Ambient fine particulate matter is associated with daily outpatient visits for ankylosing spondylitis: A time-series analysis in Beijing, China.

Exposure to ambient fine particulate matter (PM2.5) has a great impact on human body's immune system, but the correlation between PM2.5 and ankylosing spondylitis has not yet been clarified. We extracted 58,600 outpatient visits for ankylosing spondylitis from the Beijing Medical Claim Data for Employees database from 2010 to 2017. The percentage of outpatient visits following PM2.5 concentrations was estimated using generalized additive models with Poisson connections. Increase by 10 µ g/m3, PM2.5 is associated with daily outpatient visits for ankylosing spondylitis. In this test, the average concentration of PM2.5 was 86.8 ± 74.3 µ g/m3. For every 10 µg/m3 increase in PM2.5 concentration, there was a 0.34% (95% CI, 0.26-0.42%) increase in the risk of patients who visited the doctor on the same day. Females and younger patients were most susceptible to the impact of PM2.5 exposure (P＜0.05). This study revealed the relationship between exposure to PM2.5 and ankylosing spondylitis, and future research can further confirm this finding and explore the potential mechanisms.

Novel database for accA gene revealed a vertical variability pattern of autotrophic carbon fixation potential of ammonia oxidizing archaea in a permeable subterranean estuary.

The autotrophic carbon fixation pathway of ammonia-oxidizing archaea (AOA) was the 3-hydroxypropionate/4-hydroxybutyrate (3-HP/4-HB) cycle, of which the acetyl-CoA carboxylase α-submit (accA) gene is widely recognized as the indicator. To date, there is no reference database or suitable cut-off value for operational taxonomic unit (OTU) clustering to analyze the diversity of AOA based on the accA gene. In this study, a reference database with 489 sequences was constructed, all the accA gene sequences was obtained from the AOA enrichment culture, pure culture and environmental samples. Additionally, the 79% was determined as the cut-off value for OTU clustering by comparing the similarity between the accA gene and the 16S rRNA gene. The developed method was verified by analyzing samples from the subterranean estuary and a vertical variation pattern of autotrophic carbon fixation potential of AOA was revealed. This study provided an effective method to analyze the diversity and autotrophic carbon fixation potential of AOA based on accA gene.

Effect of statin therapy patterns on readmission and mortality in patients with intracerebral hemorrhage.

There is limited and inconsistent evidence for the association of statin therapy and statin treatment patterns with the risk of recurrent intracerebral hemorrhage (ICH) in patients with prior ICH. To assess the association of statin therapy and its intensity, type, initiation time, and discontinuation with the risk of recurrent ICH and mortality in Chinese patients with ICH. Patients with newly diagnosed ICH in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. Post-ICH statin users (post-diagnosis only) and nonusers (never), statin discontinuers (pre-diagnosis only) and continuers (pre- and post-diagnosis) were matched on a 1:1 propensity score, respectively. Adjusted Cox proportional risk models were used to estimate the risk ratios for ICH readmission and mortality under various statin patterns. A total of 2668 post-ICH statin users and 2668 nonusers without a history of statin use were enrolled. Post-ICH statin users had a lower risk of ICH readmission (HR, 0.57; 95% CI 0.48, 0.69) and all-cause death (0.56: 0.49, 0.63) than nonusers. Low/moderate-intensity treatment was associated with a 63% lower risk of recurrent ICH compared with nonusers (0.37: 0.29, 0.46), whereas high-intensity treatment did not reduce the risk (0.93: 0.74, 1.16). Both low/moderate-intensity (0.42: 0.36, 0.48) and high-intensity statins (0.57: 0.48, 0.69) were associated with a lower risk of all-cause mortality. The risk of ICH readmission was 53% (0.47: 0.30, 0.74) lower with adherence to rosuvastatin than with atorvastatin. Only starting medication within 30 days of the first diagnosis of ICH reduced the risk of ICH readmission (0.49: 0.40, 0.60). Among patients with a history of statin use, 1807 discontinuing and 1,807 continuing users of statins were included. The risk of ICH readmission (4.00: 3.32, 4.80) and the risk of all-cause death (4.01: 3.57, 4.50) were substantially increased in statin discontinuation compared with continued statin use. Statin therapy after ICH was associated with lower risks for ICH readmission and all-cause mortality compared with non-statin therapy, especially at low/moderate intensity and early initiation of statins after ICH. Adherence to rosuvastatin was associated with a lower risk of recurrence of ICH than atorvastatin. Among patients with a statin history prior to ICH, discontinuation of statins after ICH was associated with increased risk of ICH recurrence and death.

