Environmental pollution is a significant public health challenge worldwide, and investigating the causal relationship between environmental exposure and population health outcomes is a key objective of environmental epidemiology research. In recent years, the complexity of environmental exposures has increasingly come to the forefront, making it challenging for observational studies that dominate environmental epidemiology to accurately estimate causal effects. Causal inference methods are particularly advantageous in controlling for confounding factors, thus holding great potential in environmental epidemiology research. Researchers can use appropriate causal inference methods to simulate the process of randomization, providing strong support for revealing the causal relationship between environmental exposure and health outcomes. However, there is a lack of reviews on the application of causal inference methods in environmental epidemiology studies in China. Therefore, this study introduced the basic principles of common causal inference statistical methods in environmental epidemiology, summarized the applicable conditions, advantages and disadvantages of various methods, and provided R software implementation codes for these methods, aiming to offer guidance for optimizing research design and practicing causal inference statistical methods.

Objective This study aimed to explore the underlying mechanisms between parental neglect and depression of adolescents.Methods This study utilized data from the 2020 China Family Panel Studies(CFPS)and included 1902 adolescents aged 10～15.Correlation analysis,multivariable logistic regression,structural equation modeling,and the bootstrap method were employed to examine the relationships between parental neglect,social trust,and depressive symptoms in adolescents.Results This study found that the prevalence of depressive symptoms among adolescents was 10.9%.Parental neglect was associated with an increased risk of depressive symptoms(OR:1.772,95%CI:1.310～2.636),and social trust acted as a mediator between parental neglect and depressive symptoms(mediating effect:17.20%,P<0.001).Additionally,gender moderated the latter half of the mediation model(β:0.127,95%CI:0.016～0.236,P<0.001).Conclusion The experiences of parental neglect are closely related to higher levels of depressive symptoms among adolescents,with social trust serving as a mediating factor.This mediating effect of social trust is particularly significant among females.It is crucial to cultivate a supportive environment and develop a harmonious family atmosphere.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative. Isovalerylspiramycin I (ISP I) as a major component of carrimycin applied to upper respiratory infections, was first found to possess anti-fibrotic potential. The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis. According to our results, ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation (BDL) rats and carbon tetrachloride (CCl₄) mice. We proved that nucleotide-binding protein 2 (NUBP2) was the direct target of ISP I. ISP I through targeting NUBP2, increased the amount of vascular non-inflammatory molecule-1 (VNN1) on the cell membrane, which will inhibit oxidative stress and fibrosis. Simultaneously, the original carrimycin's protective effect on liver damage and fibrosis was verified. Therefore, our study provides potential agents for patients with liver fibrosis-related diseases, and the clear mechanism supports wide application in the clinic.

ObjectiveBased on the conjoint analysis of transcriptome and metabolome， the key genes in the phenylpropanoid biosynthesis pathway of Lonicera macranthoides were explored， which provided a basis for further exploring the synthesis and regulation mechanism of phenylpropanoid compounds in "Xianglei" L. macranthoides. MethodsThe stem， leaves， and three flowering flowers of "Xianglei" L. macranthoides were selected as experimental materials to construct transcriptome and metabolome. The transcriptome and metabolomics were conjointly analyzed by the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and weighted correlation network analysis （WGCNA）， and the key genes in the phenylpropanoid biosynthesis pathway of L. macranthoides were explored. ResultsIn this study， 77 differential phenylpropanoids and 315 differential genes were found. Through the joint analysis of transcription and metabolism， nine key differential metabolites and four key genes related to them were finally discovered. Among them， cinnamic acid， 5-O-caffeoylshikimic acid，sinapyl alcohol， and chlorogenic acid were higher in flowers， and the content of the iconic effective component， namely chlorogenic acid，decreased sharply during the withering period. Caffeic acid，ferulic acid， 5-hydroxyconiferaldehyde，p-coumaryl alcohol， and syringin were higher in leaves. These four key genes belong to the cinnamic alcohol dehydrogenase （CAD） family， 4-coumaric acid： Coenzyme A （4CL） family， hydroxycinnamyl transferase （HCT） family， and L-phenylalanine ammonlyase （PAL） family genes. ConclusionAmong the four key genes excavated from L. macranthoides， TRINITY_DN42767_c0_g6 is related to the synthesis of p-coumaryl alcohol and sinapyl alcohol. TRINITY_DN43525_c4_g1 uses caffeic acid，ferulic acid，and cinnamic acid as substrates to catalyze the next reaction. TRINITY_DN47958_c3_g4 correlates with the synthesis of 3-p-coumaroyl quinic acid and caffeoyl-CoA， and TRINITY_DN52595_c1_g2 correlates with cinnamic acid synthesis. These findings provide a basis for further exploring the synthesis and regulation mechanism of phenylpropanoids in "Xianglei" L. macranthoides.

