The complexity of glucose time series is associated with short- and long-term mortality in critically ill adults: a multi-center, prospective, observational study.

BACKGROUND: The wealth of data taken from continuous glucose monitoring (CGM) remains to be fully used. We aimed to evaluate the relationship between a promising new CGM metric, complexity of glucose time series index (CGI), and mortality in critically ill patients. METHODS: A total of 293 patients admitted to mixed medical/surgical intensive care units from 5 medical centers in Shanghai were prospectively included between May 2020 and November 2021. CGI was assessed using intermittently scanned CGM, with a median monitoring period of 12.0 days. Outcome measures included short- and long-term mortality. RESULTS: During a median follow-up period of 1.7 years, a total of 139 (47.4%) deaths were identified, of which 73 (24.9%) occurred within the first 30 days after ICU admission, and 103 (35.2%) within 90 days. The multivariable-adjusted HRs for 30-day mortality across ascending tertiles of CGI were 1.00 (reference), 0.68 (95% CI 0.38-1.22) and 0.36 (95% CI 0.19-0.70), respectively. For per 1-SD increase in CGI, the risk of 30-day mortality was decreased by 51% (HR 0.49, 95% CI 0.35-0.69). Further adjustment for HbA1c, mean glucose during hospitalization and glucose variability partially attenuated these associations, although the link between CGI and 30-day mortality remained significant (per 1-SD increase: HR 0.57, 95% CI 0.40-0.83). Similar results were observed when 90-day mortality was considered as the outcome. Furthermore, CGI was also significantly and independently associated with long-term mortality (per 1-SD increase: HR 0.77, 95% CI 0.61-0.97). CONCLUSIONS: In critically ill patients, CGI is significantly associated with short- and long-term mortality.

[Occupational hazards of crystalline silicon solar cell manufacturing industry].

The wide use of crystalline silicon solar cells in the field of new energy is an important boost for China to achieve the environmental protection goal as soon as possible. However, the production and manufacturing processes of these cells give rise to various occupational hazards at workplace, thus posing health risks to workers. This review provided an overview of production processes of crystalline silicon solar cells, the characteristics of occupational health hazards (productive dust; physical factors, productive toxicant) and proposed occupational protection suggestions.

Impact of shift work on dementia: a systematic review and dose-response meta-analysis.

OBJECTIVES: Although shift work has been reported as having a link to dementia, evidence remains inconsistent, and a comprehensive dose-response meta-analysis of the association is still lacking. We therefore conducted this meta-analysis to explore the association between shift work and the risk of dementia. STUDY DESIGN: Systematic review and dose-response meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were systematically searched. Fixed or random-effects models were used to estimate the summary relative risks (RRs) and 95% confidence intervals (95% CIs). Generalized least squares regression was used to estimate dose-response associations, and restricted cubic splines were used to examine possible linear or non-linear associations. RESULTS: Five articles (10 studies) with 72,999 participants and 23,067 cases were eventually included in the meta-analysis. The summary RRs and 95% CIs of dementia risk with shift work and night shift work versus daytime work were 1.13 (95% CI: 1.05-1.21, I2 = 46.70%) and 1.13 (95% CI: 1.03-1.24, I2 = 9.20%), respectively. The risk of dementia increased by 1% (RR = 1.01, 95% CI: 1.01-1.02, I2 = 41.3%) with each 1-year increase in the duration of shift work. We found a non-linear dose-response association between the duration of shift work and the risk of dementia (Pnon-linearity = 0.006). Though the shape of the curve was steeper with the duration of shift work <7 years, the increase was more gradual after 7 years. CONCLUSION: Our findings suggest that shift work may be a risk factor for future dementia and that controlling the length of shift work is a feasible measure that may contribute to prevent dementia.

Association of radiotherapy for prostate cancer and second primary colorectal cancer: a US population-based analysis.

