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Abstract Background To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. Methods We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20–54 and > 55 years from 1990–2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. Results From 1990–2019, the global prevalence rates of IHD, IS, and PAD in the 20–54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20–54 years group than in the > 55 years group. For PAD, DALYs among those aged 20–54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. Conclusions The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

Geothermal resources have a very broad development prospect owing to their clean nature; accurate evaluation of their potential is an important basis for the realization of fine zoning and large-scale efficient development. Here, a geothermal evaluation system is established based on reservoir, cap-rock, transportation-system, heat-source, and water-source data. The entropy weight Technique Order Preference by Similarity to an Ideal Solution (TOPSIS) and Analytic Hierarchy Process - Technique Order Preference by Similarity to an Ideal Solution (AHP-TOPSIS) methods are used to evaluate geothermal resources in Eryuan County, and the evaluation results are superimposed with equal weights, and combined with the Moran index, to determine the geothermal exploration potential. Our results show that geothermal resources in Eryuan County are abundant, being concentrated in Liantie Township, Qiaohou Town, junction of Sanying and Cibihu towns, and junction of Fengyu and Yousuo towns. The Moran index indicates that there is significant geothermal accumulation, with high geothermal values mainly distributed around the water system. Three types of geothermal models are established based on control factors. The first one is controlled by the combination of reservoir and cap rock, while the second one is controlled by heat source and the third one is controlled by the combination of reservoir and cap rock and heat source. The junctions of Sanying and Cibihu towns, and Fengyu and Yousuo towns, are evaluated to have high geothermal potential, and these may become the next favorable directions for geothermal exploration in Eryuan County.

BackgroundLing-gui-zhu-gan (LGZG) formula has been demonstrated to effectively ameliorate the clinical symptoms of patients with obesity or metabolic syndrome. This study aimed to explore both the effect and the underlying mechanisms of LGZG against obesity.MethodsMale C57BL/6N mice were randomized into four groups (n = 8): normal control (NC), obese (OB), metformin (Met), and LGZG. After 8 weeks of gavage administration, the pharmacological effects of LGZG on obesity and metabolism were investigated using biochemical parameters, histomorphological examination, and lipidomics techniques. Pivotal factors associated with white adipose tissue browning were evaluated using quantitative real-time polymerase chain reaction and western blotting.ResultsThe results revealed that LGZG reduced the levels of obesity markers, including body weights, body fat mass and food intake in obese mice. Further evaluations highlighted that LGZG restored glucose homeostasis and significantly improved insulin sensitivity in obese mice. Importantly, LGZG could adjust serum lipid profiles and regulate the lipidomic spectrum of intestinal contents, with noticeable shifts in the levels of certain lipids, particularly diacylglycerols and monoacylglycerols. Histopathological examinations of LGZG-treated mice also revealed more favorable adipose tissue structures than their obese counterparts. Furthermore, we found that LGZG upregulated the expression of several key thermogenesis-related factors, such as UCP1, PRDM16, PGC-1α, PPARα, PPARγ, CTBP1, and CTBP2 in white adipose tissues.ConclusionOur findings position LGZG as a novel strategy for preventing obesity and improving metabolic health.

Thermal storage has not yet been classified in a unified way. By analyzing the factors of thermal storage and the interactions of fluids, spaces, and solids, this study proposes a three-level classification scheme based on fluid–space–solid thermal storage and dissects the main thermal storage types in the Eryuan, Midu, and Lancang areas of Yunnan Province. The results show that the hydrothermal-karst-carbonate reservoirs of the lower Devonian Kanglang Formation, Carboniferous, and Lower Permian are the main reservoirs in the Eryuan area, the hydrothermal-fracture-carbonate reservoirs are Carboniferous and Lower Permian in the Midu area, and the hydrothermal-fracture-metamorphic reservoirs of the Manlai and Huimin formations are the main reservoirs in the Lancang area. These reservoirs are characterized by high porosity and permeability, high thermal conductivity, high thermal diffusivity, and high specific heat capacity. The classification scheme is systematic, comprehensive, and unified, is capable of conveying multiple information points, and provides a new method for geological exploration personnel to analyze the thermal storage characteristics.

Abstract Background Shared decision-making (SDM) may influence the clinical outcomes of patients with endocrine disorders. There are few studies describing perspectives towards SDM among endocrinologists in China. Methods In the first stage, we conducted a national survey using an online questionnaire about SDM among endocrinologists in China. The national survey focused on attitude and propensity, potential barriers, and the effectiveness of SDM implementation strategies. In the second stage, survey participants were further recruited to participate in a prospective cohort study in the online continuing medical education (CME) program of Peking Union Medical College Hospital in Beijing. The Shared Decision-Making Questionnaire (SDM-Q-Doc) was employed to assess the effects of online CME on physicians’ perspectives during the process of SDM, which was conducted before and after the CME course was provided. Results In the national survey, 280 endocrinologists (75.7% female, mean age 38.0 ± 4.5 years, 62.5% with a duration of practice of more than ten years) completed the questionnaire. Participants had a generally positive attitude towards SDM in clinical practice. The main perceived barriers included time consumption, information inequality between doctors and patients, and a lack of technical support and training for SDM. The main uncertainties of implementation steps included inviting patients to participate in SDM (16.3%), assisting in decision-making (15.3%), facilitating deliberation and decision-making (13.7%), and providing information on benefits and risks (12.6%). Of the physicians who participated in the national survey, 84 registered for the eight-day online CME course. The SDM-Q-Doc score increased from 87.3 ± 18.2 at baseline to 93.0 ± 9.3 at the end of the 8-day online CME training (p = 0.003, paired t test). The participants’ age, sex, education level, practice duration, the annual number of patients with rare endocrine diseases, and the annual number of patients requiring MDT or CME were not significantly related to increased SDM-Q-Doc scores after online CME (all p > 0.05). Conclusions Chinese endocrinologists had a generally positive attitude towards SDM in clinical practice. There were also several uncertainties in the implementation steps of SDM. Regardless of a physician’s educational background or prior professional experience, CME may help to improve their perspectives regarding SDM.

