[摘 要] 目的：探讨干扰素刺激基因家族成员黏病毒抵抗蛋白2（MX2）在调控肿瘤细胞对呼肠孤病毒（Reo）溶瘤敏感性中的作用及其机制。方法：选取4株具有不同耐药特征的人源肿瘤细胞，通过CCK-8法评估其对Reo的溶瘤敏感性；通过转录组测序筛选出差异表达基因MX2，qPCR法及WB法验证MX2在4株人源肿瘤细胞中的表达；使用siRNA敲低溶瘤低敏感的COC1/DDP细胞中的MX2基因。在细胞感染Reo病毒后，通过CCK-8法检测细胞存活率；qPCR法检测细胞中Reo病毒S1基因表达；免疫荧光法检测细胞内Reo病毒蛋白的积累；半数组织培养感染剂量（TCID50）法测定病毒滴度；流式细胞术分别检测细胞内Reo病毒dsRNA、活性氧（ROS）水平以及细胞凋亡率；透射电镜观察细胞内质网形态变化并采用WB法检测内质网应激相关蛋白（JNK、p-JNK、eIF2α、p-eIF2α、CHOP、PERK）的表达。结果：在4株肿瘤细胞中，SKOV3细胞对Reo溶瘤作用高度敏感，而COC1/DDP、HuH-7SRB及SNU-398细胞均为溶瘤低敏感性。转录组测序结果显示，MX2在溶瘤低敏感肿瘤细胞中的表达水平显著高于溶瘤高敏感细胞（P < 0.01）；在溶瘤低敏感性的COC1/DDP细胞中，敲低MX2显著促进Reo病毒复制、诱导细胞凋亡增加，并升高细胞内活性氧水平（均P < 0.001）。透射电镜观察显示，敲低MX2的COC1/DDP细胞感染Reo病毒后出现内质网肿胀、扩张及断裂等典型内质网应激超微结构改变。WB结果显示，内质网应激关键标志物eIF2α/p-eIF2α、PERK、CHOP及凋亡相关调节蛋白JNK/p-JNK的表达均显著上调（P < 0.05或P < 0.01）。结论：肿瘤细胞对Reo的溶瘤敏感性与其细胞内MX2表达水平密切相关。敲低MX2可显著增强Reo在细胞内的复制，进而促进ROS积累，触发内质网应激并促进凋亡。病毒复制增加与细胞凋亡激活的双重作用，最终协同增强Reo的溶瘤作用。

Objective To evaluate the short-term effects of comprehensive health management interventions for stroke high-risk population screening on the prevention and treatment of ischemic stroke, and to provide reference and basis for improving and exploring health management and prevention strategies for stroke high-risk population. Methods From 2018 to 2022, 13 community health service centers in Jiading District, Shanghai were selected in the present study. Based on information push platform, stroke risk assessment and health intervention follow-up were conducted for community residents through convenience sampling. The residents were divided into a full course intervention group (intervention group) and a routine intervention group (control group) according to different health intervention measures and forms. The incidence of ischemic stroke in the two groups of survey subjects was tracked within 36 months. Results A total of 52144 subjects were included in the study. The total number of patients in the full course intervention group was 14227, with an incidence density of 577.32/100 000 (556.49/100 000-598.12/100 000), which was lower than that of the conventional intervention group (37 917), with an incidence density of 1 485.47/100 000 (1 464.99/100 000-1 505.94/100 000) (χ²=2490.212, P<0.001). The relative risk of the full course intervention group was 0.39, and the relative risk of stroke risk factors in the full course intervention group from low to high was 0.33, 0.43, 0.45, and 0.49, respectively. The incidence density of males in the full course intervention group was 660.76 (627.46/100 000 - 694.05/100 000), with a relative risk of 0.43, and the incidence density of female patients was 509.71/100 000 (483.37/100 000 - 536.05/100 000), with a relative risk of 0.35. The overall incidence density of the population under 62 years old gourp, 62-75 years old group and over 75 years old group was 197.45/100 000 (173.09/100 000 -221.80/100 000), 608.36/100 000 (580.19/100 000-636.54/100 000), and 1 025.06/100 000 (958.51/100 000-1 091.61/100 000), with relative risks of 0.51, 0.44, and 0.38, respectively. Conclusion Comprehensive health management measures can effectively reduce the short-term risk of ischemic stroke, and should be further promoted and improved to enhance the effectiveness of stroke prevention and control.