BACKGROUND: Radiotherapy (RT) is a common treatment for prostate cancer, yet the risk of second primary colorectal cancer (SPCRC) in patients with prostate cancer undergoing RT has not been adequately studied. METHODS: This study employed a population-based cohort design using the US Surveillance, Epidemiology, and End Results (SEER) database to identify individuals diagnosed between January 1975 and December 2015. The cumulative incidence of SPCRC was estimated using Fine-Gray competing risk regression. Poisson regression analysis was used to estimate the risk associated with RT. Survival outcomes of patients with SPCRC were evaluated using the Kaplan-Meier method. RESULTS: A total of 287,607 patients diagnosed with prostate cancer were identified. The cumulative incidences were higher in patients who did not receive RT (2.00%) compared to those who underwent RT (2.47%) after 25 years. After adjustment for multiple variables, RT was associated with an increased risk of developing combined SPCRC (adjusted HR 1.590). Additionally, the overall survival was significantly lower in patients who developed colorectal cancer after receiving RT as compared to those who did not receive RT. CONCLUSION: These findings underscore the need for diligent long-term monitoring and effective management strategies to detect SPCRC in patients treated with RT for prostate cancer.

Andrographolide restored production performances and serum biochemical indexes and attenuated organs damage in Mycoplasma gallisepticum-infected broilers.

1. This study aimed to study the preventive and therapeutic effects of andrographolide (Andro) during Mycoplasma gallisepticum HS strain (MG) infection in ArborAcres (AA) broilers.2. The minimum inhibitory concentration (MIC) of Andro against MG was measured. Broiler body weight, feed efficiency, morbidity, cure rate and mortality were recorded during the experiment. Air sac lesion scores and immune organ index were calculated. Expression of pMGA1.2 in lung tissue and serum biochemical indices were examined. Histopathological examinations of immune organs, liver, trachea and lung tissue were conducted by Haematoxylin and Eosin stain.3. MIC was 3.75 µg/mL and Andro significantly inhibited the expression of pMGA1.2 (P ≤ 0.05). Compared with control MG-infected group, Andro low-dose and high-dose prevention reduced the morbidity of chronic respiratory disease in 40.00% and 50.00%, respectively. Mortality of C, D and E group was 16.67%, 10.00% and 6.67%, respectively. Cure rate of E, F, G and H group was 92.00%, 92.86%, 93.33% and 100.0%, respectively. Compared with control MG-infected group, Andro treatment significantly increased average weight gain (AWG), relative weight gain rate (RWG) and feed conversion rate (FCR) at 18 to 24 days (P ≤ 0.05). Compared with control group, Andro alone treatment significantly increased AWG in broilers (P ≤ 0.05).4. Compared with control MG-infected group, Andro significantly attenuated MG-induced air sac lesion, immune organs, liver, trachea and lung damage in broilers. Andro alone treatment did not induce abnormal morphological changes in these organs in healthy broilers. Serum biochemical analysis results showed, comparing with control MG-infected group, Andro significantly decreased the content of total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, urea, creatinine, uric acid, total cholesterol, and increased the albumin/globulin ratio and content of alkaline phosphatase, apolipoprotein B and apolipoprotein A-I in a dose-dependent manner (P ≤ 0.05).5. Andro could act as a potential agent against MG infection in broilers.

[Constructing the Bayesian network models to explore the factors related to glomerular and tubular injury].

Objective: To construct Bayesian network (BN) models to explore the factors related to glomerular injury (GI) and tubular injury (TI). Methods: A cross-sectional study was carried out. From April to November 2019, Shanxi Provincial People's Hospital performed an opportunistic screening for chronic kidney disease in 10 counties of Shanxi Province. The general data and laboratory results of blood and urine samples were collected. Chi-square test and logistic regression were used to explore the related factors of GI and TI, which were included in the construction of BN models with max-min hill-climbing (MMHC) algorithm. Results: A total of 12 269 participants were included, there were 5 198 males and 7 071 females, with a median age of 58 (40-91) years. The prevalence of GI and TI was 12.7% (1 561/12 269) and 11.6% (1 425/12 269), respectively. The BN model consisted of 8 nodes and 10 edges for GI, and 11 nodes and 17 edges for TI, respectively. BN models showed that age and glycated hemoglobin were direct related factors for GI, while gender and fasting blood glucose were indirect related factors for GI. Age, gender, fasting blood glucose and glycosylated hemoglobin were direct related factors for TI. Additionally, the area under the receiver operating characteristic curve (AUC) was 0.761 (95%CI: 0.746-0.777) and 0.753 (95%CI: 0.736-0.769) for GI and TI BN models, respectively. Conclusions: BN models allow for identifying the complex network relationships among the factors related to GI and TI. Meanwhile, Bayesian risk reasoning can provide reference value for the clinical prevention of GI and TI.

