[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.

OBJECTIVE To optimize the stir-frying process of Platycodon grandiflorum， compare the protective effect of P. grandiflorum on lung injury in mice before and after stir-frying， and preliminarily explore the characteristics of “enhanced efficacy through processing” of stir-frying P. grandiflorum. METHODS On the basis of single-factor experiment， the stir-frying time， temperature and frequency were taken as factors， and the comprehensive scores of appearance traits， platycodin D content and alcohol extract content were taken as indexes. Box-Behnken response surface experiment was designed to optimize the stir-frying process of P. grandiflorum and verify it. The mice were divided into blank control group， model group， dexamethasone group （positive control drug， 5 mg/kg）， P. grandiflorum low-dose and high-dose groups （0.6，1.2 g/kg）， fried P. grandiflorum low and high dose groups （0.6， 1.2 g/kg）， with 8 mice in each group. The treatment was given once a day for 10 consecutive days. After the last administration， acute lung injury model was established by intratracheal instillation of lipopolysaccharide. The levels of interleukin-6 （IL-6）， IL-1β， tumor necrosis factor-α （TNF-α） in serum and superoxide dismutase （SOD）， myeloperoxidase （MPO） and malondialdehyde （MDA） in lung tissue were detected， lung wet/dry weight ratio and thymus index were calculated， and the pathological changes of lung tissue were observed. RESULTS The optimum processing conditions were as follows：stir- frying temperature of 120 ℃， stir-frying time of 12 min， stir-frying frequency of 19 r/min； the comprehensive scores of the three batches of process verification were all greater than 97 points， RSD＜3% （n＝3）. The results of pharmacodynamic experiments showed that compared with blank control group， the lung dry-wet weight ratio as well as the levels of IL-6， IL-1β， TNF-α， MPO and MDA in the model group were significantly increased （P＜0.01）， the thymus index and SOD level were significantly decreased （P＜0.01）， and the lung tissue was significantly damaged. Compared with model group， above indexes of the mice in each administration group were significantly improved （P＜0.01）， and the lung tissue injury was significantly reduced. At the same dose， except for the lung dry-wet weight ratio， the above indexes of the mice in the stir-fried P. grandiflorum groups were significantly improved compared with P. grandiflorum 涵。E-mail：495758271@qq.com groups （P＜0.05）， and the lung tissue damage was further reduced. CONCLUSIONS The optimized stir-frying process is stable and feasible. The protective effect of stir-fried P.grandiflorum on acute lung injury in mice is better than that of raw products at the same dosage.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

Gap junction(GJ),also known as gap junction,is widely found between neurons and glial cells,and can connect neighboring cells and mediate the transmission of electrical sig-nals between neighboring cells.The GJ channel,which exists between neurons and mediates intercellular electrical signaling,is also known as an electrical synapse.Connexins(Cxs)are the molecular basis of GJ,and are expressed to different degrees in different neurons and glial cells.The presence of GJ mediates different functions among neurons and glial cells,which further influences the establishment of various mature neural circuits,re-flecting the importance of GJ in the maintenance of neural cir-cuits.This review summarizes the relationship between GJ and neural circuits in relation to the effects of GJ and different Cxs on neurons and glial cells,providing new research ideas for the treatment of neuropsychiatric disorders.

Objective To explore the effectiveness and safety of percutaneous coronary artery shock wave balloon angioplasty(IVL)under the guidance of intravascular ultrasound(IVUS)for the treatment of severe calcification lesions in the left main artery(LM).Methods A total of 26 patients with severe LM(mouth,body,bifurcation)calcification admitted to Jiangnan University Affiliated Hospital from October 2022 to April 2024 were included,with an average age of 72.0(61.8,75.4)years.Under the guidance of IVUS,IVL was used for pre-treatment of calcified lesions,followed by percutaneous coronary intervention(PCI)with stent/drug balloon implantation.All patients were evaluated using IVUS before and after the use of IVL and after PCI.And compare the IVUS intracavity related data before and after treatment[plaque burden(PB)、minimum lumen area(MLA)、minimum lumen diameter(MLD)]and calcification fracture number,minimum stent area(MSA),stent expansion coefficient(expansion,EXP),etc.Results There were 26 patients(2 with opening lesions,7 with body lesions,and 17 with bifurcation lesions at the end of the main trunk),including 7 with stable angina pectoris(SAP),10 with unstable angina(UA),4 with acute ST-segment elevation myocardial infarction(STEMI),and 5 with non ST-segment elevation myocardial infarction(NSTEMI).The PB at the most severe site of calcification decreased by 79.50(76.00,83.75)％compared to 80.00(76.00,83.75)％after IVL(P=0.001),MLA increased by 3.39(3.14,3.68)mm2 compared to 3.38(3.14,3.67)mm2 after IVL(P=0.039),MLD increased by 3.21(3.07,3.30)mm compared to 3.20(3.07,3.30)mm after IVL(P=0.024),and there was 100％calcification rupture(1/2 cases,2/9 cases,≥3/15 cases).The stent/drug ball was successfully implanted 100％,with EXP of(89.15±4.42)％and an MSA of 7.20(6.46,7.45)mm2.No adverse events such as death,angina or recurrent myocardial infarction occurred during the 3 months follow-up after surgery.Conclusions After evaluation by IVUS and pre-treatment with IVL,PCI was successfully completed for severe calcification lesions in LM,and IVL can be used as an option for the treatment of severe calcification in LM.

