Cerebral ischemia/reperfusion injury (CIRI) poses a significant threat to human life and health. Ginsenoside Rb3 (Rb3) is known to exhibit protective effects against myocardial ischemia, its impact on CIRI remains unclear. Therefore, we investigated the protective effects of Rb3 on CIRI and its underlying mechanisms. Our results showed that Rb3 reduced cerebral infarct volume, decreased blood-brain barrier (BBB) permeability, and improved neurological deficits in CIRI rats. Rb3 also mitigated cerebral ferroptosis and alleviated neuroinflammation, as evidenced by decreased iron levels, reduced MDA content, an improved GSH/GSSG ratio, and lower levels of TNF-α, IL-1β, and IL-6, through modulation of the NLRP3/NF-κB/GPX4 pathway. Additionally, Rb3 alleviated intestinal inflammation, improved the intestinal barrier, and corrected gut microbiota dysbiosis and reduced the microbial metabolites TMAO and LPS in CIRI rats. It is noteworthy that in pseudo germ-free rats with CIRI, fecal microbiota transplants (FMT) from Rb3-treated rats conferred similar protective effects as Rb3. Summarily, this study reveals that Rb3 reduces neuroinflammation and ferroptosis in the brains of middle cerebral artery occlusion/reperfusion (MCAO/R) rats via the NLRP3/NF-κB/GPX4 pathway in a gut microbiota-dependent manner.

AIMS:To assess the efficacy and safety of cofrogliptin for impaired glucose tolerance (IGT). METHODS:In this multicenter, double-blind, placebo-controlled phase 2 trial, IGT patients were randomized 1:1:1 to receive cofrogliptin 10 mg, cofrogliptin 25 mg or placebo once biweekly. The primary endpoint was the change from baseline in glucose total AUC0-3 h during meal tolerance test (MTT) at week 12. RESULTS:Among 261 subjects screened, 99 were enrolled. At week 12, significant mean reductions from baseline in glucose total AUC0-3 h during MTT were observed in cofrogliptin groups (10 mg: -1.75 mmol h/L, p = 0.01; 25 mg: -1.54 mmol h/L, p = 0.02) versus placebo (0.36 mmol h/L). Significant benefits were also seen with cofrogliptin for secondary endpoints of the change from baseline in Cmax of glucose during MTT 0-3 h at week 12, and the change from baseline in glucose total AUC0-3 h and Cmax of glucose during OGTT 0-3 h at week 10 versus placebo. Additionally, more cofrogliptin-treated patients achieved normoglycaemia versus placebo at week 10. The incidence of AEs was generally comparable in all groups, and all of AEs were mild or moderate. No serious AEs or severe hypoglycaemia were reported. CONCLUSION:A 12-week treatment with cofrogliptin provided significant glucose-lowering, and was safe, well tolerated.

Background Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of type 2 diabetes mellitus (T2DM). DSPN may lead to more serious complications, such as diabetic foot ulcer, amputation, and reduced life expectancy. Observational studies have suggested that vitamin D deficiency may be associated with the development of DSPN in T2DM. However, interventional studies have found that low-dose vitamin D supplementation does not significantly improve neuropathy in DSPN. This study aims to evaluate the efficacy and safety of intramuscular injection of high-dose vitamin D (HDVD) in T2DM with DSPN combined with vitamin D insufficiency. Methods and analysis We will conduct a multicenter, randomized, double-blinded, and placebo-controlled trial in four large hospitals. All eligible participants will be randomly assigned to either the vitamin D 2 supplement or placebo control group and injected intramuscularly monthly for 3 months. Additionally, anthropometric measurements and clinical data will be collected at baseline and 3 months. Adverse events will be collected at 1, 2, and 3 months. The primary outcome measure is the change in the mean Michigan Neuropathy Screening Instrument (MNSI) score at baseline and 3 months post-intervention. We will use the gold-standard liquid chromatography-tandem mass spectrometry method to distinguish between 25(OH)D 2 and 25(OH)D 3 levels. The MNSN score before the intervention will be used as a covariate to compare the changes between both groups before and after the intervention, and the analysis of covariance will be used to analyze the change in the MNSI score after HDVD supplementation. Discussion Glycemic control alone does not prevent the progression of DSPN in T2DM. Some studies have suggested that vitamin D may improve DSPN; however, the exact dose, method, and duration of vitamin D supplementation are unknown. Additionally, neuropathy repair requires HDVD supplementation to sustain adequate vitamin D levels. This once-a-month intramuscular method avoids daily medication; therefore, compliance is high. This study will be the first randomized controlled trial in China to analyze the efficacy and safety of HDVD supplementation for patients with T2DM and DSPN and will provide new ideas for pharmacological research and clinical treatment of diabetic neuropathy. Clinical trial registration https://www.chictr.org.cn/ , identifier ChiCTR2200062266.