Abstract Background Experimental and epidemiological studies have indicated an association between diabetes exposure and an increased risk of liver cancer due to nonalcoholic steatohepatitis (NASH). However, to date, no systematic study has specifically investigated the burden of NASH-related liver cancer due to exposure to high fasting plasma glucose (HFPG) levels worldwide. Methods The number and rate of deaths and disability-adjusted life years (DALYs) from HFPG-induced NASH-related liver cancer were estimated based on the results of the 2019 Global Burden of Disease Study. The estimated annual percentage changes (EAPCs) for age-standardized death or DALYs rates were calculated using a generalized linear model with a Gaussian distribution to quantify the temporal trends in the global burden of NASH-related liver cancer attributable to HFPG. The strength and direction of the association between the sociodemographic index (SDI) and death or DALY rate were measured using Spearman’s rank-order correlation. Results Globally, approximately 7.59% of all DALY and 8.76% of all mortalities of NASH-related liver cancer in 2019 were due to HFPG. The age-standardized death and DALY rates of NASH-related liver cancer attributable to HFPG increased from 1990 to 2019. The corresponding EAPCs were 0.69 (95% UI 0.48–0.89), and 0.30 (95% UI 0.05–0.56), respectively. This increasing pattern was most obvious in the high- and low-SDI regions. The age-standardized mortality and DALYs rate of NASH-related liver cancer attributable to HFPG varies considerably worldwide, with the middle SDI region having the highest death and DALY rates in 2019 (DALY 0.96 [95% UI 0.23–2.18]; death 0.05 [95% UI 0.01–0.11]). Conclusion The burden of NASH-related liver cancer attributable to HFPG has increased over the past three decades, particularly in regions with high and low SDI.

SnO2 has been extensively used in the detection of various gases. As a gas sensing material, SnO2 has excellent physical-chemical properties, high reliability, and short adsorption-desorption time. The application of the traditional SnO2 gas sensor is limited due to its higher work-temperature, low gas response, and poor selectivity. Nanomaterials can significantly impact gas-sensitive properties due to the quantum size, surface, and small size effects of nanomaterials. By applying nanotechnology to the preparation of SnO2, the SnO2 nanomaterial-based sensors could show better performance, which greatly expands the application of SnO2 gas sensors. In this review, the preparation method of the SnO2 nanostructure, the types of gas detected, and the improvements of SnO2 gas-sensing performances via elemental modification are introduced as well as the future development of SnO2 is discussed.

Accumulating evidence demonstrates the link between glucose and bone metabolism. The receptor activator of nuclear factor-kB ligand (RANKL)/the receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) axis is an essential signaling axis maintaining the balance between bone resorption and bone formation. In recent years, it has been found that RANKL and RANK are distributed not only in bone but also in the liver, muscle, adipose tissue, pancreas, and other tissues that may influence glucose metabolism. Some scholars have suggested that the blockage of the RANKL signaling may protect islet β-cell function and prevent diabetes; simultaneously, there also exist different views that RANKL can improve insulin resistance through inducing the beige adipocyte differentiation and increase energy expenditure. Currently, the results of the regulatory effect on glucose metabolism of RANKL remain conflicting. Denosumab (Dmab), a fully human monoclonal antibody that can bind to RANKL and prevent osteoclast formation, is a commonly used antiosteoporosis drug. Recent basic studies have found that Dmab seems to regulate glucose homeostasis and β-cell function in humanized mice or in vitro human β-cell models. Besides, some clinical data have also reported the glucometabolic effects of Dmab, however, with limited and inconsistent results. This review mainly describes the impact of the RANKL signaling pathway on glucose metabolism and summarizes clinical evidence that links Dmab and DM to seek a new therapeutic strategy for diabetes.

Abstract Objective To investigate the clinical characteristics of patients with multiple endocrine neoplasia type 1 (MEN1)-related insulinoma and their relationship with specific biochemical changes and to summarize the features of treatment options for the Chinese population with this disease and the impact on long-term prognosis. Methods “MEN1” and “insulinoma” were used when searching the Peking Union Medical College Hospital (PUMCH) medical record retrieval system to obtain clinical information about patients. We identified patients diagnosed with MEN1-associated insulinoma based on endocrinological, radiological, and pathological examinations, and subsequently analyzed their clinical data. Results A total of 55 patients with MEN1-associated insulinoma were included, including 29 (52.7%) men and 26 (47.3%) women. The parathyroid gland was the most commonly affected (78.2%), followed by the pituitary gland (69.1%) and adrenal gland (16.4%). Insulinoma was the first manifestation of MEN1 in at least 23.6% (13/55) of patients. Nineteen (34.5%) patients presented with initial symptoms of hypoglycemia before the age of 22 years. Among the 24 Patients with high serum calcium (Ca) had significantly lower serum insulin levels than those with normal serum Ca levels (p

Abstract Objective To analyze the clinical characteristics of patients with pancreatic cancer (PC) and diabetes and to explore the impact of diabetes duration, weight loss, and hypoglycemic drugs on the tumor biological behavior of PC. Methods This is a retrospective study on patients with PC and diabetes. Subjects were grouped according to the onset age of PC, distant metastasis, duration of diabetes, degree of weight loss (∆Wt), and type of hypoglycemic drugs. Logistic regression analysis was used to evaluate the association between diabetes duration, weight loss, hypoglycemic drugs, and early‐onset PC, distant metastasis. Results Compared with late‐onset PC, patients with early‐onset PC had a higher proportion of new‐onset DM (35 [79.5%] vs. 217 [46.9%], p

BackgroundClopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS.MethodsMEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622).ResultsSix trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD −0.00023, 95% CI −0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI −0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI −0.00096 to 0.00177) when Asian ratio of the population was elevated.ConclusionsWe raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022299622.

ObjectiveIntermittently scanned continuous glucose monitoring (isCGM) is used for unblinded or blinded monitoring of interstitial glucose. We aimed to compare the efficacy of blinded and unblinded isCGM with the FreeStyle Libre system for glycemic control in adults with type 1 diabetes (T1D).Research design and methodsThis randomized clinical trial conducted between October 2018 and September 2019 across four endocrinology practices in China included 273 adults aged ≥18 years with T1D, who were randomly divided in a 2:1 ratio into the unblinded (n = 199) or blinded isCGM group (n = 78). In the blinded group, the clinician used FreeStyle Libre Pro system for monitoring, but self-monitoring was also performed by the patients.ResultsTwo hundred sixteen (78%) participants completed the study (152 [75%] in the unblinded and 64 [82%] in the blinded group). At 12 weeks, a significant increase in TIR (3.9-10.0 mmol/L) was only observed in the unblinded group, along with a significant decrease in hyperglycemia (>13.9 mmol/L), hypoglycemia (

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus and also has hepatoprotective effects. However, the role of liraglutide treatment on liver injury in a mouse model of type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ) and its underlying mechanisms remain to be elucidated. In the present study, diabetes was initiated in experimental animals by single-dose intraperitoneal inoculation of STZ. Forty female C57BL/6J mice were equally assigned into five groups: diabetic group, insulin+diabetic group, liraglutide+diabetic group, insulin+liraglutide+diabetic group, and control group for eight weeks. Diabetic mice exhibited a significantly elevated blood glucose level and decreased body weight, and morphological changes of increased steatosis and apoptosis were observed in the liver compared with the control. Furthermore, a significant increase in the levels of malondialdehyde and inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin 1β (IL-1β) and the proapoptotic proteins caspase-3 and Bax were observed in the livers of diabetic mice, together with marked increases in antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as antiapoptotic protein Bcl-2, all of which were significantly mitigated by treatment with liraglutide, insulin, and their combinations. Interestingly, liraglutide monotherapy showed better efficacy in ameliorating liver injury in T1DM mice than insulin monotherapy, similar to the combined drug therapy. Furthermore, the expression of Wnt/β-catenin signaling pathway-associated molecules was upregulated in the liver of mice treated with liraglutide or insulin. The results of the present study suggested that liraglutide improves T1DM-induced liver injury and may have important implications for the treatment of nonalcoholic fatty liver disease (NAFLD) in patients with T1DM.

