OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

Objective: To analyze the association of participation in non-sports extracurricular tutoring classes with the prevalence of screening myopia, axial length (AL) and axial length to corneal radius ratio (AL/CR) among primary school students, so as to provide evidences for formulating myopia prevention and control policies. Methods: In December 2024, combination of convenience and cluster sampling method was used to select 2 273 students from two primary schools in Hefei City, Anhui Province. Ophthalmic examinations and questionnaire surveys were conducted to obtain information on myopia, AL, AL/CR and participation in various types of extracurricular tutoring. A binary Logistic regression model was used to analyze the association between non-sports tutoring and screening myopia, and multiple linear regression models were used to examine the associations between non-sports tutoring and AL and AL/CR. Results: Among the surveyed students, the participation rate in non-sports extracurricular tutoring classes was 64.9% , and the overall prevalence of screening myopia was 39.1%. The average AL and AL/CR were (23.60± 1.01 ) mm and (3.00±0.12), respectively. Univariate analysis showed that students who attended non-sports, music, or academic tutoring classes for ≥2 h per week had higher risks of screening myopia and greater AL/CR values than non-participants (screening myopia: OR =1.38, 1.82, 1.55; AL/CR: β =0.01, 0.03, 0.03; all P <0.05). After adjusting for sex, grade, and participation in sports tutoring, multivariate analysis indicated that participation in non-sports and musical instrument tutoring classes for ≥2 h per week remained significantly associated with higher risks of screening myopia ( OR =1.26, 1.49, both P <0.05). Multiple linear regression showed that participation in musical instrument tutoring for ≥2 h per week was positively correlated with AL ( β=0.14, P < 0.05). Conclusions Participation in non-sports extracurricular tutoring is common among primary school students. Attending non-sports tutoring classes for ≥2 h per week increases the risk of screening myopia.

Proteolysis-targeting chimeras (PROTACs) have shown considerable therapeutic potential across diverse fields such as cancer, inflammation, and neurodegenerative diseases, with numerous candidates already progressing into clinical trials. More recently, their application in antiviral therapy has been rapidly gaining momentum. This review systematically outlines the mechanistic foundations and design principles of PROTACs, highlights recent advances targeting coronaviruses (including SARS-CoV-2), hepatitis C virus, human immunodeficiency virus, and influenza viruses, and critically assesses key challenges—particularly the limited diversity of E3 ligase ligands, suboptimal oral bioavailability, and the lack of integrated platforms for druggability evaluation. Looking ahead, innovations in ligand discovery, pathway modulation, delivery technologies, and conditionally activated PROTAC designs are anticipated to overcome these barriers, ushering in a new era of precise and effective antiviral therapeutics.

Objective : To explore the risk factors of prognosis in patients with severe community-acquired pneumonia(SCAP) in different age groups. Methods : A multi-center and prospective study was conducted at 11 teaching hospitals in China from December 2017 to October 2021. Patients who met the criteria were assigned to the elderly group(≥65 years) and the non-elderly group(18-64 years) to demonstrate the clinical characteristics of SCAP. Patients were divided into survival group and death group according to whether they died in hospital, to determine the risk factors associated with mortality by multivariate logistic regression analysis. Results: A total of 170 patients with SCAP were included in the study. The age of SCAP was 20-93(65.75±15.23) years old, and the proportion of SCAP in the elderly was 58.82%(100/170). In-hospital mortality of non-elderly SCAP was 24.3%(17/70), and the in-hospital mortality of elderly SCAP was 28%(28/100). Compared with non-elderly group, patients in elderly group had higher severity score and more complications on admission, but the symptoms of fever and respiratory rate at admission were less obvious. In multivariable logistic regression analysis, the factors significantly associated with in-hospital mortality of non-elderly SCAP were pneumonia severity index(PSI) score(P=0.016,OR=1.022, 95%CI1.004-1.041) and invasive mechanical ventilation(P=0.037,OR=4.543, 95%CI1.092-18.898) on admission, and the risk factors associated with in-hospital mortality in elderly SCAP were sequential organ failure assessment(SOFA) score(P=0.006,OR=1.240, 95%CI1.063-1.446) and combined with coronary artery disease on admission(P=0.037,OR=2.834, 95%CI1.066-7.534). Conclusion In-hospital mortality for SCAP is high. PSI score and invasive mechanical ventilation are risk factors for in-hospital mortality of non-elderly patients with SCAP, and SOFA score and combined with coronary artery disease on admission are risk factors for in-hospital mortality of elderly patients with SCAP.