ObjectiveThis paper aims to investigate the distribution patterns of traditional Chinese medicine syndromes in patients with chronic hepatitis B （CHB） comorbid with metabolically associated fatty liver disease （MAFLD） and analyze their correlation with clinical characteristics and the progression of liver fibrosis. MethodsA cross-sectional study method was employed， and 506 patients with CHB comorbid with MAFLD who attended the Hepatology Outpatient Department of Public Health Clinical Center of Chengdu from June 2024 to December 2024 were enrolled. General information， traditional Chinese medicine syndromes information， laboratory indicators， and imaging examination results were collected using case report forms （CRF）. Tongue images of patients were acquired using a tongue diagnosis instrument， and tongue feature parameters were extracted using computer image processing technology. Frequency analysis， factor analysis， and cluster analysis， and other methods were used to explore syndrome categories and distribution patterns. Non-parametric tests were used to compare the differences in clinical characteristics among different syndromes. Univariate and multivariate logistic regression analyses were performed to investigate the correlation between traditional Chinese medicine syndromes and the progression of liver fibrosis. ResultsThe main traditional Chinese medicine syndromes in patients with CHB comorbid with MAFLD were mainly dominated by damp-heat accumulation syndrome， liver stagnation and spleen deficiency syndrome， and phlegm-blood stasis syndrome， with damp-heat accumulation syndrome accounting for the highest proportion （41.89%）. Compared with those without damp-heat accumulation syndrome， patients with damp-heat accumulation syndrome had significantly lower tongue proper H value， tongue coating H value， and tongue coating a^* value （P<0.05）， significantly higher tongue coating b^* value （P<0.05）， significantly increased levels of white blood cell （WBC）， red blood cell （RBC）， hemoglobin （HGB）， and glucose （GLU）， increased CAP values （P<0.05）， a higher proportion of males （P<0.05）， and a younger age （P<0.05）. Univariate and multivariate logistic regression analyses show that age， hepatitis B surface antigen （HBsAg）， diabetes， and damp-heat accumulation syndrome are independent risk factors for liver fibrosis （P<0.05）， and that damp-heat accumulation syndrome is predominantly distributed in liver fibrosis stage F0-F1. ConclusionDamp-heat accumulation syndrome is a typical syndrome in patients with CHB comorbid with MAFLD， which is significantly associated with enhanced inflammatory response， metabolic disorders， and early liver fibrosis， and is a key link in disease progression. Clinical attention and early intervention are needed.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Urinary incontinence is the most common complication after radical prostatectomy.Traditional Chinese medicine treatments for this disease,such as acupuncture,are diverse and have definite therapeutic effects.The disease is located in the bladder,and its etiology and pathogenesis are mostly related to the dysfunction of the kidney,spleen,triple energizer and other viscera.In view of the insufficiency of kidney essence,decline of the gate of vitality fire(mingmen fire),Qi deficiency leading to impaired bladder containment,compounded by obstruction of meridians from pathogenic factors including blood stasis,damp-heat,and phlegm turbidity.The"Shuanggu Yitong"acupuncture achieves"Dual fortification"through tonifying the kidney and primordial qi consolidation,combined with spleen strengthening and qi supplementation.Additionally,"purging"targets the elimination of blood stasis,phlegm turbidity,damp-heat and other solid evils.This integrated approach combines acupuncture and moxibustion modalities with reinforcing-reducing needle manipulation techniques,simultaneously addressing both the symptoms and root causes of the problem.By coordinating pathogen elimination with constitutional regulation,this method demonstrates favorable therapeutic outcomes in clinical practice and is worthy of further clinical promotion.

The blood products industry,both domestically and internationally,exhibits distinct features in product research,development,and technological innovation.International companies possess extensive expertise in developing immunoglobulins,coagulation factors,and recombinant plasma protein products,demonstrating continuous advancements-particularly in specific immunoglobulin development,long-acting formulation optimization,and manufacturing process improvements.In recent years,Chinese enterprises have also achieved notable progress in related fields,especially in immunoglobulin process refinement and the development of novel recombinant coagulation factor products.However,there remains significant scope for improvement in areas such as the application of recombinant protein technologies,efficient utilization of plasma resources,and the adoption of advanced manufacturing techniques.Additional challenges include the accumulation of patented technologies,the supply of critical raw materials,and access to comprehensive epidemiological data.Driven by ongoing advances in gene recombination technologies,innovations in drug delivery systems,digital transformation,and the rise of personalized medicine,the blood products industry is poised for broader development prospects.To foster sustained and stable domestic industry growth and enhance global competitiveness,Chinese blood product enterprises should intensify their technological accumulation,upgrade manufacturing processes,and optimize plasma resource utilization.

