLUSIONS Insulin icodec demonstrates favorable efficacy and safety profiles in the treatment of T2DM； however， attention should be paid to the risk of weight gain. Under China’s healthcare system， insulin icodec demonstrates greater economic value only when the patient’s weekly required basal insulin dose falls within a specific range，and clinical practice requires individualization.

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml -1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1-2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml -2 for PI-RADS 1-2 patients and 0.3 ng ml -2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1-2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Retrospective Studies ; Prostate/diagnostic imaging* ; Unnecessary Procedures/statistics & numerical data* ; Biopsy/statistics & numerical data* ; China ; ROC Curve

Congenital lower urinary tract obstruction (CLUTO) is a spectrum of fetal malformations caused by anatomical abnormalities of the urethra, characterized by high rates of perinatal complications and mortality. The 2024 joint guideline from the European Association of Urology (EAU) and the European Society for Paediatric Urology (ESPU) introduced systematic revisions to the comprehensive management of CLUTO. Key updates encompass advancements in prenatal and postnatal screening and precise diagnosis, refined fetal prognosis assessment, clearer indications and modality selection for prenatal intervention, optimization of postnatal treatment strategies, and the establishment of a lifelong follow-up framework within an integrated care pathway. This article elucidates these key updates by comparing the 2024 EAU/ESPU guideline with the 2022 European Rare Kidney Disease Reference Network (ERKNet) consensus. It also discusses ongoing controversies and future research directions. The aim is to provide clinicians with the latest evidence-based insights to inform practice, ultimately improving outcomes and quality of life for children with CLUTO.
Humans ; Urology ; Female ; Urethral Obstruction/therapy* ; Pregnancy ; Child ; Europe ; Prenatal Diagnosis ; Infant, Newborn ; Urethra/abnormalities*

During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Neurons/metabolism* ; Transferrin/pharmacology* ; Mice ; Methylation ; Mice, Inbred C57BL ; Adenosine/metabolism* ; RNA, Messenger/metabolism* ; Male ; Oxidative Stress/physiology*

With the rapid development of information technology， research on ancient TCM books has shifted from the traditional collation and digitization into intelligent knowledge service， thereby achieving the deep integration of ancient TCM books collation and clinical needs. Based on the clinical problem and knowledge element theory， we implemented in-depth indexing and knowledge mining for 600 kinds of ancient TCM books， built a knowledge sharing service platform for ancient TCM books by integrating database， cloud platform， knowledge graph and other technologies， and carried out the thematic literature research and developed databases for four major diseases including stroke， heart failure， liver cirrhosis， and diabetes. The digital intelligence products have been applied in hundreds of hospitals for evaluation and feedback. Finally， through "digital processing plus intelligent application"， the two-way interaction between ancient TCM books and current clinical practice is realized， and the path and paradigm of ancient TCM books knowledge serving the modern prevention and control of major diseases is formed， providing reference for the innovative utilization of ancient TCM books.

Toxoplasma gondii(T.gondii or Tg),is an obligatory intracellular parasite with humans as its intermediate hosts.In recent years,significant correlations between T.gondii infection and schizophrenia have been reported,including the possible mediating mechanisms.Currently,mechanisms and hypotheses focus on central neurotransmitters,immunity,neuroinflammation,and epigenetics;however,the exact underlying mechanisms remain unclear.In this article,we review the studies related to T.gondii infection and schizophrenia,particularly the latest research progress.Research on dopamine(DA)and other neurotransmitters,the blood-brain barrier,inflammatory factors,disease heterogeneity,and other confounders is also discussed.In addition,we also summarized the results of some new epidemiological investigations.