BackgroundConsidering that the previously developed mortality prediction models have limited applications to the Chinese population, a questionnaire-based prediction model is of great importance for its accuracy and convenience in clinical practice.MethodsTwo national cohort, namely, the China Health and Nutrition Survey (8,355 individual older than 18) and the China Health and Retirement Longitudinal Study (12,711 individuals older than 45) were used for model development and validation. One hundred and fifty-nine variables were compiled to generate predictions. The Cox regression model and six machine learning (ML) models were used to predict all-cause mortality. Finally, a simple questionnaire-based ML prediction model was developed using the best algorithm and validated.ResultsIn the internal validation set, all the ML models performed better than the traditional Cox model in predicting 6-year mortality and the random survival forest (RSF) model performed best. The questionnaire-based ML model, which only included 20 variables, achieved a C-index of 0.86 (95%CI: 0.80–0.92). On external validation, the simple questionnaire-based model achieved a C-index of 0.82 (95%CI: 0.77–0.87), 0.77 (95%CI: 0.75–0.79), and 0.79 (95%CI: 0.77–0.81), respectively, in predicting 2-, 9-, and 11-year mortality.ConclusionsIn this prospective population-based study, a model based on the RSF analysis performed best among all models. Furthermore, there was no significant difference between the prediction performance of the questionnaire-based ML model, which only included 20 variables, and that of the model with all variables (including laboratory variables). The simple questionnaire-based ML prediction model, which needs to be further explored, is of great importance for its accuracy and suitability to the Chinese general population.

The assessment of geothermal potential has gained prominence among scholars, with a focus on establishing a reliable prediction model to reduce development risks. However, little attention has been given to predicting and evaluating the geothermal potential in Dali’s Eryuan area. This study introduces a novel hierarchical model integrating remote sensing, a Geographic Information System (GIS), and geophysics for the first-ever effective prediction of geothermal potential in Eryuan. The dataset includes lithology, seismic epicenter data, fault distribution, Bouguer gravity anomalies, SRTM-DEM images, and Landsat 8 remote sensing images. These datasets are converted into evidence maps and normalized to generate distinct evidence factor layers. Using the Analytic Hierarchy Process (AHP), a hierarchical model establishes weights for each evidence factor, resulting in a comprehensive prediction map. The results reveal the overall favorable geothermal potential in Eryuan, except the central area. Key hotspots include the Niujie–Sanying–Gromwell Lake and Liantie–Qiaohou, followed by the Youshou, Dengchuan, and Xixiang towns. Validation against known hot springs confirms the model’s accuracy and reliability.

BackgroundBody mass index (BMI) is a common indicator in clinical practice, but it is not sufficient to predict insulin resistance (IR). Other anthropometric methods supplement BMI in the assessment of body composition, which can be predicted more accurately. This cross-sectional study aimed to evaluate the association between mid-upper arm circumference (MUAC), triceps skinfold (TSF) thickness, mid-arm muscle circumference (MAMC) and IR in Chinese adults.MethodsThis cross-sectional study analyzed data from the 2009 China Health and Nutrition Survey database. The study population was divided into four groups according to the MUAC quartiles, and the homeostasis mode assessment was used to evaluate the degree of IR. Logistic regression analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs), with adjustments for multiple covariates. Subgroup analyses stratified by age, sex, BMI, waist circumference (WC), smoking status, and alcohol consumption were performed.ResultsIn total, 8,070 participants were included in the analysis. As MUAC increased, BMI, TSF thickness, MAMC, and the proportion of IR tended to increase. However, we found that there was a significant negative association between MUAC and MAMC and IR in the logistic regression analysis, independent of BMI and WC, the ORs for the highest quartiles compared with the lowest quartiles were 0.662 (95%CI: 0.540-0.811) and 0.723 (95%CI: 0.609-0.860), respectively. There was no significant association was observed between the TSF thickness and IR (OR=1.035 [95%CI: 0.870-1.231]). The inverse associations were more pronounced among participants with lower BMI and WC. No significant age-specific differences were observed (P-heterogeneity > 0.05).ConclusionsAfter adjusting for BMI and WC, MUAC was negatively associated with IR in Chinese adults, and the association between MUAC and IR was derived from arm muscle instead of subcutaneous fat. MUAC could be an additional predictor of IR besides BMI and WC in clinical practice.

BackgroundPhysical activity (PA) has been associated with decreased incidence of diabetes. However, few studies have evaluated the influence of occupational and domestic PA on the risk of diabetes with a long-term follow-up. We aimed to examine the association between occupational and domestic PA and the risk of diabetes in a long-term prospective cohort of Chinese adults.MethodsA total of 10,343 adults who were followed up in the China Health and Nutrition Survey from 1997 to 2015 were included in our analysis. Occupational and domestical PA were collected with detailed seven-day data and were converted into metabolic equivalents values. Total PA included occupational, domestic, transportation, and leisure time PA. Diabetes cases were identified by self-reported doctor/health professional diagnosis of diabetes, fasting blood glucose ≥7.0 mmol/L, and glycosylated hemoglobin (HbA1c) ≥6.5%. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).ResultsDuring up to 18 years of follow-up (median 10 years), there were 575 diabetes cases documented. Occupational PA accounted for the majority of total PA (68%) in Chinese population, followed by domestic PA (25%). With adjustments for possible covariates, the highest quartiles of total PA (HR, 0.728 [95% CI, 0.570–0.929]) and occupational PA (HR, 0.765 [95% CI, 0.596–0.982]) were significantly associated with a lower risk of diabetes compared with lowest quartiles. The association between domestic PA and the risk of diabetes was insignificant (P >0.05).ConclusionHigher levels of occupational PA were associated with a decreased risk of diabetes risk in the Chinese population. Domestic PA was not associated with the incidence of diabetes.

