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.

Metabolic Disease Management Guideline for National Metabolic Management Center(2nd edition) / 中华内分泌代谢杂志

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.@*METHODS@#From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.@*RESULTS@#During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01).@*CONCLUSION@#NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai / 生物医学与环境科学（英文）

Objective@#This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease (CKD) in Shanghai community residents.@*Methods@#We used data from a cohort study of community residents who participated in three examinations in 2008, 2009, and 2013, respectively. Fasting plasma glucose (FPG) level, blood pressure (BP), and lipid levels were determined in 2,109 participants at all three visits, and CKD was evaluated between the second and the third visits. Visit-to-visit variabilities in metabolic factors were described by coefficients of variation (CV) at three visits. A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV. CKD was defined as the estimated glomerular filtration rate < 60 mL/min per 1.73 m @*Results@#A total of 200 (9.5%) participants had CKD at the third visit. Compared with the lowest quartile of CV, the highest quartile was associated with a 70% increased risk of CKD for FPG [odds ratio, @*Conclusion@#The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study / 生物医学与环境科学（英文）

Objective@#The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.@*Methods@#The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.@*Results@#A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).@*Conclusion@#An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Advances and prospectives of metabolic chamber application in endocrine and metabolic diseases / 中华内分泌代谢杂志

The metabolic chamber system is a new-developed method of energy metabolism examination by indirect calorimetry. Recently, metabolic chambers have been applied in energy expenditure affected by the changes of diet, sleep and physical activities, and metabolic diseases such as obesity and type 2 diabetes mellitus, to underlie the potential mechanisms. This review is aimed to summarize the applications of metabolic chambers in China and abroad in researches on energy metabolism involved in physiology, endocrine diseases and energy metabolism disorders. A more extensive use of metabolic chambers in clinical practice is well expected in the foreseeable big-data era.

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.

Association between Lipoprotein (a) Levels and Metabolic Syndrome in a Middle-aged and Elderly Chinese Cohort / 生物医学与环境科学（英文）

OBJECTIVE@#The association between lipoprotein (a) [Lp(a)] levels and metabolic syndrome (MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort.@*METHODS@#A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS.@*RESULTS@#In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS (30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio (OR) for prevalent MetS [multivariate-adjusted OR 0.45 (95% confidence interval 0.39-0.51); P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups.@*CONCLUSION@#Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort.

Oral treatment for obstructive sleep apnea syndrome / 华西口腔医学杂志

Obstructive sleep apnea syndrome (OSAS) is a common clinical disease with high incidence and low treating proportion, difficult evaluation, and complicated nosogenesis. OSAS can cause systematic impairments. Various treatment methods were applied in clinical setting with the tendency of cross-disciplinary promotion. Oral treatment plays an exceedingly important role in OSAS research and therapy. This study reports the oral treatment involving OSAS therapy.

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.

Strategic thinking of medical research in the era of big data-based medicine and intelligent medicine / 中华内分泌代谢杂志

The primary impetus for the development of medicine is invariably the scientific research, no matter it is in the era of evidence-based medicine, translational medicine, precision medicine, intelligent medicine, or big data-based medicine. The basic medical research unravels the nature of life and the clinical research addresses the health issues in humans. It is necessary to establish a kind of close relationship between basic researchers and clinical investigators under an organized framework, thus to open a new medical research dimension with innovative ideas and consecutive breakthroughs. (Chin J Endocrinol Metab, 2018, 34: 537-538)

Clinical characteristics and molecular diagnosis in 2 cases of P450 oxidoreductase deficiency / 中华内分泌代谢杂志

Objective To analyze clinical characteristics and gene mutation of two patients diagnosed with P450 oxidoreductase deficiency(PORD). Methods Clinical data of 2 patients with PORD was collected from Ruijin hospital. POR gene mutation was analyzed by PCR-Sanger sequencing. A retrospective analysis of literatures concerning PORD was performed. Results Patient 1, female, 16 years old, with 46,XX karyotype, presented with anorectal anomalies, clitoral hypertrophy at birth and irregular menstruation; Patient 2, female, 32 years old, with 46,XX karyotype, showed irregular menstruation and infertility, both without obvious skeletal deformity. Genetic test of POR gene mutation revealed that patient 1 carried a homozygous missense mutation (R457H) and patient 2 carried a heterozygous mutation (R223X/ Y607C). The two mutations (R223X and Y607C) are reported for the first time in China. Conclusion P450 oxidoreductase deficiency which caused by mutations in POR gene has a variety of clinical manifestations, including abnormal steroid hormone synthesis with or without Antley-Bixler syndrome. The affirmative diagnosis should rely on steroid hormone measurement and POR gene analysis.

