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Understanding the epidemiological and clinical characteristics of fatal cases infected with SARS-CoV-2 is import to develop appropriate preventable intervention programs in hospitals. Demographic data, clinical symptoms, clinical course, co-morbidities, laboratory findings, CT scans, treatments and complications of 162 fatal cases were retrieved from electric medical records in 5 hospitals of Wuhan, China. The median age was 69.5 years old (IQR: 63.0-77.25; range: 29-96). 112 (69.1%) cases were men. Hypertension (45.1%) was the most common co-morbidity, but 59 (36.4%) cases had no co-morbidity. At admission, 131 (81.9%) cases were assessed as severe or critical. However, 39 (18.1%) were assessed as moderate. Moderate cases had a higher prevalence of hypertension and chronic lung disease comparing with severe or critical cases (P

The real-time imaging of low-abundance tumor-related microRNAs (miRNAs) in living cells holds great potential for early clinical diagnosis of cancers. However, the relatively low detection sensitivity and possible false-positive signals of a probe in complex cellular matrices remain critical challenges for accurate RNA detection. Herein, we developed a novel aptamer-functionalized cruciate DNA probe that enabled amplified multiple miRNA imaging in living cells

ObjectivesOver the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study.DesignQualitative semi-structured interview study, using thematic analysis.SettingPrimary and secondary care in Beijing and Tai’an, China.ParticipantsOlder adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes.ResultsWe performed 26 interviews with participants aged 55–86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional.ConclusionsThe Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD.Trial registration numberISRCTN15986016; Pre-results.

Immunoglobulin G (IgG) functionality can drastically change from anti- to proinflammatory by alterations in the IgG N-glycan patterns. Our previous studies have demonstrated that IgG N-glycans associated with the risk factors of dementia, such as aging, dyslipidemia, type 2 diabetes mellitus, hypertension, and ischemic stroke. Therefore, the aim is to investigate whether the effects of IgG N-glycan profiles on dementia exists in a Chinese Han population. A case–control study, including 81 patients with dementia, 81 age- and gender-matched controls with normal cognitive functioning (NC) and 108 non-matched controls with mild cognitive impairment (MCI) was performed. Plasma IgG N-glycans were separated by ultra-performance liquid chromatography. Fourteen glycan peaks reflecting decreased of sialylation and core fucosylation, and increased bisecting N-acetylglucosamine (GlcNAc) N-glycan structures were of statistically significant differences between dementia and NC groups after controlling for confounders (p q p q N-glycans might contribute to be potential novel biomarkers for the neurodegenerative process risk assessment of dementia.

OBJECTIVES: Suboptimal health status (SHS), a reversible borderline condition between optimal health status and disease, has been recognized as a main risk factor for non-communicable diseases (NCDs). From the standpoint of predictive, preventive, and personalized medicine (PPPM/3PM), the early detection of SHS provides a window of opportunity for targeted prevention and personalized treatment of NCDs. Considering that immunoglobulin G (IgG) N-glycosylation levels are associated with NCDs, it can be speculated that IgG N-glycomic alteration might occur at the SHS stage. METHODS: A case–control study was performed and it consisted of 124 SHS individuals and 124 age-, gender-, and body mass index–matched healthy controls. The IgG N-glycan profiles of 248 plasma samples were analyzed by ultra-performance liquid chromatography instrument. RESULTS: After adjustment for potential confounders (i.e., age, levels of education, physical activity, family income, depression score, fasting plasma glucose, and low-density lipoprotein cholesterol), SHS was significantly associated with 16 IgG N-glycan traits at 5% false discovery rate, reflecting decreased galactosylation and fucosylation with bisecting GlcNAc, as well as increased agalactosylation and fucosylation without bisecting GlcNAc. Canonical correlation analysis showed that glycan peak (GP) 20, GP9, and GP12 tended to be significantly associated with the 5 domains (fatigue, the cardiovascular system, the digestive system, the immune system, and mental status) of SHS. The logistic regression model including IgG N-glycans was of moderate performance in tenfold cross-validation, achieving an average area under the receiver operating characteristic curves of 0.703 (95% confidence interval: 0.637–0.768). CONCLUSIONS: The present findings indicated that SHS-related alteration of IgG N-glycans could be identified at the early onset of SHS, suggesting that IgG N-glycan profiles might be potential biomarker of SHS. The altered SHS-related IgG N-glycans are instrumental for SHS management, which could provide a window opportunity for PPPM in advanced treatment of NCDs and shed light on future studies investigating the pathogenesis of progression from SHS to NCDs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-022-00278-1.

