Traumatic Brain Injury and Risk of Dementia and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Previous studies have investigated the potential role of traumatic brain injury (TBI) in subsequent development of dementia and Alzheimer's disease (AD) but reported inconsistent results. We aimed to determine the association between TBI and subsequent occurrence of dementia and AD. METHODS: We performed a systematic search in PubMed and Web of Science for studies that quantitatively investigated the association between TBI and risk of dementia and AD and were published on or before September 21, 2021. A random-effects model was used to combine the estimates. RESULTS: Twenty-five eligible articles were included in this meta-analysis. The results suggested that TBI was associated with an increased risk of dementia (pooled odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.53-2.14). However, no association was observed between TBI and AD (pooled OR = 1.02, 95% CI = 0.91-1.15). In the subgroup analysis, TBI with loss of consciousness was not associated with risk of dementia (pooled OR = 0.96, 95% CI = 0.84-1.09). Besides, Asian ethnicity, male gender, and mean age of the participants less than 65 years were associated with a higher risk of dementia. CONCLUSION: Our study suggests an increased risk of dementia among individuals with TBI, highlighting the need for more intensive medical monitoring and health education in individuals with TBI. Biological mechanisms linking TBI and the development of dementia are needed in future studies.

Causal effect of autoimmune liver diseases on cancer: Meta-analyses of cohort studies and Mendelian randomization study.

BACKGROUND AND AIMS: Prior studies suggested that patients with autoimmune liver diseases (AiLDs) had an increased risk of cancer, whereas the causal effect remained unclear. METHODS: Meta-analyses concerning the relationship between AiLD and cancer risk were performed to calculate the pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). Then, the associations with a p value of <.05 were further validated by two-sample Mendelian randomization studies. RESULTS: A total of 37 cohort studies covering more than 34 558 patients were included, and we observed an increased risk of overall cancers (pooled RR = 3.64, 95% CI: 2.64-5.03, p < .001) and cancer-related death (pooled RR = 2.48, 95% CI: 1.73-3.53, p < .001) for patients with AiLD. Besides, overall and several site-specific cancers risk were found in patients with primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC) (p < .05). However, associations between genetically predisposed AIH, PBC, and PSC and the risk of specific cancers did not reach a significant level, except for PBC and gastric cancer (OR = 0.96, 95% CI: 0.93-0.99; p = .02). CONCLUSIONS: In addition to hepatobiliary cancer, results from the meta-analyses suggest that patients with AiLD might have an increased risk of several extrahepatobiliary cancers. However, the causal role of AiLD in cancer development needs to be further investigated.

Head Injury and Amyotrophic Lateral Sclerosis: A Meta-Analysis.

BACKGROUND: Prior studies have suggested that head injury might be a potential risk factor of amyotrophic lateral sclerosis (ALS). However, the association has not been well established. We aimed to provide a synopsis of the current understanding of head injury's role in ALS. METHODS: We performed a systematic search in PubMed for observational studies that quantitatively investigated the association between head injury and ALS risk published before April 10, 2020. We used a random-effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Fourteen eligible articles including 10,703 cases and 2,159,324 controls were selected in current meta-analysis. We found that head injury was associated with an increased risk of ALS (OR = 1.38, 95% CI: 1.20-1.60) and the association was slightly stronger concerning severe head injury and ALS risk (OR = 1.69, 95% CI: 1.27-2.23). Considering the number of head injuries (N) and ALS risk, the association was weak (OR = 1.23, 95% CI: 1.10-1.37, N = 1; OR = 1.29, 95% CI: 0.89-1.86, N ≥ 2). In addition, a strong association with ALS risk was found in individuals who suffered head injury <1 year (OR = 4.05, 95% CI: 2.79-5.89), and when the time lag was set at 1-5, 5-10, and >10 years, the pooled OR was 1.13, 1.35, and 1.10, respectively. CONCLUSION: This meta-analysis indicates that head injury, especially severe head injury, could increase ALS risk. Although a strong association is found between head injury <1 year and ALS risk in the current study, this result suggests a possibility of reverse causation.

The Injuries and Helmet Use in Bike Share Programs: A Systematic Review.