Fe3O4-lignin@Pd-NPs: A highly active, stable and broad-spectrum nanocomposite for water treatment.

In this work, we report an environmentally friendly renewable nanocomposite magnetic lignin-based palladium nanoparticles (Fe3O4-lignin@Pd-NPs) for efficient wastewater treatment by decorating palladium nanoparticles without using any toxic reducing agents on the magnetic lignin abstracted from Poplar. The structure of composite Fe3O4-lignin@Pd-NPs was unambiguously confirmed by XRD, SEM, TEM, EDS, FTIR, and Zeta potential. After systematic evaluation of the use and efficiency of the composite to remove toxic organic dyes in wastewater, some promising results were observed as follows: Fe3O4-lignin@Pd-NPs exhibits highly active and efficient performance in the removal of toxic methylene blue (MB) (up to 99.8 %) wastewater in 2 min at different concentrations of MB and different pH values. Moreover, except for toxic MB, the other organic dyes including Rhodamine B (RhB), Rhodamine 6G (Rh6G), and Methyl Orange (MO) can also be removed efficiently by the composite. Finally, the easily recovered composite Fe3O4-lignin@Pd-NPs exhibits well stability and reusability, and catalytic efficiency is maintained well after ten cycles. In conclusion, the lignin-based magnetism Pd composite exhibits powerful potential practical application in industrial wastewater treatment.

The impact of heat waves and cold spells on pneumonia risk: A nationwide study.

Climate change affects human health and has been linked to several infectious diseases in recent year. However, there is limited assessment on the impact of heat waves and cold spells on pneumonia risk. This study aims to examine the association of heat waves and cold spells with daily pneumonia hospitalizations in 168 cities in China. Data on pneumonia hospitalizations between 2014 and 2017 were extracted from a national claim database of 280 million beneficiaries. We consider combining temperature intensity and duration to define heat waves and cold spells.This association was quantified using a quasi-Poisson generalized linear model combined with a distributed lag nonlinear model. Exposure-response curves and potential effect modifiers were also estimated. We found that the peak relative risk (RR) of cold spells on daily hospitalizations for pneumonia was observed in relatively mild cold spells with a threshold below the 3 days at the 2nd percentile (RR = 1.69, 95% CI: 1.46-1.92). The risk of heat waves increased with the thresholds, and the greatest risk was found for extremely heatwave period of 4 days at the 98th percentile (RR = 1.69, 95% CI: 1.46-1.92). Heat waves and cold spells are more likely to adversely affect women. In conclusion, our study provided novel and strong evidence that exposure to heat waves and cold spells was associate with increased hospital visits for pneumonia, especially in females. This is the first national study in China to comprehensively evaluate the influence of heat waves and cold spells on pneumonia risk, and the findings may offer valuable insights into the impact of climate change on public health.

TMEM44-AS1 promotes esophageal squamous cell carcinoma progression by regulating the IGF2BP2-GPX4 axis in modulating ferroptosis.

