Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.

Objective To identify genetic regulators of ionizing radiation(IR)sensitivity through clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease 9(Cas9)genome-wide screening.Methods A specialized single guide RNA(sgRNA)library was developed targeting 987 stress-response regulatory genes identified through Kyoto Encyclopedia of Genes and Genomes(KEGG),Reactome and gene ontology(GO)databases,followed by construction of sgRNA plasmids and packaging into a lentiviral library.Using colon adenocarcinoma Caco-2 cells as a model system,the Cas9-stable transgenic line was established via lentiviral transduction and antibiotic selection.Library-transduced cells underwent puromycin selection,followed by γ-irradiation(dose optimized via preliminary experiments).Post-irradiation phenotypic selection was conducted after 14 days,with subsequent next-generation sequencing of surviving cell populations to identify enriched/depleted sgRNAs.Candidate genes were functionally validated through orthogonal assays:cell counting kit-8(CCK-8)proliferation analysis,clonogenic survival assays and flow cytometric quantification of reactive oxygen species(ROS)and apoptotic markers.Results The optimized screening platform identified 281 radiation response genes(165 radiosensitive and 116 radioprotective candidates).Functional validation revealed Bcl2-associated athanogene 3(BAG3)knockdown significantly enhanced radioresistance.Proliferation was increased 1.2-1.5 fold,clonogenic survival improved 1.5-2.0 fold,and ROS was reduced by 13％-25％coupled with 32％-73％apoptosis attenuation compared to control groups.Conclusion The integrated CRISPR/Cas9 screening platform effectively identifies novel radiation response regulators,as evidenced by the discovery of BAG3 as a critical radiosensitivity determinant.This high-throughput functional genomics approach provides a robust methodology for systematically mapping molecular determinants of cellular radiation response,with potential applications in both mechanistic studies and therapeutic target discovery.

BACKGROUND:Aerobic exercise can suppress liver fibrosis in diabetic mice.However,the specific mechanism is yet to be elucidated.OBJECTIVE:To investigate the protective effect and mechanism of aerobic exercise on liver fibrosis in db/db mice via the transforming growth factor-β/Smad signaling pathway.METHODS:8-week-old male db/db mice and age-matched m/m mice were randomly divided into m/m control group,m/m+exercise group,db/db control group,and db/db+exercise group,with 10 mice in each group.Mice in the exercise group were subjected to a 12-week aerobic exercise.After the exercise,fasting blood glucose levels were measured in mice,and glucose tolerance and insulin tolerance tests were conducted.Mouse liver was extracted to calculate liver index and mouse eyeballs were taken to collect blood sample and detect biochemical indicators.Masson,oil red O and Hematoxylin-eosin staining were used to detect and analyze the pathological changes in mouse liver tissues.Immunohistochemistry was used to determine the protein expression levels of transforming growth factor-β1 and p-Smad3.Western blot analysis was applied to determine the protein expression levels of transforming growth factor-β1,Smad3,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen.RESULTS AND CONCLUSION:Compared with the m/m group and m/m+exercise group,body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels were significantly increased(P<0.01),but the high-density lipoprotein level significantly decreased(P<0.01)in the db/db group;the protein expressions of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen significantly increased(P<0.01)in the db/db group;the area under curve of glucose and insulin tolerance tests significantly increased(P<0.01)in the db/db group;and pathological staining of the liver in the db/db group showed extensive infiltration of inflammatory cells,increased lipid droplets,and significant fibrosis.In the db/db+exercise group,aerobic exercise could significantly reduce body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels(P<0.05 or P<0.01),and increase high-density lipoprotein level(P<0.05).Similarly,a marked decrease was observed in the protein expression levels of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen(P<0.05 or P<0.01)in the db/db+exercise group.In addition,the area under the curve of glucose tolerance and insulin tolerance tests significantly decreased(P<0.01,P<0.05),and pathological changes in liver tissues were significantly improved.In conclusion,aerobic exercise can attenuate liver fibrosis in diabetic mice,which may be related to the regulation of the transforming growth factor-β1/Smad signaling pathway.

