Objective To explore the mechanism by which cancer-associated fibroblasts(CAFs)regulate CD13-high expression neutrophil-like myeloid-derived suppressor cell(CD13hi-nMDSC)migration in pancreatic ductal adenocarcinoma(PDAC),so as to provide potential molecular targets and experimental evidences for immunotherapy in patients.Methods CAFs were isolated and purified from pancreatic cancer tissues of 5 PDAC patients.The phenotype and purity of CAFs were identified by immunofluorescence and flow cytometry.The expression of related factors in CAF was detected by quantitative polymerase chain reaction(qPCR)and enzyme-linked immunosorbent assay(ELISA).CAF conditioned medium and myeloid-derived suppressor cell(MDSC)migration system were constructed by Transwell to observe the migration of MDSCs and to study the specific mechanisms by which the aforementioned cytokines participate in regulating the migration of MDSCs.Results The isolated primary CAFs expressed activation biomarkers fibroblast activation protein(FAP)and α-smooth muscle actin(α-SMA),while the human foreskin fibroblasts(HFFs)of control cells did not express FAP and α-SMA.qPCR results showed that the mRNA expression levels of interleukin 6(IL-6),monocyte chemotactic protein 1(MCP-1),and stromal cell-derived factor 1(SDF-1)in CAFs were higher than those in HFFs(all P＜0.01).The contents of IL-6,MCP-1,and SDF-1 in the CAF culture supernatant were significantly higher than those in the HFF culture supernatant(all P＜0.01),and the secretion content increased with the prolongation of culture time.Compared with HFF conditioned medium and regular medium(RPMI 1640),CAF conditioned medium could recruit more total MDSCs and CD13hi-nMDSCs(all P＜0.01).The addition of SDF-1 recombinant protein alone in the culture system could induce the migration of total MDSCs and CD13hi-nMDSCs,and the addition of SDF-1 neutralizing antibodies or C-X-C motif chemokine receptor 4(CXCR4)blocking antibodies could significantly reduce the migration of CD13hi-nMDSCs induced by CAF conditioned medium(all P＜0.01).Although MCP-1 alone could also induce the migration of total MDSCs and CD13hi-nMDSCs,the number of CD13hi-nMDSCs migrating was significantly less than that of the SDF-1 experimental group.The IL-6 recombinant protein did not induce the migration of total MDSCs or CD13hi-nMDSCs.Conclusion CAFs can mediate the migration of total MDSCs and CD13hi-nMDSCs in PDAC through SDF-1/CXCR4 pathway.

Objective The efficacy of Zang Bi Formula(ZBF)in cardiac complications of rheumatoid arthritis(RA)was observed through animal experiments.Ultra-high performance liquid chromatography tandem time-of-flight mass spectrometry(UHPLC-TOF-MS)and network pharmacology was used to analyze the active ingredients,targets,and pathways of ZBF for the treatment of cardiac hypertrophy,and molecular docking was applied to verify the binding ability of the ingredients to pathway-related proteins.Methods TNF transgenic(TNF-Tg)mice were used as RA and RA-complexed cardiac hypertrophy models,and the left ventricular hypertrophy of mice was observed by echocardiography after 8 weeks of continuous gavage with ZBF,and WGA staining,HE staining,and Masson staining were used to observe and analyze the pathological changes of cardiac tissues.The chemical composition of ZBF was identified by UHPLC-TOF-MS technique.The public database was then used to screen the active ingredients and component targets and disease targets,construct interaction networks,and analyze the bioconcentration data as well as the docking ability of the active ingredients and proteins.Results In animal experiments,ZBF reduced cardiac weight index and cardiac weight tibia length ratio in TNF-Tg mice(P＜0.05,P＜0.01),attenuated cardiac hypertrophy(P＜0.001)and cardiomyocyte hypertrophy(P＜0.01),and alleviated inflammatory infiltration and fibrosis in the heart(P＜0.0001).A total of 24 compounds were identified from ZBF by UHPLC-TOF-MS.A total of 105 active ingredients of ZBF were screened by network pharmacological analysis,and 187 potential targets of ZBF for cardiac hypertrophy were constructed,and the enriched pathways with significance included PI3K-AKT signaling pathway,TNF signaling pathway,and MAPK signaling pathway.Conclusion ZBF attenuated myocardial hypertrophy and cardiomyocyte hypertrophy in TNF-Tg mice and alleviated inflammatory infiltration and fibrosis in the heart,and ZBF may be a potential drug for the treatment of RA and its cardiac complications in the clinic.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