The long non-coding RNA (lncRNA) TMEM44-AS1 is a novel lncRNA whose pro-carcinogenic role in gastric cancer and glioma has been demonstrated. However, its function in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we identified that TMEM44-AS1 was highly expressed in ESCC tissues and cells. Functionally, TMEM44-AS1 promoted ESCC cell proliferation, invasion and metastasis in vitro and in vivo. TMEM44-AS1 inhibited ferroptosis in ESCC cells, and ferroptosis levels were significantly increased after knockdown of TMEM44-AS1. Mechanistically, TMEM44-AS1 was positively correlated with GPX4 expression, and TMEM44-AS1 could bind to the RNA-binding protein IGF2BP2 to enhance the stability of GPX4 mRNA, thereby affecting ferroptosis and regulating the malignant progression of ESCC. In summary, this study reveals the TMEM44-AS1-IGF2BP2-GPX4 axis could influence cancer progression in ESCC. TMEM44-AS1 can be used as a potential treatment target against ESCC.

Ethyl caffeate combined with fluconazole exhibits efficacy against azole-resistant oropharyngeal candidiasis via the EFGR/JNK/c-JUN signaling pathway.

Ethyl caffeate (EC) is a phenylpropanoid compound derived from Elephantopus scaber. In our previous work, EC was investigated to have a strong synergistic antifungal effect against azole-resistant strains of Candida albicans when combined with fluconazole (FLU). However, the protective effect and mechanism of EC + FLU on oropharyngeal candidiasis (OPC) caused by drug-resistant strains of C. albicans have not been investigated. This study aimed to investigate the protective effect and mechanism of EC combined with FLU against C. albicans-resistant strains that lead to OPC. An OPC mouse model revealed that EC + FLU treatment reduced fungal load and massive hyphal invasion of tongue tissues, and ameliorated the integrity of the tongue mucosa. Periodic acid-Schiff staining results showed more structural integrity of the tongue tissues and reduced inflammatory cell infiltration after EC + FLU treatment. Phosphorylation of EGFR (epidermal growth factor receptor) and other proteins in the EFGR/JNK (c-Jun N-terminal kinase)/c-JUN (transcription factor Jun) signaling pathway was significantly downregulated by EC + FLU. EGFR and S100A9 mRNA expression were also reduced. The above results were verified in FaDu cells. ELISA results showed that the concentration of inflammatory factors in the cell supernatant was significantly reduced after EC combined with FLU treatment. Molecular docking revealed that EC exhibited high binding energy to EGFR. In conclusion, EC enhances the susceptibility of azole-resistant C. albicans to FLU, and the underlying mechanism is related to the inhibition of the EGFR/JNK/c-JUN signaling pathway. This result suggests that EC has potential to be developed as an antifungal sensitizer to treat OPC caused by azole-resistant C. albicans.

Short-term exposure to reduced specific-size ambient particulate matter increase the risk of cause-specific cardiovascular disease: A national-wide evidence from hospital admissions.

Evidence for the health effects of ambient PM1 (particulate matter with an aerodynamic diameter ≤ 1 µm) pollution is limited, and it remains unclear whether a smaller particulate matter has a greater impact on human health. We conducted a time-series study in 184 major cities by extracting daily hospital data on admissions for ischemic heart disease, heart failure, heart rhythm disturbances, and stroke between 2014 and 2017 from a medical insurance claims database of 0.28 billion beneficiaries. City-specific associations were estimated with over-dispersed generalized additive models. A random-effects meta-analysis was used to estimate regional and national average associations. We conducted stratified and meta-regression analyses to explore potential effect modifiers of the association. We recorded 8.83 million cardiovascular admissions during the study period. At the national-average level, a 10-µg/m3 increase in same-day PM1, PM2.5(particulate matter with an aerodynamic diameter ≤ 2.5 µm) and PM10(particulate matter with an aerodynamic diameter ≤ 10 µm) concentrations corresponded to a 1.14% (95% confidence interval 0.88-1.41%), 0.55% (0.40-0.70%), and 0.45% (0.36-0.55%) increase in cardiovascular admissions, respectively. PM1 exposure was also positively associated with all cardiovascular disease subtypes, including ischemic heart disease (1.28% change; 0.99-1.56%), heart failure (1.30% change; 0.70-1.91%), heart rhythm disturbances (1.11% change; 0.65-1.58%), and ischemic stroke (1.29% change; 0.88-1.71%). The associations between PM1 and cardiovascular admissions were stronger in cities with lower PM1 levels, higher air temperatures and relative humidity, as well as in subgroups with elder age (all P < 0.05). This study provides robust evidence of short-term associations between PM1 concentrations and increased hospital admissions for all major cardiovascular diseases in China. Our findings suggest a greater short-term impact on cardiovascular risk from PM1 in comparison to PM2.5 and PM10.

