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 systematically review the safety of budesonide inhalation aerosol in the treatment of chronic obstructive pulmonary disease.Methods PubMed,Cochrane Library,Web of Science,Embase,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect randomized controlled trials on budesonide inhalation aerosol in the treatment of chronic obstructive pulmonary disease from inception to June 30,2024.Two reviewers independently screened literature,extracted data,and assessed the risk of bias of included studies.The Meta-analysis was performed by using RevMan 5.3 software.Results A total of 52 studies with 16,768 patients were included.Meta-analysis results showed that the incidence of respiratory system adverse drug reaction(ADR)was higher in the budesonide group than in the control group,with a statistically significant difference[OR=1.18,95％CI(1.10,1.27),P＜0.001].There was no statistically significant difference in the incidence of overall ADR,central and peripheral nervous system ADR,gastrointestinal system ADR,skin ADR,urinary system ADR,infectious disease ADR,and musculoskeletal system ADR between the two groups of patients(P＞0.05).According to the subgroup analysis of the treatment course,in the 3-6 month subgroup,the incidence of ADR was higher in the budesonide group than in the control group,with a statistically significant difference[OR=1.43,95％CI(1.18,1.74),P＜0.001].In the studies with a treatment duration of more than 6 months,the incidence of ADR was higher in the budesonide group than in the control group,with a statistically significant difference[OR=1.54,95％CI(1.16,2.03),P=0.002].In the study of unknown treatment course,the incidence of ADR in the budesonide group was lower than that in the control group,and the difference was statistically significant[OR=0.39,95％CI(0.20,0.76),P=0.005].In the studies with a treatment duration of less than 3 months,the incidence of ADR in the budesonidegroup was comparable to that in the control group(P＞0.05).Conclusion The incidence of respiratory ADR caused by budesonide is higher than that of the control group.Although the incidence of overall ADR is not statistically significant,the occurrence of systemic adverse reactions should continue to be closely monitored in the future treatment of chronic obstructive pulmonary disease.

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.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To investigate the application value of dual-energy computer tomo-graphy (CT) multi-parameter imaging in predicting the pathological grade of pancreatic ductal adeno-carcinoma (PDAC).Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 147 patients with PDAC who were admitted to The Fifth Affiliated Hospital of Wenzhou Medical University from January 2017 to August 2023 were collected. There were 102 males and 45 females, aged (59±10)years. All patients underwent preoperative dual-energy CT examination and postoperative histopathological examination. The 147 patients were divided into a training set of 103 cases and a test set of 44 cases by stratified random sampling at a ratio of 7∶3. The training set was used to construct the prediction model, and the test set was used to verify the effectiveness of prediction model. Observation indicators: (1) analysis of factors affecting the pathological grade of PDAC patients in the training set; (2) construction and evaluation of the fusion prediction model for pathological grade of PDAC. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. The performance of the model was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. The Delong test was used to analyze the effec-tiveness of model. The calibration curve and decision curve of Hosmer-Lemeshow test were used to evaluate the consistency and clinical application value of the nomogram, respectively. Results:(1) Analysis of factors affecting the pathological grade of PDAC patients in the training set. Results of multivariate analysis showed that tumor cystic necrosis, vascular invasion, standardized iodine concentration (NIC) in venous phase, effective atomic number (Zeff) in venous phase, and energy spectrum curve slope (λ HU) in venous phase were all independent factors affecting the pathological grade of PDAC patients in the training set ( odds ratio=4.326, 3.887, 4.155, 5.389, 3.164, 95% confidence interval as 1.167-16.033, 1.111-13.592, 1.707-10.113, 1.284-22.613, 1.247-8.028, P<0.05). (2) Construction and evaluation of the fusion prediction model for pathological grade of PDAC. Accor-ding to the results of multivariate analysis, tumor cystic necrosis, vascular invasion, NIC in venous phase, Zeff in venous phase and λ HU in venous phase were all included to construct the clinical-imaging fusion prediction nomogram model. The AUC, accuracy, sensitivity and specificity of the fusion prediction model in the training set were 0.938 (95% confidence interval as 0.896-0.981), 87.38%, 89.74% and 85.94%, respectively. The above indicators of the fusion prediction model in the test set were 0.893 (95% confidence interval as 0.802-0.985), 84.09%, 82.35% and 85.19%, respectively. Results of Delong test showed that there was no significant difference in AUC between the training set and the test set ( Z=0.343, P>0.05). Results of Hosmer-Lemeshow test showed that the fusion prediction model had a good fit in the training set and the test set ( χ2=3.042, 7.545, P>0.05). Results of calibration curve showed that the predictive ability of the fusion prediction model was good. Conclusions:Multiple parameters in venous phase of the dual-energy CT can be used as imaging markers for preoperative evaluation of the pathological grade of patients with PDAC. Establishing a clinical-imaging fusion prediction model can effectively predict the pathological grade of PDAC.