PurposeAn end-of-fast insulin level ≥ 3 µIU/ml, C-peptide level ≥ 0.6 ng/ml, and proinsulin level ≥ 5 pmol/l with end-of-fast glucose level ≤ 3.0 mmol/l have been established as the criteria for endogenous hyperinsulinemic hypoglycemia. However, all these criteria have been proposed based on patients in Western populations. This study aimed to determine the optimal criteria using a large series of Chinese patients.MethodsThis retrospective study comprised 144 patients with surgically proven insulinoma and 40 controls who underwent a 72-h fasting test at the Peking Union Medical College Hospital(PUMCH) from 2000 to 2020. Receiver operating characteristic curves were used for analysis.ResultsIn this series of patients, the optimal diagnostic criteria for endogenous hyperinsulinemic hypoglycemia were insulin ≥ 5.5 μIU/ml, C-peptide ≥ 0.7 ng/ml, and proinsulin ≥ 12 pmol/l with end-of-fast glucose ≤ 2.8 mmol/l; the sensitivity and specificity were 99% and 100% for insulin, 100% and 100% for C-peptide, and 93% and 100% for proinsulin, respectively. The diagnostic efficacy of the criteria based on Western populations was then tested. The sensitivity and specificity of end-of-fast insulin ≥ 3 μIU/ml, C-peptide ≥ 0.6 ng/ml, and proinsulin ≥ 5 pmol/l with end-of-fast glucose ≤ 3.0 mmol/l were 100% and 83%, 100% and 80%, and 97% and 78%, respectively.ConclusionsNew and optimized diagnostic criteria for endogenous hyperinsulinemic hypoglycemia in Chinese populations have been proposed, and these criteria yield satisfactory accuracy.

ObjectiveThe adrenal glands of patients with 17-hydroxylase/17,20-lyase deficiency (17OHD) synthesize excessive 11-deoxycorticosterone(DOC) and progesterone, and produce less amount of sex steroid production. Mineralocorticoids and sex hormones play an important role in regulating glucose homeostasis. This study aimed to describe the glucose metabolism in 17OHD patients diagnosed at Peking Union Medical College Hospital (PUMCH).Design/methodsA total of 69 patients diagnosed with 17OHD after adolescence in PUMCH from 1995 to June in 2021. Among them 23 patients underwent a 3-hours oral glucose tolerance test (3hOGTT) after being diagnosed with 17OHD. Insulin response in patients with normal glucose tolerance (NGT) were further compared between the study two groups with different kalemia status. Another 19 patients were followed up to 30 years and older. All clinical data were obtained from the hospital information system of PUMCH.ResultsBaseline: (1) The average body mass index(BMI) of all patients at baseline was 20.3 ± 3.7kg/m2. Twenty-three patients underwent 3hOGTT, of whom three were diagnosed with diabetes mellitus, and one with impaired glucose tolerance (IGT). Positive correlation between the ratio of progesterone to upper limit of normal range (P times) and hyperglycaemia was exist(r=0.707, P=0.005). (2) In 19 NGT patients, the insulin concentrations at 0 minute, results of the homeostasis model assessment for β-cell function and insulin resistance were lower in the hypokalaemia group than in the normal kalemia group(7.0(5.8-13.2) vs 12.4(8.9-14.9) μIU/ml, P=0.017; 115.5(88.2-240.9) vs 253.1(177.2-305.8), P=0.048; 1.54(1.17-2.61) vs 2.47(1.91-2.98), P=0.022, respectively). Follow-up: Four patients had IGT, while seven patients had diabetes mellitus. Of the 19 patients,11 had hyperglycaemia. P times was significantly higher(7.6(5.0-11.0) vs 3.75(2.2-5.3), P=0.008) in hyperglycemia group than in the normal glucose group.ConclusionsAbnormal glucose metabolism was common in 17OHD patients, which was possibly associated with hypokalaemia and high progesterone levels. Routine monitoring on glucose metabolism in 17OHD patient should be conducted.

PurposePheochromocytoma/paraganglioma (PCC/PGL; collectively known as PPGL) can be driven by germline and somatic mutations in susceptibility genes. We aimed to investigate the mutation profile and clinical features of pathogenic genes in highly genetically heterogeneous PPGL and to preliminary explore molecular therapeutic targets in PPGL.MethodsWe established a panel of 260 genes, including susceptibility genes of PPGL and other important tumorigenic genes to sequence 107 PPGL tissues.ResultsOverall, 608 genomic mutations were identified in 107 PPGL tissues. Almost 57% of PPGL tissue samples exhibited pathogenic mutations, and the most frequently mutated gene was SDHB (15/107, 14%). SDHB and HRAS were the most commonly mutated genes in germline-mutated PPGL (25/107, 23%) and nongermline-mutated PPGL (36/107, 34%), respectively. In addition, novel pathogenic mutations were detected in sporadic PPGL. PPGL with mutations in the hypoxia pathway had an earlier onset and higher norepinephrine level than those in the kinase pathway. Receptor tyrosine kinase (RTK; 22%, 24/107), mitogen-activated protein kinase (MAPK; 14%, 15/107), and tyrosine kinase (TK; 2%, 2/107) pathways were the most frequently mutated pathways in PPGL.ConclusionOur results provided the genetic mutation profile in PPGL tissues. Genetic mutations in PPGL were mainly concentrated in the RTK, TK, and MAPK pathways, suggesting potential molecular therapeutic targets for PPGL.

ObjectiveThe aim of this study was to analyze the clinical characteristics and the pattern of long-term changes of fasting plasma C-peptide in patients with mitochondrial diabetes (MD), and to provide guidance for the diagnosis and treatment of MD.MethodsWe retrieved MD patients with long-term follow-up at Peking Union Medical College Hospital from January 2005 to July 2021 through the medical record retrieval system and retrospectively analyzed their clinical data, biochemical parameters, fasting plasma C-peptide, glycosylated hemoglobin and treatment regimens. Non-parametric receiver operating characteristic (ROC) curves were used to assess the relationship between exercise test-related plasma lactate levels and suffering from MD.ResultsA total of 12 MD patients were included, with clinical characteristics of early-onset, normal or low body weight, hearing loss, maternal inheritance, and negative islet-related autoantibodies. In addition, patients with MD exhibited significantly higher mean plasma lactate levels immediately after exercise compared to patients with type 1 diabetes mellitus (T1DM) (8.39 ± 2.75 vs. 3.53 ± 1.47 mmol/L, p=0.003) and delayed recovery time after exercise (6.02 ± 2.65 vs. 2.17 ± 1.27 mmol/L, p=0.011). The optimal cut-off points identified were 5.5 and 3.4 mmol/L for plasma lactate levels immediately after and 30 minutes after exercise, respectively. The fasting plasma C-peptide levels decreased as a negative exponential function with disease progression (Y= 1.343*e-0.07776X, R2 = 0.4154). Treatment regimens in MD patients were varied, with no metformin users and a weak correlation between insulin dosage and body weight.ConclusionsThe increased level of plasma lactate during exercise or its delayed recovery after exercise would contribute to the diagnosis of MD. Changes of fasting plasma C-peptide in MD patients over the course of the disease indicated a rapid decline in the early stages, followed by a gradual slowing rate of decline.

