Background Diarrhea disease is a common intestinal infectious disease, and its incidence is affected by meteorological conditions. A better understanding of its epidemiological patterns and influencing factors, together with the construction of reliable prediction models, is of great significance for precise public health prevention and control. Objective To clarify the epidemic characteristics of adult diarrhea disease in Shanghai, analyze the associations of meteorological factors and a web search index with adult diarrhea disease, and develop and compare forecasting models to support precise regional prevention and control. Methods Weekly surveillance data of adult diarrhea disease cases from the Shanghai Comprehensive Surveillance Information System for Diarrhea Diseases, together with concurrent meteorological observation data and web search index (Baidu index) data from 2014 to 2019, were collected. A distributed lag non-linear model (DLNM) was adopted to analyze the associations of multiple meteorological factors and the web search index with the number of diarrhea disease cases. By integrating meteorological factors and web search index data, three types of forecasting models were developed, including autoregressive integrated moving average (ARIMA), Random Forest, and extreme gradient boosting (Xgboost), and their predictive performances were evaluated. Results Adult diarrhea disease in Shanghai exhibited seasonal variation, with an major incidence peak in summer and winter peaks in some years. The number of cases declined annually after 2015. Mean temperature was significantly associated with the risk of diarrhea disease, and both low and high temperature exposures were associated with increased risks. The highest risk was observed at 32.8°C (RR=2.04, 95%CI: 1.62, 2.55), while the strongest effect of low temperature was observed at 0.9 °C (RR=1.53, 95%CI: 1.25, 1.88). When relative humidity exceeded 69%, the risk of diarrhea disease increased with relative humidity, reaching a peak at 81% (RR=1.20, 95%CI: 1.07, 1.35). When weekly cumulative precipitation exceeded 16 mm, the risk also increased with increasing precipitation, reaching a maximum at 105 mm (RR=1.23, 95%CI: 1.07, 1.42). The web search index was positively associated with the risk of diarrhea disease. Model prediction indicated that both the Random Forest model and the Xgboost model adequately captured the overall trend in diarrhea disease cases, with R² values generally exceeding 0.7. Notably, the Xgboost model demonstrated greater accuracy in capturing peak intensities. Conclusion Meteorological factors are associated with adult diarrhea disease in Shanghai. The web search index may serve as an auxiliary indicator for diarrhea forecasting. Machine learning models, with advantages in integrating multisource data, may provide effective predictive tools for the prevention and control of diarrhea disease.

Guided by the concept of holism in traditional Chinese medicine （TCM）， it is believed that spinal vertebral disorders can affect the knee joint through meridians， physical forms， the relationship among tendons， bones， qi， and blood， as well as liver-kidney zang-fu （脏腑） functions， thereby triggering knee pain. In clinical practice， for conditions such as knee joint pain with poor local therapeutic effects or unexplained knee joint pain， it is recommended to start with an examination of the spine for lesions. By adopting the spine-adjusting and knee-benefiting method， through techniques of loosening and tightening acupoints， bone setting and curve adjustment， strengthening tendons and bones， and consolidating and protecting the liver and kidneys， the spine can be restored to its normal physiological state， achieving the goal of distal tendon-bone balance， harmonization of qi and blood， and the spontaneous disappearance of knee joint pain.

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 To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Objective To analyze the current situation of the knowledge-attitude-practice among noise-exposed workers at an airport apron. Methods A total of 494 noise-exposed workers from an airport apron were selected as the study subjects using the judgmental sampling method. A self-designed "Occupational Protection Knowledge, Attitudes, and Practices Questionnaire" was used to assess the current situation of knowledge-attitude-practice on occupational protection. Results Regarding the awareness of noise hazards among the study subjects, the awareness rates of noise-induced impairment on digestive function and reproductive system were the lowest (44.9% and 37.7%, respectively). The awareness rate of noise-induced negative emotions increased with length of service (P<0.01). Regarding the occupational protection knowledge for noise, the awareness rate of occupational noise-induced deafness was “incurable” was the lowest (39.1%). The support rate for five kinds of occupational protection attitudes for noise was generally >85.0%, while only 58.3% of the study subjects consistently or frequently wearing earplugs during work. The most common source of noise hazard and protection knowledge was pre-employment training (76.9%), followed by occupational disease prevention and control campaigns (76.1%). Conclusion Noise-exposed workers in this airport apron have incomplete awareness of non-auditory system hazards caused by noise, and the awareness of knowledge of some occupational protection is relatively low. Although their attitudes toward occupational protection are positive, many workers still fail to consistently wear personal protective equipment at work.

Objective:To analyze the current situation of medical consumables management policy in China,and to provide a reference for the refined management of medical consumables.Methods:Through the policy triangle model and policy tool theory,it comprehensively analyzes the reimbursement medical consumables catalogue and payment management policy of medical insurance in China,covering the policy background,content,process,and participant dimensions.Results:The use frequency of medical consumables policy tools is not balanced,the payment management rules need to be refined,and the participation of multi-stakeholders such as patients is lacking.Conclusion:It is necessary to further strengthen the foundational management of reimbursement medical consumables catalogue,improve the access mechanism of medical consumables for medical insurance,and explore the formulation of categorized payment standards and innovative payment mechanisms.