[Visualization analysis of research hotspots in pathogenesis of diabetic nephropathy in China].

The aim of this study is to analyze the research hotspots and development trends in the field of pathogenesis of diabetic nephropathy in China from 2013 to 2022. Based on China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Science and Technology Journal Database, China Biology Medicine disc, Web of Science core collection and PubMed database, the related literatures in the field of pathogenesis of diabetic nephropathy in China from 2013 to 2022, were retrieved to establish the database, and the VOSviewer software was used for bibliometric analysis. A total of 1 664 Chinese and 2 149 English literatures are included in this study. The scientific research results from 2013 to 2022 have shown an overall increasing trend. The research hotspots in the field of pathogenesis of diabetic nephropathy in China are mainly concentrated in Podocytes, Oxidative stress, Inflammation, Renal fibrosis, Urine protein, etc. The frontier hotspots in this field include Biomarkers, Nrf2, Gut microbiota, NLRP3 inflammasome, Apoptosis, MicroRNA, etc. Through visual analysis, the research hotspots and frontier trends of the pathogenesis of diabetic nephropathy in China can be visually presented, and then provide new ideas and directions for the further in-depth research on the pathogenesis of diabetic nephropathy.

[Association between different treatment timings and adverse neonatal outcomes in pregnant women with syphilis during pregnancy].

Objective: To analyze the association between different treatment timings and adverse neonatal outcomes (premature birth, death, congenital syphilis) in syphilis-infected pregnant women. Methods: The National Management Information System for Prevention of HIV, Syphilis and HBV Mother-to-Child Transmission was used to collect information on the detection and treatment of syphilis-infected pregnant women and their newborns in Guangdong Province from October 2011 to December 2021. According to the gestational weeks of syphilis-infected pregnant women receiving penicillin treatment for the first time, they were divided into four groups: treatment in the first trimester, treatment in the second trimester, treatment in the third trimester, and no treatment during pregnancy. Multivariate logistic regression was used to analyze the association between different treatment timings and adverse neonatal outcomes in syphilis-infected pregnant women. Results: A total of 22 483 syphilis-infected pregnant women were included. The number of pregnant women who started treatment in the first trimester, second trimester, and third trimester and did not receive treatment during pregnancy were 4 549 (20.23%), 8 719 (38.78%), 2 235 (9.94%) and 6 980 (31.05%), respectively. Compared with pregnant women who started treatment in the first trimester, pregnant women who did not receive anti-syphilis treatment during pregnancy had increased risks of neonatal preterm birth (OR=1.42, 95%CI: 1.24-1.62), death (OR=4.27, 95%CI: 1.64-14.69) and congenital syphilis (OR=12.26, 95%CI: 6.35-27.45). At the same time, the risk of congenital syphilis in the newborns of pregnant women who started anti-syphilis treatment in the second trimester (OR=2.68, 95%CI: 1.34-6.16) and third trimester (OR=6.27, 95%CI: 2.99-14.80) also increased. Conclusion: Early initiation of anti-syphilis treatment during pregnancy in patients with syphilis can improve neonatal outcomes.

[Epidemiological investigation on the local epidemic situation in Zhengzhou High-Tech Zone caused by SARS-CoV-2 Delta variant].

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.

[Study on optimization of image processing parameters of pneumoconiosis by DR].

Objective: To explore the effect of different post-processing parameters of digital radiography (DR) on the quality of chest X-ray for pneumoconiosis diagnosis, and to provide suggestions on parameter setting suitable for this kind of DR machine. Methods: From January 1, 2022 to June 30, 2022, the chest films of 35 workers in the department of radiology of Hangzhou occupational disease prevention and treatment hospital were randomly selected and printed after setting different image post-processing parameters. The quality of chest film was evaluated by the measurement of optical densitometer and the combination of subjective and objective by professional physicians. Results: When the density is set to 2 and the contrast/detail contrast is 4.5, the optical density of each area of DR chest film meets the requirements of chest X-ray quality, and the qualified rate of physician quality evaluation is the highest. Conclusion: Reasonable setting of image post-processing parameters can improve the quality of chest radiograph.

Development of ruminating behavior in Holstein calves between birth and 30 days of age.

