Causal association of monocytes with chronic kidney disease and the mediation role of frailty: A study integrating large-scale two-sample Mendelian randomization and single-cell analysis.

BACKGROUND: Recent research reported that frailty was prevalent among adults with chronic kidney disease (CKD) in clinical trials, and monocytes illustrated a similar difference in these two diseases compared to the normal. However, the scientific evidence for a causal relationship between these two diseases was lacking, with further exploration into whether monocytes co-regulate them. METHODS: We aimed to integrate large-scale Mendelian randomization (MR) and single-cell transcriptome analysis to determine whether there was a causal relationship between frailty and CKD (Bidirectional two-sample Mendelian determined the causal direction), whether monocytes impacted them, and whether the two diseases shared genetic variation sites. Based on 441 Genome-wide association study datasets, this study utilized five MR methods, multiple sensitivity analysis, and corresponding single-cell transcriptome datasets as proof. RESULTS: The association between frailty and CKD was significantly causal, and frailty increased the risk of CKD in patients (OR (95 %CI): 3.5597 (1.8369-6.8982), p = 0.000168909). The exposure monocyte can increase the risk of frailty and CKD in patients, especially with high expression of HLA genes in these cells. The existing two-sample MR results cannot reject the hypothesis that monocytes increase the risk of CKD by inducing frailty. rs9275271' 1mb genetic location above and below had been proven to be an effective genetic space for both frailty and CKD. CONCLUSION: We conducted the largest MR to date on frailty, monocyte, and CKD, and found a significant causal association between frailty and CKD, with the single-cell analysis confirmed. The exposure monocytes increased the risk of frailty and CKD, particularly with high expression of HLA genes in these cells. We identified a potential common genetic variant space, rs9275271, associated with frailty and CKD, providing insights into the genetic basis of these conditions.

Causal effects of gut microbiome on HIV infection: a two-sample mendelian randomization analysis.

BACKGROUND: The causal association between gut microbiome and HIV infection remains to be elucidated. We conducted a two-sample mendelian randomization analysis to estimate the causality between gut microbiome and HIV infection. METHODS: Publicly released genome-wide association studies summary data were collected to perform the mendelian analysis. The GWAS summary data of gut microbiome was retrieved from the MiBioGen consortium, which contains 18 340 samples from 24 cohorts. GWAS summary data of HIV infection was collected from the R5 release of FinnGen consortium, including 357 HIV infected cases and 218 435 controls. The SNPs were selected as instrumental variables according to our selection rules. And SNPs with a F-statistics less than ten were regarded as weak instrumental variables and excluded. Mendelian randomization analysis was conducted by five methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. The Cochran's Q test and MR-Egger intercept test were performed to identify heterogeneity and pleiotropy. Leave-one-out analysis were used to test the sensitivity of the results. RESULTS: Fifteen gut microbiota taxa showed causal effects on HIV infection according to the MR methods. Four taxa were observed to increase the risk of HIV infection, including Ruminococcaceae (OR: 2.468[1.043, 5.842], P: 0.039), Ruminococcaceae UCG005 (OR: 2.051[1.048, 4.011], P: 0.036), Subdoligranulum (OR: 3.957[1.762, 8.887], P < 0.001) and Victivallis (OR: 1.605[1.012, 2.547], P=0.044). Erysipelotrichaceae was protective factor of HIV infection (OR: 0.278[0.106, 0.731], P < 0.001) and Methanobrevibacter was also found to be associated with reduced risk of HIV infection (OR: 0.509[0.265, 0.980], P=0.043). Horizontal pleiotropy was found for Fusicatenibacter (P<0.05) according to the MR-Egger regression intercept analysis. No heterogeneity was detected. CONCLUSION: Our results demonstrate significant causal effects of gut microbiome on HIV infection. These findings facilitate future studies to develop better strategies for HIV prophylaxis through gut microbiome regulation. Further explorations are also warranted to dissect the mechanism of how gut microbiome affects HIV susceptibility.

Exploring relevant factors of cognitive impairment in the elderly Chinese population using Lasso regression and Bayesian networks.