Objective To investigate the distribution and antibiotic resistance profiles of the bacterial strains isolated from urine samples in a tertiary Traditional Chinese Medicine hospital in Shanghai in the 12-year period from 2010 through 2021 for better empirical antibiotic use in clinical practice.Methods The clinical data of patients with urinary tract infection,including the species and antibiotic resistance of the bacterial strains isolated from urine samples from January 2010 to December 2021 were retrospectively analyzed.Results A total of 5 231 nondupliate bacterial strains were isolated,among which E.coli was the most common(52.8％),followed by Enterococcus spp(19.1％)and Klebsiella spp(11.1％).Most of the urinary isolates(76.0％)were isolated from the elderly aged 60-89,and only 3.1％of the strains were isolated from the young people aged under 44.Most of the bacterial strains were isolated from female patients(75.8％),however,more P.aeruginosa and A.baumannii were isolated from male patients compared to female patients(55.3％vs 44.7％and 67.7％vs 32.3％).About 13.7％of the strains were collected from the Department of Nephrology,more than the strains from any other clincial department.In intensive care unit(ICU),the proportion of E.coli was the lowest,while the proportion of Enterococcus spp was the highest.Enterobacterales showed lower resistance raets to carbapenems,cephamycin,amikacin,cefepime,and β-lactam/β-lactamase inhibitor combinations.P.aeruginosa showed higher susceptibility rates to carbapenems,aminoglycosides and β-lactam/β-lactamase inhibitor combinations compared to A.baumannii(≥54.6％vs≤39.8％).Gram-positive cocci were highly sensitive to glycopeptide antibiotics.No SS.aureus or E.faecalis isolates were found resistant to vancomycin.About 2.7％of the E.faecium isolates were resistant to vancomycin.The prevalence of drug-resistant bacteria was the highest in elderly patients,and in the strains isolated from ICU and emergency department.Conclusions Compared with general hospitals,a high proportion of elderly patients were treated in this hospital.It should be more cautious in the treatment of patients with urinary tract infection.The major bacterial species isolated from urine were E.coli,Enterococcus,and K.pneumoniae.Empirical treatment should be prescribed considering patient age and gender as well as the species and distribution of pathogenic bacteria.Urine culture and antibiotic susceptibility testing should be performed proactively.Appropriate antimicrobial agents should be selected according to the results of antimicrobial susceptibility testing.Antimicrobial ressitance surveillance should also be strengthened.

Objective:To explore effect of oleanolic acid on allergic rhinitis(AR)and its potential mechanism.Methods:Peripheral blood mononuclear cells(PBMCs)were isolated by density gradient centrifugation.Real-time quantitative PCR was used to detect expressions of Foxp3,IL-17A,Beclin1,and RORγt mRNA in nasal mucosa;flow cytometry was employed to assess proportion of Treg and Th17 cells in PBMCs;Western blot was utilized to determine expressions of RORγt,LC3-Ⅰ,LC3-Ⅱ,Beclin1,and P62 proteins in nasal mucosal.Mice were randomly divided into Control,ovalbumin(OVA),L-oleanolic acid,H-oleanolic acid,DSGC,3-MA and H-oleanolic acid+Rapa groups.Histological changes were observed by HE staining and Periodate Schiff(PAS)staining.Serological changes,expressions of IL-17A,IL-10,eosinophilic cationic protein(ECP)and anti-OVA-specific antibodies were detected by ELISA.Results:AR patients had Th17/Treg imbalance and activated autophagy.Oleanolic acid restored Th17/Treg balance and inhibited autophagy in vitro.In vivo experiments demonstrated that oleanolic acid inhibited OVA-induced allergic nasal symptoms and activation of autophagy pathway,which was same as regulation of 3-MA,while Rapa could weaken effects of high dose of oleanolic acid.Moreover,oleanolic acid reduced infiltration of different inflammatory cells of nasal lavage fluid,prevented damages to epithelial cells,and improved nasal mucosal thickness and mucus secretion.Oleanolic acid regulated balance of mouse Th17/Treg-associated cytokines expressions.Conclusion:Oleanolic acid can be used to treat AR,whose effect is realized through inhibiting autophagy to regulate Th17/Treg balance.