Ruminating behavior accompanies the development of the rumen and the intake of solid feed in calves. However, few studies have reported on the emergence and development of rumination. In this study, we observed ruminating behavior changes of 56 Holstein calves (body weight at birth = 40.1 ± 3.96 kg; mean ± standard deviation) from birth to 30 d of age under the feeding management of suckling calves that were only fed pelleted concentrate feed and milk. All calves were housed in individual pens equipped with infrared cameras. We explored feed intake within 30 d of age, body weight on 61 d of age, and other apparent indicators, including the age of first eating the bedding, duration of non-nutritive oral behavior at 25 and 30 d of age, total starter feed intake within 30 d of age, average daily starter feed intake within 30 d of age, and duration of ruminating behavior at 25 and 30 d of age for all calves, to further explore the effects of the age of first ruminating behavior (AFR). The AFR fitted the normal distribution and ranged from 15 to 20 d of age for 50% of the experimental population. The AFR was positively correlated with the age of first eating the bedding and duration of non-nutritive oral behavior at 30 d of age. Total starter feed intake within 30 d of age, average daily starter feed intake within 30 d of age, duration of ruminating behavior at 25 and 30 d of age, and duration of eating the bedding at 25 and 30 d of age were negatively correlated with AFR. Overall, to the best of our knowledge, this is the first study that has analyzed the correlation between AFR and other indicators. We found that earlier AFR was associated with shorter duration of non-nutritive oral behavior, longer durations of rumination and eating the bedding, and higher feed intake by 30 d of age.

Cohort study evaluation of New Chinese Diabetes Risk Score: a new non-invasive indicator for predicting type 2 diabetes mellitus.

OBJECTIVES: We aimed to evaluate the predictive power of new Chinese Diabetes Risk Score (NCDRS) for type 2 diabetes mellitus (T2DM) based on a large prospective cohort study. STUDY DESIGN: Large prospective cohort study. METHODS: The baseline examination of the Rural Chinese Cohort Study was initiated in 2007-2008 and followed up in 2013-2014 in Luoyang city, Henan Province of China. The NCDRS included age, sex, body mass index, waist circumference, systolic blood pressure, and family history of diabetes. Cox's proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The predictive capability of NCDRS was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 9,860 participants were included in the present analysis, and during a median follow-up of 6.01 years, 653 of them developed T2DM. In the multivariate models, the risk of T2DM showed a significant increasing trend (Ptrend <0.001): with NCDRS of 18-23, 24-29, and >29 versus <18, the HR was 1.85 (95% CI 1.30-2.64), 2.99 (2.14-4.18), and 3.97 (2.84-5.54), respectively. The predictive value was higher for NCDRS than for the previous Chinese diabetes risk score: AUC 0.675 (95% CI 0.666-0.684) and optimal cut-off of 24 (P < 0.001). Similar results were observed by sex. Especially, the predictive value of NCDRS was high among young people (aged 20-39 years): AUC 0.751 (0.732-0.769). CONCLUSIONS: Our study, based on a large prospective cohort, suggests that NCDRS is a reliable indicator for the identification of T2DM in rural China, especially in younger populations.

[China guideline for the screening, early detection and early treatment of esophageal cancer (2022, Beijing)].

Esophageal cancer (EC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demonstrated that screening and early detection are effective in reducing the incidence and mortality of EC. The development of the guideline for EC screening and early detection in line with epidemic characteristics of EC in China will greatly promote the homogeneity and standardization, and improve the effect of EC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of EC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of EC screening and provide scientific evidence for the EC prevention and control in China.

[China guideline for the screening, early detection and early treatment of gastric cancer (2022, Beijing)].

Gastric cancer (GC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demons-trated that screening, early detection and early treatment are effective in reducing the incidence and mortality of GC. The development of the guideline for GC screening, early detection and early treatment in line with epidemic characteristics of GC in China will greatly promote the homogeneity and standardization, and improve the effect of GC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of GC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of GC screening and provide scientific evidence for the GC prevention and control in China.

[A cross-sectional study on the clinical phenotypes of rheumatoid arthritis].

OBJECTIVE: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. METHODS: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. RESULTS: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. CONCLUSION: Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.

[A multi-center, randomized controlled study on the effect of Saccharomyces boulardii combined with triple therapy for the initial eradication of Helicobacter pylori infection].