Objective To addresses the challenges arising from the rapid expansion of pharmaceutical clinical trials and the growing demands for quality management,this paper investigates the application of low-code technology in project management.Its goals are to enhance the operational efficiency and execution capabilities of clinical trial institutions,ensure trial quality and safety,and accelerate the translation of pharmaceutical scientific achievements.Methods A brainstorming session was conducted to analyze the technical and functional requirements for managing pharmaceutical clinical trial projects.Utilizing the ＂template design＂ and ＂decision analysis＂ functionalities of low-code technology,the study adopted a modular and visually driven data management approach to develop a system compliant with Good Clinical Practice(GCP)standards.This system integrates key functionalities,including project progress management,funding management,drug inventory management,and quality control.Its effectiveness was evaluated through real-world operation and performance validation.Results The system had demonstrated stable operation with substantial improvements in practical application.Compared with conventional management approaches,it significantly enhanced project management efficiency:the time required for project schedule management was reduced by 80%,the efficiency of financial processing increased by 95%,drug inventory management efficiency improved by 75%,and the time spent on quality control was shortened by 60%.Conclusion The pharmaceutical clinical trial project management system developed using low-code technology offers substantial advantages and promising application potential.It represents a critical practice in applying digital and intelligent tools to advance pharmaceutical productivity in the medical and healthcare sectors.

Objective:To identify the risk factors of venous thromboembolism (VTE) in postoperative renal transplantation recipients by Meta-analysis, and to provide evidence-based reference for clinical staff to develop early VTE prevention strategies.Methods:PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP database, Wanfang database and Chinese Biomedical Literature Database were searched to collect the studies on the risk factors of postoperative VTE in kidney transplant recipients. The search period was from the establishment of the database to March 10, 2024. After literature screening, data extraction and quality evaluation were conducted independently by two researchers, Meta-analysis was performed using RevMan 5.3 software.Results:A total of 15 literatures with 20 influencing factors were included. Meta-analysis showed that age ( MD = 6.36, 95% CI 2.56-10.17, P<0.05), body mass index ( MD = 1.83, 95% CI 0.15-3.50, P<0.05), VTE history ( OR = 2.04, 95% CI 1.08-3.86, P<0.05), blood transfusion history ( OR = 3.77, 95% CI 2.43-5.83, P<0.05), glomerular filtration rate ( MD = -5.54, 95% CI -9.93 - -0.91, P<0.05), donor age ( MD = 3.18, 95% CI 1.10-5.25, P<0.05), combination of malignant tumor ( OR = 2.87, 95% CI 1.45-5.68, P<0.05), end-stage renal disease as polycystic kidney disease ( OR = 1.76, 95% CI 1.39-2.22, P<0.05), and interstitial nephritis ( OR = 1.60, 95% CI 1.06-2.40, P<0.05) were the influencing factors for postoperative VTE in renal transplant recipients. Conclusions:Clinical medical staff should actively identify high-risk groups for VTE after kidney transplantation by considering the 8 influencing factors determined by this study, and take targeted measures early to reduce the risk of postoperative VTE.

[Purpose]To analyze the incidence and mortality of liver cancer in Fusui County of Guangxi Zhuang Autonomous Region in 2019 and the trend of change from 201 1 to 2019.[Meth-ods]Based on the incidence and mortality data of liver cancer in Fusui County from 2011 to 2019,the crude incidence rate,crude mortality rate,age-standardized rate by Chinese standard population(ASIRC/ASMRC),age-standardized rate by world standard population(ASMRW/ASM-RW),disability-adjusted life years(DALY),years of life lost(YLL),years of lived with disability(YLD)were calculated.The Joinpoint linear regression model was used to calculate the average annual percentage change(AAPC)of the ASIRC/ASMRC and DALY rate of liver cancer in Fusui County from 2011 to 2019.[Results]In 2019,there were 345 new cases and 298 deaths of liver cancer in Fusui County,accounting for 28.49％and 35.86％of all new cases and death cases of malignant tumors in Fusui County,respectively.The crude incidence rate,ASIRC and ASIRW were 74.71/105,67.55/105 and 65.63/105,respectively;the crude mortality rate,ASMRC and ASMRW were 64.53/105,58.78/105 and 56.88/105,respectively.In 2019,ASIRC/ASMRC of men were higher than those of women(105.32/105 and 95.67/105 for men;27.26/105 and 19.11/105 for women).The peak incidence and mortality rates were in the 65～69 and 80～84 age groups,re-spectively.The incidence rate of liver cancer in Fusui County declined from 82.50/105 in 2011 to 67.55/105 in 2019,with an AAPC of-3.01％(P=0.024),but the mortality rate did not have sig-nificant changes(AAPC=-1.44％,P=0.224).The rate of DALY decreased from 14.51/105 to 10.36/105,with an AAPC of-2.82％(P=0.050).[Conclusion]The incidence rate and DALY rate of liv-er cancer in Fusui County showed an overall decreasing trend from 2011 to 2019,but still re-mained at a high level.It is necessary to further strengthen the prevention,screening and early treatment of liver cancer in this region,especially for men and the elderly.