Age-related disease burdens increased over time, and whether plasma peptides can be used to accurately predict age in order to explain the variation in biological indicators remains inadequately understood. Here we first developed a biological age model based on plasma peptides in 1890 Chinese Han adults. Based on mass spectrometry, 84 peptides were detected with masses in the range of 0.6-10.0 kDa, and 13 of these peptides were identified as known amino acid sequences. Five of these thirteen plasma peptides, including fragments of apolipoprotein A-I (m/z 2883.99), fibrinogen alpha chain (m/z 3060.13), complement C3 (m/z 2190.59), complement C4-A (m/z 1898.21), and breast cancer type 2 susceptibility protein (m/z 1607.84) were finally included in the final model by performing a multivariate linear regression with stepwise selection. This biological age model accounted for 72.3% of the variation in chronological age. Furthermore, the linear correlation between the actual age and biological age was 0.851 (95% confidence interval: 0.836-0.864) and 0.842 (95% confidence interval: 0.810-0.869) in the training and validation sets, respectively. The biological age based on plasma peptides has potential positive effects on primary prevention, and its biological meaning warrants further investigation.

Suboptimal health status (SHS), a physical state between health and disease, is a subclinical and reversible stage of chronic disease. Previous studies have shown alterations in the intestinal microbiota in patients with some chronic diseases. This study aimed to investigate the association between SHS and intestinal microbiota in a case‐control study with 50 SHS individuals and 50 matched healthy controls. Intestinal microbiota was analysed by MiSeq 250PE. Alpha diversity of intestinal microbiota in SHS individuals was higher compared with that of healthy controls (Simpson index, W = 2238, P = .048). Beta diversity was different between SHS and healthy controls (P = .018). At the phylum level, the relative abundance of Verrucomicrobia was higher in the SHS group than that in the controls (W = 2201, P = .049). Compared with that of the control group, nine genera were significantly higher and five genera were lower in abundance in the SHS group (all P

The increasing prevalence of hyperuricemia has been recognized as an emerging public health concern in both developed and developing countries. Hyperuricemia is a metabolic condition characterized by an elevated serum uric acid, and associated with renal damage, diabetes, autoimmune disorders, and cardiovascular diseases. Although human genetic variation has been recognized as a factor, posttranslational cellular processes and glycan biomarkers have not been studied extensively for susceptibility to hyperuricemia. We evaluated whether immunoglobulin (Ig)G N-glycans play a role in hyperuricemia in the general population. This cross-sectional study enrolled 635 participants (208 men and 427 women), ages ≥18 years, from a community-based population in Beijing, China. The IgG N-glycan composition of serum was analyzed by an ultraperformance liquid chromatography method. The prevalence of hyperuricemia observed in this sample was 5.98% (14.9% in men and 1.6% in women). Serum uric acid level was positively correlated with glycan peaks (GP)1, GP2, GP4, GP6, GP10, and GP11, whereas it was negatively correlated with GP12, GP13, GP14, GP15, GP18, and GP20. The combination of GP9, GP10, body mass index, and gender distinguished individuals with hyperuricemia from subjects without hyperuricemia, with an area under the curve value of 0.849 (95% confidence interval: 0.784-0.915). These findings collectively suggest a possible link between hyperuricemia and IgG N-glycans, which might be potentially mediated through inflammation-related mechanisms. Additional research on glycan biomarkers in independent and community-based population samples might allow the development of glycan diagnostics for hyperuricemia and gout in the future.

Objective. The present study aimed to explore the association between SUA and NAFLD in women with different menstrual statuses. Methods. A total of 6043 women were selected from the Jidong and Kailuan communities for inclusion in the present study. The SUA levels of participants were divided into quartiles. NAFLD was determined by abdominal ultrasonography. Data from laboratory tests and clinical examination were collected, and basic information was obtained from standardized questionnaires. The menstrual status was stratified into menstrual period, menopause transition period, and postmenopause. Multivariate logistic regression models were used to determine the relationship between menstrual status, SUA, and NAFLD. Results. The levels of SUA in subjects with NAFLD in the menstrual period, menopause transition period, and postmenopause were 268.0 ± 71.1, 265.6 ± 67.8, and 286.7 ± 75.8 (mmol/L), respectively, and were higher than those in subjects without NAFLD. The adjusted odds ratios (ORs) with 95% confidence interval (CI) for NAFLD among participants in the menopause transition period and postmenopausal period were 1.10 (0.89–1.37) and 1.28 (1.04–1.58), respectively, compared with the menstrual period women. Compared to the lowest quartile of SUA, the adjusted ORs with 95% CI of the highest quartile for NAFLD were 2.24 (1.69–2.99) for females in the menstrual period, 1.92 (1.10–3.37) for females in the menopause transition period, and 1.47 (1.06–2.03) for females in postmenopause. Conclusions. Menstrual status was significantly correlated with NAFLD. High levels of SUA were associated with NAFLD in females during the three menstrual periods.

