By selecting stable and detectable drug prototypes or metabolites in sewage samples, near real-time detection of disease conditions can be achieved. This study selected oseltamivir carboxylate, the primary metabolite of first-line antiviral oseltamivir, as a biomarker. Based on the concentration of oseltamivir carboxylate in wastewater, the consumption and usage rate of oseltamivir were calculated by reverse engineering. Quarterly sampling was conducted at 46 urban sewage treatment plants in representative 5 cities in the middle and lower reaches of the Yangtze River, from November 2022 to December 2023. The concentration range of oseltamivir acid in sewage samples is 1.270−1 279 ng/L, the daily mass load of oseltamivir per 1 000 inhabitants in the surveyed cities ranged from 9.560 to 544.7 mg/d, and the average utilization rate is 0.06‰−3.63‰. The research results indicate that in March 2023, Wuxi City experienced a spring influenza peak, while Bengbu, Tongling, Suzhou, and Changzhou City experienced a small summer influenza peak in May. In November and December 2023, Wuxi, Changzhou, and Bengbu City experienced a winter influenza peak, the results are consistent with the official statistics of the National Center for Disease Control and Prevention and the National Influenza Center, which reflect the influenza epidemic situation in southern cities. The integration of this methodology with clinical diagnostic rates could provide near real-time data support for future influenza prevention and control strategies.

Background::Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods::About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health.Results::At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion::Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

Objective:To screen T-cell exhaustion-related signature genes as the prognostic marker for osteosarcoma and establish a prognostic model for osteosarcoma patients based on weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)-COX regression analysis. Methods:GSE21257 dataset was downloaded from Gene Expression Omnibus(GEO)database for the establishment of the prognostic model for osteosarcoma.4 T-cell exhaustion-related gene sets were downloaded from The Molecular Signatures Database(MisgDB)and their enrichment scores in GSE21257 samples were calculated by single sample gene set enrichment analysis(ssGSEA).WGCNA was carried out to screen the gene module that is highly associated with T-cell exhaustion based on ssGSEA results followed by GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)analysis of the biological processes and signaling transduction pathways that those genes are involved in.The signature genes that are highly associated with the prognosis of osteosarcoma patients were obtained through LASSO-COX regression and a prognostic model was established based on these signature genes.Osteosarcoma-related expression profile data from the GSE21257 and TAEGET datasets on XENA were downloaded from the Gene Expression Omnibus.Clinical information for the training and validation sets was obtained.T-cell exhaustion-related genes were screened using a weighted correlation network analysis.Realtime fluorescence quantitative PCR,COX regression analysis,external dataset and nomogram were used to evaluate the reliability and accuracy of the prognostic model.A immunotherapy-related dataset was used to assess the efficacy of this prognostic model for the prediction of patients'responses to immunotherapy. Results:Analysis results based on the ssGSEA scores showed that T-cell exhaustion-related genes were related to the metastasis and age of osteosarcoma patients.Many T-cell exhaustion-related genes were found to be differentially expressed in metastatic and non-metastatic osteosarcoma patients.1 256 T-cell exhaustion-related genes were identified through WGCNA and these candidate markers were mainly distributed in structures like secretory granule membranes and endocytic vesicles and were involved in T-cell activation.COX regression analysis screened 68 significant prognostic markers out of the 1 256 genes,and 12 signature genes were further confirmed with LASSO-COX regression analysis.A prognostic model was established based on the 12 signature genes.Results of real-time fluorescence quantitative PCR showed a similar trend in the expression of most of the signature genes in different osteosarcoma cell lines.COX regression analysis of the internal and external datasets verified that the risk score calculated with the prognostic model was an independent prognostic factor for osteosarcoma patients,and high-risk score was associated with poor prognosis of the patients.Receiver operating characteristic(ROC)curves demonstrated excellent prognostic efficacy of the model.Nomogram analysis verified the prognostic model is highly accurate and reliable in predicting the prognosis of osteosarcoma patients.Analysis using the immunotherapy-related dataset indicated that this prognostic model could also be used to predict patients'responses to immunotherapy. Conclusion:The 12 signature gene(CD300LB,TRO,SNX3,VENTX,PPM1M,DOT1L,CDC37,NAT9,TRMT1,PPP1R3C,CHTF18 and NSUN5)-based prognostic model can effectively predict the prognosis and responses to immune check-point inhibitors for osteosarcoma patients,which may provide evidence for the prediction of prognosis as well as the selection of immunotherapy plans in clinical practice.