Objectives: This study aimed to investigate the LEF-1-mediated Wnt/beta-catenin pathway for its biological functions and prognostic value in colon cancer (CC). Furthermore, the potential molecular mechanism of beta-sitosterol in CC was investigated in vitro.Methods: Clinical information and gene expression profiles from CC patients were obtained based on Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, we applied R software "Limma" package for the differential analysis of LEF-1 between cancer and para-carcinoma tissue samples. Kaplan-Meier (KM) survival analysis was adopted for analyzing whether LEF-1 was of prognostic significance. Moreover, gene set enrichment analysis (GSEA) was adopted for pathway enrichment analysis and visualization. In addition, CCK8, plate cloning, scratch and high-content screening (HCS) imaging assays were performed to examine the therapeutic efficacy of beta-sitosterol in human CC HCT116 cells. siRNA technology was employed to knock down LEF1 expression in HCT116 cells. qRT-PCR and Western-blot (WB) analysis were carried out to analyze the HCT-116 mRNA and protein expression levels, respectively.Results: LEF-1 was up-regulated within CC and acted as an oncogenic gene. LEF-1 up-regulation predicted the dismal prognostic outcome and activated the Wnt/beta-catenin pathway. beta-sitosterol effectively suppressed HCT116 cells proliferation and invasion. For the mechanism underlying beta-sitosterol, beta-sitosterol was found to significantly down-regulate LEF-1 gene and protein expression and disrupt Wnt/beta-catenin pathway transmission in HCT116 cells. After suppressing LEF-1 expression, its downstream targets including C-myc, Survivin and CCND1 were also down-regulated.Conclusion: According to our results, LEF-1 down-regulation can effectively block Wnt/beta-catenin pathway, inhibit CC cell growth and migration. Collectively, beta-sitosterol can be used to treat CC, which can provide anti-tumor activity by targeting LEF-1.

Cerebral ischemia/reperfusion injury (CIRI) seriously threatens human life and health. Scutellarin (Scu) exhibits neuroprotective effects, but little is known about its underlying mechanism. Therefore, we explored its protective effect on CIRI and the underlying mechanism. Our results demonstrated that Scu rescued HT22 cells from cytotoxicity induced by oxygen and glucose deprivation/reoxygenation (OGD/R). Scu also showed antioxidant activity by promoting nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, upregulating heme oxygenase-1 (HO-1) expression, increasing superoxide dismutase (SOD) activity, and inhibiting reactive oxygen species (ROS) generation in vitro. Additionally, Scu reduced nuclear factor-kappa B (NF-κB) activity and the levels of pro-inflammatory factors. Interestingly, these effects were abolished by Nrf2 inhibition. Furthermore, Scu reduced infarct volume and blood-brain barrier (BBB) permeability, improved sensorimotor functions and depressive behaviors, and alleviated oxidative stress and neuroinflammation in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Mechanistically, Scu-induced Nrf2 nuclear accumulation and inactivation of NF-κB were accompanied by an enhanced level of phosphorylated protein kinase B (p-AKT) both in vitro and in vivo. Pharmacologically inhibiting the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway blocked Scu-induced Nrf2 nuclear translocation and inactivation of NF-κB, as well as its antioxidant and anti-inflammatory activities. In summary, these results suggest that Scu exhibits antioxidant, anti-inflammatory, and neuroprotective effects in CIRI through Nrf2 activation mediated by the PI3K/Akt pathway.