Polyphenols are secondary metabolites of plants and used as effective antioxidants in dietary supplements, whose main sources are fruits, vegetables, and grains. To clarify the content and distribution of polyphenols in different fruit species samples accurately, a rapid and sensitive ultrahigh-pressure liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method combining dispersive liquid-liquid microextraction (DLLME) was developed for quantitative determination of fifteen polyphenol compounds in fruit juice. In this method, the targets were first extracted from 1 g of fruit juice sample using 10 mL of 80% ethanol solution by ultrasonic-assisted extraction (UAE). Then, 1.0 mL of UAE extracted solution, 60 μL of n-octanol and 2.0 mL of H2O were performed in the following DLLME procedure. A C18 reversed-phase column, ZORBAX SB (100 × 4.6 mm, 3.5 μm), was proposed under gradient elution with 0.1% formic acid aqueous solution and methanol mobile phases for the determination of 15 polyphenols, allowing us to obtain polyphenolic profiles in less than 23.0 min. Under the optimum conditions, the enrichment factors ranged from 162 to 194. The results showed that the 15 polyphenols had linear correlation coefficients (R2) more than 0.99. The limits of detection (LODs) were between 18.3 and 103.5 ng/g, and the average recoveries were between 96.9 and 116.3% with interday relative standard deviations (RSDs) ranging from 4.4 to 8.2% in all cases. The method was successfully applied to the analysis of real fruit juice samples and presented itself as a simple, rapid, practical, and environment-friendly technique.

Abstract Background Previous studies on the effects of lipotoxicity and oxidative stress on islet beta cell function mainly focused on patients with diabetes, whereas studies on normal glucose tolerance (NGT) are few. The aim of this study was to explore the relationships among triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), oxidative stress indicators, insulin resistance, and beta cell function in populations with different glucose and lipid metabolism states. Methods A total of 517 individuals were recruited from a rural community in Beijing, China. Glucose metabolism status was defined according to the results of a 75-g oral glucose tolerance test (OGTT). Dyslipidemia was defined as abnormal TG, HDL-c, or LDL-c levels. The population was divided into four groups: individuals with normal glucose and lipid levels (group A, n = 62); those with dyslipidemia alone (group B, n = 82); those with dysglycemia alone (group C, n = 121); and those with dysglycemia and dyslipidemia (group D, n = 247). Oxidative stress indicators, including superoxide dismutase (SOD), glutathione reductase (GR) and 8-hydroxydeoxyguanosine (8-OHdG), were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI30, DI120) were calculated to assess insulin resistance and islet beta cell function, respectively. Stratified multiple linear regression analysis was used to explore relationships between TG, HDL-c, LDL-c, oxidative stress indicators, and insulin resistance (natural log transformation of HOMA-IR, LnHOMA-IR) and beta cell function (natural log transformation of DI30, Ln DI30). Results Compared with the control group, populations with dyslipidemia and/or dysglycemia showed significantly increased insulin resistance. Dyslipidemia aggravated insulin resistance and beta cell dysfunction in individuals with dysglycemia. Stratified regression analysis showed that TG positively correlated with LnHOMA-IR in individuals with normal glucose levels (beta = 0.321, 0.327, P = 0.011, 0.003 in groups A and B, respectively) and negatively correlated with LnDI30 in participants with dyslipidemia (beta = − 0.225, − 0.122, P = 0.035, 0.048 in groups B and D, respectively). Reduced serum SOD levels in individuals with dysglycemia plus dyslipidemia were observed, and a negative association between TG and SOD levels was found (r = − 0.461, P

Abstract Background The shape of the glucose response curve during an oral glucose tolerance test (OGTT) can predict β-cell function and insulin resistance. However, there have been few studies conducted on Chinese people. Thus, we aimed to verify the usefulness of the glucose response curve in a large Chinese population. Methods A total of 9059 OGTT (3-h tests) were categorized into either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, the Matsuda Index, the insulinogenic index, and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. Results The shape of the OGTT glucose response curve was monophasic in 87.3% and multiphasic in 12.7% of participants. Individuals in the multiphasic group were younger compared to those in the monophasic group (38.6 ± 13.6 vs. 35.4 ± 13.5, P

IntroductionPrevious studies on the surgical outcomes of aldosterone-producing adenoma (APA) patients were mainly based on the histopathological diagnosis of HE staining or adrenal venous sampling (AVS) instead of the functional pathology. The aim of the present study was to evaluate the surgical outcomes of APA patients based on the functional pathological diagnosis of APA according to HISTALDO (histopathology of primary aldosteronism) consensus.MethodsClinical data of 137 patients with suspected APA were analyzed retrospectively. All patients had hypertension and spontaneous hypokalemia. In all patients, CT showed a unilateral solitary hypodense adrenal lesion, and a contralateral adrenal gland of normal morphology. Tumors were removed and immunostained for CYP11B2, and their pathology were identified based on HISTALDO consensus. Patients were followed up 6 to 24 months after operation.ResultsAmong 137 cases of presumptive APA diagnosed by CT, 130 (95%) cases were pathologically diagnosed with classical pathology, including 123 APA(90%) and 7 aldosterone-producing nodule (APN) (5%). 7 cases (5%) had non-functioning adenoma (NFA) with aldosterone-producing micronodule (APM) or multiple aldosterone-producing micronodule (MAPM) in the surrounding adrenal tissue. In all 137 patients, hypertension was complete or partial clinical success postoperatively. Complete clinical success was achieved in 73 (53%), and partial clinical success was achieved in 64 (47%) cases. Serum potassium level recovered to normal in all. In 123 patients with APA, complete clinical success was reached in 67 (54%), and partial clinical success was reached in 56 (46%) cases. Gender, duration of hypertension and the highest SBP were significant independent predictors for cure of APA after surgery. A multiple logistic regression model integrating the three predictors was constructed to predict the outcome, which achieved a sensitivity of 72.4% and a specificity of 73.1%.ConclusionThe specificity of CT in the diagnosis of APA and APN patients with hypokalemia was 95%. All patients achieved complete or partial clinical success after surgery. Gender, duration of hypertension and the highest SBP were independent predictors for the postoperative cure of APA.

Abstract Background Malignant insulinoma is extremely rare and accounts for only 10% of total insulinoma cases. The goal of this study is to retrospectively analyze clinical data from 15 patients with malignant insulinoma treated at Peking Union Medical College Hospital (PUMCH) from 1984 to April 2017. Methods “Malignant insulinoma” was used as the keywords in the PUMCH medical record retrieval system to search and obtain patients’ clinical information. We identified subjects diagnosed with malignant insulinoma based on clinical or surgical pathological signs and subsequently analyzed their clinical data. Results Eight males and seven females with a median age at diagnosis of 40 years (38–54 years) were included. Eight patients (53%) had developed metastases at diagnosis, while the others (46.67%) developed metastases during the follow-up visits. The major sites of metastasis were the liver (86.7%), local tissues and blood vessels (33%) and abdominal lymph nodes (13%). All patients displayed neuroglycopenic (100%) and/or autonomic (60%) symptoms, mostly during fasting periods (73.3%), with an average blood glucose level of 1.66 ± 0.51 mmol/L. A total of 93% of the patients had one primary pancreatic lesion, 53% had a lesion in the head of the pancreas, and 47% had a lesion in the tail of the pancreas, with diameters ranging between 0.9 and 6.0 cm. Most liver metastases were multiple lesions. Selective celiac arteriography yielded 100% sensitivity for both primary pancreatic lesions and liver metastases. Most patients received synthetical treatments, including surgery, chemoembolization, and octreotide. Conclusions Malignant insulinomas have a similar diagnostic process to that of benign insulinomas but require far more comprehensive therapies to alleviate hypoglycemic symptoms and extend patients’ survival.