Objective: To assess the efficacy and safety of Saccharomyces boulardii (S. boulardii) in combination with triple therapy as a first-line regimen for the eradication of Helicobacter pylori (H. pylori) in non-ulcer dyspepsia (NUD) patients. Methods: A total of 497 Helicobacter pylori-positive patients who underwent gastroscopy and diagnosed with NUD were enrolled from June 2018 to January 2020 in 9 medical centers across China. Participants were segmentedly randomly divided into 3 groups. Patients in group A received S. boulardii for 14 days and triple therapy for 10 days, while patients in group B received bismuth quadruple group for 10 days, and patients in group C received triple therapy for 10 days. The H. pylori status was determined by the 13C-urea breath test on the 44th day of the treatment. Symptom improvement and adverse reactions were assessed on the 14th and 44th day. Results: There were 229 males and 268 females in all 497 patients enrolled. They were aged 18-69 (46.1±11.8) years and 472 of them (158 cases in group A, 159 cases in group B, and 155 cases in group C) completed the trial. The intention-to-treat (ITT) eradication rates in patients in patients A, B and C were 77.8% (126/162), 80.1% (137/171) and 65.2% (107/164) respectively, and per protocol-based (PP) eradication rates were 79.7% (126/158), 86.2% (137/159) and 69.0% (107/155) respectively. The differences were statistically significant in ITT and PP analysis among 3 groups (ITT: χ²=11.14, P<0.01; PP: χ²=13.86, P<0.01). There was no significant difference between eradication rates of two quadruple therapys(all P>0.05), but both of them were significantly higher than that of standard triple therapy (both P<0.05). Statistics revealed that both quadruple therapys led to significantly higher symptom improvement of belching compared with that of standard triple therapy in day 14 (P<0.05). The relief of abdominal distension and belching symptom scores of group A were significantly higher than those of group C in day 44(all P<0.05). There was no serious adverse event reported. The incidence of diarrhea in group A was significantly lower than those in the other two groups (both P<0.05). Conclusions: The combination of S. boulardii and triple therapy can achieve a better eradication effect on H. pylori infection with NUD, and has advantages in symptom relief and safety.

Inactivation of TMEM106A promotes lipopolysaccharide-induced inflammation via the MAPK and NF-κB signaling pathways in macrophages.

Pattern recognition receptors, such as Toll-like receptors (TLRs), play an important role in the host defense against invading microbial pathogens. Their activation must be precisely regulated, as inappropriate activation or overactivation of TLR signaling pathways may result in inflammatory disorders, such as septic shock or autoimmune diseases. TMEM106A is a type II transmembrane protein constitutively expressed in macrophages. Our current study demonstrated that TMEM106A levels were increased in macrophages upon lipopolysaccharide (LPS) stimulation, as well as in the peripheral monocytes of patients with sepsis. Tmem106a knockout mice were more sensitive to lipopolysaccharide (LPS)-induced septic shock than wild-type mice. Further experiments indicated that Tmem106a ablation enhanced the expression of CD80, CD86 and major histocompatibility complex (MHC)-II in mouse macrophages upon LPS stimulation, accompanied with up-regulation of tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-ß and inducible nitric oxide synthase (iNOS), indicating the activation of macrophages and polarization towards the M1 inflammatory phenotype. Moreover, elevated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling were found to be involved in the LPS-induced inflammatory response in Tmem106a-/- macrophages. However, this effect was largely abrogated by macrophage deletion in Tmem106a-/- mice. Therefore, deficiency of Tmem106a in macrophages may enhance the M1 polarization in mice, resulting in inflammation. This suggests that TMEM106A plays an important regulatory role in maintaining macrophage homeostasis.

Integrating genome-wide association and transcriptome prediction model identifies novel target genes for osteoporosis.

