OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

Abstract: Objective　To understand the situation of drug-resistant tuberculosis screening and epidemiological characteristics of multi-drug resistant tuberculosis (MDR-TB) and pre-extensively drug resistant tuberculosis (pre-XDR-TB) in Changsha, in order to provide a scientific basis for improving the quality of drug-resistant tuberculosis prevention and control in the city. Methods　Demographic information and drug susceptibility date of etiologically positive pulmonary tuberculosis patients in Changsha from 2018 to 2021 were collected, the successful rate of resistance screening, incidence and tendency in MDR-TB and pre-XDR-TB in patients included in this study were statistically analyzed accordingly. 　　Results From 2018 to 2021, the successful screening rates were 86.2%, 87.7%, 81.9% and 71.5% for MDR-TB and 82.2%, 84.8%, 76.9% and 68.2% for pre-XDR-TB, respectively. In each year, MDR-TB patients identified accounted for 7.6% (101/1 222), 6.5%(124/1 774), 6.6%(110/1 555) and 6.3%(99/1 478), and pre-XDR-TB patients identified accounted for 3.6%(46/1 219), 3.8%(69/1 766), 4.4%(69/1 495) and 4.6%(69/1 436), correspondingly. The incidence of MDR-TB showed a slowly downward trend, while the incidence of pre-MDR-TB showed a slowly upward trend, with neither decreasing nor increasing trends being statistically significant (（χ2=1.947，0.806，P>0.050). The incidence of MDR-TB in the retreatment failure population was 66.6% (2/3), and the others, failure initial treatment and recrudescence populations were 23.5% (19/81), 16.7% (2/12) and 15.2% (70/461), respectively. Similar to the incidence above, the incidence of pre-XDR-TB was 16.7% (2/12) among patients who failed in initial treatment, and 12.2% (9/74), 9.8% (43/439), and 4.5% (2/44) among the others, recrudescence and returned patients, respectively. The incidence rates of MDR-TB and pre-XDR-TB in different populations were significantly different (χ2=117.600，59.030，P<0.05). Conclusions There are still areas for improvement in tuberculosis drug resistance surveillance system in Changsha. On the premise of paying attention to patients in retreatment failure, other, initial treatment failure and relapse patients, high sensitivity molecular drug susceptibility testing, and scientifically efficient screening strategies must be explored.

Objective: To evaluate the occupational health risk of organic solvents in major posts of printing industry, and to provide technical reference to take targeted risk control measures. Methods: In January 2021, the contact ratio method was used to assess the occupational health risk of organic solvents in the major posts of 84 printing enterprises in Shantou, and Monte Carto method was used to estimate the probability distribution of risk levels in the majorpostsin January 2021. Results: The highest probability of risk assessment in printing and membranecovering post is Level 4 (high risk) , which are 76.2% and 67.6% respectively; the highest probability of simulation evaluation result in oil blending, dispensing and cleaning post is Level 3 (medium risk) ; and the simulation evaluation result in glueing post are mostly Level 3 (medium risk) and Level 4 (high risk) , the probability of which are 45.7% and 54.3% respectively. Conclusion: The occupational health risk of organic solvents in the major posts is generally middle-high risk level, and then the occupational health risk control of organic solvents in major posts of printing industry should be strengthened.
Air Pollutants, Occupational/analysis* ; Industry ; Occupational Exposure/analysis* ; Occupational Health ; Risk Assessment ; Solvents

OBJECTIVE: To investigate the effect of interference of P2X4 receptor expression in tumor-associated macrophages (TAMs) on invasion and migration of glioma cells. METHODS: C57BL/6 mouse models bearing gliomas in the caudate nucleus were examined for glioma pathology with HE staining and expressions of Iba-1 and P2X4 receptor with immunofluorescence assay. RAW264.7 cells were induced into TAMs using conditioned medium from GL261 cells, and the changes in mRNA expressions of macrophage polarization-related markers and the mRNA and protein expressions of P2X4 receptor were detected with RT-qPCR and Western blotting. The effect of siRNA-mediated P2X4 interference on IL-1β and IL-18 mRNA and protein expressions in the TAMs was detected with RT-qPCR and Western blotting. GL261 cells were cultured in the conditioned medium from the transfected TAMs, and the invasion and migration abilities of the cells were assessed with Transwell invasion and migration experiment. RESULTS: The glioma tissues from the tumor-bearing mice showed a significantly greater number of Iba-1-positive cells, where an obviously increased P2X4 receptor expression was detected (P=0.001), than the brain tissues of the control mice (P < 0.001). The M2 macrophage markers (Arg-1 and IL-10) and M1 macrophage markers (iNOS and TNF-α) were both significantly up-regulated in the TAMs derived from RAW264.7 cells (all P < 0.01), but the up-regulation of the M2 macrophage markers was more prominent; the expression levels of P2X4 receptor protein and mRNA were both increased in the TAMs (P < 0.05). Interference of P2X4 receptor expression significantly lowered the mRNA(P < 0.01)and protein (P < 0.01, P < 0.05)expression levels of IL-1β and IL-18 in the TAMs and obviously inhibited the ability of the TAMs to promote invasion and migration of the glioma cells (P < 0.05). CONCLUSION Interference of P2X4 receptor in the TAMs suppresses the migration and invasion of glioma cells possibly by lowering the expressions of IL-1β and IL-18.
Animals ; Culture Media, Conditioned ; Glioma ; Interleukin-18 ; Mice ; Mice, Inbred C57BL ; RNA, Messenger ; Receptors, Purinergic P2X4/metabolism* ; Tumor-Associated Macrophages