Objective:To investigate the current prevalence and control status of coal-burning-borne endemic fluorosis in key areas of the disease in Zhenxiong County of Yunnan Province, thereby providing scientific basis for formulating subsequent prevention strategies and measures.Methods:From October to November 2023, a simple random sampling method was used to conduct a survey in three key townships (towns) in Zhenxiong County, Chishuiyuan Town, Yanyuan Town, and Linkou Yi and Miao Ethnic Township. Three administrative villages were selected from each township (town) as survey sites, and dental fluorosis examination on children aged 8 - 12 years who were born and lived in the local area was conducted. Thirty households were selected from each survey site, the use of household stoves and the formation of related healthy living behaviors were investigated. At the same time, a survey was conducted among primary school students and housewives to investigate their knowledge of coal-burning-borne endemic fluorosis prevention and control. The control and elimination of endemic areas were evaluated according to the "Assessment Protocol for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:A total of 1 172 children were examined, and the detection rate of dental fluorosis was 7.76% (91/1 172), with a dental fluorosis index of 0.11. A total of 295 households were investigated, and the qualified improved stoves rate and the correct use rate of qualified improved stoves were 95.59% (282/295) and 100% (282/282), respectively. The correct drying rate of edible corn and chili peppers was 79.66% (235/295). The awareness rates of coal-burning-borne endemic fluorosis prevention and control knowledge among housewives and primary school students were 46.69% (409/876) and 82.49% (440.5/534), respectively. Among the 9 villages investigated, two villages had met the criteria for eliminating endemic disease areas, two villages had met the criteria for controlling endemic disease areas, and the remaining 5 villages were uncontrolled.Conclusions:After implementing the comprehensive prevention and control measures mainly based on changing stoves, coal-burning-borne endemic fluorosis condition in Zhenxiong County has been effectively controlled, but there is still a significant gap between the elimination goals of some endemic fluorosis areas. Therefore, it is necessary to continue to strengthen prevention and control measures and promote health education.

Objective:To assess the impact of different exercise modalities on cognitive and physical functions in elderly patients with cognitive frailty using a network meta-analysis based on frequency theory.Methods:A comprehensive computer and manual search was conducted in PubMed, Web of Science, Embase, CINAHL, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for randomized controlled trials on the effects of exercise training on cognitive and physical functions in elderly patients with cognitive frailty. The search covered studies published until December 31, 2023. To ensure the rigor of the study, two researchers independently screened the literature, evaluated the quality using the Cochrane risk of bias tool, and extracted data. Statistical analysis was conducted using Stata 14.0 software.Results:A total of 16 studies were included, involving 10 different exercise interventions (Baduanjin, Tai Chi Chuan, Mindfulness-based Tai Chi Chuan, Otago exercise, high-intensity interval training, dual-task exercise training, multicomponent exercise, aerobic exercise, resistance exercise, and combined aerobic and resistance exercise). The network meta-analysis results showed that, compared with non-exercise control groups, Baduanjin and dual-task exercise training improved cognitive function in elderly patients with cognitive frailty ( P<0.05), with Baduanjin showing the best effect ( SUCRA=0.79). Multicomponent exercise improved frailty ( P<0.05) with the best effect ( SUCRA=1.00), it also improved grip strength ( P<0.05), with the best effect ( SUCRA=0.89). Multicomponent exercise and dual-task exercise training improved walking speed ( P<0.05), multicomponent exercise had the best effect ( SUCRA=1.00) . Conclusions:Baduanjin has an advantage in improving cognitive function in elderly patients with cognitive frailty, while multicomponent exercise is more effective in improving frailty, grip strength, and walking speed. However, the conclusions of this study need further validation.

Objective:To investigate the current prevalence and control status of coal-burning-borne endemic fluorosis in key areas of the disease in Zhenxiong County of Yunnan Province, thereby providing scientific basis for formulating subsequent prevention strategies and measures.Methods:From October to November 2023, a simple random sampling method was used to conduct a survey in three key townships (towns) in Zhenxiong County, Chishuiyuan Town, Yanyuan Town, and Linkou Yi and Miao Ethnic Township. Three administrative villages were selected from each township (town) as survey sites, and dental fluorosis examination on children aged 8 - 12 years who were born and lived in the local area was conducted. Thirty households were selected from each survey site, the use of household stoves and the formation of related healthy living behaviors were investigated. At the same time, a survey was conducted among primary school students and housewives to investigate their knowledge of coal-burning-borne endemic fluorosis prevention and control. The control and elimination of endemic areas were evaluated according to the "Assessment Protocol for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:A total of 1 172 children were examined, and the detection rate of dental fluorosis was 7.76% (91/1 172), with a dental fluorosis index of 0.11. A total of 295 households were investigated, and the qualified improved stoves rate and the correct use rate of qualified improved stoves were 95.59% (282/295) and 100% (282/282), respectively. The correct drying rate of edible corn and chili peppers was 79.66% (235/295). The awareness rates of coal-burning-borne endemic fluorosis prevention and control knowledge among housewives and primary school students were 46.69% (409/876) and 82.49% (440.5/534), respectively. Among the 9 villages investigated, two villages had met the criteria for eliminating endemic disease areas, two villages had met the criteria for controlling endemic disease areas, and the remaining 5 villages were uncontrolled.Conclusions:After implementing the comprehensive prevention and control measures mainly based on changing stoves, coal-burning-borne endemic fluorosis condition in Zhenxiong County has been effectively controlled, but there is still a significant gap between the elimination goals of some endemic fluorosis areas. Therefore, it is necessary to continue to strengthen prevention and control measures and promote health education.