Association of Metformin Use with Iron Deficiency Anemia in Urban Chinese Patients with Type 2 Diabetes.

BACKGROUND: Previous evidence yielded contradictory findings on the relationship between metformin and anemia. This study aims to assess whether metformin use is associated with iron-deficiency anemia (IDA) risk in patients with type 2 diabetes (T2D) in Beijing, China. METHODS: Overall, 60,327 newly diagnosed T2D patients were included based on a historical cohort study design. The information pertaining to these patients was gathered from the Beijing Medical Claim Data for Employees Database. These patients were then categorized into the metformin and non-metformin groups and matched on a 1:1 propensity score based on their initial antidiabetic prescription. The Cox proportional hazards models were utilized to calculate the incidences and the hazard ratios (HRs). RESULTS: The study enrolled 27,960 patients with type 2 diabetes, with 13,980 patients in each of the initial glucose-lowering prescription groups: metformin and non-metformin. During a median follow-up period of 4.84 years, 4832 patients developed IDA. The incidence of IDA was significantly lower in the metformin group (26.08/1000 person-years) than in the non-metformin group (43.20/1000 person-years). Among the three groups divided by the proportion of days covered by metformin, we found a negative correlation between the proportion of days covered by metformin and the risk of IDA. The risk of IDA in patients with a proportion of days covered by metformin of <20%, 20-79%, and ≥80% was 0.43 (0.38, 0.48), 0.37 (0.34, 0.42), and 0.91 (0.85, 0.98), respectively, compared to the non-metformin group. We also performed subgroup analyses and sensitivity analyses: the incidence of IDA in the metformin group was lower than that in the non-metformin group in all subgroups, and the protective effect was more significant in subgroups of patients aged ≥65, with Charlson comorbidity index (CCI) ≥2, and with gastric acid inhibitor use. CONCLUSIONS: In Chinese patients with T2DM, metformin treatment was associated with a decreased risk of IDA admission, and this risk responded positively to the proportion of days covered by metformin. These findings suggest that metformin may have a pleiotropic effect on IDA in patients with type 2 diabetes. Our study has important clinical implications for the management of patients with diabetes and other conditions that increase the risk of IDA.

Ferroptosis-associated circular RNAs: Opportunities and challenges in the diagnosis and treatment of cancer.

Ferroptosis is an emerging form of non-apoptotic regulated cell death which is different from cell death mechanisms such as autophagy, apoptosis and necrosis. It is characterized by iron-dependent lipid peroxide accumulation. Circular RNA (circRNA) is a newly studied evolutionarily conserved type of non-coding RNA with a covalent closed-loop structure. It exhibits universality, conservatism, stability and particularity. At present, the functions that have been studied and found include microRNA sponge, protein scaffold, transcription regulation, translation and production of peptides, etc. CircRNA can be used as a biomarker of tumors and is a hotspot in RNA biology research. Studies have shown that ferroptosis can participate in tumor regulation through the circRNA molecular pathway and then affect cancer progression, which may become a direction of cancer diagnosis and treatment in the future. This paper reviews the molecular biological mechanism of ferroptosis and the role of circular RNA in tumors and summarizes the circRNA related to ferroptosis in tumors, which may inspire research prospects for the precise prevention and treatment of cancer in the future.

Is statin therapy after ischaemic stroke associated with increased intracerebral hemorrhage? The association may be dependent on intensity of statin therapy.