In this study, we integrated large-scale GWAS summary data and used the predicted transcriptome-wide association study method to discover novel genes associated with osteoporosis. We identified 204 candidate genes, which provide novel clues for understanding the genetic mechanism of osteoporosis and indicate potential therapeutic targets. INTRODUCTION: Osteoporosis is a highly polygenetic disease characterized by low bone mass and deterioration of the bone microarchitecture. Our objective was to discover novel candidate genes associated with osteoporosis. METHODS: To identify potential causal genes of the associated loci, we investigated trait-gene expression associations using the transcriptome-wide association study (TWAS) method. This method directly imputes gene expression effects from genome-wide association study (GWAS) data using a statistical prediction model trained on GTEx reference transcriptome data. We then performed a colocalization analysis to evaluate the posterior probability of biological patterns: associations characterized by a single causal variant or multiple distinct causal variants. Finally, a functional enrichment analysis of gene sets was performed using the VarElect and CluePedia tools, which assess the causal relationships between genes and a disease and search for potential gene's functional pathways. The osteoporosis-associated genes were further confirmed based on the differentially expressed genes profiled from mRNA expression data of bone tissue. RESULTS: Our analysis identified 204 candidate genes, including 154 genes that have been previously associated with osteoporosis, 50 genes that have not been previously discovered. A biological function analysis found that 20 of the candidate genes were directly associated with osteoporosis. Further analysis of multiple gene expression profiles showed that 15 genes were differentially expressed in patients with osteoporosis. Among these, SLC11A2, MAP2K5, NFATC4, and HSP90B1 were enriched in four pathways, namely, mineral absorption pathway, MAPK signaling pathway, Wnt signaling pathway, and PI3K-Akt signaling pathway, which indicates a causal relationship with the occurrence of osteoporosis. CONCLUSIONS: We demonstrated that transcriptome fine-mapping identifies more osteoporosis-related genes and provides key insight into the development of novel targeted therapeutics for the treatment of osteoporosis.

Gender-specific SBNO2 and VPS13B as a potential driver of osteoporosis development in male ankylosing spondylitis.

To identify the critical genes and pathways that related to OP development in male AS patients, bioinformatic gene analysis and qRT-PCR validation were performed. SBNO2 and VPS13B were identified as the potential target for OP development, which may be valuable for the prevention of OP in male AS patients. INTRODUCTION: Osteoporosis (OP) is common in men with ankylosing spondylitis (AS). The specific pathogenesis of OP in AS, however, is still unclear. The present study attempted to identify potential genes associated with the development of OP in males with AS. METHODS: Gene expression profiles were downloaded from the GSE73754 and GSE35959 datasets from the Gene Expression Omnibus (GEO). Data from OsteoporosAtlas were downloaded as a supplement. Differentially expressed genes (DEGs) were determined with the limma package. The overlapping DEGs between male AS-related genes and OP-related genes were determined. The DEGs were validated by qRT-PCR in the blood samples of males with AS. Weighted gene co-expression network analysis (WGCNA) was utilized to establish a co-expression network to identify the hub genes. RESULTS: A total of 17 overlapping DEGs were identified; 6 genes in 17 overlapping DEGs were verified as the essential genes in the pathogenesis of OP in male AS by qRT-PCR analysis. After WGCNA, the modules of MEblue (> 0.6) and MEred (> 0.8) were screened out by the correlation analysis and were determined to function mainly in MAPK signaling pathway and osteoclast differentiation. Analysis of the two modules revealed VPS13B and SBNO2 as key genes due to the high degree of correlation. Both genes play an important role in bone metabolism regulation in male AS. Two hub genes MYD88 in MEblue and NCK1 in MEred with high degree of connectivity were selected. CONCLUSIONS: Gender-specific SBNO2 and VPS13B may be key genes involved in OP in male AS.

Adherence to antihypertensive medications for secondary prevention of cardiovascular disease events: a dose-response meta-analysis.

OBJECTIVES: The aim of the study was to explore the association between adherence to antihypertensive medications (AHMs) and the risk of recurrence of cardiovascular disease (CVD) events in patients with a history of CVD events from cohort studies. STUDY DESIGN: This is a dose-response meta-analysis. METHODS: PubMed and Embase databases were searched up to March 4, 2021, to identify English-language reports of cohort studies that assessed the association of AHM adherence with risk of recurrence of CVD events. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by using a fixed- or random-effects model. Restricted cubic splines were used to evaluate the possible linear or non-linear association. RESULTS: We included nine cohort studies (54,349 patients) in the present meta-analysis. The pooled RR of CVD events was 0.66 (95% CI, 0.54-0.78) for the highest versus lowest AHM adherence category. We did not find any evidence of non-linearity association between AHM adherence and risk of CVD events (Pnon-linearity = 0.534); for patients with a history of CVD events, the risk of CVD events was reduced by 9% for each 20% increase in AHM adherence (RR, 0.91; 95% CI, 0.85-0.97). The results of sensitivity analysis and subgroup analysis were virtually unchanged. CONCLUSIONS: The high level of adherence to AHM is an effective strategy for preventing recurrence of CVD events. Patients with a history of CVD events should adhere to AHM.