BACKGROUND:Aerobic exercise can suppress liver fibrosis in diabetic mice.However,the specific mechanism is yet to be elucidated.OBJECTIVE:To investigate the protective effect and mechanism of aerobic exercise on liver fibrosis in db/db mice via the transforming growth factor-β/Smad signaling pathway.METHODS:8-week-old male db/db mice and age-matched m/m mice were randomly divided into m/m control group,m/m+exercise group,db/db control group,and db/db+exercise group,with 10 mice in each group.Mice in the exercise group were subjected to a 12-week aerobic exercise.After the exercise,fasting blood glucose levels were measured in mice,and glucose tolerance and insulin tolerance tests were conducted.Mouse liver was extracted to calculate liver index and mouse eyeballs were taken to collect blood sample and detect biochemical indicators.Masson,oil red O and Hematoxylin-eosin staining were used to detect and analyze the pathological changes in mouse liver tissues.Immunohistochemistry was used to determine the protein expression levels of transforming growth factor-β1 and p-Smad3.Western blot analysis was applied to determine the protein expression levels of transforming growth factor-β1,Smad3,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen.RESULTS AND CONCLUSION:Compared with the m/m group and m/m+exercise group,body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels were significantly increased(P<0.01),but the high-density lipoprotein level significantly decreased(P<0.01)in the db/db group;the protein expressions of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen significantly increased(P<0.01)in the db/db group;the area under curve of glucose and insulin tolerance tests significantly increased(P<0.01)in the db/db group;and pathological staining of the liver in the db/db group showed extensive infiltration of inflammatory cells,increased lipid droplets,and significant fibrosis.In the db/db+exercise group,aerobic exercise could significantly reduce body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels(P<0.05 or P<0.01),and increase high-density lipoprotein level(P<0.05).Similarly,a marked decrease was observed in the protein expression levels of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen(P<0.05 or P<0.01)in the db/db+exercise group.In addition,the area under the curve of glucose tolerance and insulin tolerance tests significantly decreased(P<0.01,P<0.05),and pathological changes in liver tissues were significantly improved.In conclusion,aerobic exercise can attenuate liver fibrosis in diabetic mice,which may be related to the regulation of the transforming growth factor-β1/Smad signaling pathway.

Objective:To assess the impact of different exercise modalities on cognitive and physical functions in elderly patients with cognitive frailty using a network meta-analysis based on frequency theory.Methods:A comprehensive computer and manual search was conducted in PubMed, Web of Science, Embase, CINAHL, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for randomized controlled trials on the effects of exercise training on cognitive and physical functions in elderly patients with cognitive frailty. The search covered studies published until December 31, 2023. To ensure the rigor of the study, two researchers independently screened the literature, evaluated the quality using the Cochrane risk of bias tool, and extracted data. Statistical analysis was conducted using Stata 14.0 software.Results:A total of 16 studies were included, involving 10 different exercise interventions (Baduanjin, Tai Chi Chuan, Mindfulness-based Tai Chi Chuan, Otago exercise, high-intensity interval training, dual-task exercise training, multicomponent exercise, aerobic exercise, resistance exercise, and combined aerobic and resistance exercise). The network meta-analysis results showed that, compared with non-exercise control groups, Baduanjin and dual-task exercise training improved cognitive function in elderly patients with cognitive frailty ( P<0.05), with Baduanjin showing the best effect ( SUCRA=0.79). Multicomponent exercise improved frailty ( P<0.05) with the best effect ( SUCRA=1.00), it also improved grip strength ( P<0.05), with the best effect ( SUCRA=0.89). Multicomponent exercise and dual-task exercise training improved walking speed ( P<0.05), multicomponent exercise had the best effect ( SUCRA=1.00) . Conclusions:Baduanjin has an advantage in improving cognitive function in elderly patients with cognitive frailty, while multicomponent exercise is more effective in improving frailty, grip strength, and walking speed. However, the conclusions of this study need further validation.