Background The mechanism by which normal body mass index (BMI) with central adiposity (NWCA) increases the risk of the diseases has not been completely elucidated. The inflammatory role of immunoglobulin G (IgG) N-glycosylation in obesity defined by BMI or central adiposity defined by waist-to-hip ratio (WHR) was reported, respectively. We undertook this three-center cross-sectional study to determine the association between the IgG N-glycans and NWCA. Methods The participants were categorized into four different phenotypes: normal BMI with normal WHR (NW), normal BMI with central adiposity (NWCA), obesity with normal WHR (ONCA) and obesity with central adiposity (OCA). The IgG N-glycans were analyzed using ultra-performance liquid chromatography analysis of released glycans, and differences among groups were compared. Results In total, 17 out of 24 initial IgG N-glycans were significantly different among the four groups (NW, ONCA, NWCA and OCA) (P

Background The antiviral therapy has been considered as an ordinary intervention for COVID-19 patients. However, the effectiveness of antiviral therapy is uncertain. This study was designed to determine the association between the antiviral therapy and in-hospital mortality among severe COVID-19 patients. Methods This study enrolled severe COVID-19 patients admitted to four designated hospitals in Wuhan, China. The use of antiviral treatments, demographics, laboratory variables, co-morbidities, complications, and other treatments were compared between survival and fatal cases. The association between antiviral agents and in-hospital mortality were analyzed. Results In total, 109 severe COVID-19 patients (mean age 65.43) were enrolled for analysis, among which, 61 (56.0%) patients were discharged alive, and 48 (44.0%) died during hospitalization. We found no association between lopinavir/ritonavir (LPV/r) treatment and the in-hospital mortality (odds ratio (OR) = 0.195, 95% confidence interval (CI) = 0.023-1.679). Besides, ribavirin (OR = 0.738, 95% CI = 0.344-1.582), oseltamivir (OR = 0.765, 95% CI = 0.349-1.636), and interferon-alpha (IFN-α) (OR = 0.371, 95% CI = 0.112-1.236) were not associated with the in-hospital mortality. However, arbidol monotherapy (OR = 5.027, 95% CI = 1.795-14.074) or the combination of arbidol and oseltamivir (OR = 5.900, 95% CI = 1.190-29.247) was associated with an increased in-hospital mortality. In addition, the multiple logistic regression identified a significant association between the use of arbidol and the in-hospital mortality (adjusted OR = 4.195, 95% CI = 1.221-14.408). Conclusions Our findings indicated that LPV/r, IFN-α, ribavirin, or oseltamivir have no beneficial effects on the prognosis of severe COVID-19 patients, whereas the use of arbidol is associated with increased in-hospital mortality.

Background. Extensive studies have been carried out to investigate the association between obesity and the risk of rheumatoid arthritis (RA); however, the results of the current reported original studies remain inconsistent. This study aimed to clarify the relationship between body mass index and rheumatoid arthritis by conducting an updated overall and dose-response meta-analysis. Methods. The relevant literature was searched using the PubMed and Embase databases (through 20 September 2018) to identify all eligible published studies. Random-effect models and dose-response meta-analyses were used to estimate the pooled risk ratio (RR) with a 95% confidence interval (CI). Subgroup analyses were also conducted based on the characteristics of the participants. Sensitivity analyses and publication bias tests were also performed to explore potential heterogeneity and bias in the meta-analysis. Results. Sixteen studies that included a total of 406,584 participants were included in the meta-analysis. Compared to participants with normal weight, the pooled RRs of rheumatoid arthritis were 1.12 (95% CI, 1.04-1.20) in overweight and 1.23 (95% CI, 1.09-1.39) in obese participants. There was evidence of a nonlinear relationship between body mass index (BMI) and RA (P for nonlinearity less than 0.001 in the overall meta-analysis, P for nonlinearity=0.025 in the case-control studies, P for nonlinearity=0.0029 in the cohort studies). No significant heterogeneity was found among studies (I2=10.9% for overweight and I2=45.5% for obesity). Conclusion. The overall and dose-response meta-analysis showed that increased BMI was associated with an increased risk for rheumatoid arthritis, which might present a prevention strategy for the prevention or control of rheumatoid arthritis. The nonlinear relationship between BMI and RA might present a personal prevention strategy for RA.