To investigate the injury effects of bike share programs and the helmet usage status in bike share programs. We conducted a systematic review of peer reviewed scientific literature. Searches were conducted in three databases (Pubmed, Scopus, and Web of Science) on March 1 2020 to identify all articles on the injury incidence related to bike share programs and the helmet usage status in bike share programs. Titles, abstracts, and full-text articles were screened to identify all articles relevant to the themes by two authors independently, and discrepancies were resolved after discussion with the third author. Standardised data extraction and quality assessment (The Newcastle-Ottawa Scale) were implemented. A sum of 491 records after removing duplicates was identified, 181 fulltext articles were screened, and 13 studies were included in the review. The primary outcome are injuries of bike share users and unhelmeted rate among bike share users as well as the unhelmeted rate among personal bike users. Two studies evaluated the injuries related to bike share users, but have inconclusive results. A total of 11 studies reported the unhelmeted rates in bike share programs ranging from 36.0 to 88.9%. There is a significant change in bike injuries with the implementation of bike share programs. Moreover, the unhelmeted rate of bike share users was generally higher than that of personal bike users, which may result from helmets' accessibility and users' safety perception.

[Epidemiology, Treatment, and Epidemic Prevention and Control of the Coronavirus Disease 2019: a Review].

This review summarizes the ongoing researches regarding etiology, epidemiology, transmission dynamics, treatment, and prevention and control strategies of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with comparison to severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and pandemic H1N1 virus. SARS-CoV-2 may be originated from bats, and the patients and asymptomatic carriers are the source of epidemic infection. The virus can be transmitted human-to-human through droplets and close contact, and people at all ages are susceptible to this virus. The main clinical symptoms of the patients are fever and cough, accompanied with leukocytopenia and lymphocytopenia. Effective drugs have been not yet available thus far. In terms of the prevention and control strategies, vaccine development as the primary prevention should be accelerated. Regarding the secondary prevention, ongoing efforts of the infected patients and close contacts quarantine, mask wearing promotion, regular disinfection in public places should be continued. Meanwhile, rapid detection kit for serological monitoring of the virus in general population is expected so as to achieve early detection, early diagnosis, early isolation and early treatment. In addition, public health education on this disease and prevention should be enhanced so as to mitigate panic and mobilize the public to jointly combat the epidemic.

Variants in the PSCA gene associated with risk of cancer and nonneoplastic diseases: systematic research synopsis, meta-analysis and epidemiological evidence.

Variants in the prostate stem cell antigen (PSCA) gene have been linked with risk of multiple cancers and other diseases. But results have been inconclusive and no systematic research synopsis has been available. We did a comprehensive meta-analysis to investigate associations between variants in this gene and risk of nine cancers and four nonneoplastic diseases based on data from 55 publications including 81 961 cases and 442 932 controls. We graded levels of cumulative epidemiological evidence of a significant association using the Venice criteria and false-positive report probability tests. We performed functional annotation for these variants using data from the Encyclopedia of DNA Elements Project and other public databases. We found that six variants were nominally significantly associated with an increased or reduced risk of three cancers and three nonneoplastic diseases (P < 0.05). Cumulative evidence of an association was graded as strong for rs2294008 [odds ratio (OR) = 1.32, P = 5.1 × 10-33], rs2976392 (OR = 1.29, P = 1.8 × 10-8), rs9297976 (OR = 0.75, P = 1.4 × 10-7), rs2976391 (OR = 1.38, P = 6.1 × 10-5) and rs138377917 (OR = 0.53, P = 0.008) with gastric cancer, rs2294008 with bladder cancer (OR = 1.15, P = 8.0 × 10-19), gastritis (OR = 1.35, P = 1.2 × 10-5), duodenal ulcer (OR = 0.68, P = 2.4 × 10-57) and gastric ulcer (OR = 0.88, P = 1.7 × 10-7). Data from the Encyclopedia of DNA Elements Project and other databases showed that these variants and other variants correlated with them might fall in putative functional regions. In conclusion, this study provides summary evidence that variants in the PSCA gene are associated with risk of gastric and bladder cancer, gastritis, as well as duodenal and gastric ulcer and highlights the significant role of this gene in the pathogenesis of these diseases.

Cumulative evidence for relationships between multiple variants in the VTI1A and TCF7L2 genes and cancer incidence.

