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Abstract. Background:. The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. Methods:. A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. Results:. The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors (χ2 = 29.5, P 0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P 0.82 after adjustment for potential confounders. Conclusions:. We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.

Objective. This study aimed to analyse the etiology and clinical characteristics of hypercalcemic crisis in a large cohort of Chinese patients and summarised our clinical experience in the management of this serious endocrinological emergency. Methods. This was a retrospective analysis of a cohort of patients with hypercalcemic crisis hospitalized in the First Medical Center of Chinese PLA General Hospital between January 2009 and March 2024. The general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, and prognosis were analysed. Results. A total of 155 patients with hypercalcemic crisis (91 males and 64 females) with a mean age of 54.60 ± 16.99 years old were enrolled. The most frequent disease-causing hypercalcemic crisis was hyperparathyroidism (41.94%), followed by solid malignancy (41.29%) and multiple myeloma (9.03%), et al. Patients mainly presented with symptoms of the digestive system (78.10%), nervous system (63.30%), skeletal system (59.60%), urinary system (59.50%), and cardiovascular system (34.90%). These 155 patients with hypercalcemic crisis got effective therapies that included simultaneous administration of intravenous injection (IV) isotonic saline, subcutaneous calcitonin, bisphosphonate, or hemodialysis in serious cases. After emergency treatment, all the symptoms in the patients were relieved obviously. The cure rate of hypercalcemic with etiological treatments was 84.50% (131/155). Conclusion. Hypercalcemic crisis is a serious endocrinological emergency with a variety of etiologies and a high risk of mortality. A prompt diagnosis and the implementation of a comprehensive and effective treatment can efficiently alleviate this endocrinological emergency. Etiological treatment targeting different causes can improve prognosis significantly.

Abstract Background Patients with type 2 diabetes mellitus (T2DM) usually have higher blood viscosity attributed to high blood glucose that can decrease blood supply to the pancreas. A mild increase in blood pressure (BP) has been reported as a potential compensatory response that can maintain blood perfusion in the islet. However, how BP influences beta-cell function in T2DM subjects remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels. Methods This is a cross-sectional study of 615 T2DM patients, whose clinical data were extracted from hospital medical records. Beta-cell function was assessed by insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic BP (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function. Results After adjustment of potential confounders, in participants with HbA1c ≥ 10%, the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.227, 95% CI 0.053–0.402), an association specific to participants with

Abstract Background The coexistence of primary hyperparathyroidism (PHPT) and giant toxic nodular goiter is very rare. Moreover, PHPT could be easily overlooked because hyperthyroidism may also lead to hypercalcemia. A 99mTc-MIBI scan of the parathyroid glands is often negative when they are concomitant. Case presentation Here, we report a rare case of the coexistence of giant toxic nodular goiter and PHPT that had been ignored for many years but was successfully treated with an ultrasound-guided parathyroid adenoma microwave ablation (MWA). Conclusion Reoperation for PHPT carries an increased risk of cure failure and complications. Thermal ablation has been proven effective in inactivating hyperfunctioning parathyroid lesions and in normalizing both serum parathyroid hormone (PTH) and calcium.

BackgroundCastleman Disease (CD) is a group of diseases with characteristic lymph node histopathology, characterized by marked enlargement of deep or superficial lymph nodes. Adrenal CD is rarely reported, and an accurate preoperative diagnosis of adrenal CD is difficult.MethodWe report four cases of CD in the adrenal gland confirmed by pathology and review the characteristics of this rare disease, highlighting the necessity of diagnostic evaluation and follow-up of the patients.ResultsAll of the patients sought medical advice because of adrenal incidentalomas. No significant abnormalities were presented in the biochemistry or endocrine systems. The imaging suggested a moderate-to-large mass with uneven moderate contrast enhancement of the adrenal region, similar to a pheochromocytoma. All cases were misdiagnosed as pheochromocytomas before operation and finally confirmed by histopathology. Three cases were pathologically diagnosed as hyaline vascular CD, and one case was diagnosed as plasma cell CD. All the patients are alive without recurrence after a median follow-up of 8 years.ConclusionThe adrenal CD should be considered after excluding pheochromocytoma and malignancy in the adrenal region. The long-term prognosis of patients with complete resection of the mass is excellent.