Older adults are highly susceptible to developing cognitive impairment(CI). Various factors contribute to the prevalence of CI, but the potential relationships among these factors remain unclear. This study aims to explore the relevant factors associated with CI in Chinese older adults and analyze the potential relationships between CI and these factors.We analyzed the data on 6886 older adults aged≥60 from the China Health and Retirement Longitudinal Study (CHARLS) 2018. Lasso regression was initially used to screening variables. Bayesian Networks(BNs) were used to identify the correlates of CI and potential associations between factors. After screening with Lasso regression, 11 variables were finally included in the BNs. The BNs, by establishing a complex network relationship, revealed that age, education, and indoor air pollution were the direct correlates affecting the occurrence of CI in older adults. It also indicated that marital status indirectly influenced CI through age, and residence indirectly linked to CI through two pathways: indoor air pollution and education.Our findings underscore the effectiveness of BNs in unveiling the intricate network linkages among CI and its associated factors, holding promising applications. It can serve as a reference for public health departments to address the prevention of CI in the elderly.

Using an extended information-motivation-behavioral skills model to explain HPV vaccination intention among men who have sex with men only and men who have sex with men and women.

Men who have sex with men and women (MSMW) have been reported to differ in psychosocial and sexual behavior patterns from men who have sex with men only (MSMO). However, results regarding the differences in HPV vaccination intention/behavior were inconclusive. We compared HPV vaccination intention between MSMO and MSMW and analyzed the differences in potentially associated factors in China. MSM participants were recruited online using a snowball sampling method. Cross-sectional data were collected via a questionnaire based on the extended information-motivation-behavioral skills model. Structural equation modeling was conducted to examine the relationship between the variables, followed by multi-group analysis to test differences between groups. Of 914 MSM, 77.68% were MSMO and 22.32% were MSMW. MSMW had a higher rate of reluctance to vaccinate than MSMO (23.53% vs. 16.20%, p = .016). Differences between the two groups were statistically significant in risky sexual behavior, behavioral skills, and promotional attitude. In both groups, promotional attitude was the most significant predictor of vaccination intention. Vaccination intention was directly influenced by motivation and indirectly by risky sexual behavior in MSMO, but not significantly in MSMW. Additionally, the direct effect of information on behavioral skills in MSMW was significantly greater than that in MSMO, but we did not find any effect of behavioral skills on vaccination intention. MSMW had lower vaccination intention than MSMO. MSMO may be influenced by risky sexual behavior and motivation, positively impacting their vaccination intention, unlike MSMW. Targeted strategies could help promote HPV vaccination, especially in MSMW.

A robust primary liver cancer subtype related to prognosis and drug response based on a multiple combined classifying strategy.

The recurrence or resistance to treatment of primary liver cancer (PLL) is significantly related to the heterogeneity present within the tumor. In this study, we integrated prognosis risk score, mRNAsi index, and immune characteristics clustering to classify patients. The four subtypes obtained from the combined classification are associated with PLC's prognosis and drug response. In these subtypes, we observed mRNAsiH_ICCA subtype, the intersection between high mRNAsi and immune characteristics clustering A, had the worst prognosis. Specifically, immune characteristics clustering B (ICC_B) had high drug sensitivity in most drugs regardless of the value of mRNAsi. On the other hand, patients with low mRNAsi responded better to ten drugs including KU-55933 and NU7441, while patients with high mRNAsi might benefit from drugs like Leflunomide. By matching the specific characteristics of each combined subtype with the drug-induced cell line expression profile, we identified a group of potential therapeutic drugs that might regulate the expression of disease signature genes. We developed a feasible multiple combined typing strategy, hoping to guide therapeutic selection and promote the development of precision medicine.

Integrating Machine Learning and Mendelian Randomization Determined a Functional Neurotrophin-Related Gene Signature in Patients with Lower-Grade Glioma.