Genetic studies have linked the VTI1A-TCF7L2 region with risk of multiple cancers. However, findings from these studies were generally inconclusive. We aimed to provide a synopsis of current understanding of associations between variants in the VTI1A-TCF7L2 region and cancer susceptibility. We conducted a comprehensive research synopsis and meta-analysis to evaluate associations between 17 variants in this region and risk of seven cancers using data from 32 eligible articles totaling 224,656 cancer cases and 324,845 controls. We graded cumulative evidence of significant associations using Venice criteria and false-positive report probability tests. We also conducted analyses to evaluate potential function of these variants using data from the Encyclopedia of DNA Elements (ENCODE) Project. Eight variants showed a nominally significant association with risk of individual cancer (p < 0.05). Cumulative epidemiological evidence of an association was graded as strong for rs7903146 [odds ratio (OR) = 1.05, p = 4.13 × 10-5 ] and rs7904519 (OR = 1.07, p = 2.02 × 10-14 ) in breast cancer, rs11196172 (OR = 1.11, p = 2.22 × 10-16 ), rs12241008 (OR = 1.13, p = 1.36 × 10-10 ) and rs10506868 (OR = 1.10, p = 3.98 × 10-9 ) in colorectal cancer, rs7086803 in lung cancer (OR = 1.30, p = 3.54 × 10-18 ) and rs11196067 (OR = 1.18, p = 3.59 × 10-13 ) in glioma, moderate for rs12255372 (OR = 1.12, p = 2.52 × 10-4 ) in breast cancer and weak for rs7903146 (OR = 1.11, p = 0.007) in colorectal cancer. Data from ENCODE suggested that seven variants with strong evidence and other correlated variants might fall within putative functional regions. Collectively, our study provides summary evidence that common variants in the VTI1A and TCF7L2 genes are associated with risk of breast, colorectal, lung cancer and glioma and highlights the significant role of the VTI1A-TCF7L2 region in the pathogenesis of human cancers.

Mycobacterium tuberculosis PE25/PPE41 protein complex induces activation and maturation of dendritic cells and drives Th2-biased immune responses.

Mycobacterium tuberculosis evades innate host immune responses by parasitizing macrophages and causes significant morbidity and mortality around the world. A mycobacterial antigen that can activate dendritic cells (DCs) and elicit effective host innate immune responses will be vital to the development of an effective TB vaccine. The M. tuberculosis genes PE25/PPE41 encode proteins which have been associated with evasion of the host immune response. We constructed a PE25/PPE41 complex gene via splicing by overlapping extension and expressed it successfully in E. coli. We investigated whether this protein complex could interact with DCs to induce effective host immune responses. The PE25/PPE41 protein complex induced maturation of isolated mouse DCs in vitro, increasing expression of cell surface markers (CD80, CD86 and MHC-II), thereby promoting Th2 polarization via secretion of pro-inflammatory cytokines IL-4 and IL-10. In addition, PE25/PPE41 protein complex-activated DCs induced proliferation of mouse CD4(+) and CD8(+) T cells, and a strong humoral response in immunized mice. The sera of five TB patients were also highly reactive to this antigen. These findings suggest that interaction of the PE25/PPE41 protein complex with DCs may be of great immunological significance.

The Mycobacterium bovis BCG prime-Rv0577 DNA boost vaccination induces a durable Th1 immune response in mice.

Tuberculosis remains a major global health problem and effective vaccines are urgently needed. In this study, we used the combined DNA- and protein-based vaccines of immunodominant antigen Rv0577 to boost BCG and evaluated their immunogenicity in BALB/c mice. Our data suggest that the booster vaccine may substantially enhance the immunogenicity of BCG and strengthen both CD4+ T cell-mediated Th1 and CD8+ T cell-mediated cytolytic responses. Compared with the protein-based vaccine, the DNA-based vaccine can induce more durable Th1 immune response, characterized by high levels of antibody response, proliferation response, percentages of CD4+/CD8+ and cytokine secretion in antigen-stimulated splenocyte cultures. In conclusion, we for the first time, developed a protein- and plasmid DNA-based booster vaccine based on Rv0577. Our findings suggest that antigen Rv0577-based DNA vaccine is immunogenic and can efficiently boost BCG, which could be helpful in the design of an efficient vaccination strategy against TB.

