Objective:To investigation the situation of water improvement projects in villages affected by drinking water-type endemic fluorosis in Qinghai Province and the prevalence of dental fluorosis among children, in order to provide a basis for consolidating the achievements in prevention and control of drinking water-type endemic fluorosis and adjusting prevention and control measures.Methods:The monitoring data on drinking water-type endemic fluorosis were collected from the disease prevention and control centers in various counties of Qinghai Province from 2021 to 2023, the situation of water improvement projects, the fluorine content of domestic drinking water and the prevalence of dental fluorosis in children aged 8 to 12 years old were retrospectively analyzed.Results:From 2021 to 2023, the numbers of villages affected by drinking water-type endemic fluorosis in Qinghai Province were 338, 335, and 328, respectively. The numbers of water improvement projects were 125, 127 and 124, respectively. The normal operation rates were 100%, 100% and 99.19% (123/124), respectively. The qualified rates of water fluoride level were 100%, 99.21% (126/127) and 99.19% (123/124), respectively. The detection rates of dental fluorosis among children aged 8 to 12 were 4.34% (515/11 877), 5.70% (646/11 331) and 4.48% (490/10 943), respectively. There was a statistically significant difference in the detection rate of dental fluorosis among children in different years (χ 2 = 22.79, P < 0.001). Conclusions:The overall operation status of water improvement project in villages affected by drinking water-type endemic fluorosis in Qinghai Province is generally good, but there has been some relaxation in management and maintenance in the later stage, and there is a phenomenon of project intermittency. The detection rate of dental fluorosis among children aged 8 to 12 remains low, and endemic fluorosis caused by drinking water is under continuous control.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Objective:Exploring the effect of Pinocembrin(Pino)regulating the Ras homolog gene family member A/Rho associated with curly helix binding protein kinase(RhoA/ROCK)signaling pathway of Ras homologous gene family members on the malignant biological behavior of gastric cancer cells.Methods:Cultivate human gastric cancer cells MGC803 with different concentrations of Pino(0～240μmol/L),detect cell survival rate using CCK-8 method,and screen for the optimal drug concentration.MGC803 cells were rseparated into MGC803 group(Control group),Pino-L group,Pino-M group,Pino-H group,and Pino-H+RhoA agonist CN03 group.The clone formation experiment was applied to detect the number of clones formed of cells in each group.Assessment of cell apoptosis using flow cytometry.Tran-swell invasion and migration experiments were used to detect the number of cells undergoing migration and invasion in each group;Detection of RhoA/ROCK signaling pathway and expression of epithelial mesenchymal transition related proteins in MGC803 cells using Western blot method.Results:Compared with the MGC803 group,the cell survival rate,clone formation number,migration cell number,and invasion cell number were all reduced in the Pino-L group,Pino-M group,and Pino-H group,and RhoA was also present in the cells,ROCK2,The expression levels of vimentin and N-cadherin gradually decreased(P<0.05),while the apoptosis rate and E-cadherin expression level gradually in-creased(P<0.05).The Pino-H+CN03 group reversed the trend of changes in the above indicators).Conclusion:Pino can prevent malignant biological behavior of gastric cancer cells,which may be related to the inhibition of the RhoA/ROCK signaling pathway.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by fatigue.Methods:COPD patients enrolled in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of acute exacerbations in the past year, smoking status, biofuel exposure, occupational exposure, modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1)/forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, tuberculosis, cardiovascular disease, diabetes mellitus) were collected. Fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, with a score ≤43 defined as fatigue. Patients were divided into fatigue and non-fatigue groups, and multivariate regression analysis was used to screen factors associated with fatigue in COPD patients. Results:A total of 597 COPD patients were included, of which 280(46.9%) had fatigue symptoms. Compared with non-fatigue patients, fatigue patients had lower FEV 1%pred, FEV 1/FVC, and body mass index (BMI), higher CAT and mMRC scores, and a higher proportion of occupational exposure, bronchiectasis, and treatment with long-acting β 2-agonists (LABA)/long-acting muscarinic antagonists (LAMA)/inhaled corticosteroids (ICS) (all P<0.05). Multivariate regression analysis showed that high CAT