Pheochromocytoma/paraganglioma (PPGL) has a high genetic heterogeneity with 40% germline variants in known pathogenic genes. Data in Chinese on this aspect are scanty. To detect the genetic and clinical profile of Chinese PPGL patients, we examined the variants of 12 known germline pathogenic genes (SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, RET, NF1, MAX, TMEM127, and KIF1B) by next-generation sequencing and Sanger sequencing in 314 Chinese PPGL subjects. Twenty nine percent of Chinese PPGL patients had germline variants and SDHB was the most frequently mutated (14.6%). The most frequent SDHB variants were in exon 2, exon 7, and IVS 7. Pathogenic variants were more likely to occur in metastatic PPGL patients, paragangliomas, and patients under 30, with the ratio being 50.7% (35/69), 35.9% (56/156), and 49.5% (52/105), respectively. Our cohort included 314 patients from a single setting. The genetic and clinical features of Chinese PPGL patients were unique in some aspects compared to their non-Chinese counterparts. Identification of genotype-phenotype relation can serve as an effective tool for genetic prioritization and clinical decision-making.

BackgroundThe data on the relationship between normal-ranged serum uric acid (SUA), β-cell function, and non-alcoholic fatty liver disease (NAFLD) are complicated and insufficient. Moreover, uric acid is excreted by kidney, and SUA levels may be affected by renal function. Thus, we introduced a renal function-normalized index [serum uric acid to creatinine ratio (SUA/Cr)] into the study and explored the association between SUA/Cr, C‐peptide and NAFLD in a Chinese population with normal SUA levels by a cross-sectional analysis.Materials and MethodsA total of 282 individuals with normal SUA levels and different glucose tolerance status from a diabetes project were included in the study (mean age = 53.7± 10.5 years; women = 64.50%). NAFLD was diagnosed by abdominal ultrasonography (NAFLD, n=86; without NAFLD, n=196). Trapezoid formula was used to calculate area under the curve of C‐peptide (AUCCP) from 4 points (including 0, 30,60, and 120min) during 2-h oral glucose tolerance test. Spearman correlation analysis was used to explore the correlation between SUA/Cr, AUCCP and NAFLD risk factors. Multiple logistic regression analysis was used to explore the association between SUA/Cr or AUCCP and NAFLD. Mediation analysis was used to explore whether AUCCP mediated the association between SUA/Cr and NAFLD.ResultsIndividuals with NAFLD had significantly higher SUA/Cr and AUCCP than those without NAFLD(P

Background: Alterations in mitochondrial DNA are potentially associated with oxidative stress and may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the association between mitochondrial DNA copy number (mtDNAcn) and NAFLD was not consistent. In addition, the association between inflammation and NAFLD has not been established yet. The present study, based on a Chinese population of individuals with different glucose statuses, aimed to explore the association between leukocyte mtDNAcn, markers of oxidative stress, and inflammation and NAFLD.Methods: A total of 318 participants from a diabetes project were included. NAFLD was diagnosed by ultrasonography. Leukocyte mtDNAcn was determined by PCR assay. The levels of the inflammation markers tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) and the oxidative stress markers glutathione reductase (GR), superoxide dismutase (SOD), and 8-oxo-2′-deoxyguanosine (8-oxo-dG) were also measured.Results: Participants with NAFLD (n = 105) exhibited significantly higher leukocyte mtDNAcn, IL-6, and 8-oxo-dG (all P < 0.05). Pearson correlation analysis indicated mtDNAcn was negatively associated with age, uric acid, SOD, and TNF-α, but was positively associated with 8-oxo-dG (all P < 0.05). Univariate logistic regression analysis revealed that mtDNAcn was positively associated with NAFLD [odds ratio (OR) = 1.617, 95% confidence interval (CI) = 1.036–2.525; P = 0.034]. However, after adjustment for 8-oxo-dG, this association was no longer statistically significant (OR = 1.534, 95% CI = 0.979–2.403, P = 0.062). Moreover, the stress marker 8-oxo-dG was independently associated with NAFLD after adjustment for mtDNAcn, IL-6, glucose tolerance status, and other conventional NAFLD risk factors (OR = 1.707, 95% CI =1.142–2.550, P = 0.009). Mediation analysis indicated that 8-oxo-dG fully mediated the effect of mtDNAcn on the incidence of NAFLD (direct effect β = 0.5221, 95% CI = −0.0648 to 1.2504; indirect effect β = 0.0946, 95% CI = 0.0049–0.2463).Conclusions: In a Chinese population, the association between leukocyte mtDNAcn and NAFLD was fully mediated by high levels of 8-oxo-dG. Thus, oxidative stress may be an important driver of NAFLD, and clinical interventions aimed at decreasing oxidative stress to improve NAFLD warrant further research.

Background: Diabetes is a global disease with rapidly increasing prevalence in the world. Glycated hemoglobin (HbA1c) as an important indicator of diabetes could reflect the average serum glucose level over 120 days. However, when using HbA1c to diagnose diabetes, it is important to consider other factors that may impact HbA1c level including age, race/ethnicity, detection method, and co-morbidities. Here we report a case of diabetes with normal hemoglobin but reduced HbA1c.Case report: A 57-year-old female patient was diagnosed with diabetes by oral glucose tolerance test results. However, the HbA1c level was repeatedly decreased, glycated albumin level was high, with normal levels of hemoglobin and albumin, and a slightly elevated level of bilirubin. Moreover, life span of red blood cells was significantly shortened. Further examination of whole exome sequencing of the patient and her daughter showed heterozygous variant in PIEZO1 gene (c.6017T > A) in both, which is associated with dehydration hereditary stomatocytosis (DHS). After this diagnosis, we changed nateglinide to sitagliptin to reduce the burden of the pancreas islet function.Conclusion: In case of abnormally low HbA1c, we recommend that GA and reticulocyte should be measured simultaneously. Moreover, the methodology for hemoglobin measurement and the diseases that could cause abnormal quantity and quality of red blood cells and hemoglobin be considered.

