Objective To investigate the efficacy of subcutaneous flap and/or pedicled penile skin flap combined with advancement flap coverage technique in the treatment of urethrocutaneous fistula(UCF)secondary to failed repair and to improve the success rate. Methods The clinical data of 36 UCF patients after urethral repair admitted to our hospital during Jan. 2020 and Jan. 2024 were retrospectively analyzed. According to the location and surrounding condition of the fistula, the fistula was closed without tension, the subcutaneous flap and/or pedicled penile skin flap was combined with advancement flap coverage technique. The effects of the treatment were followed up. Successful repair was defined as unobstructed urination, no recurrence of fistula and no urethral stricture. Results The patients' age was(25.7±11.6)years, and the diameter of fistula was(8.1±2.2)mm. UCF occurred in 24 cases after hypospadias repair, and in 12 cases after the repair of other urethral injuries, including 2 cases of urethral compression injury after improper indwelling catheterization, 2 cases of urethral stone removal, 2 cases of urethral diverticulum repair, 2 cases of circumcision repair, 1 case of congenital anal atresia repair, and 3 cases of other urethral repair. The primary repair success rate was 83.3%(30/36). Among the 6 patients with unsuccessful primary repair, 3 were cured with a secondary repair, 1 was cured after wound dressing, and 2 were lost to follow-up. The primary repair success rates of penile shape, penile scrotal junction, and perineal urethral skin fistulas were 82.1%(23/28), 83.3%(5/6), and 100%(2/2), respectively. The primary repair success rates for fistulas with diameter ≤1.0 cm and＞1.0 cm were 85.2%(23/27)and 77.8%(7/9), respectively; for single and two urethrocutaneous fistulas, the success rates were 84.8%(28/33)and 66.7%(2/3); for patients with 1 and ≥2 previous repair attempts, the success rates were 87.5%(14/16)and 80.0%(16/20). During the follow-up of(15.1±3.5)months, no recurrence of fistula occurred, and all patients experienced unobstructed urination with a maximum urinary flow rate of(19.5±4.2)mL/s. Conclusion The failure rate of UCF repair is still high. Based on the location of the fistulas and the condition of the surrounding tissue, the surgical success rate can be improved by utilizing subcutaneous flap and/or pedicled penile skin flap combined with advancement flap coverage technique. This approach allows for tension-free suturing and multi-layer closure of the fistula.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

PURPOSE: Lateral patellar compression syndrome (LPCS) is characterized by a persistent abnormally high stress exerted on the lateral articular surface of the patella due to lateral patellar tilt without dislocation and lateral retinaculum contracture, leading to anterior knee pain. The purpose of this study is to evaluate the efficacy and prognosis of lateral retinaculum release (LRR) combined with chondroplasty in the treatment of LPCS. METHODS: This retrospective study evaluated 40 patients who underwent LRR combined with chondroplasty for LPCS between 2020 and 2021. The assessment included improvement in postoperative tenderness and knee joint function. Patients were evaluated using the Lysholm, Tegner, and International Knee Documentation Committee 2000 scoring systems, as well as the visual analog scale, both preoperatively and postoperatively, with the paired comparisons analyzed using a t-test. Additionally, intraoperative observations were made regarding knee joint lesions, including cartilage damage and osteophyte formation, with analysis by the Chi-square test. RESULTS: The visual analog scale score for tenderness showed a significant decrease after surgery (p < 0.001). Evaluation of knee joint function also indicated significant improvements, as demonstrated by increased Lysholm, Tegner, and International Knee Documentation Committee 2000 scores postoperatively (p < 0.001, p = 0.011, p < 0.001, respectively). Furthermore, all LPCS patients included in the study presented with cartilage injuries and osteophyte formation. Significant differences were noted in the incidence of cartilage damage and osteophyte formation at different locations within the knee among patients with LPCS. CONCLUSION LRR combined with chondroplasty is an effective surgical approach for treating patients with LPCS, with satisfactory recovery observed at the 1-year follow-up. Additionally, the incidence of cartilage damage and osteophyte formation in LPCS patients varies significantly depending on the specific location within the knee joint.
Humans ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Patella/surgery* ; Knee Joint/physiopathology* ; Recovery of Function ; Young Adult ; Treatment Outcome ; Cartilage, Articular/surgery* ; Adolescent