Abstract Background To determine the efficacy and safety of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in Chinese adults with type 2 diabetes mellitus (T2DM). Methods In this single-center, double-blinded, randomized, placebo-controlled phase II trial, 91 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 45) or placebo (n = 46) three times with 4-week intervals and followed up for 48 weeks from October 2015 to December 2018. The primary endpoint was the percentage of patients with glycated hemoglobin (HbA1c) levels of

Abstract Long noncoding RNAs (lncRNAs) are involved in diabetes related diseases. However, the role of lncRNAs in the pathogenesis of type 2 diabetes with macrovascular complication (DMC) has seldomly been recognized. This study screened lncRNA profiles of leukocytes from DMC patients and explored protective role of lncRNA LYPLAL1-DT in endothelial cells (EC) under high glucose (HG) and inflammatory conditions (IS). Between DMC and healthy controls, 477 differential expression lncRNAs (DE-lncRNAs) were identified. The enrichment and pathway analysis showed that most of the DE-lncRNAs belonged to inflammatory, metabolic, and vascular diseases. A total of 12 lncRNAs was validated as significant DE-lncRNAs in expanding cohorts. Furthermore, these DE-lncRNAs were shown to be significantly related to hypoxia, HG, and IS in EC, especially lncRNA LYPLAL1-DT. LYPLAL1-DT overexpression results in the promotion of the proliferation, and migration of EC, as well as an elevation of autophagy. Overexpressed LYPLAL1-DT reduces the adhesion of monocytes to EC, boosts anti-inflammation, and suppresses inflammatory molecules secreted in the medium. Mechanistically, LYPLAL1-DT acts as competing endogenous RNA (ceRNA) by downregulating miR-204-5p, therefore enhancing SIRT1 and protecting EC autophagy function; thus, alleviating apoptosis. Finally, exosome sequencing revealed LYPLAL1-DT expression was 4 times lower in DMC cells than in healthy samples. In general, we identified LYPLAL1-DT having protective effects on EC as ceRNA mediated through the miR-204-5p/SIRT1 pathway. Therefore, it inhibits the autophagy of EC as well as modulating systemic inflammation. This approach could be regarded as a new potential therapeutic target in DMC.

Abstract. Backgrounds:. Inadequate sleep duration is associated with a higher risk of type 2 diabetes and the relationship is nonlinear. We aim to assess the curve relationship between night sleep duration and the incidence of type 2 diabetes in China. Methods:. A cohort of 11,539 participants from the REACTION study without diabetes at baseline (2011) were followed until 2014 for the development of type 2 diabetes. The average number of hours of sleep per night was grouped. Incidence rates and odds ratios (ORs) were calculated for the development of diabetes in each sleep duration category. Results:. Compared to people who sleep for 7 to 8 h/night, people with longer sleep duration (≥9 h/night) had a greater risk of type 2 diabetes (OR: 1.27; 95% CI: 1.01–1.61), while shorter sleep (

Abstract Background Studies have demonstrated the relationship between the fatty liver index (FLI) and metabolism, while few research reported its relationship with hyperuricemia (HUA). This study aimed to predict HUA by determining the relationship between the baseline FLI and HUA events and by validating the FLI–HUA correlation through follow-up. Methods This study was a community-based cohort study involving 8851 adults in China. We performed anthropometric assessments and analyzed baseline and follow-up blood samples. HUA was defined as a uric acid level of > 420 µmol/L (7 mg/dL). Results Patients with HUA had a higher prevalence of diabetes mellitus, lipid metabolism disorders, and hypertension and higher FLI values than those with normal uric acid levels (P

PurposeThe hemoglobin glycation index (HGI) quantifies the mismatch between glycated hemoglobin A1c and average glycemia among individuals. Currently, it is unknown the potential role of HGI in exhaustively evaluating the progression of glucose metabolism/the risk of developing diabetes mellitus. Therefore, this study aimed to investigate the association between HGI and the risk of incident diabetes.MethodsA total of 7,345 participants aged at least 40 years and without diabetes were divided into three groups according to the tertile of their baseline HGI level and followed for a median of 3.24 years to track new-onset diabetes. Using multivariate Cox regression analyses, we explored the association between the HGI, both categorized and continuous, and incident diabetes.ResultsDuring follow-up, 742 subjects (263 males and 479 females) developed diabetes mellitus. Higher HGI was associated with an increased risk of diabetes, even when adjusted for confounding factors, and every standard deviation increase in HGI was associated with a significant risk increase of 30.6% for diabetes (hazard ratio 1.306, 95% confidence interval 1.232–1.384).ConclusionsParticipants with a higher HGI were at a higher risk of future diabetes, irrespective of their glycemic conditions. Consequently, HGI may be employed to identify individuals at high risk for diabetes.