Recent researches reported that neurotrophins can promote glioma growth/invasion but the relevant model for predicting patients' survival in Lower-Grade Gliomas (LGGs) lacked. In this study, we adopted univariate Cox analysis, LASSO regression, and multivariate Cox analysis to determine a signature including five neurotrophin-related genes (NTGs), CLIC1, SULF2, TGIF1, TTF2, and WEE1. Two-sample Mendelian Randomization (MR) further explored whether these prognostic-related genes were genetic variants that increase the risk of glioma. A total of 1306 patients have been included in this study, and the results obtained from the training set can be verified by four independent validation sets. The low-risk subgroup had longer overall survival in five datasets, and its AUC values all reached above 0.7. The risk groups divided by the NTGs signature exhibited a distinct difference in targeted therapies from the copy-number variation, somatic mutation, LGG's surrounding microenvironment, and drug response. MR corroborated that TGIF1 was a potential causal target for increasing the risk of glioma. Our study identified a five-NTGs signature that presented an excellent survival prediction and potential biological function, providing new insight for the selection of LGGs therapy.

Mononuclear phagocyte system-related multi-omics features yield head and neck squamous cell carcinoma subtypes with distinct overall survival, drug, and immunotherapy responses.

BACKGROUND: Recent research reported that mononuclear phagocyte system (MPS) can contribute to immune defense but the classification of head and neck squamous cell carcinoma (HNSCC) patients based on MPS-related multi-omics features using machine learning lacked. METHODS: In this study, we obtain marker genes for MPS through differential analysis at the single-cell level and utilize "similarity network fusion" and "MoCluster" algorithms to cluster patients' multi-omics features. Subsequently, based on the corresponding clinical information, we investigate the prognosis, drugs, immunotherapy, and biological differences between the subtypes. A total of 848 patients have been included in this study, and the results obtained from the training set can be verified by two independent validation sets using "the nearest template prediction". RESULTS: We identified two subtypes of HNSCC based on MPS-related multi-omics features, with CS2 exhibiting better predictive prognosis and drug response. CS2 represented better xenobiotic metabolism and higher levels of T and B cell infiltration, while the biological functions of CS1 were mainly enriched in coagulation function, extracellular matrix, and the JAK-STAT signaling pathway. Furthermore, we established a novel and stable classifier called "getMPsub" to classify HNSCC patients, demonstrating good consistency in the same training set. External validation sets classified by "getMPsub" also illustrated similar differences between the two subtypes. CONCLUSIONS: Our study identified two HNSCC subtypes by machine learning and explored their biological difference. Notably, we constructed a robust classifier that presented an excellent classifying prediction, providing new insight into the precision medicine of HNSCC.

Efficacy and Safety of High-Dose Vitamin D Supplementation vs Solifenacin or Standard Urotherapy for Overactive Bladder Dry in Children: A Randomized Clinical Trial.

PURPOSE: We investigated the efficacy and safety of high-dose vitamin D supplementation (VDS) plus standard urotherapy (SU) in managing overactive bladder dry in children. MATERIALS AND METHODS: A 3-arm, randomized clinical trial was performed at an academic center in China between January 2023 and June 2023. Eligible patients (n=303) were randomized to receive 8 weeks of high-dose VDS (vitamin D3 drops encapsulated as soft capsules, 2400 IU/d) plus SU (VDS + SU group; n=100), solifenacin (5-10 mg/d) plus SU (SOL + SU group; n=102), or SU alone (SU group; n=101). Reduction in voiding frequency was the primary outcome. Secondary outcomes encompassed improvement in urgency, nocturia, quality of life score, pediatric lower urinary tract symptom score, and participant satisfaction. Treatment-emergent adverse events were recorded within each group. RESULTS: Participants had a median age of 82.0 months and their baseline mean vitamin D level was 22.64 ng/mL. The VDS + SU group showed greater improvements in voids/d than the SOL + SU group (median difference 3.0; 95% CI, 2.0 to 3.5; P < .001) and the SU group (median difference 4.0; 95% CI, 3.0 to 5.0; P < .001) after intervention. The VDS + SU group also showed the greatest improvement in quality of life and pediatric lower urinary tract symptom scores. Patient satisfaction was similar between the SOL + SU and SU groups. The VDS + SU group did not exhibit a heightened risk of treatment-emergent adverse events compared to the other groups. CONCLUSIONS: High-dose VDS plus SU was effective and well-tolerated in managing overactive bladder dry in children, suggesting its potential as a novel therapeutic option for this population.