Climate change has been referred to as one of the greatest threats to human health, with reports citing likely increases in extreme meteorological events. In this study, we estimated the relationships between temperature and outpatients at a major hospital in Qingdao, China, during 2015-2017, and assessed the morbidity burden. The results showed that both low and high temperatures were associated with an increased risk of outpatient visits. High temperatures were responsible for more morbidity than low temperatures, with an attributed fraction (AF) of 16.86%. Most temperature-related burdens were attributed to moderate cold and hot temperatures, with AFs of 5.99% and 14.44%, respectively, with the young (0-17) and male showing greater susceptibility. The results suggest that governments should implement intervention measures to reduce the adverse effects of non-optimal temperatures on public health-especially in vulnerable groups.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Ambulatory Care/statistics & numerical data* ; Cardiovascular Diseases/therapy* ; Child ; Child, Preschool ; China/epidemiology* ; Cold Temperature/adverse effects* ; Cost of Illness ; Digestive System Diseases/therapy* ; Facilities and Services Utilization/statistics & numerical data* ; Female ; Hot Temperature/adverse effects* ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Poisson Distribution ; Respiratory Tract Diseases/therapy* ; Risk Factors ; Young Adult

Suicide,a major public health problem,is the death caused by injuring oneself with the intent to die.In this paper,we reviewed the genes encoding serotonin system,calcium voltage-gated channel subunit alpha1 C,γ-aminobutyric acid,and spindle and kinetochore associated complex subunit 2,as well as their related brain regions,from the perspective of imaging genetics,aiming to provide new ideas for the research and intervention on suicidal behavior.
Brain ; Humans ; Suicidal Ideation ; Suicide

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5

Background::In consideration of the difficulty in diagnosing high heterogeneous glioma, valuable prognostic markers are urgent to be investigated. This study aimed to verify that connective tissue growth factor (CTGF) is associated with the clinical prognosis of glioma, also to analyze the effect of CTGF on the biological function.Methods::In this study, glioma and non-tumor tissue samples were obtained in 2012 to 2014 from the Department of Neurosurgery of Nanfang Hospital of Southern Medical University, Guangzhou, China. Based on messenger RNA (mRNA) data from the Cancer Genome Atlas (TCGA) and CCGA dataset, combined with related clinical information, we detected the expression of CTGF mRNA in glioma and assessed its effect on the prognosis of glioma patients. High expression of CTGF mRNA and protein in glioma were verified by reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blotting. The role of CTGF in the proliferation, migration, and invasion of gliomas were respectively identified by methylthiazoletetrazolium assay, Transwell and Boyden assay in vitro. The effect on glioma cell circle was assessed by flow cytometry. For higher expression of CTGF in glioblastoma (GBM), the biological function of CTGF in GBM was investigated by gene ontology (GO) analysis. Results::In depth analysis of TCGA data revealed that CTGF mRNA was highly expressed in glioma (GBM, n= 163; lowly proliferative glioma [LGG], n = 518; non-tumor brain tissue, n = 207; LGG, t = 2.410, GBM, t = 2.364, P < 0.05). CTGF mRNA and protein expression in glioma (86%) was significantly higher than that in non-tumor tissues (18%) verified by collected samples. Glioma patients with higher expression of CTGF showed an obviously poorer overall survival (35.4 and 27.0 months compared to 63.3 and 55.1 months in TCGA and Chinese Glioma Genome Atlas (CGGA) databases separately, CGGA: χ2 = 7.596, P = 0.0059; TCGA: χ2 = 10.46, P = 0.0012). Inhibiting CTGF expression could significantly suppress the proliferation, migration, and invasion of gliomas. CTGF higher expression had been observed in GBM, and GO analysis demonstrated that the function of CTGF in GBM was mainly associated with metabolism and energy pathways ( P < 0.001). Conclusions::CTGF is highly expressed in glioma, especially GBM, as an unfavorable and independent prognostic marker for glioma patients and facilitates the progress of glioma.