score ( OR=2.312, 95% CI: 1.366-3.911), high mMRC score ( OR=1.484, 95% CI: 1.053-2.091), occupational exposure ( OR=1.513, 95% CI: 1.082-2.116), comorbid bronchiectasis ( OR=2.452, 95% CI: 1.102-5.457), low BMI ( OR=0.935, 95% CI: 0.891-0.981), and high CAT-energy score ( OR=1.301, 95% CI: 1.149-1.473) were risk factors for fatigue in COPD patients. The CAT-energy score was highly correlated with the FACIT-F score ( r=0.260, P<0.001), and a CAT-energy score ≥2 could preliminarily screen COPD patients with fatigue. Conclusions:COPD patients with comorbid fatigue have a heavy symptom burden, are more likely to have a history of occupational exposure and bronchiectasis, and the CAT-energy score is of great reference value for screening COPD patients with fatigue.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by anorexia.Methods:This cross-sectional study included patients registered in the RealDTC study from May 2023 to December 2023. Demographic data, COPD Assessment Test (CAT) score, modified Medical Research Council (mMRC) dyspnea questionnaire score, Clinical COPD Questionnaire (CCQ) score, forced expiratory volume in one second (FEV 1), forced expiratory volume in the first second predicted of percentage (FEV 1%pred), FEV 1/forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade, GOLD group, number of acute exacerbations and hospitalizations in the past year, and score of the Functional Assessment of Anorexia Cachexia Therapy-Anorexia/Cachexia Subscale-12 (FAACT-A/CS-12) were collected. Patients with a FAACT-A/CS-12 score ≤30 were diagnosed as having anorexia. Multivariate logistic regression analysis was used to evaluate the influencing factors of anorexia in COPD patients. Results:A total of 617 COPD patients were included, of whom 109(17.7%) had anorexia. Compared with non-anorexia patients, COPD patients with anorexia had higher age, CAT, mMRC and CCQ scores, and more acute exacerbations and hospitalizations in the past year, while body mass index, FEV 1, FEV 1%pred and FEV 1/FVC were lower (all P<0.05). The proportions of patients with primary education or below, GOLD 3-4 grade and GOLD E group were higher in COPD patients with anorexia (all P<0.05). Logistic regression analysis showed that a CAT score of 10-<20 [odds ratio ( OR)=4.017, 95% confidence interval ( CI): 1.673-59.645], a CAT score of 20-<30 ( OR=9.686, 95% CI: 3.777-24.842), a CAT score of ≥30 ( OR=78.286, 95% CI: 7.654-800.689) and ≥1 hospitalization in the past year ( OR=2.050, 95% CI: 1.292-3.254) were independent risk factors for anorexia in COPD patients (all P<0.05). Conclusions:COPD patients with anorexia have poor lung function, high symptom burden and high risk of acute exacerbation. Clinicians should pay attention to the management of COPD patients with anorexia and take corresponding intervention measures.

Objective:To analyze the clinical characteristics of frailty in elderly patients with chronic obstructive pulmonary disease (COPD).Methods:COPD patients aged ≥65 years registered in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of exacerbations in the past year, exposure to risk factors (smoking, biomass fuel exposure, occupational exposure), modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, pulmonary tuberculosis, cardiovascular disease, diabetes mellitus) were collected. According to Fried′s frailty phenotype, patients meeting any 3 of the 5 criteria were defined as frail and divided into a frailty group and a non-frailty group. Multivariate regression analysis was used to screen the related factors of frailty in elderly COPD patients, and the receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of related factors for frailty assessment. Results:A total of 496 elderly COPD patients were included, of which 144(29.0%) had comorbid frailty. The frailty group had lower mass body index (BMI), FEV 1%pred, and FEV 1/FVC, higher mMRC and CAT scores, more exacerbations and hospitalizations in the past year (all P<0.001), and higher proportions of patients with junior high school education or below, Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E, and GOLD grades 3 and 4 (all P<0.05). Multivariate regression analysis showed that low education level ( OR=2.117, 95% CI: 1.119-4.003), low BMI ( OR=0.927, 95% CI: 0.867-0.991), GOLD grade 4 ( OR=4.251, 95% CI: 1.477-12.235), high CAT score ( OR=1.174, 95% CI: 1.127-1.224), and high mMRC score ( OR=4.578, 95% CI: 3.364-6.231) were independent risk factors for frailty in elderly COPD patients (all P<0.05). The ROC curve showed that CAT score (AUC=0.78) and mMRC score (AUC=0.81) had the highest AUC for assessing frailty in elderly COPD patients. Conclusions:Elderly COPD patients with frailty have lower BMI, worse lung function, and more severe symptom burden. The results provide clinical reference for the management of frail elderly COPD patients.