BACKGROUND: There has been concern that statin therapy may be associated with an increased risk of intracerebral hemorrhage (ICH). We investigated whether the intensity and type of statin therapy instituted after ischemic stroke (IS) were associated with risk of future ICH in a region of northern China with a high incidence of stroke. METHODS: Newly diagnosed IS patients who were not treated with lipid-lowering drugs in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. The primary exposure variable was any statin prescription within 1 month of the first documented stroke diagnosis. High-intensity statin therapy was defined as atorvastatin ⩾ 80 mg, simvastatin ⩾ 80 mg, pravastatin ⩾ 40 mg, and rosuvastatin ⩾ 20 mg per day or equivalent combination. An adjusted Cox proportional hazards model was used to estimate the hazard ratio (HR) for ICH during follow-up in groups exposed and not exposed to statins. RESULTS: Of 62,252 participants with IS and 628 ICH readmissions were recorded during a median follow-up of 3.17 years. The risk of ICH among statin users (N = 43,434) was similar to that among nonusers (N = 18,818) with an adjusted HR and 95% confidence interval (CI) of 0.86 (0.73, 1.02). Compared with non-statin therapy, patients with low/moderate-intensity therapy had a lower risk of ICH (0.62: 0.52, 0.75), while patients with high-intensity therapy had a substantially higher risk (2.12: 1.72, 2.62). For patients with different types of statin therapy, adherence to rosuvastatin had the lowest risk of ICH compared to adherence to atorvastatin (0.46: 0.34, 0.63), followed by simvastatin (0.60: 0.45, 0.81). CONCLUSION: In patients with IS, any statin therapy was not associated with an increased risk of ICH. However there appeared to be differential risk according to the dose of statin with high-intensity statin therapy being associated with an increased risk of ICH, while low/moderate-intensity therapy was associated with a lower risk.

Metformin treatment and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in Beijing, China.

Background: Metformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China. Methods: All patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Results: Among 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend <0.001). The risk of DPN was 1.53-fold (1.30, 1.81) and 4.31-fold (3.76, 4.94) higher in patients with daily doses of 1.0-2.0 g and >2.0 g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P<0.05 for interaction test). Among patients taking vitamin B12 at baseline, there was no increased risk of DPN in the metformin group (1.92: 0.79, 4.69). Conclusions: In Chinese patients with T2DM, metformin treatment was associated with an increased risk of DPN admission and this risk responds positively to the daily dose of metformin. In particular, metformin use was a major risk factor for DPN in younger patients. Concomitant use of vitamin B12 may avoid the increased risk of DPN associated with metformin use.

Long non-coding RNA HOXC-AS1 exerts its oncogenic effects in esophageal squamous cell carcinoma by interaction with IGF2BP2 to stabilize SIRT1 expression.

BACKGROUND: Long non-coding RNA HOXC cluster antisense RNA 1 (HOXC-AS1) is a novel lncRNA whose cancer-promoting effect in gastric cancer and nasopharyngeal carcinoma has already been demonstrated. However, its functions in esophageal squamous cell carcinoma (ESCC) remains unknown. LncRNAs can interact with RNA-binding proteins (RBPs) and affect gene expression levels through post-transcriptional regulation. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a widely studied RBP, and sirtuin 1 also known as SIRT1 has been reported to be involved in cancer progression. METHODS: Establishment of in vivo models, HE and immunohistochemistry staining verified the oncogenic effect of HOXC-AS1. The interaction relationship between HOXC-AS1, IGF2BP2 and SIRT1 was verified by RNA pulldown and RNA immunoprecipitation (RIP) assay. Relative expression and stability changes of genes were detected by qPCR and actinomycin D experiments. Finally, the effect of HOXC-AS1-IGF2BP2-SIRT1 axis on ESCC was verified by rescue experiments. RESULTS: HOXC-AS1 is highly expressed in ESCC cells and plays oncogenic effects in vivo. qPCR showed the positive relationship between HOXC-AS1 and SIRT1 following HOXC-AS1 knockdown or overexpression. RNA-pulldown, mass spectrometry and RIP assay demonstrated that IGF2BP2 is an RBP downstream of HOXC-AS1. Then, RIP and qPCR showed that IGF2BP2 could bind to SIRT1 mRNA and knockdown IGF2BP2 resulted in decreased SIRT1 mRNA level. Finally, a series of rescue assay showed that the HOXC-AS1-IGF2BP2-SIRT1 axis can affect the function of ESCC. CONCLUSION: LncRNA HOXC-AS1 acts as an oncogenic role in ESCC, which impacts ESCC progression by interaction with IGF2BP2 to stabilize SIRT1 expression.