Objective:To observe effectiveness of combining diffusion tensor imaging (DTI) with motor evoked potentials (MEPs) in evaluating the upper limb motor functioning of stroke survivors.Methods:Thirty-seven stroke survivors with upper limb motor dysfunction were selected. At the 4th, 12th and 24th week after their onset, each was were assessed using Fugl-Meyer Upper Limb (FMA-UE) scoring, the National Institutes of Health stroke scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index (BI) and hemiplegic hand function classification. DTI was also applied and MEPs were measured. The patients were divided into an MEP positive group and an MEP negative group according to the existence of the MEP waveform. The DTI and MEP parameters were correlated with the FMA-UE scores, linear regressions were evaluated and a receiver operating characteristics curve was prepared to estimate the utility of DTI in predicting hand function. The sensitivity and specificity of MEPs in predicting hand function recovery were evaluated.Results:The asymmetry index (FAa) of the average anisotropy score of the posterior limb of the internal capsule and the FAa of the cerebral peduncle were both significantly correlated with the FMA-UE scores at the 12th and 24th weeks. The best cut-off points for predicting functional recovery of a patient′s hand were 0.155 for the FAa of the posterior limb of the internal capsule and 0.145 for the cerebral peduncle. Among the 37 patients, the MEPs of 8 (the MEP positive group) could be extracted, and their hand functions recovered completely. The sensitivity of the MEPs in predicting the complete recovery of hand function was 80% with 100% specificity. The linear regression analysis showed 77% prediction accuracy for the FAa and MEPs of the cerebral peduncle for upper limb motor function at the 24th week after onset. In the MEP negative group, two patients completely recovered their hand function, with one′s FAa less than 0.145, and the other′s more than 0.145. When the MEP was negative, the sensitivity of DTI in predicting the recovery of hand function was 50% with 81.5% specificity.Conclusions:DTI combined with MEPs can be used as an index to evaluate the prognosis of upper limb motor function in stroke patients.

Objective To systematically review the safety of budesonide inhalation aerosol in the treatment of chronic obstructive pulmonary disease.Methods PubMed,Cochrane Library,Web of Science,Embase,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect randomized controlled trials on budesonide inhalation aerosol in the treatment of chronic obstructive pulmonary disease from inception to June 30,2024.Two reviewers independently screened literature,extracted data,and assessed the risk of bias of included studies.The Meta-analysis was performed by using RevMan 5.3 software.Results A total of 52 studies with 16,768 patients were included.Meta-analysis results showed that the incidence of respiratory system adverse drug reaction(ADR)was higher in the budesonide group than in the control group,with a statistically significant difference[OR=1.18,95％CI(1.10,1.27),P＜0.001].There was no statistically significant difference in the incidence of overall ADR,central and peripheral nervous system ADR,gastrointestinal system ADR,skin ADR,urinary system ADR,infectious disease ADR,and musculoskeletal system ADR between the two groups of patients(P＞0.05).According to the subgroup analysis of the treatment course,in the 3-6 month subgroup,the incidence of ADR was higher in the budesonide group than in the control group,with a statistically significant difference[OR=1.43,95％CI(1.18,1.74),P＜0.001].In the studies with a treatment duration of more than 6 months,the incidence of ADR was higher in the budesonide group than in the control group,with a statistically significant difference[OR=1.54,95％CI(1.16,2.03),P=0.002].In the study of unknown treatment course,the incidence of ADR in the budesonide group was lower than that in the control group,and the difference was statistically significant[OR=0.39,95％CI(0.20,0.76),P=0.005].In the studies with a treatment duration of less than 3 months,the incidence of ADR in the budesonidegroup was comparable to that in the control group(P＞0.05).Conclusion The incidence of respiratory ADR caused by budesonide is higher than that of the control group.Although the incidence of overall ADR is not statistically significant,the occurrence of systemic adverse reactions should continue to be closely monitored in the future treatment of chronic obstructive pulmonary disease.

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.