Objective:To analyze the risk factors associated with future exacerbations in patients with chronic obstructive pulmonary disease (COPD) who have no history of exacerbation in the past year.Methods:COPD patients with no exacerbation history in the past year, registered in the RealDTC study from January 2018 to December 2023, were enrolled. Demographic data, COPD Assessment Test (CAT) scores, modified Medical Research Council (mMRC) dyspnea questionnaire scores, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, GOLD groups, and inhaled medication regimens were collected. All patients were followed up for one year, and the number of exacerbations was recorded. Patients were divided into an exacerbation group and a non-exacerbation group based on the occurrence of exacerbations during the follow-up period. Logistic regression analysis was used to screen the influencing factors for exacerbations in COPD patients. Results:A total of 2 901 COPD patients were included, among which 633 patients (21.8%) experienced exacerbations during the follow-up period. Compared with the non-exacerbation group, patients in the exacerbation group were older, with higher CAT and mMRC scores, lower body mass index (BMI), FEV 1%pred, and FEV 1/FVC. The proportions of patients with high school education or above and those using long-acting β 2-agonist (LABA) + long-acting muscarinic antagonist (LAMA) medications were also lower (all P<0.05). Logistic regression analysis showed that age ( OR=1.010, 95% CI: 1.000-1.021), CAT score ≥20 ( OR=1.415, 95% CI: 1.074-1.865), education level of junior high school or below ( OR=1.243, 95% CI: 1.003-1.540), LABA + LAMA inhalation ( OR=0.605, 95% CI: 0.432-0.848), and BMI ( OR=0.969, 95% CI: 0.943-0.995) were independent risk factors for future exacerbations in COPD patients with no exacerbation history in the past year (all P<0.05). Conclusions:The risk of future exacerbations remains high in COPD patients with no exacerbation history in the past year. High CAT scores, low education levels, and low BMI are associated with future exacerbations. Clinicians should pay close attention to the management of such patients and implement appropriate interventions.

Objective:To analyze the differences in determination of fluoride level in drinking water by ion-selective electrode method and high-throughput rapid determination method.Methods:The precision test was carried out by using the two methods to measure two kinds of fluoride standard substances, water samples of external quality control assessment from 2021 to 2023 (two kinds each year) and the fluoride level in three drinking water samples (for 5 times/each sample). Accuracy testing was conducted by measuring the external quality control assessment water samples and the spiked recovery rates drinking water, and water samples were grouped (water fluoride ≤1.00, > 1.00 mg/L) and analyzed according to the "Hygienic Standards for Drinking Water" (GB 5749-85). SPSS 23.0 software was used for statistical analysis of the measurement results.Results:(1) The correlation coefficients ( r) of the working curves of the two methods were both > 0.990, meeting the quality control requirements. (2) In the precision test, when comparing the results of the two methods for detecting two kinds of fluoride standard substances, there was no statistically significant difference ( F = 0.36, 0.15, P = 0.564, 0.707), and the coefficients of variation ( CV) were all < 5%. The CV of the detection results of the external quality control assessment water samples and drinking water samples were < 5%. (3) In the accuracy test, when the fluoride concentration in water was ≤1.00 mg/L, there was no statistically significant difference in the spiked recovery rates between the two methods ( F = 0.49, P = 0.504). When the fluoride concentration in water was > 1.00 mg/L, there was a statistically significant difference in the spiked recovery rates between the two methods ( F = 24.75, P = 0.003). Conclusions:The ion-selective electrode method has the advantages of wide detection range and wide adaptability, while the high-throughput rapid determination method has high accuracy. Testing personnel can weigh and choose the appropriate determination method based on the actual laboratory conditions and sample concentration range.