【Objective】 To investigate the effects of radical prostatectomy (RP) or brachytherapy (BT) on the prognosis of patients with high-risk prostate cancer as initial treatment, in order to provide a reference for the selection of clinical treatment options. 【Methods】 The clinical data of 133 191 patients diagnosed with high-risk prostate cancer and treated with RP or BT during 2005 and 2014 were extracted from the SEER database.The 5-year and 10- year cancer-specific survival (CSS) and overall survival (OS) were compared with K-M analysis and univariate and multivariate Cox regression.The clinical data of another 253 patients diagnosed with high-risk prostate cancer in Subei People’s Hospital during 2015 and 2020 were collected, including 153 patients who received RP and 100 patients who received BT.The 5-year biochemical progress-free survival (bPFS) and CSS were compared with K-M analysis. 【Results】 Univariate analysis of SEER data showed that BT was associated with a higher risk of death (HR=1.319, 95%CI: 1.256-1.386, P<0.001); age, marital status and TNM stage were associated with higher risk of death (P<0.001).Multivariate analysis, adjusted for relevant variables, showed that BT did not result in a higher risk of death compared with RP (HR=0.964, 95%CI:0.924-0.996, P=0.808). The OS curve showed that the longer the observed survival time, the better OS of RP as compared to BT (P<0.001); however, the CSS survival curve showed that the longer the observed survival time, the better CSS of BT compared to RP (P<0.001).The single-center data analysis showed no significant difference between BT and RP in the 5-year bPFS (P=0.263) and CSS (P=0.946). 【Conclusion】 For patients with high-risk prostate cancer, there is a significant difference in the prognosis of the two treatments if there is no adjustment of age, marital status, TNM stage and other factors, and the efficacy of RP is better than that of BT, especially in patients with survival more than 10 years.However, there is no statistically significant difference in the prognosis after the possible confounding factors are adjusted.Therefore, the initial treatment choice for these patients should be weighed from multiple perspectives, and patients’ choices must be respected after they are fully informed.

Objective: To evaluate the health risk of drinking water in Ningbo City, Zhejiang Province from 2021 to 2022, so as to provide insights into ensuring the safety of drinking water. Methods: The monitoring data of drinking water from 2021 to 2022 in Ningbo City were collected from the Chinese Disease Prevention and Control Information System. The routine indicators and disinfectant indicators (radioactivity indicators were excluded) of drinking water were evaluated according to the reference limits issued by Standards for Drinking Water Quality (GB 5749-2006), and the qualification rates were calculated. The indicators with detection rate higher than 50% were selected, and assessed the carcinogenic and non-carcinogenic risks via drinking water using the risk assessment model recommended by the United States Environmental Protection Agency. Results: A total of 1 678 samples were monitored in Ningbo City from 2021 to 2022. Sodium hypochlorite was the main disinfectant among 1 558 samples from centralized water supply (1 079 samples, 64.30%), and none of the 120 samples from decentralized water supply underwent disinfection treatment. The qualification rate of 88.38%, and the pollutants with a detection rate higher than 50% were nitrate, fluoride, trichloromethane and aluminum. The median carcinogenic risk value of trichloromethane was 2.964×10-6 (interquartile range, 3.909×10-6), and the median hazard quotient values of nitrate, fluoride, trichloromethane and aluminum were 1.631×10-2 (interquartile range, 1.361×10-2), 3.955×10-2 (3.164×10-2), 2.231×10-2 (2.942×10-2) and 2.136×10-4 (6.573×10-4), respectively. Conclusion The carcinogenic and non-carcinogenic risks through drinking water for 17 pollutants in drinking water of Ningbo City from 2021 to 2022 were at low levels.