[Prokaryotic Expression of Rv0757 Gene in Mycobacterium tuberculosis and the Effect of Its Coding Protein on the Function of Macrophage].

OBJECTIVE: To construct recombinant plasmid pET28a-Rv0757 with Mycobacterium tuberculosis (Mtb) Rv0757 gene, and to determine the effect of the protein of Rv0757 gene on ANA-1 cells. METHODS: We recombined the amplified Rv0757 gene into theprokaryotic plasmid pET28a (+). The expressed product was identified by SDS-PAGE and Western blot. Murine macrophages were treated with purified protein PhoP. Survived cells, lactic dehydrogenase (LDH), nitric oxide (NO), and cell apoptosis were detected after the treatment. RESULTS: We successfully constructed the recombinant plasmid pET28a-Rv0757. The target protein was confirmed by SDS-PAGE and Western blot. The protein had no significant effect on cell numbers and LDH activities in the culture supernatant, but it inhibited the release of NO and apoptosis of ANA-1 cells. CONCLUSION: pET28a-Rv0757 plasmid with prokaryotic expression was successfully constructed. The targetprotein has no toxicity on macrophages, but it can inhibit NO release and cell apoptosis of ANA-1.

Expression and clinical significance of interleukin-6 pathway in cholangiocarcinoma.

Background: Cholangiocarcinoma (CCA) is a typical inflammation-induced malignancy, and elevated serum interleukin-6 (IL-6) levels have been reported to be linked to the onset and progression of CCA. We aim to investigate the potential prognostic value of the IL-6 pathway for CCA. Methods: We detected the expressions of IL-6, IL-6R, glycoprotein (gp130), C-reactive protein (CRP), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) in CCA tissue microarray using multiplex immunofluorescence. Furthermore, the clinical associations and prognostic values were assessed. Finally, single-cell transcriptome analysis was performed to evaluate the expression level of IL-6 pathway genes in CCA. Results: The results revealed that the expression of IL-6 was lower, while the expression of STAT3 was higher in tumor tissues compared to normal tissues. Especially in tumor microenvironment, the expression of IL-6 pathway genes was generally downregulated. Importantly, gp130 was strongly correlated with JAK2 in tumor tissues, while it was moderately correlated with JAK2 in normal tissue. Although none of the gene expressions were directly associated with overall survival and disease-free survival, our study found that IL-6, IL-6R, CRP, gp130, and JAK2 were inversely correlated with vascular invasion, which is a risk factor for poor prognosis in patients with CCA. Conclusion: The findings from this study suggest that the IL-6 signaling pathway may have a potential prognostic value for CCA. Further investigation is needed to understand the underlying molecular mechanisms of the IL-6 pathway in CCA.

Assessing the causal association of trauma with subsequent psychiatric disorders by a Mendelian randomization study trauma and common psychiatric disorders.

Objective: Trauma has been proposed as a risk factor for the development of psychiatric disorders. This study aimed to determine the causal role of trauma in six common psychiatric disorders. Methods: We obtained summary-level data for genetic variants associated with trauma and the corresponding association with psychiatric disorders from previous genome-wide association studies. Two-sample Mendelian randomization analyzes were performed to estimate the causal association between trauma and psychiatric disorders, with inverse variance weighted used as the main method. Results: Genetically predisposed trauma was associated with an increased risk of psychiatric disorders [odds ratio (OR) =1.24, 95%, confidence interval (CI), 1.09-1.40], anxiety disorder (OR = 1.30, 95% CI, 1.10-1.52) and schizophrenia (OR = 1.48, 95% CI, 1.18-1.84). However, the associations between trauma and sleep disorder (OR = 1.17, 95% CI, 1.01-1.35), as well as depression (OR = 1.09, 95% CI, 1.02-1.16) did not reach a Bonferroni corrected significance level. Besides, no association was observed between trauma and risk of bipolar disorder (OR = 1.21, 95% CI, 0.98-1.48) and eating disorder (OR = 1.28, 95% CI, 0.88-1.86). Conclusion: Trauma might be causally associated with an increased risk of some common psychiatric disorders such as anxiety disorder and schizophrenia. However, little evidence supported an association between trauma and risk of depression, bipolar disorder, sleep disorder, and eating disorder. Our findings offered novel insights into the trauma-mediated development mechanism of psychiatric disorders, and psychological intervention to patients with trauma may be an effective prevention strategy for psychological diseases.