More than 700 million confirmed cases of Coronavirus Disease-2019 (COVID-19) have been reported globally, and 10–60% of patients are expected to exhibit “post-COVID-19 symptoms,” which will continue to affect human life and health. In the absence of safer, more specific drugs, current multiple immunotherapies have failed to achieve satisfactory efficacy. Ginseng, a traditional Chinese medicine, is often used as an immunomodulator and has been used in COVID-19 treatment as a tonic to increase blood oxygen saturation. Ginsenosides are the main active components of ginseng. In this review, we summarize the multiple ways in which ginsenosides affect post-COVID-19 symptoms, including inhibition of lipopolysaccharide, tumor necrosis factor signaling, modulation of chemokine receptors and inflammasome activation, induction of macrophage polarization, effects on Toll-like receptors, nuclear factor kappa-B, the mitogen-activated protein kinase pathway, lymphocytes, intestinal flora, and epigenetic regulation. Ginsenosides affect virus-mediated tissue damage, local or systemic inflammation, immune modulation, and other links, thus alleviating respiratory and pulmonary symptoms, reducing the cardiac burden, protecting the nervous system, and providing new ideas for the rehabilitation of patients with post-COVID-19 symptoms. Furthermore, we analyzed its role in strengthening body resistance to eliminate pathogenic factors from the perspective of ginseng-epidemic disease and highlighted the challenges in clinical applications. However, the benefit of ginsenosides in modulating organismal imbalance post-COVID-19 needs to be further evaluated to better validate the pharmacological mechanisms associated with their traditional efficacy and to determine their role in individualized therapy.

Cells have been increasingly known to release extracellular vesicles (EVs) to the extracellular environment under physiological and pathological conditions. A plethora of studies have revealed that EVs contain cell-derived biomolecules and are found in circulation, thereby implicating them in molecular trafficking between cells. Furthermore, EVs have an effect on physiological function and disease development and serve as disease biomarkers. Given the close association between EV circulation and vascular disease, this review aims to provide a brief introduction to EVs, with a specific focus on the EV cargoes participating in pathological mechanisms, diagnosis, engineering, and clinical potential, to highlight the emerging evidence suggesting promising targets in vascular diseases. Despite the expansion of research in this field, some noticeable limitations remain for clinical translational research. This review makes a novel contribution to a summary of recent advances and a perspective on the future of EVs in vascular diseases.

Stroke is one of the leading causes of death and disability in the world, of which ischemia accounts for the majority. There is growing evidence of changes in synaptic connections and neural network functions in the brain of stroke patients. Currently, the studies on these neurobiological alterations mainly focus on the principle of glutamate excitotoxicity, and the corresponding neuroprotective strategies are limited to blocking the overactivation of ionic glutamate receptors. Nevertheless, it is disappointing that these treatments often fail because of the unspecificity and serious side effects of the tested drugs in clinical trials. Thus, in the prevention and treatment of stroke, finding and developing new targets of neuroprotective intervention is still the focus and goal of research in this field. In this review, we focus on the whole processes of glutamatergic synaptic transmission and highlight the pathological changes underlying each link to help develop potential therapeutic strategies for ischemic brain damage. These strategies include: (1) controlling the synaptic or extra-synaptic release of glutamate, (2) selectively blocking the action of the glutamate receptor NMDAR subunit, (3) increasing glutamate metabolism, and reuptake in the brain and blood, and (4) regulating the glutamate system by GABA receptors and the microbiota–gut–brain axis. Based on these latest findings, it is expected to promote a substantial understanding of the complex glutamate signal transduction mechanism, thereby providing excellent neuroprotection research direction for human ischemic stroke (IS).

Introduction: Network pharmacology approaches enable an effective exploration of the natural product target space, thus providing a systematic approach to expand the protein target space involved in various complex diseases. Sophorae Tonkinesis Radix Et Rhizoma (STRR) have been used in treating hepatocellular carcinoma (HCC) in China. However, the active ingredient is unclear.Methods: In this study, the Traditional Chinese Medicine (TCM) databases were employed to screen and identify interrelated active ingredients of STRR. The potential targets of STRR for the treatment of hepatocarcinoma were identified by systematic pharmacology and bioinformatics approaches. In parallel, molecular docking was used to obtain the strength of ingredients bound with core targets. Further, in order to confirm efficacy, it is necessary to test and verify the prediction through a series of studies, such as in vitro experiments.Results: Collecting 14 ingredients regulated HCC from STRR. Results of systematic pharmacology and bioinformatics studies have shown that 8 predictive targets of STRR were collected to treat HCC. Furthermore, the core genes were determined by constructing protein-protein interaction (PPI) networks and performing topological analysis. The results showed that the effect of withaferin A may be closely related with epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase 1 (MAPK1). In vitro studies showed that withaferin A exerts anti-HCC activity by down-regulating MAPK1 and EGFR.Conclusion: The potential mechanisms of STRR treatment for HCC involve multiple components, targets, and pathways. The study found that withaferin A has strong anticancer activity, playing a crucial role through MAPK1 and EGFR targets.