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult ; Humans ; Cardiovascular Diseases/prevention & control* ; East Asian People ; Prospective Studies ; Risk Factors ; Smoking

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≽ 140 mmHg or diastolic blood pressure ≽ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88-0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11-1.16) in participants with zinc intake ≽ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day.
Adult ; Humans ; Cohort Studies ; Zinc ; Diet ; Hypertension/epidemiology* ; Eating ; China/epidemiology*

Objective To investigate the correlation between the proportion of peripheral blood follicular T helper cells(Tfh cells)and intracellular interleukin-21(IL-21)content with blue light retinal injury.Methods Brown Norway(BN)rats were randomly divided into 4 groups and were exposed to blue light for 3 hours a day to establish retinal light damage model.According to the duration of illumination,the rats was divided into 0 days(control group),3 days(3 d group),7 days(7 d group)and 14 days(14 d group).The proportion of Tfh cells and content of IL-21 in Tfh cells in peripheral blood of each group was detected by flow cytometry and ELISA sepa-rately after illumination.Electroretinogram(ERG)was used to evaluate retinal function.The changes of fundus in rats were observed by fundus photography.The thickness of outer nuclear layer of retina was analyzed by HE staining.Results After retinal blue light injury,with the extension of illumination time,the proportion of Tfh cells in peripheral blood and intracellular IL-21 content both increased(P<0.05).ERG showed that retinal function decreased after light damage and aggravated with the extension of illumination time,the latency and ampli-tudes of A-wave and B-wave increased and decreased respectively(P<0.05).The retinal fundus of rats showed depigmentation in 3 d,and the retinal vessels became thinner and exudate with the extension of illumination time.HE staining showed that the outer nuclear layer of retina(ONL)became thinner(P<0.05).Correlation analy-sis indicated that the proportion of Tfh cells in peripheral blood and the intracellular IL-21 content could jointly reflect the degree of injury(P<0.000 1),and the proportion of Tfh cells in peripheral blood was negatively corre-lated with ONL thickness and the amplitude of a and b waves,positively correlated with the peak time of a and b waves,(P<0.0001).Conclusion The proportion of Tfh cells in peripheral blood and the intracellular IL-21 content were increased after blue light damage to retina,and were significantly increased with the extension of light time with a certain correlation.

In order to promote the connotation construction of the resident standardized training bases and improve the training quality, a tertiary hospital made key breakthroughs against the existing problems in the base under the guidance of national key training base standards in September 2020. Optimization and innovation were explored in terms of residential teaching supervision, performance appraisal system, regular teaching meeting, educational fund management, pilot project of full-time residential teaching secretaries, clinical skill center construction, cultivation of faculty development, and so on. These experiments have paved the way to high quality and sustainable development of residents standardized training. By the end of December 2021, the hospital had achieved significant progress in such aspects as residential teaching atmosphere, resident learning initiative, and training base branding. These achievements improved the quality of resident standardized training of the hospital in general, and provided a reference for promoting the high-quality development of residential training in China.

Objective:To investigate the association between shift work and the risk of lower extremity osteoarthritis.Methods:The study population came from the Dongfeng-Tongji cohort established in 2008. In September 2008, the Dongfeng Motor Company in Hubei Province was to recruit all retired workers who voluntarily participated in the survey as the research objects. During the follow-up conducted from April to October 2013, a total of 14 438 retired workers, i.e. all of the participants who underwent physical examination were investigated about demographic characteristics, lifestyles, occupation history, and lower extremity joint-related medical history, and additionally completed lower extremity joint examinations. After excluding individuals with missing data regarding lower extremity osteoarthritis, with the history of lower extremity joint trauma, or with history of rheumatoid arthritis (N=532), data from 13 906 participants was analyzed in the study. Multivariate logistic regression models were used to estimate the association between shift work and lower extremity osteoarthritis. After stratified by the duration of shift work, multivariate logistic regression models were used to analyze the relationship between the duration after leaving from shift work and lower extremity osteoarthritis.Results:Finally, a total of 13 906 retired employees included 7 560 (54.4%) females with a mean age of 64.74 (standard deviation 8.23) years old. 5 537 (39.8%) workers had ever engaged in shift work, including 2 004 (14.4%) workers with 1-9 years of shift work and 3 533 (25.4%) workers with ≥ 10 years of shift work. The prevalence of lower extremity osteoarthritis was 7.0%, while the prevalence of knee osteoarthritis and hip osteoarthritis were 6.7% and 0.7%, respectively. Compared with daytime workers, shift workers showed a 22% increase in the risk of lower extremity osteoarthritis ( OR=1.22, 95 %CI:1.06-1.40). Each 5-year increase in the duration of shift work was associated with a 4% increase in the risk of lower extremity osteoarthritis ( OR=1.04, 95 %CI:1.01-1.08). With the extension of the duration after leaving from shift work, the risk of lower extremity osteoarthritis decreased. Similar relationships were found between shift work and the risk of knee osteoarthritis, as well as hip osteoarthritis. Conclusion:Shift work was associated with the increased risk of lower extremity osteoarthritis.