Short-term exposure to ambient fine particulate matter and psoriasis: A time-series analysis in Beijing, China.

Background: Ambient fine particulate matter (PM2.5) adversely affects human health and has been linked to a variety of skin disorders. However, little is known about the effects of PM2.5 on psoriasis. Methods: The Beijing Medical Claim Data for Employees database recorded 500,266 outpatient visits for psoriasis during 2010-2017. A generalized additive quasi-Poisson model was used to examine the relationship between daily PM2.5 concentrations and outpatient visits for psoriasis with stratification by sex, age, and season. Results: Short-term exposure to PM2.5 was associated with outpatient visits for psoriasis-related health concerns. A same-day increase of 10 µg/m3 in PM2.5 concentrations was associated with a 0.29% (95% confidence interval: 0.26-0.32%) increase in daily outpatient visits for psoriasis. Female and older patients appeared to be more sensitive to the effects of PM2.5 (P < 0.05). Conclusions: Short-term elevations in PM2.5 concentrations may be associated with exacerbations in psoriasis. Further work is warranted to confirm the findings and elucidate the underlying biological mechanisms.

Association of metformin and depression in patients with type 2 diabetes.

BACKGROUND: Emerging evidence showed metformin may have pleiotropic effects on ameliorating depression. However, whether metformin was associated with decreased risk of depression remains unclear. METHODS: A historical cohort study was conducted based on a medical claim database from 2010 to 2017 in Beijing, China. Patients newly diagnosed with T2D were classified into the metformin and non-metformin groups according to their initial antidiabetic prescription. The incidences of depression between the groups were compared using Cox proportional regression model. RESULTS: There were 193,624 (37.4 %) and 323,930 (62.6 %) T2D patients in the metformin and non-metformin groups. The mean age was 54.9 (SD: 13.1) years and 53.9% were females. With a median follow-up of 3.2 years, 64,963 patients developed depression. The adjusted incidence of depression in the metformin group (30.6, 95 % CI: 30.1, 31.0 per 1000 person-years) was significantly lower than in the non-metformin group (39.6, 95 % CI: 39.3, 40.0 per 1000 person-years, P < 0.001). The metformin group was significantly associated with a lower risk of depression compared with the overall non-metformin group (HR: 0.77, 95% CI: 0.75, 0.78), as well as compared with α-glucosidase inhibitors (HR: 0.73, 95 % CI: 0.71, 0.74), sulfonylureas (HR: 0.84, 95 % CI: 0.82, 0.86), and glinides (HR: 0.85, 95 % CI: 0.82, 0.88), except for thiazolidinediones (HR: 0.96, 95 % CI: 0.91, 1.01). The association between metformin and lower depression risk was significant in all the age and sex subgroups. CONCLUSIONS: Metformin was associated with a lower risk of depression compared with other oral hypoglycemic agents, indicating a potential pleiotropic effect on depression.

Type 2 Diabetes Risk and Lipid Metabolism Related to the Pleiotropic Effects of an ABCB1 Variant: A Chinese Family-Based Cohort Study.