Research progress on the genes related to androgens in polycystic ovary syndrome / 中华内分泌代谢杂志

Polycystic ovary syndrome( PCOS) is one of the most common endocrine disorders in women of reproductive age, resulting in several health complications such as menstrual dysfunction, infertility, hirsutism, acne, obesity, and metabolic syndrome. PCOS is recognized to be a complex polygene disease. Although the cause of PCOS has not been fully clarified, hyperandrogenism is one of the key pathogenesises of PCOS. In this article, we reviewed the effects of genes related to androgen biosynthesis,metabolism,reserve,action and regulation on the pathogenesis of PCOS based on the research progress in the candidate gene studies, genome wide association studies, as well as its epigenetics.

Association of age at menarche with the risks of diabetes mellitus and metabolic syndrome in adulthood in Shanghai Jiading community postmenopausal women / 中华内分泌代谢杂志

Objective To investigate the association of age at menarche with the risks of diabetes and metabolic syndrome ( MS) in adulthood in Shanghai community postmenopausal women. Methods A total of 10375 residents over 40 years in Jiading, Shanghai were identified by a cluster sampling method. After taking standardized questionnaire surveys, physical examinations, and biochemical parameters testing, we gathered their lifestyle and medicine information. A total of 4723 postmenopausal women were enrolled in the study. The population was divided into three groups according to age at menarche, and their risks of MS and diabetes in various groups were compared. Results After multivariate adjustment, postmenopausal women with a menarche age<15 years had a 29％increased risk of diabetes(95％CI 1.03-1.61) and a 45％ increased risk of MS(95％ CI 1.20-1.76) in adulthood, compared with those with menarcheal age at 15-18 years. Among the five components of MS, earlier age of menarche was associated with higher risks of hypertriglyceridemia, low high density lipoprotein-cholesterol, and central obesity. Conclusions In Shanghai Jiading community postmenopausal women, age at menarche is associated with the risk of diabetes and MS, independent of the body mass index in adulthood.

The clinical analysis of severe adrenal Cushing′s syndrome / 中华内分泌代谢杂志

Objective To investigate the methods and efficacy of treatment on severe adrenal Cushing′s syndrome. Methods The clinical data of 22 cases with severe adrenal Cushing′s syndrome ( severe group) , and 136 cases with mild or moderate adrenal Cushing′s syndrome ( non-severe group) were reviewed. The clinical features were analyzed by comparing the differences between these two groups when patients were admitted to hospital. We discussed the clinical managements of patients with severe adrenal Cushing′s syndrome by comparing the differences with non-severe group after preoperative preparation, and with themselves before and after preoperative preparation. The effects of surgery were evaluated by comparing the differences between pre-operation and post-operation on patients with severe adrenal Cushing′s syndrome. Results At admission, serum/urine cortisol, disease course, and blood pressure were significantly higher in the severe group than those in non-severe group ( P＜0.05 or P＜0.01) , serum potassium and ACTH level were decreased significantly in the severe group than those innon-severegroup[(3.01±0.75vs3.62±0.48)mmol/L,P＜0.01;(6.47±2.91vs8.21±3.22)pg/ml,P＜0.01] . However, no significant difference was observed in diastolic blood pressure, serum potassium, and fasting plasma glucose between these two groups after preoperative preparation (all P＞0.05). And then, we performed adrenalectomy. The symptoms of 22 cases with severe adrenal Cushing′s syndrome were obviously alleviated after 3 months. During follow-up, 5 cases of primary bilateral macronodular adrenal hyperplasia ( BMAH) and 1 case of primary pigmented nodular adrenocortical disease ( PPNAD ) were treated with contralateral adrenalectomy. Conclusion Sufficient preoperative preparation is essential for patients with severe adrenal Cushing′s syndrome because of its high level serum cortisol with severe complications. If preparation fails before surgery, cortisol-lowering medication or emergency unilateral adrenalectomy is necessary. Severe patients with BMAH and PPNAD were firstly performed unilateral adrenalectomy and followed-up closely, and then, contralateral adrenalectomy is needed when the recurrence of hypercortisolism recognized.