Objective To evaluate the baseline characteristics and short-term safety of lecanemab in treatment of Alzheimer's disease(AD)in Chinese patients in a real-world study.Methods A mul-ticenter,retrospective,observational study was conducted on 646 AD patients who were continu-ously recruited and receved of lecanemab therapy in 84 medical centers from June 26,2024 to March 1,2025.Their clinical data,including baseline Mini-mental state examination(MMSE)score and clinical dementia rating(CDR)score before and after treatment,were collected,and the CDR-global score(CDR-GS)and CDR-sum of box score were calculated.The incidences of infu-sion-related reactions(IRR)and amyloid-related imaging abnormalities(ARIA),including ARIA with edema and effusion(ARIA-E)and ARIA with hemosiderin deposit(ARIA-H)within 3 months of treatment were observed and recorded.Apolipoprotein E(ApoE)genetic test was per-formed on 454 patients.Baseline characteristics and short-term safety of the patients were ana-lyzed.Results There were 301 patients(46.59％)having a baseline CDR-GS score of 0.5 and 345(53.41％)patients had a CDR score of 1.In the 454 patients receiving genetic test,the ApoEε4 carriers accounted for 31.27％(202 cases),including 17 cases of ApoEε4 homozygous carriers(8.42％).The incidence of IRR was 4.95％(32/646),which mainly occurred during the first infu-sion(90.63％,29/32),and there were 96.88％(31/32)of mild and 3.13％(1/32)of moderate IRR,with main manifestations of fever,dizziness,vomiting,etc.Sixteen patients(2.48％)experienced ARIA,including 5(31.25％)ARIA-E,10(62.50％)ARIA-H,and 1(6.25％)ARIA-E and ARIA-H.For the 5 patients with ARIA-E,2 were symptomatic,and in terms of radiographic severity,3 cases were mild and 2 cases were moderate ARIA-E.In the 10 patients with ARIA-H,all of them had no clinical symptoms,and in terms of radiographic severity,6 had mild and 4 had moderate ARIA-H.Among the 17 ApoEε4 homozygous patients,only one patient(5.88％)experi-enced ARIA-H with a moderate radiographic severity.Multivariate analysis showed that age in-creased the trend of ARIA risk,but no statistical difference was observed(P=0.056).Conclusion In this real-world study in China,AD patients receiving lecanemab treatment have the characteris-tics of being younger in age but higher disease severity.Short-term follow-up data suggest that lecanemab has good safety.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

Objective:To investigate alterations in brain function among elderly patients with interstitial cystitis/bladder pain syndrome(IC/BPS)during the resting state.Methods:We prospectively recruited seven elderly patients with IC/BPS admitted to the Urology Department of Beijing Hospital from December 2023 to May 2024 as the experimental group, and concurrently selected twelve elderly healthy individuals as the control group.After enrollment, all participants underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans.General clinical data, including age and gender, as well as standardized assessment scores from the Interstitial Cystitis Symptom Index(ICSI), Interstitial Cystitis Problem Index(ICPI), Visual Analogue Scale(VAS), Self-Rating Anxiety Scale(SAS), and Self-Rating Depression Scale(SDS), were collected.The data were processed using Matlab.This study employed a paired sample t-test to analyze the differences in gray matter volume between the two groups.The functional activities of the subjects' brains were analyzed using regional homogeneity(ReHo)and low-frequency amplitude(ALFF)algorithms.Based on the identified abnormal brain regions, further functional connectivity(FC)analysis was conducted to explore the connectivity patterns among the functional brain regions.Results:No significant differences were observed in age( t=-0.68, P=0.536)or gender( χ2=0.019, P=0.891)between the experimental group and the control group.The scores of SAS and SDS in the experimental group were significantly higher than those in the control group( P<0.001).No significant difference was observed in cerebral gray matter volume between the two subject groups.In contrast to the control group, the ALFF value of the left superior parietal lobe(MNI: x, y, z=-21, -66, 60; t=12.530 5)was elevated in elderly patients with IC/BPS, and the ReHo value of the left precuneus(MNI: x, y, z=-9, -54, 63; t=9.410 3)was also increased.Through FC analysis, it was revealed that elderly IC/BPS patients exhibited significantly lower FC values between the left superior parietal lobule and the central sulcus(MNI: x, y, z=21, 15, 3; t=-27.835 6), as well as between the left anterior cingulate and the left posterior cingulate gyrus(MNI: x, y, z=-12, 0, 42; t=-8.738 9)in comparison with the control group. Conclusions:In contrast to normal individuals, elderly IC/BPS patients demonstrate functional aberrations in the left superior parietal lobule and the left precuneus.Moreover, a decrease in functional connectivity is observed between the left superior parietal lobule and the central sulcus, as well as between the left precuneus and the left posterior cingulate gyrus.These abnormal functional alterations in the brain may be implicated in the maintenance and development of symptoms in IC/BPS patients.This study conducted research from the perspective of central nervous system regulation, presenting possible directions for further exploration of the pathophysiological mechanisms of IC/BPS.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