As a vital pivot for the human circulatory system, the brain-gut axis is now being considered as an important channel for many of the small immune molecules’ transductions, including interleukins, interferons, neurotransmitters, peptides, and the chemokines penetrating the mesentery and blood brain barrier (BBB) during the development of an ischemic stroke (IS). Hypoxia-ischemia contributes to pituitary and neurofunctional disorders by interfering with the molecular signal release and communication then providing feedback to the gut. Suffering from such a disease on a long-term basis may cause the peripheral system’s homeostasis to become imbalanced, and it can also lead to multiple intestinal complications such as gut microbiota dysbiosis (GMD), inflammatory bowel disease (IBD), necrotizing enterocolitis (NEC), and even the tumorigenesis of colorectal carcinoma (CRC). Correspondingly, these complications will deteriorate the cerebral infarctions and, in patients suffering with IS, it can even ruin the brain’s immune system. This review summarized recent studies on abnormal immunological signal exchange mediated polarization subtype changes, in both macrophages and microglial cells as well as T-lymphocytes. How gut complications modulate the immune signal transduction from the brain are also elucidated and analyzed. The conclusions drawn in this review could provide guidance and novel strategies to benefit remedies for both IS and relative gut lesions from immune-prophylaxis and immunotherapy aspects.

Background Metabolic reprogramming is one of the essential features of tumorigenesis. Herein, this study aimed to develop a novel metabolism-related gene signature for head and neck squamous cell carcinoma (HNSCC) patients. Methods The transcriptomic and clinical data of HNSCC samples were collected from The Cancer Genome Atlas (TCGA) and GSE65858 datasets. The metabolism-related gene-based prognostic signature (MRGPS) was constructed by the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (K-M) survival curves were plotted for evaluating its predicting performance. At the same time, univariate along with multivariate analysis was carried out to explore its correlation with clinicopathologic factors. Furthermore, GSEA analysis was performed to explore the signaling pathways affected by MRGPS. We also analyzed the associations of MRGPS with the tumor immune microenvironment (TIME), as well as identified potential compounds via Connectivity Map (CMap) and molecular docking. Results A total of 12 differentially expressed metabolism-related genes were identified and selected to construct the MRGPS. Notably, this signature performed well in predicting HNSCC patients' survival and could serve as an independent prognostic factor in multiple datasets. In addition to the metabolism-related pathway, this signature could also affect some immune-related pathways. The results indicated that MRGPS is correlated with immune cells infiltration and anti-cancer immune response. Furthermore, we identified cephaeline as a potential therapeutic compound for HNSCC. Conclusion Taken together, we established an MRGs-based signature that has the potential to predict the clinical outcome and immune microenvironment, which help to search for potential combination immunotherapy compounds and provide a promising therapeutic strategy for treating HNSCC patients.

Diabetic nephropathy (DN) is one microvascular complication of diabetes. About 30% of diabetic patients can develop DN, which is closely related to the high incidence and mortality of heart diseases, and then develop end-stage renal diseases. Therefore, early detection and screening of high-risk patients with DN is important. Herein, we explored the differences of serum transcriptomics between DN and non-DN in type II diabetes mellitus (T2DM) patients. We obtained 110 target genes using weighted correlation network analysis. Gene Ontology enrichment analysis indicates these target genes are mainly related to membrane adhesion, alpha-amino acid biosynthesis, metabolism, and binding, terminus, inhibitory synapse, clathrinid-sculpted vesicle, kinase activity, hormone binding, receptor activity, and transporter activity. Kyoto Encyclopedia of Genes and Genomes analysis indicates the process of DN in diabetic patients can involve synaptic vesicle cycle, cysteine and methionine metabolism, N-Glycan biosynthesis, osteoclast differentiation, and cAMP signaling pathway. Next, we detected the expression levels of hub genes in a retrospective cohort. Then, we developed a risk score tool included in the prediction model for early DN in T2DM patients. The prediction model was well applied into clinical practice, as confirmed by internal validation and several other methods. A novel DN risk model with relatively high prediction accuracy was established based on clinical characteristics and hub genes of serum detection. The estimated risk score can help clinicians develop individualized intervention programs for DN in T2DM. External validation data are required before individualized intervention measures.