Independent and joint effect of brachial-ankle pulse wave velocity and body mass index level on incident diabetes with hypertension / 中华内分泌代谢杂志

Objective To investigate whether brachial-ankle pulse wave velocity(baPWV),independently and jointly with the level of body mass index(BMI),affect the risk of incident diabetes with hypertension. Methods The effects of baPWV and BMI level on incident diabetes with hypertension were evaluated using Kaplan-Meier curves (log-rank test) and multi logistical regression models after adjustment for various confounding factors. Results A total of 2 222 participants were recruited in this study. Higher baPWV (Q4) was associated with a greater risk of incident diabetes with hypertension simultaneously compared with baPWV in the lower quartiles(Q1-Q3),with HR 4.16(95% CI 2.14,8.09)in the crude model,2.52(95% CI 1.10,5.78) in modelI,and 2.45(95% CI 1.05, 5.70)in modelⅡ.The highest risk of diabetes with hypertension simultaneously was in the group with high baPWV and BMI≥25 kg/m2,with HR 11.50(95% CI 4.5,29.9)in the crude model,4.20(95% CI 1.4,13.1)in modelI,and 4.30(95% CI 1.4,13.3) in modelⅡ. Conclusions The joint effect of baPWV and BMI level on incident diabetes with hypertension simultaneously is a better predictor than their independent effect. The risk of incident diabetes with hypertension markedly increases in the subjects with BMI≥25 kg/m2and higher baPWV.

Implication of ACE Trial results / 中华内分泌代谢杂志

Pre-diabetes is at increased risk of development of type 2 diabetes and future cardiovascular events. Preventing the progression of pre-diabetic populations to diabetes is important. The Acarbose Cardiovascular Evaluation(ACE) trial was the largest pre-diabetes intervention study conducted in China. The study found that acarbose treatment can significantly reduce the risk of new-onset diabetes in IGT patients with CVD on the basis of life interventions,but the cardiovascular benefits for the population are not significant. ACE study showed that acarbose can prevent the conversion of IGT to diabetes,which plays a key role in the prevention of diabetes.

Fasting: Recent development and prospects / 中华内分泌代谢杂志

Fasting is a dietary intervention based on restricted energy intake, which has different forms of frequency and intensity, and is effective at reducing body weight and improving metabolic health. The cellular and molecular mechanisms of fasting involve lipolysis, increase of thermogenesis, regulation of autophagy, modulation of β cell regeneration and suppression of inflammation. This review focuses on the updates of patterns, benefits, and mechanisms of fasting.

Thymic carcinoid associated to Multiple Endocrine Neoplasia type 1 / 中华内分泌代谢杂志

Thymic carcinoid is an uncommon component of Multiple Endocrine Neoplasia Type 1 (MEN1).The low penetrance and the high mortality made TH-NET one of the most fatal tumor components of MEN1.Here we are discussing the pathology and pathogenesis, as well as epidemiology, screening strategy, diagnosis, therapies, and analysis of prognostic factors of thymic carcinoid associated to MEN1.

Association between neck circumference and cardiovascular risk factors in middle-aged and elderly nondiabetic people in Jiading District, Shanghai / 上海交通大学学报（医学版）

Objective· To investigate the association between neck circumference (NC) and cardiovascular risk factors among middle-aged and elderly people without diabetes in Jiading District in Shanghai.Methods· A cross-sectional study was conducted among 4 657 nondiabetic inhabitants aged 40 and above in Jiading District,Shanghai from August 2014 to July 2015.Clinical information collection,anthropometric measurements,and biochemical analyses were performed.The objects were divided into 4 groups according to the quartiles of NC in order to analyze association between NC and cardiovascular risk factors.Results· With increase of NC,the prevalences of abdominal obesity,insulin resistance,hypertension,and dyslipidemia all increased as well as waist circumference,body mass index (BMI),blood pressure,lipid profile,fast blood glucose,and HOMA-IR level (all Ptrend ＜0.01).Multiple Logistic regression analysis showed that individuals in Q2,Q3 and Q4 group had significantly higher risk of abdominal obesity,insulin resistance,hypertension,and dyslipidemia compared with those in Q1 group after age,sex,smoking,drinking,physical activity,BMI,waist circumference,systolic blood pressure,C-reactive protein,fast blood glucose,and lipid profile were corrected (all Ptrend ＜0.01).Conclusion· NC is positively and independently correlated with cardiovascular risk factors in middle-aged and elderly nondiabetic people in Jiading District in Shanghai.