Objective To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.Methods Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/-male mice,which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTX fl/-control mice(M-Con)and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/-(M-KO),as well as female Ncr1-iCre-UTXfl/fl control mice(F-Con)and UTX-deficient female mice Ncr1-iCre+UTXfl/fl(F-KO).UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules.Moreover,flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells(CD3-CD19-NK1.1+),maturation makers KLRG1 and CD11b,activation receptors NKG2D and CD69,and effector molecules,including perforin,granzyme B,CD107a,and IFN-γ.Then pulmonary NK cells were sorted and co-cultured with B16F10 cells,and the apoptosis of the melanoma cells was measured with flow cytometry.Results Compared with the M-Con mice,the M-KO mice presented less number of pulmonary tumor nodules(P<0.05),increased proportion and quantity of NK cells in the tumor microenvironment(P<0.01),though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b,enhanced expression level of cytotoxic molecule perforin(P<0.01),but no changes in the expression of effector molecule granzyme B,degranulation marker CD107a and cytokine IFN-γ in NK cells.Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells(P<0.05).Compared with the F-Con mice,the F-KO mice had no statistical difference in the number of pulmonary tumor nodules,but larger proportion and number of NK cells(P<0.05),decreased ratio of KLRG1 to CD11b(P<0.01),elevated level of perforin but decreased levels of granzyme B,CD107a and IFN-γ in NK cells(P<0.01).The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KO female mice(P<0.05).Conclusion NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.

Objective This study aimed to explore the underlying mechanisms between parental neglect and depression of adolescents.Methods This study utilized data from the 2020 China Family Panel Studies(CFPS)and included 1902 adolescents aged 10～15.Correlation analysis,multivariable logistic regression,structural equation modeling,and the bootstrap method were employed to examine the relationships between parental neglect,social trust,and depressive symptoms in adolescents.Results This study found that the prevalence of depressive symptoms among adolescents was 10.9%.Parental neglect was associated with an increased risk of depressive symptoms(OR:1.772,95%CI:1.310～2.636),and social trust acted as a mediator between parental neglect and depressive symptoms(mediating effect:17.20%,P<0.001).Additionally,gender moderated the latter half of the mediation model(β:0.127,95%CI:0.016～0.236,P<0.001).Conclusion The experiences of parental neglect are closely related to higher levels of depressive symptoms among adolescents,with social trust serving as a mediating factor.This mediating effect of social trust is particularly significant among females.It is crucial to cultivate a supportive environment and develop a harmonious family atmosphere.