The single nucleotide polymorphism (SNP) rs4148727 in ABCB1 (encoding p-glycoprotein) is associated with lipid levels; however, its association with type 2 diabetes (T2DM) and its the genetic correlation with lipid profiles and T2DM are unclear. We included 2300 participants from 593 families. A generalized estimating equations (GEE) model and Cox regression models were used to estimate the SNP's effects on T2DM and lipid profiles. The participation of the SNP in T2DM pathogenesis through lipid-associated pathways was tested using mediation analysis. The G allele of the SNP was related to a 32% (6-64%, p = 0.015) increase in T2DM risk. It was also associated with a 10% (1-20%, p = 0.029), 17% (3-32%, p = 0.015), and 4% (1-7%, p = 0.015) increment in total cholesterol (TC), triglyceride (TG), and apolipoprotein A (Apo-A) concentrations, respectively. According to the mediation analysis, only TG (6.9%) and Apo-B (4.0%) had slight but significant mediation effects on the total impact of the SNP on T2DM. The pleiotropic effects of the ABCB1 variant on T2DM and lipids likely act via different pathways. The biological mechanisms should be verified in a future study.

Glucosamine Use Is Associated with a Higher Risk of Cardiovascular Diseases in Patients with Osteoarthritis: Results from a Large Study in 685,778 Subjects.

Glucosamine is widely used around the world and as a popular dietary supplement and treatment in patients with osteoarthritis in China; however, the real-world cardiovascular risk of glucosamine in long-term use is still unclear. A retrospective, population-based cohort study was performed, based on the Beijing Medical Claim Data for Employees from 1 January 2010 to 31 December 2017. Patients newly diagnosed with osteoarthritis were selected and divided into glucosamine users and non- glucosamine users. The glucosamine users group was further divided into adherent, partially adherent, and non-adherent groups according to the medication adherence. New-onset cardiovascular diseases (CVD) events, coronary heart diseases (CHD), and stroke, were identified during the observational period. COX proportional regression models were used to estimate the risks. Of the 685,778 patients newly diagnosed with osteoarthritis including 240,419 glucosamine users and 445,359 non-users, the mean age was 56.49 (SD: 14.45) years and 59.35% were females. During a median follow-up of 6.13 years, 64,600 new-onset CVD, 26,530 CHD, and 17,832 stroke events occurred. Glucosamine usage was significantly associated with CVD (HR: 1.10; 95% CI: 1.08−1.11) and CHD (HR: 1.12; 95% CI: 1.09−1.15), but not with stroke (HR: 1.03; 95% CI: 0.99−1.06). The highest CVD risk was shown in the adherent group (HR: 1.68; 95% CI: 1.59−1.78), followed by the partially adherent group (HR: 1.26, 95% CI: 1.22−1.30), and the non-adherent group (HR: 1.03; 95% CI: 1.02−1.05), with a significant dose−response relationship (p-trend < 0.001). In this longitudinal study, adherent usage of glucosamine was significantly associated with a higher risk for cardiovascular diseases in patients with osteoarthritis.

GWAS-associated bacteria and their metabolites appear to be causally related to the development of inflammatory bowel disease.

BACKGROUND: Accumulating evidence has suggested that the imbalance of gut microbiota is commonly observed in patients with inflammatory bowel disease (IBD). However, it remains unclear whether dysbiosis is a cause or consequence of chronic intestinal inflammation. We aimed to investigate the causal relationships of gut microbiota and metabolites with IBD, including ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We applied two-sample Mendelian randomization using summary statistics from the gut microbiota genetic consortium (n = 1812), the Framingham Heart Study (n = 2076) and the International IBD Genetics Consortium (n = 86,640). RESULTS: Using the genetic approach, the increase in OTU10032 unclassified Enterobacteriaceae was associated with higher risks of IBD (OR, 1.03; 95% CI, 1.00-1.06; P = 0.033) and CD (1.04; 1.01-1.08; P = 0.015). Importantly, an Enterobacteriaceae-related metabolite taurine was positively associated with risks of IBD (1.04; 1.01-1.08; P = 0.016) and UC (1.05; 1.01-1.10; P = 0.024). Notably, we also found betaine, a downstream product of Enterobacteriaceae metabolism, was causally associated with a higher risk of CD (1.10; 1.02-1.18; P = 0.008). In addition, increased Erysipelotrichaceae family were causally related to lower risks of IBD (0.88; 0.78-0.98; P = 0.026) and UC (0.86; 0.75-0.99; P = 0.042), and Actinobacteria class (0.80; 0.65-0.98; P = 0.028) and Unclassified Erysipelotrichaceae (0.79; 0.64-0.98; P = 0.036) were associated with lower risks of UC and CD, respectively. CONCLUSIONS: Our finding provided new insights into the key role of gut metabolites such as taurine and betaine in host-microbiota interactions of IBD pathogenesis, indicating that host-microbe balance strongly influences inflammatory conditions.