Ethnicity Disparities in the Prevalence, Awareness, Treatment, and Control Rates of Hypertension in China.

Objectives: Previous studies reported that there were disparities in hypertension management among different ethnic groups, and this study aimed to systematically determine the prevalence, awareness, treatment, and control rates of hypertension in multiple Chinese ethnic groups. Methods: We searched Embase, PubMed, and Web of Science for articles up to 25 October, 2022. The pooled prevalence, awareness, treatment, and control rates of hypertension were estimated with 95% confidence intervals (CI). The heterogeneity of estimates among studies was assessed by the Cochran Q test and I 2 statistic. Meta-regression analyses were conducted to identify the factors influencing the heterogeneity of the pooled prevalence, awareness, treatment, and control rate of hypertension. Results: In total, 45 publications including 193,788 cases and 587,826 subjects were eligible for the analyses. The lowest prevalence was found in the Han group (27.0%), and the highest prevalence was in the Mongolian population (39.8%). The awareness rates ranged from 24.4% to 58.0% in the four ethnic groups. Both the highest treatment and control rates were found in the Mongolian population (50.6% and 16.0%, respectively), whereas the Yi group had the lowest control rate (8.0%). In addition, the study year, the mean age of subjects, mean body mass index of subjects, tobacco use (%), alcohol use (%), residence (urban%), and education (primary school%) had varied effects on heterogeneity. Conclusions: These findings highlight the disparities in prevalence, awareness, treatment, and control rates of hypertension in a different ethnic population of China, which could provide suggestions for making targeted prevention measures.

Hepatitis B and C virus infections and the risk of biliary tract cancers: a meta-analysis of observational studies.

BACKGROUND: Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important risk factors for hepatocellular carcinoma. However, their effect on other hepatobiliary cancers, such as biliary tract cancers (BTCs), is not well established. We aimed to investigate associations between HBV or HCV infection and BTCs risk by conducting a systematic review and meta-analysis. METHODS: We searched PubMed to identify all relevant articles published before June 9, 2021. Meta-analysis was performed to calculate pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The meta-analysis was evaluated by heterogeneity testing, sensitivity analyses, and publication bias assessment. RESULTS: In total, 48 articles involving 69,723 cases and 4,047,574 controls were obtained to calculate the associations between HBV or HCV infection and the risk of BTCs. We found that both HBV and HCV infections were associated with the risk of BTCs, with pooled ORs of 2.16 (95% CI 1.73-2.69) and 2.12 (95% CI 1.62-2.77), respectively. Subgroup analyses by ethnicity suggested that HBV infection could increase the risk of BTCs in both Asian (OR = 2.29, 95% CI 1.76-2.97) and Caucasian (OR = 1.80, 95% CI 1.18-2.75) populations. In addition, HCV infection resulted in a higher increased risk of BTCs in Caucasian populations than in Asian populations (OR = 3.93 vs. 1.51, P = 0.014). In particular, significantly increased risks of intrahepatic cholangiocarcinoma (ICC) were identified in individuals with HBV (OR = 3.96, 95% CI 3.05-5.15) or HCV infection (OR = 2.90, 95% CI 2.07-4.08). CONCLUSIONS: This study suggests that both HBV and HCV infections are risk factors for BTCs, particularly ICC, highlighting the necessity of cancer screening for BTCs in patients with either HBV or HCV infection.

Association Between Systemic Lupus Erythematosus and Cancer Morbidity and Mortality: Findings From Cohort Studies.

Background: Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization. Methods: A systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization. Results: A total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79, P<0.001) and cancer-related death (RR=1.52, 95%CI, 1.36-1.70, P<0.001) in patients with SLE. Subgroup analysis by site-specific cancer showed that SLE was a risk factor for 17 site-specific cancers, including six digestive cancers (esophagus, colon, anus, hepatobiliary, liver, pancreatic), five hematologic cancers (lymphoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma), as well as cancer in lung, larynx, cervical, vagina/vulva, renal, bladder, skin, and thyroid. In addition, further mendelian randomization analysis verified a weakly association between genetically predisposed SLE and lymphoma risk (odds ratio=1.0004, P=0.0035). Conclusions: Findings from our study suggest an important role of SLE in carcinogenesis, especially for lymphoma. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42021243635.