Objective This study estimated the disability burden of diabetes attributable to smoking,alcohol consumption,and obesity among oilemployees.It provides a comprehensive assessment of the major chronic disease burden attributable to these factors,offering a scientific basis for risk factor prevention and control.Methods Years lived with disability(YLD)was used as the burden indicator for diabetes among oilemployees.Based on the counterfactual attribution method within the comparative risk assessment framework,the population attributable fraction(PAF)for diabetes due to different behavioral risk factors was estimated.The attributable risk was calculated using the exposure rates of risk factors and their relative risk(RR)associated with related diseases,which was then used to compute the attributable YLD.A proportional change model was used to predict the YLD rates of chronic diseases among oilfield employees in 2030 under different risk factor control scenarios,calculating the YLD that could be avoided through risk factor control.Results According to the PAF calculated using the proportional risk assessment framework,the attributable burden of diabetes due to smoking,alcohol consumption,and obesity was higher in male employees than in females,with older females having a higher attributable burden,while middle-aged and young males had a higher burden.For males,achieving control targets for smoking,alcohol consumption,and obesity by 2030 would result in a decrease in diabetes YLD rates by 17.53％,3.52％,and 56.20％,respectively,compared to natural trends.For females,achieving these targets would decrease YLD rates by 1.18％,1.32％,and 26.47％,respectively.The largest decrease in YLD rates for both male and female employees occurred under the obesity control scenario.Conclusion By studying health risk factors and disease burdens among employees,oil companies can develop and implement targeted health management plans,enhancing employee health protection and improving work efficiency and productivity.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin Ⅰ(ISP Ⅰ)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP Ⅰ in protecting against liver fibrosis.According to our results,ISP Ⅰ not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP Ⅰ.ISP Ⅰ through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carri-mycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides po-tential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.

In recent years, the relationship between intestinal flora dysbiosis and abnormal bile acid metabolism and anxiety has received widespread attention. This article discussed the biological mechanism of the pathogenesis of anxiety from the perspective of intestinal flora and bile acid metabolism, in order to provide new ideas and theoretical basis for the TCM prevention and treatment of anxiety. According to TCM, spleen and stomach belong to earth, liver and gallbladder belong to wood, when spleen qi is healthy, the normal distribution of water and grain essence can be achieved, so that the liver can be nourished, qi and blood is sufficient, and its excretory function is normal, and the bile is sufficient. Once the spleen is not healthy, the distribution of water and grain essence is good, affecting the metabolism of fluids, resulting in phlegm and dampness, the qi is not smooth, can affect the liver's excretory function; liver and wood depression for a long time, transgressing the spleen and earth, qi and blood lack of biochemical sources, the formation of soil congestion and wood depression of the pathological phenomenon will appear. From the viewpoint of modern medicine and molecular biology, changes in the structure of intestinal flora affect the organism through neurological, endocrine, immune and metabolic pathways, which is consistent with the pathogenesis of "congestion of the earth"; disorders in the metabolism of bile acids can lead to changes in neurotransmitters and synaptic structure in the brain, causing anxiety symptoms, which is consistent with the characteristics of "wood depression". The bile acid metabolism disorder can cause neurotransmitter and synaptic structure changes in the brain, causing anxiety symptoms, which is consistent with the characteristics of "wood depression". It is important to regulate the intestinal flora and bile acid metabolism pathway to ease the liver and strengthen the spleen to improve anxiety.

Objective This study estimated the disability burden of diabetes attributable to smoking,alcohol consumption,and obesity among oilemployees.It provides a comprehensive assessment of the major chronic disease burden attributable to these factors,offering a scientific basis for risk factor prevention and control.Methods Years lived with disability(YLD)was used as the burden indicator for diabetes among oilemployees.Based on the counterfactual attribution method within the comparative risk assessment framework,the population attributable fraction(PAF)for diabetes due to different behavioral risk factors was estimated.The attributable risk was calculated using the exposure rates of risk factors and their relative risk(RR)associated with related diseases,which was then used to compute the attributable YLD.A proportional change model was used to predict the YLD rates of chronic diseases among oilfield employees in 2030 under different risk factor control scenarios,calculating the YLD that could be avoided through risk factor control.Results According to the PAF calculated using the proportional risk assessment framework,the attributable burden of diabetes due to smoking,alcohol consumption,and obesity was higher in male employees than in females,with older females having a higher attributable burden,while middle-aged and young males had a higher burden.For males,achieving control targets for smoking,alcohol consumption,and obesity by 2030 would result in a decrease in diabetes YLD rates by 17.53％,3.52％,and 56.20％,respectively,compared to natural trends.For females,achieving these targets would decrease YLD rates by 1.18％,1.32％,and 26.47％,respectively.The largest decrease in YLD rates for both male and female employees occurred under the obesity control scenario.Conclusion By studying health risk factors and disease burdens among employees,oil companies can develop and implement targeted health management plans,enhancing employee health protection and improving work efficiency and productivity.