Gut microbiome dysbiosis in men who have sex with men increases HIV infection risk through immunity homeostasis alteration.

Objectives: Recent studies pointed out that gut microbiome dysbiosis in HIV infection was possibly confounded in men who have sex with men (MSM), but there is a lack of evidence. It also remained unclear how MSM-associated gut microbiome dysbiosis affected human health. This study aimed to compare the differences in gut microbiome changes between HIV and MSM and reveal the potential impacts of MSM-associated gut microbiome dysbiosis on the immune system. Methods: We searched available studies based on the PubMed database, and all gut microbiome changes associated with HIV infection and MSM were extracted from the enrolled studies. The gutMgene database was used to identify the target genes and metabolites of the gut microbiome. Bioinformatic technology and single-cell RNA sequencing data analysis were utilized to explore the impacts of these gut microbiome changes on human immunity. Results: The results showed significant overlaps between the gut microbiome associated with HIV and that of MSM. Moreover, bioinformatic analysis revealed that gut microbiome dysbiosis in MSM had an impact on several pathways related to immunity, including the IL-17 signaling pathway and Th17 cell differentiation. Additionally, target genes of MSM-associated gut microbiome were found to be highly expressed in monocytes and lymphocytes, suggesting their potential regulatory role in immune cells. Furthermore, we found that MSM-associated gut microbiome could produce acetate and butyrate which were reported to increase the level of inflammatory factors. Conclusion: In conclusion, this study highlighted that MSM-associated gut microbiome dysbiosis might increase the risk of HIV acquisition by activating the immune system. Further studies are expected to elucidate the mechanism by which gut microbiome dysbiosis in MSM modulates HIV susceptibility.

A Study of the Relationship between Men Who Have Sex with Men Stigma and Depression: A Moderated Mediation Model.

(1) Background: Men who have sex with men (MSM) have a high prevalence of depression due to stigma. However, whether resilience and social support play a moderating role in the effects of stigma on depression remains to be tested. This study constructed a moderated mediation model to explore the mediating role of perceived stigma in the relationship between enacted stigma and depression and whether this relationship is moderated by social support. (2) Methods: MSM were recruited during November-December 2022 using a non-probability sampling method, and a total of 1091 participants were included. Enacted stigma, perceived stigma, resilience, social support, and depressive symptoms were measured. Mediation and moderated mediation models were used to analyze the relationships between these variables. (3) Results: Moderated mediation analyses show that enacted stigma indirectly affects depression through perceived stigma (ß = 0.315, 95% confidence interval = 0.221 to 0.421). Social support had a positive moderating effect between enacted stigma and depressive symptoms (ß = 0.194, p < 0.001) and a negative moderating effect between perceived stigma and depressive symptoms (ß = -0.188, p < 0.001). (4) Resilience and perceived stigma mediated the relationship between enacted stigma and depression, and the relationship between enacted stigma, perceived stigma, and depression was moderated by social support. Reducing stigma while increasing social support has the potential to alleviate depressive symptoms among Chinese MSM.

Factors Influencing Intention on Condom Use During Sexual Intercourse With Regular Female Partners Among Men Who Have Sex With Men in Western China: A Structural Equation Modeling Analysis.

BACKGROUND: Given the rapid rise in HIV infection among men who have sex with men (MSM) in China, they may be a potential bridge for HIV transmission to the general female population, and increasing condom use is an important protective measure. This study aimed to explore factors that influence the intention of condom use during sexual intercourse with regular female partners among MSM in Western China, based on the Health Action Process Approach model. METHODS: This study used a baseline sample from a cohort study of the National Science and Technology Major Project. A nonprobability sampling method was adopted to recruit MSM from western China. Information on sociodemographic characteristics, HIV-related characteristics, sexual behavior, and constructs of the Health Action Process Approach model was collected through structured questionnaires, and the data were analyzed using a structural equation model. RESULTS: Among 232 participants, 62.9% (146 of 232) intended to use condoms every time they had sex with their regular female partners during the following 3 months. The results of the structural equation model showed that self-efficacy had the greatest influence on behavioral intention (ß = 0.398, P < 0.001), followed by negative outcome expectancy (ß = -0.303, P < 0.05). In addition, risk perception (ß = 0.206, P < 0.05) and positive outcome expectancy (ß = 0.270, P < 0.01) had indirect effects on intention, whereas self-efficacy played a mediating role in these indirect influencing factors. CONCLUSIONS: Risk perception, outcome expectancy, and self-efficacy are predictors of condom use intention, with self-efficacy in particular serving as a significant medium for future interventions. These findings could provide a reference for future targeted interventions to reduce the likelihood of HIV transmission from MSM to the female population.