Clinical trials play a crucial role in advancing the field of human health care. The registration of clinical trials can effectively identify potential publication bias and prevent unnecessary duplication of research efforts, serving as a source of transparent data for health care professionals and researchers, enhancing the quality of clinical research, and presenting more transparent, standardized, authentic, and useful clinical trials. To enhance the capacity for evidence production in traditional medicine from the source, the International Traditional Medicine Clinical Trial Registry (ITMCTR), a cross-regional registry focusing on the theme of traditional medicine, was established. Under the current registration background, this study aims to introduce the problems and current status related to clinical trial registration, as well as the features and functions of the ITMCTR. The results of this study illustrate the necessity of establishing a specialized registration platform for traditional medicine to assist researchers in understanding the basic background of registration and relevant information regarding registration platforms, regardless of whether their research is related to traditional medicine or not. Ultimately, the results of this work will help researchers choose the appropriate platform for more efficient and transparent registration.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective The efficacy of Zang Bi Formula(ZBF)in cardiac complications of rheumatoid arthritis(RA)was observed through animal experiments.Ultra-high performance liquid chromatography tandem time-of-flight mass spectrometry(UHPLC-TOF-MS)and network pharmacology was used to analyze the active ingredients,targets,and pathways of ZBF for the treatment of cardiac hypertrophy,and molecular docking was applied to verify the binding ability of the ingredients to pathway-related proteins.Methods TNF transgenic(TNF-Tg)mice were used as RA and RA-complexed cardiac hypertrophy models,and the left ventricular hypertrophy of mice was observed by echocardiography after 8 weeks of continuous gavage with ZBF,and WGA staining,HE staining,and Masson staining were used to observe and analyze the pathological changes of cardiac tissues.The chemical composition of ZBF was identified by UHPLC-TOF-MS technique.The public database was then used to screen the active ingredients and component targets and disease targets,construct interaction networks,and analyze the bioconcentration data as well as the docking ability of the active ingredients and proteins.Results In animal experiments,ZBF reduced cardiac weight index and cardiac weight tibia length ratio in TNF-Tg mice(P＜0.05,P＜0.01),attenuated cardiac hypertrophy(P＜0.001)and cardiomyocyte hypertrophy(P＜0.01),and alleviated inflammatory infiltration and fibrosis in the heart(P＜0.0001).A total of 24 compounds were identified from ZBF by UHPLC-TOF-MS.A total of 105 active ingredients of ZBF were screened by network pharmacological analysis,and 187 potential targets of ZBF for cardiac hypertrophy were constructed,and the enriched pathways with significance included PI3K-AKT signaling pathway,TNF signaling pathway,and MAPK signaling pathway.Conclusion ZBF attenuated myocardial hypertrophy and cardiomyocyte hypertrophy in TNF-Tg mice and alleviated inflammatory infiltration and fibrosis in the heart,and ZBF may be a potential drug for the treatment of RA and its cardiac complications in the clinic.

Objective:To study the optimization of defecation treatment in patients with chronic constipation under different positions and angles by "simulation contrast agent".Methods:The clinical data of 78 patients with chronic constipation in Handan Central Hospital from April 2020 to April 2022 were retrospectively analyzed. Among them, 26 patients were examined by 90°conventional defecography position (conventional position group), 26 patients by 60° to 89° defecography position (61° to 89° position group), and 26 patients by 30° to 59° Asian squat defecography position (Asian squat position group). The results of defecography, constipation score and defecography abnormality were compared among the three groups.Results:The encysted rectum, internal rectal intussusception and descending distance of perineum in 61° to 89° position group and Asian squat position group were significantly lower than those in conventional position group: (2.71 ± 0.25) and (2.11 ± 0.66) mm vs. (3.06 ± 0.23) mm, (9.06 ± 1.78) and (8.55 ± 2.81) mm vs. (10.22 ± 1.59) mm, (11.52 ± 2.70) and (10.52 ± 2.93) mm vs. (12.52 ± 3.43) mm, the indexes in Asian squat position group were significantly lower than those in 61° to 89° position group, and there were statistical differences ( P<0.01); the anal right angle and the anal right angle in force discharge state in 61° to 89° position group and Asian squat position group were significantly higher than those in conventional position group: (120.47 ± 3.35)° and (122.44 ± 3.33)° vs. (118.19 ± 3.66)°, (19.99 ± 3.47)° and (20.25 ± 2.69)° vs. (18.77 ± 2.79)°, the indexes in Asian squat position group were significantly higher than those in 61° to 89° position group, and there were statistical differences ( P<0.01); there was no statistical difference in resting anal right angle among the three groups ( P>0.05). The Longo outlet obstructive constipation score, Wexner constipation score and constipation severity score in 61° to 89° position group and Asian squat position group were significantly lower than those in conventional position group: (14.41 ± 2.66) and (12.24 ± 3.49) scores vs. (16.64 ± 3.37) scores, (13.79 ± 2.74) and (12.83 ± 3.08) scores vs. (15.76 ± 3.56) scores, (13.34 ± 2.72) and (12.31 ± 2.52) scores vs. (16.08 ± 3.57) scores, the indexes in Asian squat position group were significantly lower than those in 61° to 89° position group, and there were statistical differences ( P<0.01). The detection rates of abnormal defecography in conventional position group, 61° to 89° position group and Asian squat position group were 96.15% (25/26), 84.62% (22/26) and 69.23% (18/26), and there was statistical difference ( P<0.05); among them, the detection rate of abnormal defecography in Asian squat position group was significantly lower than that in conventional position group, and there was statistical difference ( P<0.05). Conclusions:The defecation function and imaging indexes are optimized in patients with chronic constipation based on the guidance of "simulation contrast agent" adopted the Asian squat position, and their significantly.