Objective:To analyze awareness, willingness, the status of using, and related factors of HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) in Shaanxi Province to provide a reference for the next step of HIV prevention and control strategy.Methods:Using a cross-sectional study design from March to May 2022, with the assistance of MSM social organizations in Xi'an, relying on the network platform and MSM Social organizations, a convenient sampling method was used to recruit MSM with an estimated sample size of 900. The inclusion criteria were male aged ≥18, having had same-sex sexual intercourse in the last twelve months, HIV-negative or unknown status of infection. An electronic questionnaire was made with the help of questionnaire-star and an anonymous self-administered questionnaire was used to collect information on socio-demographic characteristics, sexual behavior, awareness and using of PrEP, etc. A logistic regression model was used to analyze related factors of PrEP awareness and use in MSM. SPSS 25.0 software was used for statistical analysis. Results:Among 981 MSM subjects, 76.55% (751/981) had heard of PrEP, and 42.51% (417/981) were aware of PrEP. Among those who knew about PrEP, 74.34% (310/417) had homosexual sexual activity in the last six months, 99.03% (307/310) were willing to use PrEP, and 40.97% (127/310) were using PrEP. The multivariate logistic regression analysis model results showed that nationality (other ethnic groups:a OR=4.48,95% CI:1.28-15.68),education level (high school or technical secondary school: a OR=3.01,95% CI:1.49-6.07; universities or colleges: a OR=2.86,95% CI:1.47-5.57; master degree: a OR=5.10,95% CI:2.37-10.98), monthly income 5 000-10 000 yuan (a OR=1.70,95% CI: 1.00-2.88), tested for HIV in the past 12 months (a OR=1.87,95% CI:1.34-2.61) were related factors of PrEP knowledge awareness. Singlehood (a OR=0.46,95% CI:0.26-0.81) and consulted professionals about PrEP (a OR=9.56,95% CI:4.58-19.96) were related factors of PrEP use. Conclusions:The proportion of willingness to use PrEP was higher among MSM in Shaanxi Province, but the awareness rate and utilization rate of MSM for PrEP were low. The cognition of PrEP should be further improved to promote the correct use of PrEP among MSM.

To evaluate the effect of bronchoalveolar lavage (BAL) on the clinical prognosis of children with macrolide drug-resistant Mycoplasma pneumoniae pneumonia (MRMPP) in a retrospective cohort study based on propensity score matching (PSM).A retrospective cohort study based on propensity score matching retrospectively collected the clinical data of hospitalized patients diagnosed with mycoplasma macrolide drug-resistant pneumonia (MRMPP) in Respiratory Department of Hunan Children′s Hospital from January 2020 to August 2023. According to whether bronchoalveolar lavage (BAL) was performed during hospitalization, the children were divided into BAL group and non-BAL group, and the baseline information of the two groups was matched by propensity scores, and the clinical prognosis was compared. A total of 302 children were screened, and 150 cases were successfully matched, including 59 cases in the BAL group and 91 cases in the non-BAL group. The results showed that the differences between the non-BAL group and the BAL group before PSM( P<0.05) were significantly different in age [(4.60±2.97)years vs (5.41±3.02) years, t=-2.273, P=0.024], shortness of breath (9.4% vs 22.5%, χ 2=9.864, P=0.002), and radiographic manifestations [lung interstitial changes (29.8% vs 15.3%, χ 2=8.009, P=0.005), lung consolidation (17.3% vs 55.9%, χ 2=48.457, P<0.001), spotted flaky infiltrates (52.4% vs 27.9%, χ 2=17.056, P<0.001)], bacterial infection (3.2% vs 9.2%, χ 2=4.845, P=0.028), duration of azithromycin or doxycycline use [4(2, 5) days vs 5(3, 6) days, Z=-2.374, P=0.018], White Blood Cell Count at admission [7.94 (6.25, 10.34)×10 9/L vs 7.21 (5.65, 9.01)×10 9/L, Z=-2.445, P=0.014], D Dimer [0.58 (0.44, 0.83) μg/ml vs 0.80 (0.52, 1.12) μg/ml, Z=-3.154, P=0.002], but there was no significant difference between the two groups in the above indexes after PSM ( P>0.05). The duration of hospitalization, cough relief, disappearance of rales and fever in the BAL group was shortened in the BAL group compared with that in the non-BAL group [5 (4, 7) days vs 7 (5, 8) days, Z=-2.373, P=0.018], and the difference was statistically significant ( P<0.05). Linear regression analysis of PSM cohort study showed that BAL was negatively correlated with fever time (β=-4.369, 95% CI:-8.600--0.138, P<0.05). In conclusion, BAL can shorten the fever time of MRMPP, and early BAL in addition to conventional treatment has a positive effect on the prognosis of children.