Association between daytime napping and cognitive impairment among Chinese older population: a cross-sectional study.

BACKGROUND: Both napping and nighttime sleep duration have been reported to be associated with cognitive function in older adults, whereas little is known about the association between daytime napping and cognitive impairment in different nighttime sleep duration subgroups. This study aimed to explore the correlation between daytime napping and cognitive impairment across nighttime sleep duration subgroups. METHODS: A cross-sectional study was conducted by using the fourth survey of China Health and Retirement Longitudinal Study (CHARLS). We utilized the Mini-Mental State Examination (MMSE) scale to define cognitive impairment, and the daytime napping and nighttime sleep duration was self-reported by individuals. We applied the Restricted Cubic Spline (RCS) to analysis the dose-response relationships between daytime napping and cognitive impairment. And the multivariate Logistic Regression Model (LRM) was performed to evaluate the association of daytime napping and cognitive impairment. RESULTS: A total of 3,052 individuals were included, of which 769 were cognitive impairment. The RCS showed there were non-linear association between daytime napping and cognitive impairment in all participants group and longer nighttime sleep duration subgroup (PNon-linear < 0.05, PDaytime napping < 0.05). The LRM revealed no napping (OR = 1.62, 95%CI 1.14-2.30) and excessive napping (1.64 95%CI 1.09-2.48) were related to cognitive impairment in longer nighttime sleep duration subgroup. CONCLUSIONS: Daytime napping had nonlinear association with cognitive impairment in Chinese elderly population. No napping and excessive daytime napping (>90 minutes) were related to cognitive impairment in participants with 7 and more hours nighttime sleep duration.

Psychological Health and Risk Factors of College Students within the Context of the COVID-19 Pandemic: A Cross-Sectional Study.

BACKGROUND: Students are a priority population in mental health research. This study aimed to explore the risk factors of anxiety and depression symptoms among college students in Chongqing, a megacity under the impact of COVID-19, and to provide a basis for determining the priorities of public health policies and implementing effective educational health care interventions. METHODS: In this cross-sectional study conducted in Chongqing, China, the data came from web-based stratified random sampling. Anxiety and depression symptoms were measured by the Self-Rating Anxiety Scale (SAS) and the Center for Epidemiological Studies Depression Scale (CES-D), respectively, and risk factors were analyzed by logistic regression. RESULTS: Data were obtained from 915 college students (34.75% were male, and 65.25% were female) with age (20.29 ± 1.51) in Chongqing, China. The prevalence rates of anxiety and depression were 19.78% and 22.62%, respectively. Logistic regression analysis revealed that the risk factors of anxiety symptoms were associated with junior years, sleep time of less than 6 h a day, influence on career planning, and depression symptoms. Comprehensive, science and engineering, and medicine disciplines, having siblings, poorer mastery of study, and anxiety symptoms were risk factors for developing depression symptoms. CONCLUSIONS: During the pandemic, college students experienced varying degrees of anxiety and depression. Our research findings highlight the necessity of universities and relevant departments providing precise mental health education for college students under major public health emergencies.

Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Increasing evidence highlights the significant role of immune-related genes (IRGs) in ACC progression and immunotherapy, but the research is still limited. Based on the Cancer Genome Atlas (TCGA) database, immune-related molecular subtypes were identified by unsupervised consensus clustering. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were employed to further establish immune-related gene signatures (IRGS). An evaluation of immune cell infiltration, biological function, tumor mutation burden (TMB), predicted immunotherapy response, and drug sensitivity in ACC patients was conducted to elucidate the applicative efficacy of IRGS in precision therapy. ACC patients were divided into two molecular subtypes through consistent clustering. Furthermore, the 3-gene signature (including PRKCA, LTBP1, and BIRC5) based on two molecular subtypes demonstrated consistent prognostic efficacy across the TCGA and GEO datasets and emerged as an independent prognostic factor. The low-risk group exhibited heightened immune cell infiltration, TMB, and immune checkpoint inhibitors (ICIs), associated with a favorable prognosis. Pathways associated with drug metabolism, hormone regulation, and metabolism were activated in the low-risk group. In conclusion, our findings suggest IRGS can be used as an independent prognostic biomarker, providing a foundation for shaping future ACC immunotherapy strategies.

A structural equation modeling approach to investigate HIV testing willingness for men who have sex with men in China.

BACKGROUND: A substantial risk of contracting Human immunodeficiency virus (HIV) exists among men who have sex with men (MSM), and HIV infection rates have been rising. This study aimed to analyze the factors influencing the Chinese MSM population's intention to test for HIV. METHODS: Nonprobability sampling techniques were employed in June 2022 to recruit MSM in Chongqing and Sichuan, China. The data were analyzed using structural equation modeling (SEM), which is based on the knowledge-attitude-behavior (KAB) theory. RESULTS: Among 1687 participants, 964 (57.1%) of the MSM were willing to have an HIV test. The results of the structural equation modeling (SEM) showed that knowledge, attitude, and behavior all influenced the testing intention, with attitude having the greatest impact (total effect of 0.22). CONCLUSION: HIV testing needs to be increased among MSM as they exhibit a moderate willingness to test. Improving education on HIV knowledge and risk behavior might enhance the willingness of MSM to test for HIV in China.

The Potential Risk Compensation after Receiving HPV Vaccination among Men Who Have Sex with Men in Southwest China: A HAPA-Based Analysis.

Background: men who have sex with men (MSM) are a high-risk group for human papillomavirus (HPV) infection, and the HPV vaccine is effective in preventing it. However, according to risk compensation theory, people may increase sexual risk behaviors after receiving HPV vaccination. Based on the Health Action Process Approach (HAPA), this study investigated the influencing factors to predict intention to reduce condom use (risk compensation intention) among MSM after taking HPV vaccination in southwest China. Methods: we conducted a cross-sectional study among 948 MSM in southwest China using a non-probability sampling method and an electronic questionnaire including sociodemographic characteristics, sexual risk behavior characteristics, HPV-related prevention behavior, and the HAPA scale. Confirmatory factor analysis was performed using a structural equation model. Results: among 948 MSM, the incidence rate of reducing the frequency of condom use was 14.1%. The structural equation model showed that self-efficacy (ß = -0.378, p = 0.020) and positive outcome expectancy (ß = 0.366, p < 0.05) had greater effects on behavioral intention, followed by negative outcome expectancy (ß = -0.296, p < 0.05) and risk perception (ß = -0.232, p < 0.05). Conclusions: risk compensation may not be a major barrier to receiving HPV vaccination among MSM. Nevertheless, the recognition of possible risk compensation is necessary to implement appropriate interventions to reduce the occurrence of risk compensation.

Antihypertensive drugs may not delay the symptom progression of Parkinson's disease: A 2-year follow-up study.

Background: Parkinson's disease (PD) is one of the most common neurodegenerative disease, and half of PD patients have hypertension as well. The effect of antihypertensive drugs on the progression of PD has been less studied. The focus of this study was on the changes in dopamine transporter (DAT) levels to assess the effect of antihypertensive drugs on the progression of PD. Methods: Data from 321 drug-naïve patients from the Parkinson's Disease Progression Marker Initiative (PPMI) were collected over a 2-year period. Patients were divided into the PD with arterial hypertension (AH) group (102 cases) with antihypertensive drugs, the PD with other cardiovascular risk factors (CVRFs) group (60 cases) with antidiabetic and/or lipid-lowering drugs, and the pure PD group (159 cases) without CVRFs. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Hoehn-Yahr (H&Y) stage were used to assess progression. DAT semiquantitative values were used to evaluate damage to dopaminergic neurons in the substantia nigra, including the contralateral and ipsilateral count density ratio and asymmetry index. Results: There were no significant differences among the three groups in MDS-UPDRS score and H&Y stage. Changes in DAT levels among the three groups were without distinct differences in the first year and second year. In each group, DAT decreased more in the first year than in the second year. There was no decrease in DAT uptake in the PD with AH group compared with the other groups during the follow-up period. Conclusions: There is no evidence that antihypertensive drugs can delay PD progression within 2 years.