The health of women and children serves as the cornerstone of comprehensive public health and represents a crucial barometer for measuring social progress and civilization. It directly impacts family well-being and social harmony. As a national-level guidance center for complex disease diagnosis and treatment, Beijing's critical maternal care center, and the designated consultation hospital for pregnancy complicated by rheumatic immune and endocrine disorders, Peking Union Medical College Hospital bears significant responsibilities in managing complex medical cases and implementing counterpart assistance programs. Confronted with diverse and complicated maternal sources, particularly emergency cases lacking standardized prenatal care, the hospital has established a multi-tiered, whole-process, and comprehensive maternal-infant safety management system. Through implementing high-risk maternal management protocols, optimizing critical care procedures, promoting informatization development, and enhancing multidisciplinary collaboration, Peking Union Medical College Hospital has substantially improved the efficiency of critical maternal care and maternal-infant safety assurance. This paper systematically summarizes the institutional development experience in maternal management and explores potential optimization approaches, aiming to provide valuable references for enhancing maternal-infant safety management systems in domestic healthcare institutions.

Objective To construct a differential diagnosis model for systemic lupus erythematosus(SLE)from other autoimmune diseases based on the conventional test indicators in clinical laboratory,so as to improve the diagnostic efficacy of the existing test indicators.Methods The data of 178 SLE patients(SLE group)and 196 patients with other autoimmune diseases(control group)diagnosed in Sichuan Provincial People's Hospital from Apr.2022 to Mar.2023 were retrospectively analyzed.The differences in the levels of 19 clinical routine indicators between the 2 groups were analyzed.The least absolute shrinkage and selection operator(LASSO)regression was used to screen for test indicators with non-zero coefficients.These indicators were then used in logistic regression to construct a Nomogram model for SLE differential diagnosis.Model performance was assessed using receiver operating characteristic(ROC)curves and decision curve analysis.Results The levels of anti-cardiolipin antibody immunoglobulin(Ig)G,anti-cardiolipin antibody IgA,high-sensitivity C reactive protein(hs-CRP),D-dimer,and thrombin time(TT)in the SLE group were significantly higher than those in the control group(all P＜0.05),while the levels of IgM,complement 3(C3),complement 4(C4),prothrombin time(PT),and activated partial thromboplastin time(APTT)in the SLE group were significantly lower than those in the control group(all P＜0.05).Through LASSO regression,IgM,C3 and C4 were selected as the most likely indicators with non-zero coefficients.Multivariate logistic regression analysis showed that the differential diagnosis model was Logit P=4.18-1.34 × IgM-1.70 × C3-6.61 × C4.The area under the curve of this model was 0.80(95％confidence interval 0.76-0.85),with a sensitivity of 0.77 and a specificity of 0.74.Decision curve analysis demonstrated favourable clinical utility within a threshold probability range of 0.2-0.9.Conclusion The present model,constructed using the clinical routine indicators,such as IgM,C3 and C4,is helpful for the differential diagnosis of SLE from other autoimmune diseases and has good clinical application value.

To analyze inpatient mortality cases in a tertiary general hospital in Beijing based on diagnosis-related groups (DRG), with the aim of providing references for healthcare quality management.