Observational studies highlight associations of IgG N-glycosylation with rheumatoid arthritis (RA); however, the causality between these conditions remains to be determined. Standard and multivariable two-sample Mendelian randomization (MR) analyses integrating a summary genome-wide association study for RA and IgG N-glycan quantitative trait loci (IgG N-glycan-QTL) data were performed to explore the potentially causal associations of IgG N-glycosylation with RA. After correcting for multiple testing (p < 2 × 10−3), the standard MR analysis based on the inverse-variance weighted method showed a significant association of genetically instrumented IgG N-glycan (GP4) with RA (odds ratioGP4 = 0.906, 95% confidence interval = 0.857–0.958, p = 5.246 × 10−4). In addition, we identified seven significant associations of genetically instrumented IgG N-glycans with RA by multivariable MR analysis (p < 2 × 10−3). Results were broadly consistent in sensitivity analyses using MR_Lasso, MR_weighted median, MR_Egger regression, and leave-one-out analysis with different instruments (all p values 0.05). In conclusion, our MR analysis incorporating genome-wide association studies and IgG N-glycan-QTL data revealed that IgG N-glycans were potentially causally associated with RA. Our findings shed light on the role of IgG N-glycosylation in the development of RA. Future studies are needed to validate our findings and to explore the underlying physiological mechanisms in the etiology of RA.

BACKGROUND China is expected to face among the largest increase of people with dementia worldwide in the coming decades, seriously challenging the Chinese healthcare system. Approximately 40% of all dementia cases might be attributable to potentially modifiable risk factors, suggesting the potential to delay or prevent dementia when targeting these risk factors. Mobile health (mHealth) may improve the accessibility of such dementia prevention strategies in China, given the wide and increasing use of smartphones by the entire Chinese population, including older adults. OBJECTIVE The aim of this qualitative study is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, facilitating development and cultural adaptation of a coach-supported mHealth platform for the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study. METHODS We performed semi-structured interviews with older adults, aged 55 and over, from Beijing and Tai’an, China, with an increased dementia risk without a diagnosis of dementia, who possess a smartphone. Participants were recruited through seven hospitals that participate in the PRODEMOS study, and were purposively sampled on age, sex, living situation, and history of CVD and diabetes. Data were analysed using thematic analysis. RESULTS Between February and December 2019 we performed 26 interviews with participants aged 55-86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations, and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese behaviours as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the burden put on family members. However, time-consuming family and other social obligations could also impede healthy behaviours, such as regular physical activity and a healthy diet. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional. CONCLUSIONS In spite of their clear appreciation of healthy lifestyles, Chinese older adults express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for CVD and dementia.

Mammary gland hyperplasia (MGH) is very common, especially among young and middle-aged women. New diagnostics and biomarkers for MGH are needed for rational clinical management and precision medicine. We report, in this study, new findings using a glycomics approach, with a focus on immunoglobulin G (IgG) N-glycosylation. A cross-sectional study was conducted in a community-based population sample in Beijing, China. A total of 387 participants 40–65 years of age were enrolled in this study, including 194 women with MGH (cases) and 193 women who had no MGH (controls). IgG N-glycans were characterized in the serum by ultra-performance liquid chromatography. The levels of the glycan peaks (GPs) GP2, GP5, GP6, and GP7 were lower in the MGH group compared with the control group, whereas GP14 was significantly higher in the MGH group (p

Background Since the outbreak of COVID-19, the application of appropriate treatment strategy for COVID-19 patients, notably for the severe patients, was a huge challenge in case management. Therefore, we aimed to evaluate the effectiveness of antiviral treatment in severe COVID-19 patients.Methods A retrospective cohort study was conducted from January 8, 2020 to March 9, 2020 in four designated hospitals of COVID-19 in Wuhan, China. 138 severe COVID-19patients with above 18 years were included in this study. 109 patients receiving the antiviral treatment were selected in antiviral group. The remaining 29 patients were in control group. The primary outcome of the study was in-hospital death and length of hospitalization. Secondary outcomes included ICU admission, length of stays in ICU, use of mechanical ventilation, length of mechanical ventilation, and the development of complications. Univariate analysis and Kaplan-Meier curves were used to examined the association between antiviral treatment and the clinical outcomes of the COVID-19 patients.Results 48 (44.0%) and 15 (51.7%) deaths were occurred in antiviral and control groups, respectively. Antiviral treatment was not associated with the rate of fatal outcome in COVID-19 patients (P > 0.05). Among the survival patients, the median length of hospitalization was 11.0 days (IQR: 6.5–18.0) and 16.0 days (IQR: 8.5–26.0) in antiviral and control groups, respectively. No significant association was identified between the antiviral treatment and the length of hospitalization in survival patients (P > 0.05). Moreover, the antiviral treatment was not statistically associated with ICU admission, mechanical ventilation and length of mechanical ventilation (P > 0.05, respectively). However, the length of ICU stays in deaths was different both groups (P vs 13.8%, P

