Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). @*Methods@#We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. @*Results@#Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. @*Conclusion@#The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Gold nanorods-mediated efficient synergistic immunotherapy for detection and inhibition of postoperative tumor recurrence

Tumor recurrence after surgery is the main cause of treatment failure. However, the initial stage of recurrence is not easy to detect, and it is difficult to cure in the late stage. In order to improve the life quality of postoperative patients, an efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously. In this paper, two kinds of theranostic agents based on gold nanorods (AuNRs) platform were prepared. AuNRs and quantum dots (QDs) in one agent was used for the detection of carcinoembryonic antigen (CEA), using fluorescence resonance energy transfer (FRET) technology to indicate the occurrence of

New insights into the growing diabetes epidemic in China: middle-aged obesity-related insulin resistance becomes the major threat / 中华内分泌代谢杂志

Delineation of the relationship between insulin resistance, β cell dysfunction, and obesity is crucial for the prevention and effective management of diabetes. Previous studies have indicated that, compared with type 2 diabetes in Caucasian, type 2 diabetes in East Asians is characterized primarily by β cell dysfunction rather than insulin resistance. This pathophysiological characterization of diabetes in East Asians is mainly derived from Japanese and Asian-American populations, whereas data from mainland China are scarce. Over the past four decades, China has witnessed a substantial rise in obesity, in parallel with the transitions from principally active lifestyles and calorie-restricted diets to sedentary life styles and energy-dense, western diets. Obesity is an insulin resistance state and the major factor driving the worldwide epidemic of diabetes. It is unknown whether, and if so how, obesity affects the two primary mechanisms, insulin resistance and β cell dysfunction, responsible for the development of diabetes in the Chinese population. Recently, the Lancet Diabetes & Endocrinology published an original research paper from the China Cardiometabolic Disease and Cancer Cohort Study (4C). From a public health perspective, the results of this study reinforce the urgency of tackling obesity as a major preventive strategy for the epidemic of type 2 diabetes in China.

Interplay between diet and genetic susceptibility in obesity and related traits / 医学前沿

The incidence of obesity has been rapidly increasing, and this condition has become a major public health threat. A substantial shift in environmental factors and lifestyle, such as unhealthy diet, is among the major driving forces of the global obesity pandemic. Longitudinal studies and randomized intervention trials have shown that genetic susceptibility to obesity may interact with dietary factors in relation to the body mass index and risk of obesity. This review summarized data from recent longitudinal studies and intervention studies on variations and diets and discussed the challenges and future prospects related to this area and public health implications.

Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis / 医学前沿

Type 2 diabetes (T2D) has been associated with a high prevalence of depression.We aimed to determine the causal relation by performing a Mendelian randomization (MR) study using 34 T2D risk genetic variants validated in East Asians as the instrumental variable (IV). An MR analysis was performed involving 11 506 participants from a large longitudinal study. The T2D genetic risk score (GRS) was built using the 34 typical T2D common variants. We used T2D_GRS as the IV estimator and performed inverse-variance weighted (IVW) and Egger MR analysis. The T2D_GRS was found to be associated with depression with an OR of 1.21 (95% CI: 1.07-1.37) after adjustments for age, sex, body mass index, current smoking and drinking, physical activity, education, and marital status. Using T2D_GRS as the IV, we similarly found a causal relationship between genetically determined T2D and depression (OR: 1.84, 95% CI: 1.25-2.70). Though we found no association between the combined effect of the genetic IVs for T2D and depression with EggerMR(OR: 0.95, 95%CI: 0.42-2.14), we found an association for T2D and depression with IVW (OR: 1.75, 95% CI: 1.31-2.46) after excluding pleiotropic SNPs. Overall, the MR analyses provide evidence inferring a potential causal relationship between T2D and depression.

Association between gallstone and non-alcoholic fatty liver disease in middle-aged and elderly Chinese in Shanghai local communities / 中华内分泌代谢杂志

Objective To investigate the association between gallstone and non-alcoholic fatty liver disease (NAFLD)in middle-aged and elderly Chinese. Methods A cross-sectional study was conducted in 8934 Chinese adults from Jiading District, Shanghai. Questionnaire interview, anthropometric measurements, biochemical evaluation, and abdominal ultrasonography were performed in all the participants. Results Compared with participants without gallstone,individuals with gallstone had significantly higher prevalence of NAFLD(28.8% and 42.9%,respectively;P<0.01). Using participants without gallstone as the reference,participants with gallstone were associated with an increased risk of NAFLD after adjustment for multiple covariatesodds ratios(OR)and 95% confidence interval(CI)was 1.39(1.45-1.69). In addition,compared with participants without cholecystectomy, participants with cholecystectomy were associated with an increased risk of NAFLD(OR=1. 44, 95% CI 1. 04-1.99). Conclusion The presence of gallstone and cholecystectomy were positively associated with NAFLD in middle-aged and elderly Chinese.

Association of low-grade albuminuria with carotid intima-media thickness / 中华内分泌代谢杂志

Objective To analyze the association of elevated carotid intima-media thickness(CIMT)with low-grade albuminuria in a community-based population. Methods A total of 10 375 participants aged 40 years or older were recruited using cluster sampling from Jiading district, Shanghai. Standardized questionnaires were adopted to collect information on health status and lifestyles. Anthropometric measurements including weight, height, and blood pressure, and biochemical tests for blood and urine were performed. CIMT was detected by B-mode ultrasound examinations. 9 523 subjects were included for final analysis. All these subjects were divided into 4 groups according to sex-specific urinary albumin to creatinine ratio ( UACR ) quartiles. CIMT≥upper decile of the population was defined as elevated CIMT and low-grade albuminuria was defined as UACR≥sex-specific upper quartile. The relationship between UACR and CIMT was investigated by multiple logistic regression analysis. Results The prevalence of elevated CIMT in this population aged 40 years or older with albuminuria in normal range was 21. 44%. Comparing to participants without elevated CIMT, those with elevated CIMT showed higher level of UACR (4. 79 vs 4. 51 mg/g, P<0. 01). The metabolic status was deteriorated with the increment of UACR level. The prevalences of elevated CIMT were 18. 99%, 19. 24%, 20. 20%, and 27. 33% from the lowest to highest UACR quartile, respectively(Ptrend<0. 01). After adjusting for some conventional cardiovascular risk factors, multiple logistic regression revealed that compared with the participants in the lowest quartile of UACR, those in the highest quartile had a 1. 25-fold risk of elevated CIMT. Conclusions This study shows that low-grade albuminuria is positively associated with elevated CIMT, independent of conventional cardiovascular risk factors in middle-aged and elderly adults.

Epidemiological studies on the association of bisphenol A with diabetes and obesity / 中华内分泌代谢杂志

As one of the important environmental endocrine disruptors,the effects of bisphenol A (BPA)are recently focused on its association with endocrine and metabolic diseases.Experimental studies have shed light on the potential mechanisms that BPA affects the development of diabetes and obesity.Epidemiological studies that aimed to provide clinical evidence have contributed substantially to the debate on BPA.