The Mediation and Moderation Effect Association among Physical Activity, Body-Fat Percentage, Blood Pressure, and Serum Lipids among Chinese Adults: Findings from the China Health and Nutrition Surveys in 2015.

Physical activity (PA) is of benefit and particularly important for cardiovascular disease risk factors as being sedentary becomes a lifestyle habit. Research into Chinese complex association among physical activity, body-fat percentage (BF%), blood pressure, and serum lipids is limited. The present study is based on an observational study among adults (>18 years old) residing in fifteen provinces in China. Data of 10,148 adult participants in the 2015 China Health and Nutrition Survey (CHNS) were analyzed. The simple mediation effect models with covariates were utilized to assess the association among PA and blood pressure or serum lipids, and BF% was played as a mediator. The serial multiple-mediator models with covariates were constructed to the further analysis of the relationship between PA and blood pressure, and BF% was the mediator 1 and blood lipids were the mediator 2. Based on the above hypothesis, the moderated mediation models with covariates were used to analyze the association among PA, BF%, and blood pressure; in addition, BF% was used as the mediator and blood lipids played as the moderator. In the simple mediation models, the model with a dependent variable was high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C); BF% was played as the partly mediation effect and the proportion of contribution was 0.23 and 0.25, respectively. In the serial multiple-mediator models, blood lipids, as the second mediator, played the mediation effect; however, the effect was smaller than the BF%. In the moderated mediation model, blood lipids had the moderation effect as the moderator variable. HDL-C played a moderating role in the latter pathway of the "PA→BF%→SBP/DBP" mediation model, and LDL-C/TC played a moderating role in the direct effect of the "PA→BF%→DBP". In conclusion, BF% played a mediating role in the relationship between PA and blood pressure. HDL-C, LDL-C, and TC were more likely to act as moderating variables in the mediation model "PA→BF%→SBP/DBP". PA could directly and indirectly benefit to control the CVD risk factors simultaneously.

Dysregulation of lipid metabolism in the pseudolobule promotes region-specific autophagy in hepatitis B liver cirrhosis.

BACKGROUND: Chronic hepatitis B (CHB) infection leads to liver cirrhosis (LC), the end stage of liver fibrosis. The precise diagnosis and effective therapy for hepatitis B cirrhosis are still lacking. It is highly necessary to elucidate the metabolic alteration, especially the spatial distribution of metabolites, in LC progression. METHODS: In this study, LC-MS/MS together with an airflow-assisted ionization mass spectrometry imaging system was applied to analyze and compare the metabolites' spatial distribution in healthy control (HC) and hepatitis B LC tissue samples. The liver samples were further divided into several subregions in HC and LC groups based on the anatomical characteristics and clinical features. RESULTS: Both the LC-MS/MS and mass spectrometry imaging results indicated separated metabolite clusters between the HC and LC groups. The differential metabolites were mainly concentrated in lipid-like molecules and amino acids. The phosphatidylcholines (PCs), lysoPCs, several fatty acids, and amino acids reduced expression in the LC group with region specific. Acyl-CoA thioesterase 2 and choline/ethanolamine phosphotransferase 1, which regulate PC and fatty acid metabolism, were significantly decreased in the pseudolobule. Meanwhile, the increased expression of LC3B and p62 in the pseudolobule indicated the upregulation of autophagy. CONCLUSIONS: Hepatitis B LC induced region-specific autophagy by increasing the expression of LC3B and p62 in the pseudolobule and by dysregulation of unsaturated fatty acids, amino acids, and PC metabolism. The mass spectrometry imaging system provided additional metabolites' spatial information, which can promote biomarker screening technology and support the exploration of novel mechanisms in LC.