Cumulative Evidence for Associations Between Genetic Variants in Interleukin 6 Receptor Gene and Human Diseases and Phenotypes.

Background: Genetic studies have linked polymorphisms in the interleukin 6 receptor (IL6R) gene to the risk of multiple human diseases and phenotypes, yet have reported inconsistent results. We aimed to synthesize current knowledge of variants in the IL6R gene on the risk of diseases and phenotypes. Methods: We searched the Medline and Embase databases to identify relevant publications. Meta-analysis was performed utilizing DerSimonian and Laird random-effects model. We also graded cumulative evidence for significant associations. Furthermore, phenome-wide analyses and functional annotations were performed for variants with strong evidence. Results: We included 155 studies for evaluating the associations between 80 polymorphisms in the IL6R gene and the risk of 102 human diseases and 98 phenotypes. We conducted 58 main meta-analyses, and 41 significant associations were identified. Strong evidence was assigned to 29 associations that investigated ten variants (rs2228145, rs4129267, rs7529229, rs4537545, rs7518199, rs4845625, rs4553185, rs4845618, rs4845371, and rs6667434) related to the risk of four cardiovascular diseases (coronary heart disease, coronary artery disease, atherosclerosis, and abdominal aortic aneurysms), four inflammatory diseases (rheumatoid arthritis, Crohn's disease, dermatitis, and asthma), and concentration of four phenotypes (C-reactive protein, fibrinogen, IL-6, and sIL-6R). Furthermore, phenome-wide analysis verified that rs2228145 associated with asthma and dermatitis risk. Functional analyses indicated that these polymorphisms fall within exon, enhancer regions. Conclusions: Our study comprehensively summarizes current data on the genetic architecture of the IL6R gene and highlights the pharmacological targeting potential of IL-6R on cardiovascular and inflammatory diseases.

The association between altitude and the prevalence of hypertension among permanent highlanders.

Hypertension (HTN) is a growing contributor to the global disease burden, and it is prevalent among people living at high altitudes (H-ALTs). This study aimed to explore the relationship between altitude and the prevalence of HTN among inhabitants living at H-ALTs. We searched electronic databases, including PubMed, Embase, and Web of Science, up to April 30, 2022. The quality of included studies was assessed using the Joanna Briggs Institute (JBI) checklist for prevalence studies. A total of 1273 articles were screened, and 32 studies (86,487 participants) were eligible for further analyses. The pooled prevalence among highlanders was 28.7%. General additive model (GAM)-based meta-regression analysis was conducted to explore the association between altitude and the prevalence of HTN. A curve-shaped line was found between altitude and the prevalence of HTN (ß = 0.998, p = 0.039) after adjusting for factors including publication year, sample size, age, sex, ethnic group, body mass index (BMI), smoking and alcohol consumption. The turning point was observed at 3300 m. The predictive parameter indicated that the smoothness and goodness of model fit were good (GCV = 0.014, R2 = 0.60, respectively). The findings may provide clues for further mechanistic studies that can improve HTN prevention among highlanders.

Effect of antihypertensive medications on sleep status in hypertensive patients.

Purpose: Antihypertensive medication is an effective way to control blood pressure. However, some studies reported that it may affect patients' sleep quality during the treatment. Due to the inconsistency of present results, a comprehensive systematic review and network meta-analysis are needed. Methods: Electronic databases (MEDLINE, EMBASE, WEB OF SCIENCE, PUBMED) were searched up to April 10th, 2021 including no restriction of publication status. Randomized controlled trials (RCTs) or quasi-experimental studies or cohort studies were eligible. The network meta-analysis was used within a Bayesian framework. Results: Finally, 16 publications (including 12 RCTs and 4 quasi-experimental studies) with 404 subjects were included in this study. Compared to placebo, the results of the network meta-analysis showed that diuretics were effective in improving sleep apnea with a mean difference (MD) of - 15.47 (95% confidence interval [CI]: - 23.56, - 6.59) which was consistent with the direct comparison result (MD: - 17.91; 95% CI - 21.60, - 14.23). In addition, diuretics were effective in increasing nocturnal oxygen saturation with an MD of 3.64 (95% CI 0.07, 7.46). However, the effects of ß-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and the others on sleep apnea were not statistically significant. Additionally, the effects of antihypertensive medication on the total sleep time (min), rapid eye movement (%), and sleep efficiency (%) were not statistically significant. Conclusion: Our study found that diuretics could effectively reduce the severity of sleep apnea in hypertensive patients. However, the effects of antihypertensive drugs on sleep characteristics were not found. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00391-8.