目的 了解北京社区绝经后女性骨折发生情况,探讨骨质疏松性骨折二级预防策略.方法 选取2016年3月至2017年11月就诊于北京市朝阳区太阳宫社区卫生服务中心和香河园社区卫生服务中心的绝经后女性,共2866人.填写自行设计的骨质疏松症危险因素调查问卷,了解受访者骨折发生的类型(暴力性或非暴力性)、部位和发生年龄.分析女性一生中不同年龄段骨折发生的特点.结果 受访的绝经后女性平均年龄(62.39±6.94)岁,受访的2866人中有635人(19.61％)在受访时至少已有一次骨折史,其中有73人(2.54％)发生了两次或两次以上骨折.58.64％的暴力性骨折发生在绝经前,80％的脆性骨折发生在绝经后,这两种类型骨折发生的年龄具有显著统计学差异.在所有的典型部位脆性骨折当中,前臂远端骨折占比最大,为50.43％,发生的平均年龄为(56.0±11.76)岁;髋部骨折发生占比8.33％,平均发生年龄为(59.8±12.69)岁.结论 女性绝经后发生的骨折主要是脆性骨折,其中前臂远端脆性骨折较髋部脆性骨折至少早3年发生.加强对已发生前臂远端脆性骨折的绝经后女性的管理,对预防再发骨质疏松性骨折(尤其是髋部骨折)的效益较大.

Aims . The current study aims to explore if a family history of diabetes can influence the efficiency of lifestyle intervention on insulin secretion and study the insulin resistance in Chinese men and women with metabolic syndrome in a cohort with a 2-year follow-up. Methods . 151 individuals (90 individuals did not have a family history of diabetes (DMFH (-)) and 61 with a family history of diabetes (DMFH (+)) with metabolic syndrome participated in the lifestyle intervention program at baseline and finished with 1-year follow-up. 124 individuals have two-year follow-up data. A family history of diabetes was ascertained by self-report. Lifestyle interventions were individual sessions on lifestyle changes. Results . During the 1-year follow-up, Ln Insulinogenic index ( Δ baseline−1year = 0.29 ± 0.65, P = 0.001) and 30-min glucose ( Δ baseline−1year = −0.41 ± 1.71, P = 0.024) changed significantly in the DMFH(-) group; in the DMFH(+) group, Ln ISIm ( Δ baseline−1year = −0.22 ± 0.60, P = 0.022) and 30-min glucose ( Δ baseline−1year = 0.53 ± 1.89, P = 0.032) changed significantly, and there was no significant change of other parameters. The change of 30 min glucose during a 1-year intervention has shown a significant difference between the two groups ( P = 0.002). During the 2 years intervention, Ln Insulinogenic index changed significantly in the DMFH(-) group ( Δ baseline−1year = 0.33 ± 0.66, P < 0.001 and Δ baseline−2year = 0.43 ± 1.17, P = 0.034). Fasting insulin ( Δ baseline−2year = 2.95 ± 8.69, P = 0.034), 2 h insulin ( Δ baseline−2year = 23.75 ± 44.89, P = 0.002), Ln HOMA-B ( Δ baseline−2year = 0.43 ± 1.02, P = 0.009), Ln HOMA-IR ( Δ baseline−2year = 0.53 ± 1.04, P = 0.002), Ln ISIm ( Δ baseline−2year = 0.52 ± 0.95, P = 0.004), and Ln Insulinogenic index ( Δ baseline−2year = 0.66 ± 1.18, P = 0.047) changed significantly after 2 years of intervention, compared to the baseline in the DMFH(+) group. The change of Ln ISIm ( P = 0.023), fasting ( P = 0.030), and 2 h insulin ( P = 0.007) during the 2-year intervention has shown a significant difference between the two groups. Family history of diabetes was related with a 0.500 unit increase in 2-year ISIm ( P = 0.020) modified by lifestyle intervention adjusted for age, baseline BMI, sex, and baseline waist circumference and a 0.476 unit increase in 2-year ISIm ( P = 0.027) with extra adjustment for weight change. Conclusions . Patients with a family history of diabetes benefit more from lifestyle intervention in regard to insulin resistance than those without a family history of diabetes adjusting for age, baseline BMI, sex, baseline waist circumference, and weight change.