Transcatheter aortic valve replacement (TAVR) has emerged as the first-line treatment for aortic valve stenosis. Coronary obstruction is a severe complication of TAVR, with mortality rates exceeding 30%. Coronary obstruction can be classified as acute or delayed based on the timing of the onset, and as direct or indirect obstruction according to the underlying mechanism. Risk factors for predicting coronary obstruction include a small sinus of Valsalva diameter, excessively long native leaflets, low coronary height, and small sinotubular junction height and diameter. Accurate preoperative assessment of these anatomical parameters using CT is crucial for selecting the appropriate valve type, size, and implantation depth. Preventive technical strategies for coronary obstruction include intraoperative interventional treatments (such as the "Chimney" stenting technique), leaflet modification (such as the BASILICA technique), and alignment of the annulus and coronaries. These techniques have demonstrated significant efficacy in reducing the incidence of coronary obstruction and associated mortality. This paper reviews the epidemiology, classification, and mechanisms of coronary obstruction, with a particular focus on the identification, prevention, and treatment of high-risk patients. The aim is to highlight the importance of recognizing and managing coronary risks during TAVR and to provide actionable recommendations for the prevention and treatment of coronary obstruction in clinical practice.
Humans ; Transcatheter Aortic Valve Replacement/methods* ; Risk Factors ; Aortic Valve Stenosis/surgery* ; Postoperative Complications/prevention & control* ; Coronary Occlusion/etiology*

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

OBJECTIVE: Paridis Rhizoma (Chonglou in Chinese), a traditional Chinese herbal medicine, has been shown have strong anti-tumor effects. Paris saponin VII (PSVII), an active constituent isolated from Paridis Rhizoma, was demonstrated to significantly suppress the proliferation of BxPC-3 cells in our previous study. Here, we aimed to elucidate the anti-pancreatic ductal adenocarcinoma (PDAC) effect of PSVII and the underlying mechanism. METHODS: Cell viability was determined by CCK-8, colony formation, and cell migration assays. Cell apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry with annexin V/propidine iodide (Annexin V/PI) and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. Pyroptosis was evaluated by morphological features, Hoechst 33342/PI staining assay, and release of lactate dehydrogenase (LDH). JC-1 fluorescent dye was employed to measure mitochondrial membrane potential. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the levels of proteins or mRNAs. The effect in vivo was assessed by a xenograft tumor model. RESULTS: PSVII inhibited the viability of PDAC cells (BxPC-3, PANC-1, and Capan-2 cells) and induced gasdermin E (GSDME) cleavage, as well as the simultaneous cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP). Knockdown of GSDME shifted PSVII-induced pyroptosis to apoptosis. Additionally, the effect of PSVII was significantly attenuated by Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-FMK), on the induction of GSDME-dependent pyroptosis. PSVII also elevated intracellular ROS accumulation and stimulated Bax and Caspase-3/GSDME to conduct pyroptosis in PDAC cells. The ROS scavenger N-acetyl cysteine (NAC) suppressed the release of LDH and inhibited Caspase-9, Caspase-3, and GSDME cleavage in PDAC cells, ultimately reversing PSVII-induced pyroptosis. Furthermore, in a xenograft tumor model, PSVII markedly suppressed the growth of PDAC tumors and induced pyroptosis. CONCLUSION These results demonstrated that PSVII exerts therapeutic effects through Caspase-3/GSDME-dependent pyroptosis and may constitute a novel strategy for preventing chemotherapeutic resistance in patients with PDAC in the future.