The Causal Relationships Between Extrinsic Exposures and Risk of Prostate Cancer: A Phenome-Wide Mendelian Randomization Study.

BACKGROUND: Prostate cancer is the second most common cancer in males worldwide, and multitudes of factors have been reported to be associated with prostate cancer risk. OBJECTIVES: We aim to conduct the phenome-wide exposed-omics analysis of the risk factors for prostate cancer and verify the causal associations between them. METHODS: We comprehensively searched published systematic reviews and meta-analyses of cohort studies and conducted another systematic review and meta-analysis of the Mendelian randomization studies investigating the associations between extrinsic exposures and prostate cancer, thus to find all of the potential risk factors for prostate cancer. Then, we launched a phenome-wide two-sample Mendelian randomization analysis to validate the potentially causal relationships using the PRACTICAL consortium and UK Biobank. RESULTS: We found a total of 55 extrinsic exposures for prostate cancer risk. The causal effect of 30 potential extrinsic exposures on prostate cancer were assessed, and the results showed docosahexaenoic acid (DHA) [odds ratio (OR)=0.806, 95% confidence interval (CI): 0.661-0.984, p=0.034], insulin-like growth factor binding protein 3 (IGFBP-3) (OR=1.0002, 95%CI: 1.00004-1.0004, p=0.016), systemic lupus erythematosus (SLE) (OR=0.9993, 95%CI: 0.9986-0.99997, p=0.039), and body mass index (BMI) (OR=0.995, 95%CI: 0.990-0.9999, p=0.046) were associated with prostate cancer risk. However, no association was found between the other 26 factors and prostate cancer risk. CONCLUSIONS: Our study discovered the phenome-wide exposed-omics risk factors profile of prostate cancer, and verified that the IGFBP-3, DHA, BMI, and SLE were causally related to prostate cancer risk. The results may provide new insight into the study of the pathogenesis of prostate cancer.

Addictive behavior and incident gallstone disease: A dose-response meta-analysis and Mendelian randomization study.

Background: Previous studies have suggested associations between addictive behavior and gallstone disease (GSD) risk, yet conflicting results exist. It also remains unclear whether this association is causal or due to confounding or reverse associations. The present study aims to systematically analyze the epidemiological evidence for these associations, as well as estimate the potential causal relationships using Mendelian randomization (MR). Methods: We analyzed four common addictive behaviors, including cigarette smoking, alcohol intake, coffee, and tea consumption (N = 126,906-4,584,729 participants) in this meta-analysis based on longitudinal studies. The two-sample MR was conducted using summary data from genome-wide associations with European ancestry (up to 1.2 million individuals). Results: An observational association of GSD risk was identified for smoking [RR: 1.17 (95% CI: 1.06-1.29)], drinking alcohol [0.84 (0.78-0.91)], consuming coffee [0.86 (0.79-0.93)], and tea [1.08 (1.04-1.12)]. Also, there was a linear relationship between smoking (pack-years), alcohol drinking (days per week), coffee consumption (cups per day), and GSD risk. Our MRs supported a causality of GSD incidence with lifetime smoking [1.008 (1.003-1.013), P = 0.001], current smoking [1.007 (1.002-1.011), P = 0.004], problematic alcohol use (PAU) [1.014 (1.001-1.026), P = 0.029], decaffeinated coffee intake (1.127 [1.043-1.217], P = 0.002), as well as caffeine-metabolism [0.997 (0.995-0.999), P = 0.013], and tea consumption [0.990 (0.982-0.997), P = 0.008], respectively. Conclusion: Our study suggests cigarette smoking, alcohol abuse, and decaffeinated coffee are causal risk factors for GSD, whereas tea consumption can decrease the risk of gallstones due to the effect of caffeine metabolism or polyphenol intake.