Objective:To investigate the association of anti-thyroglobulin antibody (TgAb) and anti-thyroperoxidase antibody (TPOAb) with the risk of thyroid cancer of thyroid nodules.Methods:Clinical data of 2 287 patients with thyroid nodules who underwent ultrasound-guided fine-needle aspiration cytology (FNAC) in China-Japan Friendship Hospital from January 2014 to January 2017, were retrospectively reviewed. The association between thyroid autoantibody and the risk of thyroid cancer in thyroid nodules were analyzed.Results:The positive rates of TPOAb [19.2% (333/1 732) vs. 9.9% (55/555),χ2=25.897, P<0.01] and TgAb [26.6% (461/1 732) vs. 10.5%(58/555),χ2=62.614, P<0.01] in female patients were significantly higher than those in male patients. The proportions of cytology grade Ⅰ-Ⅳ were 14.2% (79/555), 57.7% (320/555), 6.0% (33/555), 3.6% (20/555), 6.1%(34/555) and 12.4% (69/555) in males, and 10.6% (184/1 732), 63.5% (1 099/1 732), 6.0%(104/1 732), 3.5% (61/1 732), 5.9% (102/1 732) and 10.5% (182/1 732) in females, respectively ( P>0.05). Univariate analysis showed that there were no significant differences in positive rates of TPOAb [ 17.1% (66/387) vs.17.5% (248/1 419), χ2=0.038, P>0.05] and TgAb [23.5%(91/387) vs. 23.3% (331/1 419), χ2=0.006, P>0.05] between the malignant group (grade Ⅴ－Ⅵ, n= 387) and the benign group (grade Ⅱ, n=1 419). Multivariate regression analyses showed that age≤30 ( OR=12.80, 95% CI:4.43-37.03) and age 31-50 ( OR=6.62, 95% CI:2.37-18.50) compared with age>70, nodule size≤1.0 cm ( OR=2.75, 95% CI:1.19-6.40) and nodule size 1.1-2.0 cm ( OR=2.43, 95% CI:1.05-5.60) compared with size>4.0 cm, thyroid stimulating hormone(TSH) level 2.38-4.20 mIU/L ( OR=1.87, 95% CI:1.16-3.00) and TSH>4.20 mIU/L ( OR=1.86, 95% CI:1.13-3.06) compared with TSH 0.27-1.29 mIU/L were significantly associated with the risk of malignancy. In patients with thyroid nodules ≤2.0 cm, there were no significant differences in the positive rate of TPOAb [18.1% (158/875) vs. 16.9%(49/290)], TgAb [24.9% (218/875) vs. 21.0% (61/290)] between benign group and malignant group (χ2=0.201, χ2=1.800, both P>0.05). In patients with nodules>2.0 cm, there was no significant difference in TPOAb between benign and malignant groups [13.2%(54/410) vs. 20.0% (12/60), χ2=2.022, P>0.05]; however, the positive rate of TgAb in malignant group was significantly higher than that in benign group [33.3% (20/60) vs. 18.8% (77/410), χ2=6.768, P=0.02]. In patients with the nodules>2.0 cm, after adjusting for age, gender, TSH level and nodule size, logistic regression analysis showed that positive TGAb was an independent risk factor of malignancy ( OR=2.83, 95% CI:1.49-5.37, P<0.01). Conclusion:The elevated TPOAb level is not associated with increased cancer risk in thyroid nodules; while the elevated thyroglobulin antibody is associated with increased cancer risk in patients with thyroid nodules>2.0 cm.