Importance of healthy lifestyle factors and ideal cardiovascular health metrics for risk of heart failure in Chinese adults.

BACKGROUND: The relative importance of healthy lifestyle factors and cardiovascular health metrics for the risk of heart failure is uncertain in Chinese populations. We aimed to compare the strength of associations between healthy lifestyle factors and ideal cardiovascular health metrics in the risk of heart failure in middle-aged Chinese adults. METHODS: A healthy lifestyle score (HLS) was constructed using smoking, drinking, physical activity, diet, body mass index and waist circumference, and compared with a more comprehensive set of metrics that included cardiovascular-disease risk biomarkers (blood pressure, blood glucose and blood lipids) in addition to the HLS. This broader set of factors [called 'ideal cardiovascular health metrics' (ICVHMs)] was evaluated in 487 197 participants in the China Kadoorie Biobank. RESULTS: A total of 4208 incident cases of heart failure were recorded during a median follow-up of 10 years. Both HLS [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.85, 0.91] and ICVHMs (0.87: 0.84, 0.89) were inversely associated with risk of heart failure (P < 0.001 for linear trend). Compared with participants with 0-1 HLS, the multivariable-adjusted HR of those with 4-5 HLS was 0.68 (0.59, 0.77). Compared with participants with 0-2 ICVHMs, the adjusted HR (95% CIs) of those who had 7-8 ICVHMs was 0.47 (0.36, 0.60). ICVHMs were more strongly predictive of risk of heart failure (area under curve, 0.61 vs 0.58, P < 0.001) than healthy lifestyle factors alone. CONCLUSIONS: Higher levels of healthy lifestyle factors and ICVHMs were each inversely associated with heart failure, and lifestyle factors combined with cardiometabolic factors improved the prediction of heart failure compared with healthy lifestyle factors alone.

Association of healthy lifestyle including a healthy sleep pattern with incident type 2 diabetes mellitus among individuals with hypertension.

BACKGROUND: Evidence is limited regarding the association of healthy lifestyle including sleep pattern with the risk of complicated type 2 diabetes mellitus (T2DM) among patients with hypertension. We aimed to investigate the associations of an overall healthy lifestyle including a healthy sleep pattern with subsequent development of T2DM among participants with hypertension compared to normotension, and to estimate how much of that risk could be prevented. METHODS: This study examined six lifestyle factors with T2DM cases among hypertension (227,966) and normotension (203,005) and their interaction in the UK Biobank. Low-risk lifestyle factors were defined as standard body mass index (BMI), drinking alcohol in moderation, nonsmoking, engaging in moderate- to vigorous-intensity physical activity, eating a high-quality diet, and maintaining a healthy sleep pattern. RESULTS: There were 12,403 incident T2DM cases during an average of 8.63 years of follow-up. Compared to those with 0 low-risk lifestyle factors, HRs for those with 5-6 were 0.14 (95% CI 0.10 to 0.19) for hypertensive participants, 0.13 (95% CI 0.08 to 0.19) for normotensive participants, respectively (ptrend < 0.001). 76.93% of hypertensive participants were considerably less likely to develop T2DM if they adhered to five healthy lifestyle practices, increased to 81.14% if they followed 6-factors (with a healthy sleep pattern). Compared with hypertension adults, normotensive people gain more benefits if they stick to six healthy lifestyles [Population attributable risk (PAR%) 83.66%, 95% CI 79.45 to 87.00%, p for interaction = 0.0011]. CONCLUSIONS: Adherence to a healthy lifestyle pattern including a healthy sleep pattern is associated with lower risk of T2DM in hypertensives, and this benefit is even further in normotensives.