Purpose: The aim of this study is to examine the effects of different kinds of calcium channel blockers (CCBs) on primary aldosterone-producing adenoma (APA) mainly with KCNJ5 mutations. Primary cultured APA cells were treated with different calcium channel blockers (L/T type CCB benidipine, T-type CCB mibefradil and L-type CCB nifedipine), and aldosterone secretagogues with or without nifedipine. Aldosterone level, aldosterone synthase (CYP11B2) mRNA expression and cell proliferation were detected. The results showed that all three CCBs significantly inhibit aldosterone secretion and CYP11B2 mRNA expression. Benidipine was relatively more effective than mibefradil or nifedipine. In addition, only mibefradil marginally inhibited cell proliferation. Adrenocorticotropin (ACTH) had a much stronger effect in stimulating aldosterone secretion and promoting cell proliferation from APA's than angiotensin II (ATII). Different from ACTH and ATII, potassium had no effect. Nifedipine inhibited the basal and ACTH-, ATII-elicited aldosterone secretion. Twenty three of 24 APAs had somatic KCNJ5 mutation. In conclusion, benidipine, mibefradil and nifedipine significantly inhibit aldosterone secretion in primary cultured APA cells.

Context: Metastatic pheochromocytoma/paraganglioma (MPP) therapy mainly involves radionuclide therapy, chemotherapy, and targeted therapy. In recent years, temozolomide (TMZ) showed great promise in some MMP patients, especially those with SDHB germline mutation. We reported a patient with MPP who did not have any known germline genetic change and responded remarkably well to TMZ monotherapy.Case presentation: The patient was a 41-year-old woman with local and distant recurrence (soft tissues and bone metastases) of retroperitoneal paraganglioma. She suffered from dizziness, palpitation, sweating, weight loss and constipation, with the blood pressure fluctuating substantially from 130/100 mmHg to 190/120 mmHg, although she was on phenoxybenzamine and metoprolol medication. The patient showed clinical and radiological response after 3-cycle TMZ therapy. Upon 15 cycles of TMZ therapy, her symptoms were dramatically alleviated, urinary norepinephrine excretion decreased from 1,840 μg/24 h to 206 μg/24 h, and CT showed that the lesions further shrank. Molecular profiling of the tumor tissue of the patient revealed hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter and a negative immunostaining for MGMT. Globally, only 26 cases of MPP treated with TMZ have been described so far. TMZ is effective, especially in patients with SDHB mutation, which can be explained by the silencing of MGMT expression as a consequence of MGMT promoter hypermethylation in SDHB-mutated tumors. Although, in general, patients with SDHB mutation or MGMT promoter hypermethylation have better response to TMZ, there are also exceptions. Severe side effects are uncommon, with only 17.4% patients experiencing Grade 3 toxicities, including lymphopenia, and hypertension.Conclusions: TMZ is effective and safe in MPP patients, and, it may work better on patients with SDHB-related MPP. Measurement of MGMT expression might help assess the tumor sensitivity to TMZ but this needs further systematic investigation.

Objectives. In this study, we assessed the effects of dietary magnesium on leukocyte telomere length (LTL). Designs. The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings. Dietary magnesium intake is associated with peripheral blood leukocyte telomere length (LTL). However, few epidemiological studies have evaluated the effects of magnesium on LTL in the clinical setting. Participants. This cross-sectional analysis included 467 participants (34.8% men). Measurements. Serum blood lipid profile, HbA1c, oxidative stress, and proinflammatory mediator levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Regression models and simple regulatory models were used for data analysis. Results. There was an inverse relationship between dietary magnesium and LTL (P

Abstract Pd functionalized TiO2 nanoparticles were synthesized by a facile hydrothermal method. The structure, morphology, surface chemical states and surface area were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and N2 adsorption-desorption isotherms, respectively. The as-synthesized pure and Pd functionalized TiO2 nanoparticles were used to fabricate indirect-heating gas sensor, and the gas-sensing characteristics towards butane were investigated. At the optimum temperature, the sensors possess good response, selectivity, response/recovery, repeatability as well as long-term stability. Especially for the high response, the response of 7.5 mol% Pd functionalized TiO2 nanoparticles based sensor reaches 33.93 towards 3000 ppm butane, which is about 9 times higher than that of pure TiO2 nanoparticles. The response and recovery time are 13 and 8 s, respectively. Those values demonstrate the potential of using as-synthesized Pd functionalized TiO2 nanoparticles as butane gas detection, particularly in the dynamic monitoring. Apart from these, a possible mechanism related to the enhanced sensing performance is also investigated.

Background: The gut microbiota plays important roles in the occurrence and development of obesity and diabetes through participating in nutrient absorption and metabolism. Microecological regulation is likely to be key to understanding the effects of Chinese medicine. The Linggui Zhugan (LGZG) formula is a well-known Chinese medicine for controlling obesity in the clinic. However, its pharmacological effects and mechanism of action in diabetes require further exploration.Objective: To evaluate the effects of LGZG on body weight, glycemic control, lipid levels, and gut microbiota in high-fat diet-induced diabetic mice.Methods: High-fat diet-induced diabetic mice were subjected to an 8-week protocol of LGZG administration. We then evaluated the pharmacological effects of LGZG and its influence on gut microbes in fecal samples using the 16S rRNA-based microbiome profiling technique.Results: LGZG administration significantly reduced body weight and body fat mass in diabetic mice. Compared with the high-fat diet control group, LGZG favorably influenced blood glucose control, decreased blood glucose levels, and increased glucose tolerance, accompanied by an improvement in lipid metabolism. Furthermore, the global community composition and relative abundance of many taxa differed between mice fed chow or a high-fat diet. As expected, LGZG supplementation altered the general community structure of gut microbiota, the Firmicutes/Bacteroidetes ratio, and the relative abundance of certain bacteria, such as Bacteroides, Lactobacillus, Oscillospira, and Helicobacter.Conclusion: LGZG effectively controlled obesity and relieved insulin resistance, which may be closely related to its impact on gut microbiota.

ObjectivesTo explore doctors’ knowledge, willingness, concerns and the countermeasures to the most stringent antimicrobial stewardship regulations of China which implemented in August 2012.DesignCross-sectional survey. A pretested 32-point structured questionnaire was distributed to doctors by sending a web link via the mobile phone application WeChat through snowball sampling methods and email groups of medical academic societies.SettingChina.ParticipantsDoctors.Primary and secondary outcome measuresThe questionnaire inquired about the doctors’ experiences, knowledge, willingness, concerns and the countermeasures to the stewardship policies.ResultsTotal of persons in the groups was 19 791, among them 1194 submitted the answers, within them, 807 were doctors. Doctors had a mean age of 39.0 years. The majority (78.9% in 2012, 89.1% in 2016) reported that they were willing or very willing to accept the regulations. Almost all respondents (93.2%) felt the stewardship regulations had the potential to adversely affect the prognosis of patients who would have been prescribed antimicrobials before they were implemented, and >65% (65.7% in 2012, 66.9% in 2016) of doctors were often or always concerned about the prognosis of these patients. In 2012, 32% of doctors prescribed restricted antimicrobials or suggested patient self-medication with restricted antimicrobials to address doctors’ concerns, and this number decreased to 22.6% in 2016. Although compulsory antimicrobial stewardship training was frequent, less than half of respondents (46.8%) responded correctly to all three knowledge questions.ConclusionAntimicrobial stewardship regulations had some positive effect on rational antimicrobial use. Willingness and practice of doctors towards the regulations improved from 2012 to 2016. Knowledge about rational antimicrobial use was still lacking. Doctors found ways of accessing restricted antibiotics to address their concerns about the prognosis of patients, which undermined the implementation of the stewardship regulations.