Abstract Aims/Introduction To investigate the differential effects of maternal versus paternal history of diabetes on the risks for diabetes and prediabetes, as well as on insulin secretion and resistance in Chinese individuals. Materials and Methods From the 2007 to 2008 China National Diabetes and Metabolism Disorders Study, 39,244 participants were included and divided into four categories: negative parental history, paternal history only (PH), maternal history only (MH), and both paternal and maternal history. Results The age‐ and sex‐standardized prevalence rates of diabetes in the negative parental history, PH, MH, and both paternal and maternal history groups were 8.59, 12.56, 15.86 and 29.81%, respectively. The prevalence rates of impaired glucose metabolism were 24.13, 25.41, 31.13 and 50.80%, with the prevalence in the MH group being significantly higher than that in the PH group. Compared with that in the FH0 group, the risks of diabetes in the PH, MH, and both paternal and maternal history groups were 2.01‐, 2.67‐ and 6.37‐fold greater, and the risks of impaired glucose metabolism were 1.28‐, 1.65‐ and 3.45‐fold greater. In addition, MH had a significantly greater impact on impaired glucose metabolism than PH (PMHvsPH = 0.0292). Regression analyses suggested MH was associated with homeostatic model assessment for β‐cell function (β[SE] = −0.0910[0.0334], P = 0.0065), insulinogenic index (−0.1866[0.0550], P = 0.0007), homeostatic model assessment for insulin resistance (0.0662[0.0227], P = 0.0036) and Matsuda Index [−0.0716(0.0203), P = 0.0004]. PH was specifically associated with homeostatic model assessment for insulin resistance (0.1343[0.0267], P < 0.0001) and Matsuda Index (−0.1566[0.0243], P < 0.0001), but the effects were stronger than those of MH (PMHvsPH = 0.0431, 0.0054). Conclusions MH and PH differentially influence the risks for diabetes, insulin secretion, and insulin resistance in the Chinese population, suggesting they participate in the pathogenesis of diabetes through different mechanisms.

目的:分析以糖尿病为首发表现的17q12微缺失综合征，探讨青少年的成人起病型糖尿病5型（MODY5）与17q12微缺失综合征之间的关系以及后者常见的基因型和临床表型。方法:对2例表现为青少年发病的糖尿病，同时合并胰腺及肾脏发育异常、低镁血症的患者进行基因分析，先以二代测序法检测MODY相关基因突变，再用低深度全基因组测序（CNV-seq）检测与受检人临床表型相关的致病性拷贝数变异（CNV），并对患者的精神状况进行评估。使用术语17q12微缺失综合征、MODY5、肝细胞核因子1B（HNF1B）、低镁血症进行文献检索，分析MODY5和17q12微缺失综合征二者的关系。结果:2例患者二代测序常规分析均未能发现MODY相关基因突变。进一步CNV分析，发现2例患者均为17q12部位1.40 Mb大片段缺失导致的17q12微缺失综合征，包含HNF1B全基因缺失而导致MODY5。2例患者都有糖尿病家族史，但基因检测证实2例患者父母均无17q12微缺失，均为新发变异。1例患者表现轻度自闭症状。结论:基于17q12微缺失的HNF1B全基因缺失是MODY5常见的基因变异类型，对临床可疑MODY5患者进行基因检测时，在二代测序的基础上，应常规进行CNV等的分析，确认患者是否存在HNF1B基因缺失或17q12的微缺失。

Objective:To investigate the prevalence and explore the clinical characteristics and risk factors of diabetic cardiac autonomic neuropathy (CAN) in type 2 diabetic patients in Beijing.Methods:This research is a multi-center, randomized, cross-sectional study. From October 2015 to April 2016, type 2 diabetes mellitus (T2DM) patients in 13 hospitals in the urban and suburban areas of Beijing were randomly sampled for questionnaire, physical examination and laboratory examination. Patients were divided into CAN group and non-CAN group according to the results of cardiovascular autonomic reflex tests (CART). The independent t test, the Wilcoxon rank-sum test and the chi-square test were used to compare the differences of continuous data and categorical data between the two groups. Multivariate logistic regression was used to analyze risk factors for CAN. Results:A total of 1 975 patients with T2DM were included, including 1 236 patients (62.6%) in CAN group and 739 patients (37.4%) in non-CAN group. Compared with non-CAN group, CAN group had older age, longer duration of diabetes, higher glycated hemoglobin A 1c, larger metformin dosage, longer metformin medication time, fewer patients receiving higher education, and more complicated with coronary heart disease, peripheral vascular disease and hypertension ( P<0.05). The most common manifestations of CAN included dizziness, standing instability, weakness, postprandial fullness, frequent urination, nocturia, urgent urination and upper body sweating ( P<0.05). Logistic regression analysis showed that age was an independent risk factor for CAN in T2DM patients (OR=1.040, 95%CI 1.008 to 1.072, P=0.012). Conclusions:The prevalence of CAN in patients with type 2 diabetes in Beijing is high. CAN is often associated with a variety of autonomic neuropathy symptoms and age is an independent risk factor for CAN.