Objective: To explore the efficacy of focal radiofrequency ablation (RFA) in the treatment of low-to-intermediate risk localized prostate cancer and its impact on postoperative urinary control and sexual function recovery，in order to explore the feasibility of minimally invasive methods for the treatment of localized prostate cancer. Methods: Clinical data of 28 patients with low-to-intermediate risk localized prostate cancer who underwent RFA in Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School during Jun.2017 and Feb.2021 were retrospectively analyzed.The 5-year failure-free survival (FFS) rate，surgery related complications，postoperative urinary control and sexual function were collected.The differences between the survival curves of patients in the low-risk and intermediate-risk subgroups were assessed with log-rank test and Breslow test. Results: All surgeries were successfully completed under local anesthesia.During the median follow-up of 43 (40-49) months，the 5-year FFS rate predicted by Kaplan-Meier method was 78.57%; 25 patients (89.29%) did not experience surgery-related complications; 27 patients (96.43%) were able to control urination; 1 patient developed new-onset sexual dysfunction.There was no significant difference in the survival curves between patients in the low-risk and intermediate-risk groups (P>0.05). Conclusion: RFA for patients with low-to-intermediate risk localized prostate cancer has good clinical efficacy，little impact on urinary control and sexual function recovery，and few postoperative complications，which can be used as one of the treatment options for these patients.

Objective To investigate the effectiveness of continuous improvement projects based on FOCUS-PDCA on the pathogen sample submission rate before antimicrobial therapy for inpatients.Methods FOCUS-PDCA was used to improve the pathogen sample submission rate in Affiliated Hospital of Nantong University from Jun.to Jul.2023.The inpatients from Jan.to May 2023(before improvement)were enrolled as control group,and the inpatients from Aug.to Dec.2023(after improvement)were enrolled as improvement group.The utilization rate of antibiotics,the submission rate of pathogen samples,the submission rate of clinical microbial samples and the detection rate of multidrug-resistant organisms were compared between the 2 groups.Results The utilization rate of therapeutic antimicrobial agents(32.18％vs 32.93％,P=0.003)and antimicrobial consumption intensity(39.99 defined daily dose[DDD]/100 patient-days vs 44.19 DDD/100 patient-days)in the improvement group were significantly lower than those in the control group.The pathogen sample submission rates before antimicrobial therapy and key antimicrobial combination therapy in the improvement group were significantly higher than those in the control group(52.01％vs 23.64％,87.74％vs 77.71％;both P＜0.001).The qualified rate of microbial specimens in the improvement group was significantly higher than that in the control group(88.77％vs 80.11％,P＜0.001).The detection rates of multidrug-resistant organisms and carbapenem-resistant Klebella pneumoniae in the improvement group were significantly lower than those in the control group(40.45％vs 48.42％,29.65％vs 43.17％;both P＜0.001).Conclusion The continuous improvement projects based on FOCUS-PDCA can improve the pathogen sample submission rate,reduce the detection rate of multidrug-resistant organisms,and promote standardized hospital infection quality management.

Objective:To investigate the pathogenetic characteristics of clinical isolates of Streptococcus suis in Henan Province from 2020 to 2023. Methods:Eight clinical isolates of S. suis in Henan Province from 2020 to 2023 were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and real-time fluorescence polymerase chain reaction (PCR). Serotype and virulence genes were detected by the serum agglutination test and PCR, and antibiotic susceptibility was evaluated using the microbroth dilution method. Multilocus sequence typing (MLST), minimum core genome (MCG), identification of antibiotic resistance genes, and core genome single nucleotide polymorphism (cgSNP) analysis were conducted using whole genome sequencing. Results:The results showed that eight S. suis strains isolated from humans were mainly serotype 2 (75.0%), while the rest were serotype 14 (25.0%). ST353 (62.5%) was the predominant genotype, followed by ST1 (25.0%) and ST7 (12.5%). All isolates belonged to the MCG1 group. The virulence genotypes of these isolates were primarily mrp(NA2)/ sly+/ ef+/ gapdh+(75.0%), while the remaining were mrp(EU)/ sly+/ ef+/ gapdh+(25.0%). These isolates carried tetracycline, macrolide, lincosamide and aminoglycoside resistance genes, and their resistance rates to tetracycline, erythromycin and clindamycin were 100.0%, 87.5% and 87.5%, respectively, and 62.5% strains were intermediate-resistant to penicillin. The cgSNP analysis indicated that these isolates were closer to the isolates from Guangdong, Zhejiang and Guangxi Provinces, with five ST353 strains and one ST7 strain belonging to Clade Ⅰ, and two ST1 strains belonging to Clade Ⅱ. Conclusion:The human isolates of S. suis in Henan Province are mainly ST353, harboring multiple virulence and antibiotic resistance genes.