Objective To conduct a retrospective cohort study on the influencing factors of poor prognosis of young and middle-aged patients with pulmonary tuberculosis. Methods Selecting 426 young and middle-aged patients who were diagnosed with pulmonary tuberculosis in our hospital from January to December 2018 as the research subjects. Collecting the social demography information of all patients and the information of potential factors affecting the prognosis (allergy history, smoking history, drinking history, BMI level, disease information, treatment information, etc.) and discussing the factors affecting the prognosis of young and middle-aged pulmonary tuberculosis patients and their effects. Results The average age of 426 patients was (41.93±5.17) years old, the average BMI of them was (21.97±3.15) kg/m2, and an average course of disease of them was (2.76±0.99) years. There was no significant difference in the basic sexual information between men and women. In this study, a total of 128 patients with poor prognosis were retrospectively followed up, including 90 males and 38 females. The detection rate of males was significantly higher than that of females (χ²=16.976, P<0.05). The detection rate of poor prognosis was lower in patients with lower BMI levels (F=12.774, P<0.001) and longer disease course (F=3.704, P<0.001). In addition, the proportion of patients with poor prognosis who had a history of smoking (χ²=18.850, P<0.001) and had comorbidities was higher (χ²=38.924, P<0.001), and the proportion of patients with ≥ 3 lung field lesions (χ²=127.207, P<0.001) and those with pulmonary cavities (χ²=32.566, P<0.001) were also higher, with statistically significant differences compared to those with good prognosis. Among those with poor prognosis, the proportion of regular treatment was lower (χ²=16.715, P<0.001), and the proportion of adverse reactions was higher (χ²=17.315, P<0.001). At the same time, a total of 128 cases with poor prognosis were retrospectively followed up in this study, and the incidence of poor prognosis was higher in males than in females (χ²=16.976，P<0.05) . At the same time , research has shown that the detection rate of poor prognosis has a potential positive correlation with lower BMI, longer disease duration, smoking history, comorbidities, ≥ 3 lung field lesions, and the presence of pulmonary cavities, while there is a potential negative correlation with regular treatment, both P<0.05. In the study, univariate regression equations were used to discuss the impact of potential factors on adverse prognosis. It can be seen that male, emaciated body type, disease course ≥ 5 years, smoking history, number of lung field lesions ≥ 3, pulmonary cavities, and comorbidities are potential risk factors, with HR>1 and P<0.05; Regular treatment suggests a potential protective factor, with an HR of 0.341 and P<0.05. Multivariate regression analysis further suggests that male, emaciated body type, smoking history, pulmonary cavities, and comorbidities are potential risk factors, with HR>1 and P<0.05; Regular treatment still showed potential protective factors, with an HR of 0.408, P<0.05. Conclusion: Male, emaciated body type, disease course ≥ 5 years, smoking history, number of lung field lesions ≥ 3, presence of pulmonary cavities and comorbidities are potential risk factors, while regular treatment suggests potential protective factors. Conclusion More targeted disease control and management should be implemented for middle-aged and young patients with pulmonary tuberculosis based on the aforementioned influencing factors to improve their prognosis.

Background As the population ages, there has been a growing focus on the decline in fertility. Research has identified age and fertility history as the primary influencing factors. Nevertheless, there is a deficiency in fundamental data regarding the fertility status among different industries. Objective To investigate the fertility status and influencing factors among female workers aged 22-35 years in different industries. Methods From July 2020 to February 2021, a cross-sectional survey was conducted using a staged sampling approach. This survey specifically targeted 22-35-year-old married female workers with a history of pregnancy in industries such as education, healthcare, finance, and telecommunications, totaling 22903 participants. The survey encompassed industry, demographic characteristics, pregnancy history, time to pregnancy (TTP), and other influencing factors. The influencing factors of decline in fertility were identified by chi-square test and Cox proportional hazards regression. Subsequent industry-specific Cox proportional hazards regression models were used to compared fertility decline patterns across a spectrum of industries after selected influencing factors were adjusted. Results Among the 22903 respondents, 19194 valid questionnaires were collected, with a valid recovery rate of 83.8%. The cumulative pregnancy rates (CRP) of 1-6 months and 1-12 months for the 22-35-year-old female workers were 67.23% and 91.33% respectively. The multivariate analysis showed that region, age, education level, personal annual income, housework time, coping style, gravidity, parity, and spontaneous abortion were influencing factors of fertility decline (P<0.05). Female workers with ≥3 gravidities and ≥2 spontaneous abortions had a higher risk of fertility decline, with hazard ratios (HR) and associated 95% confidence interval (95%CI) of 0.633 (0.582, 0.688) and 0.785 (0.670, 0.921) respectively (P<0.01). Compared to the education industry, the healthcare and finance industries showed a higher risk of fertility decline, with HR (95%CI) values of 0.876 (0.834, 0.920) and 0.909 (0.866, 0.954), respectively (P<0.05). These two HR (95%CI) values remained statistically significant [0.899 (0.852, 0.948) and 0.882 (0.833, 0.934) respectively, P<0.05)] after further adjustment with nine influencing factors such as region and age. Conclusion Regions, age, education level, personal annual income, housework time, coping style, pregnancy and childbirth times, and natural abortion times are influencing factors of fertility decline in female workers. Compared to the education industry, the healthcare and finance industries have a higher risk of declining fertility.