Background. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse reaction caused by specific drugs. However, little information is available about sequelae following DIHS/DRESS resolution from an endocrinologist’s perspective. This study aimed to investigate the endocrine sequelae following DIHS/DRESS, from clinical feature to etiology. Methods. We retrospectively analyzed the patients diagnosed with DIHS/DRESS in Peking Union Medical College Hospital (PUMCH) during the period of 1 January 2012 to 31 December 2017, and those who developed endocrine disorders after DIHS/DRESS were further examined. We also reviewed the literature, from 1 January 2000 to 31 December 2017, on involvement of endocrine glands in DIHS/DRESS patients. Results. Three patients developed both autoimmune thyroid disease (AITD) and type 1 diabetes (T1DM)/fulminant type 1 diabetes (FT1DM) of the 45 patients. Seven cases involving more than two endocrine glands were reported in the literature. Our results indicated that DIHS/DRESS is a potential etiological factor of autoimmune polyendocrine syndrome (APS), especially APS III. Conclusions. Patients require careful long-term follow-up after DIHS/DRESS. Involvement of endocrine glands, especially FT1DM, should always be monitored in patients with a history of DIHS/DRESS. This study indicated that DIHS/DRESS could lead to APS, especially APS III, providing novel insights into the etiological factors of APS.

Objective. Previous studies have revealed dysregulated circulating microRNAs (miRNAs) in patients with type 1 diabetes (T1D). Here, we explored the serum levels of miR-21, miR-25, miR-146a, and miR-181a in patients with autoimmune diabetes (T1D and latent autoimmune diabetes of adults (LADA)) compared with type 2 diabetes (T2D) and nondiabetic individuals. Design, patients, and measurements. The serum levels of miR-21, miR-25, miR-146a, and miR-181a in patients with T1D (n = 29), LADA (n = 16), and T2D (n = 31) and in nondiabetic individuals (n = 19) were determined by quantitative real-time polymerase chain reaction, and receiver-operating characteristic (ROC) curves were evaluated to determine the discriminatory performances of these four miRNAs. Furthermore, target genes and pathways potentially modulated by these four miRNAs were predicted by bioinformatics analysis to investigate the possible functions of these miRNAs in autoimmune diabetes. Subsequently, multiple logistic regression analysis was performed to identify independent predictors for autoimmune diabetes, and a nomogram was established. Results. miR-21, miR-25, miR-146a, and miR-181a were significantly downregulated in the serum of patients with autoimmune diabetes compared with those in T2D patients and nondiabetic individuals (p

Objective. To investigate the association of polymorphisms in uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor (PPARγ) with glucolipid metabolism in Chinese Han population. Methods. Five hundred eighty-nine subjects were divided into normal glucose tolerance (NGT) group (n=198) and abnormal glucose tolerance group (n=358). HbA1c, blood lipid profile, plasma glucose, and insulin were determined. Insulin sensitivity (HOMA-IR and Matsuda index (ISIM)) and insulin secretion indexes (HOMA-β, early and total phase disposition index) were evaluated. Eight potential functional SNPs in UCP2 and 7 in PPARγ were selected. SNPs were genotyped on Sequenom MassARRAY platform. Results. The GG genotype of rs2920502 in PPARγ was associated with decreased risk of impaired glucose tolerance (G allele: OR: 0.818, 95%CI: 0.526–0.969, P=0.042; GG: OR: 0.715, 95%CI: 0.527–0.97, P=0.031). The TT genotype of rs3856806 in PPARγ was associated with increased risk of impaired glucose tolerance (T allele: OR: 1.46, 95%CI: 1.055–2.017, P=0.022; TT: OR: 1.58, 95%CI: 1.104–2.761, P=0.032). The GG genotype of rs2920502 in PPARγ had better blood glucose and increased insulin secretion and had lower HOMA-IR than GC/CC genotypes. Conclusion. It probably could prevent insulin resistance in early stage by classifying the genotype of rs649446 and rs7109266 in UCP2. The GG genotype of rs2920502 in PPARγ had a decreased risk for diabetes. The TT genotype of rs3856806 in PPARγ had an increased risk for diabetes.

High aspect ratio silver nanowires (AgNWs) with ultra-long length and thin diameter were synthesized through bromine ion (Br−)-assisted one-step synthesis method. The bromine ions were used as pivotal passivating agent. When the molar ratio of Br−/Cl− was 1:4, the average diameter of AgNWs was as low as ~40 nm, the average length was as high as ~120 μm, and the aspect ratio reached 2500. Networks of AgNWs were fabricated using as-prepared high-quality AgNWs as conducting material and hydroxyethyl cellulose (HEC) as the adhesive polymer. As a result, a low sheet resistance down to ~3.5 Ω sq−1 was achieved with a concomitant transmittance of 88.20% and a haze of 4.12%. The ultra-low sheet resistance of conductive film was attributed to the long and thin AgNWs being able to form a more effective network. The adhesion of the AgNWs to the substrate was 0/5B (ISO/ASTM). The insights given in this paper provide the key guidelines for bromine ion-assisted synthesis of long and thin AgNWs, and further designing low-resistance AgNW-based conductive film for optoelectronic devices.

In this study, waste red bricks were incorporated with iron oxides (goethite and hematite) and used for the removal of diclofenac (DCF) from aqueous solutions. The prepared waste red bricks were systematically characterized by XRF, XRD, BET, and SEM. The batch experiments were systematically conducted by investigating the adsorption kinetics, isotherms, thermodynamics, pH, and ionic strength effect. Results showed that the incorporation of iron oxides could enhance the adsorption capacity of DCF onto waste bricks, while the increased effect of hematite was better than goethite. DCF was adsorbed rapidly onto waste bricks, and the adsorption kinetic fitted the pseudo-second-order model perfectly, which could be attributed to the strong interaction between DCF and iron oxides. The increasing pH values decreased the adsorption capacity greatly, which may be due to the electrostatic repulsive interactions. The adsorption of DCF onto waste bricks was an exothermic reaction, and the adsorption isotherms fitted well with the Langmuir model. This study offers new guidelines for the utilization of construction waste, and shows useful methods for the elimination of micropollutants from aqueous solution.