Objective:To investigate the association between shift work and the risk of lower extremity osteoarthritis.Methods:The study population came from the Dongfeng-Tongji cohort established in 2008. In September 2008, the Dongfeng Motor Company in Hubei Province was to recruit all retired workers who voluntarily participated in the survey as the research objects. During the follow-up conducted from April to October 2013, a total of 14 438 retired workers, i.e. all of the participants who underwent physical examination were investigated about demographic characteristics, lifestyles, occupation history, and lower extremity joint-related medical history, and additionally completed lower extremity joint examinations. After excluding individuals with missing data regarding lower extremity osteoarthritis, with the history of lower extremity joint trauma, or with history of rheumatoid arthritis (N=532), data from 13 906 participants was analyzed in the study. Multivariate logistic regression models were used to estimate the association between shift work and lower extremity osteoarthritis. After stratified by the duration of shift work, multivariate logistic regression models were used to analyze the relationship between the duration after leaving from shift work and lower extremity osteoarthritis.Results:Finally, a total of 13 906 retired employees included 7 560 (54.4%) females with a mean age of 64.74 (standard deviation 8.23) years old. 5 537 (39.8%) workers had ever engaged in shift work, including 2 004 (14.4%) workers with 1-9 years of shift work and 3 533 (25.4%) workers with ≥ 10 years of shift work. The prevalence of lower extremity osteoarthritis was 7.0%, while the prevalence of knee osteoarthritis and hip osteoarthritis were 6.7% and 0.7%, respectively. Compared with daytime workers, shift workers showed a 22% increase in the risk of lower extremity osteoarthritis ( OR=1.22, 95 %CI:1.06-1.40). Each 5-year increase in the duration of shift work was associated with a 4% increase in the risk of lower extremity osteoarthritis ( OR=1.04, 95 %CI:1.01-1.08). With the extension of the duration after leaving from shift work, the risk of lower extremity osteoarthritis decreased. Similar relationships were found between shift work and the risk of knee osteoarthritis, as well as hip osteoarthritis. Conclusion:Shift work was associated with the increased risk of lower extremity osteoarthritis.

Objective:To investigate the expression of microRNA-155 (miR-155) in serum and kidney of C57BLKS/db (db/db) mice and its role in the pathogenesis of diabetic kidney disease (DKD).Methods:The db/db mice ( n=24) were divided into 6, 8, and 10 weeks old groups ( n=8) with age increasing according to the random number table, and C57BL/6 mice of the same age were used as control group. The expression of miR-155 in mouse serum and kidney tissue was determined using real-time quantitative PCR. The mRNA and protein expression of Ets-1, eNOS, AGTR1 in renal tissues was verified by real-time quantitative PCR, Western blotting and immunohistochemistry. Results:Compared with the control group, the expression of miR-155 in serum of db/db mice at 6, 8 and 10 weeks of age were significantly increased (all P<0.01), and the increase of miR-155 was most obvious at 10 weeks of age ( P<0.01). Meanwhile the expression of miR-155 in kidney tissues of 6, 8 and 10 weeks old db/db mice was significantly up-regulated (all P<0.01), and the highest expression of miR-155 was at 10 weeks of age ( P<0.01). Immunohistochemistry showed that Ets-1, eNOS and AGTR1 were localized in glomerular endothelial cells. The results of real-time quantitative PCR showed that the mRNA expression of Ets-1, eNOS and AGTR1 were down-regulated in the kidney tissues of db/db mice at 6, 8 and 10 weeks of age compared to the control(all P<0.05), and the level of down-regulation was the most obvious at 10 week. Western blotting results showed that there was no significant change in Ets-1, eNOS and AGTR1 in 6-week-old db/db mice compared to the control group; the eNOS protein expression was down-regulated at 8 weeks of age ( P<0.05); the expression of AGTR1 protein was down-regulated ( P<0.05), and the protein expression of Ets-1 and eNOS were significantly down-regulated at 10-week age (both P<0.01). Conclusions:The expression of miR-155 in serum and kidney tissues of db/db mice increases during the progression of DKD, while the expression of miR-155 target genes Ets-1, eNOS and AGTR1 decreases with the progression of DKD. MiR-155 may participate in the development and progression of DKD by inhibiting its target genes Ets-1, eNOS and AGTR1, affecting endothelial cell function.