Prospective studies have shown that abnormally circulating cholesterol is associated with the risk of dementia. However, whether the association is causal or not remains unclear. We attempt to infer the causal association in a MR meta-analysis by using ApoE gene polymorphisms as instrument variables. Studies with dementia risk (27 studies) or circulating lipid levels (7 studies) were included, with totally 3136 dementia patients and 3103 healthy controls. The analyses showed that carriers of ε2 allele significantly were of decreased risk of AD (OR = 0.70; 95% CI: 0.58–0.84; P P P P P P P P

Background The mechanism by which normal body mass index (BMI) with central adiposity (NWCA) increases the risk of the diseases has not been completely elucidated. The inflammatory role of immunoglobulin G (IgG) N-glycosylation in obesity defined by BMI or central adiposity defined by waist-to-hip ratio (WHR) was reported, respectively. We undertook this three-center cross-sectional study to determine the association between the IgG N-glycans and NWCA. Methods The participants were categorized into four different phenotypes: normal BMI with normal WHR (NW), normal BMI with central adiposity (NWCA), obesity with normal WHR (ONCA) and obesity with central adiposity (OCA). The IgG N-glycans were analyzed using ultra-performance liquid chromatography analysis of released glycans, and differences among groups were compared. Results In total, 17 out of 24 initial IgG N-glycans were significantly different among the four groups (NW, ONCA, NWCA and OCA) (P

The increasing prevalence of hyperuricemia has been recognized as an emerging public health concern in both developed and developing countries. Hyperuricemia is a metabolic condition characterized by an elevated serum uric acid, and associated with renal damage, diabetes, autoimmune disorders, and cardiovascular diseases. Although human genetic variation has been recognized as a factor, posttranslational cellular processes and glycan biomarkers have not been studied extensively for susceptibility to hyperuricemia. We evaluated whether immunoglobulin (Ig)G

BACKGROUND: The prevalence of diabetes, constituted chiefly by type 2 diabetes mellitus (T2DM), is a global public health threat. Suboptimal health status (SHS), a physical state between health and disease, might contribute to the progression or development of T2DM. METHODS: We conducted a prospective cohort study, based on the China Suboptimal Health Cohort Study (COACS), to understand the impact of SHS on the progress of T2DM. We examined associations between SHS and T2DM outcomes using multivariable logistic regression models and constructed predictive models for T2DM onset based on SHS. RESULTS: A total of 61 participants developed T2DM after an average of 3.1 years of follow-up. Participants with higher SHS scores had more T2DM outcomes (p = 0.036). Moreover, compared with the lowest quartile of SHS scores, participants with fourth, third, and second quartile SHS scores were found to be associated with a 1.7-fold, 1.6-fold, and 1.5-fold risk of developing T2DM, respectively. The predictive model constructed with SHS had higher discriminatory power (AUC = 0.848) than the model without SHS (AUC = 0.795). CONCLUSIONS: The present study suggests that a higher SHS score is associated with a higher incidence of T2DM. SHS is a new independent risk factor for T2DM and has the capability to act as a predictive tool for T2DM onset. The evaluation of SHS combined with the analysis of modifiable risk factors for SHS allows the risk stratification of T2DM, which may consequently contribute to the prevention of T2DM development. These findings might require further validation in a longer-term follow-up study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13167-019-0159-9) contains supplementary material, which is available to authorized users.

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from the MEGASTROKE collaboration with 40,585 stroke cases and 406,111 controls. The weighted median (WM), the penalized weighted median (PWM), the inverse variance weighted (IVW), the penalized inverse variance weighted (PIVW), the robust inverse variance weighted (RIVW), and the Mendelian randomization-Egger (MR-Egger) methods were conducted for the MR analysis to estimate a causal effect and detect the directional pleiotropy. Results: No significant association between genetically determined TL with overall IS, LAS, or CES were found (all p &gt, 0.05). SVS was associated with TL by the RIVW method (odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.54&ndash, 0.97, p = 0.028), after excluding rs9420907, rs10936599, and rs2736100. Conclusions: By a series of causal inference approaches using SNPs as IVs, no strong evidence to support the causal effect of shorter TL on IS and its subtypes were found.