This study was aimed at studying the phenotypic and molecular characteristics of a Salmonella Grumpensis isolate from a patient with diarrhea in Shanghai,to provide evi-dence for the prevention of salmonellosis.Biochemical identifi-cation,serum agglutination testing,antimicrobial susceptibility testing,and whole genome sequencing(WGS)were performed on isolate 2023JD76.Global Salmonella Grumpensis genome sequences were searched and downloaded for serotyping predic-tion,multilocus sequence typing(MLST),prediction of anti-microbia resistance genes and virulence genes,and phylogenetic analysis of 2023JD76.The 2023JD76 strain was identified as Salmonella Grumpensis(13,23:d:1,7)with ST2060,and was susceptible to 20 antimicrobial agents.Strain 2023JD76 carried the aminoglycoside resistance gene aac(6')-Iaa and five types of virulence genes:the adhesion genes csg and rat;the secretion and transport genes sip and inv;the typhoid toxin genes cdt and plt;the invasive gene nutrient metabolism factor mgt;and the antimicrobial peptide resistance factor mig.Global S.Grumpensis strains harbored ten types of antimicrobial resistance genes whose prevalence ranged from 58.33％to 100％.The global genome sequences of S.Grumpensis were divided into two lineages.Lineage I was dominated by ST751(88.89％,16/18),and lineage Ⅱ was dominated by ST2060(89.47％,17/19).The genome sequence of strain 2023JD76 belonged to lineage Ⅱ,and was closely related to the genome sequences from human fecal and human cerebrospinal fluid.This study provides the first report of a S.Grumpensis isolate from the stool of a patient with diarrhea in China.Considerable variability in antimicrobial resistance genes was observed among genome sequences from different sources,and the strains harbored a substantial number of virulence genes.Enhanced surveillance should be emphasized to prevent a potential risk of global dissemination.

The implementation of amplicon sequencing and metagenomic sequencing methods in the whole-genome sequen-cing for MPXV testing was compared,to provide a technical reference for sequencing,tracing,and epidemic prevention and control of MPXV.For amplicon sequencing,targeted amplification of the viral whole genome was performed on MPXV DNA,and was followed by next-generation sequencing of the amplification products.For metagenomic sequencing,next-generation sequencing was performed directly on MPXV DNA.After the sequences were obtained,software such as CLC and IGV were used to analyze the effective data percentage,sequencing depth,and whole-genome sequencing coverage under different sequen-cing depths for both sequencing methods,to evaluate sequencing quality.Nextclade was used to analyze virus typing,muta-tions,and deletions.Subsequently,the similarity and completeness of sequences obtained through both sequencing methods were further compared.On the basis of mapping to the refer-ence sequence of strain MPXV-M5312_HM12_Rivers(Gen-Bank number NC_063383.1),the percentage effective data obtained from amplicon sequencing and metagenomic sequen-cing was 99.72％and 7.54％,respectively,with a sequencing depth range of 0× to 334 839 ×,and 44 × to 1 000 ×.On the basis of a sequencing depth of 10 ×,the site coverage of the above was 90.3％and 100％,respectively.IGV was used to validate the whole-genome coverage under different sequencing depths.The depth coverage of whole-genome sites for metagenomic sequencing was uniform,whereas that of the whole-genome sites for amplicon sequencing was uneven and significantly differed.Virus typing and sequence similarity analysis indicated that the viral sequences obtained with the two sequencing methods all belonged to the Ⅱb B.1 lineage of MPXV.Comparison with the reference sequence indicated that metagenomic sequencing identified 73 nucleotide mutation sites,whereas amplicon sequen-cing identified 68 mutation sites.Further analysis demonstrated that seven common mutation sites of Ⅱb B.1 were not detected in the amplicon sequencing,and two false positive private mutation sites were identified.Amplicon or metagenomic sequencing methods thus can be flexibly used in MPXV virus whole-genome sequencing.Amplicon sequencing yields more effective data,whereas metagenomic sequencing provides better uniformity of coverage and sequence accuracy.This study provides a prelimi-nary understanding of the efficacy of each method and may serve as a technical reference for improving the success rate of whole-genome sequencing of MPXV.