BackgroundOverweight and obesity are well-known risk factors for type 2 diabetes mellitus (T2DM). The effect of the maximum body mass index (BMImax), which indicates the highest body weight before the diagnosis of T2DM, is not fully understood. This study aimed to explore the predictive value of BMImax in the progression of diabetes.MethodsThis prospective study recruited 2018 subjects with normal glucose tolerance in Beijing, China. The subjects were followed up for eight years, and the association between BMImax and glucose outcomes was evaluated.ResultsNinety-seven of the 2,018 participants developed diabetes by the end of the study. Compared to individuals with normal glucose tolerance, those who developed diabetes were characterized by higher levels of fasting plasma glucose (FPG), 2 h postload glucose (PBG), glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-c), a higher prevalence of a familial history of diabetes and a lower level of high‐density lipoprotein cholesterol (HDL-c). Multivariate regression analysis of sex-stratified groups suggested that FPG, HbA1c, SBP and familial history of diabetes were independent risk factors for diabetes, but that BMImax was a unique indicator for female patients.ConclusionsBMImax might be an independent predictor of T2DM in females, but it does not seem to be associated with the risk of diabetes in males. BMImax could be regarded as an indicator in the prevention and management of diabetes.

Background and objectiveMild autonomous cortisol secretion (MACS) presents with a marked female preponderance, but whether the sex difference in its distribution has any relevance to the presentation and outcome of the disease is unknown. The aim of this study was therefore to compare biochemical indices of hypercortisolism and impaired glucose metabolism between male and female patients with MACS.MethodWe enrolled a total of 98 patients with autonomous/possible autonomous cortisol secretion in our study, and indices of hypercortisolism and glucose metabolism were collected and compared between the male and female patients. Logistic regression models were used to evaluate the association between sex and cortisol-secretory ability, as well as between the latter and glucose metabolism. In addition, we conducted further stratified analyses according to the degree of autonomous cortisol secretion and menopausal status.ResultsCortisol levels at 00:00 and 08:00 h after a 1-mg dexamethasone suppression test (DST) and low-dose DST were significantly higher in female than in male MACS patients, and the inhibition rate of 1-mg DST was lower in the women than in the men. This significant difference still remained after adjusting for age, BMI, and the course of the disease. Logistic regression analysis revealed a significant association between autonomous cortisol secretion and fasting C-peptide, as well as with the C-peptide-to-glucose ratio in females relative to male patients. In addition, stratified analyses indicated that this association was observed only among women with autonomous cortisol secretion and who were premenopausal.ConclusionThe level of autonomic cortisol secretion in female patients with MACS was higher than in male patients, and the association between autonomous cortisol secretory ability and glucose homeostasis was only noted in patients with autonomous cortisol secretion and in premenopausal women. This phenomenon will, however, require closer follow-up.

Abstract Background Prediabetes has become a pandemic. This study aimed to identify a better predictor for the incidence of prediabetes, which we hypothesize to be the triglyceride-glucose (TyG) index, a simplified insulin resistance index. We compared its predictive value with the other common risk factors of prediabetes. Methods The participants of this analysis were derived from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 4543 participants without initial prediabetes or diabetes were followed up for 3.25 years. Using multivariate logistic regression model, the associations between baseline obesity, lipid profiles and non-insulin-based insulin resistance indices with the incidence of prediabetes were analyzed. To assess which is better predictor for the incidence of prediabetes, the area under curves (AUCs) calculated from the receiver operating characteristic curve analyses were used to evaluate and compare with the predictive value of the different indices. Results During the 3.25 years, 1071 out of the 4543 participants developed prediabetes. Using the logistic regression analysis adjusted for some potential confounders, the risk of incidence of prediabetes increased 1.38 (1.28–1.48) fold for each 1–SD increment of TyG index. The predictive ability (assessed by AUCs) of TyG index for predicting prediabetes was 0.60 (0.58–0.62), which was superior to the indices of obesity, lipid profiles and other non-insulin-based insulin resistance indices. Although the predictive ability of the TyG index was overall similar to fasting plasma glucose (FPG) (P = 0.4340), TyG index trended higher than FPG in females (0.62 (0.59–0.64) vs. 0.59 (0.57–0.61), P = 0.0872) and obese subjects (0.59 (0.57–0.62) vs. 0.57 (0.54–0.59), P = 0.1313). TyG index had superior predictive ability for the prediabetic phenotype with isolated impaired glucose tolerance compared with FPG (P

Long noncoding RNAs (lncRNAs) have been reported to have multiple functions and can be used as markers of various diseases, including diabetes. This study was conducted to determine the lncRNA profile in leukocytes from patients with type 2 diabetes (T2D). Differential expression of lncRNAs in T2D and type 1 diabetes (T1D) was also examined. RNA sequencing was performed in a critically grouped sample of leukocytes from T2D patients and healthy persons. A total of 845 significantly differentially expressed lncRNAs were identified, with 260 downregulated and 585 upregulated lncRNAs in T2D. The analysis of functions of DE-lncRNA and constructed co-expression networks (CNC) showed that 21 lncRNAs and 117 mRNAs harbored more than 10 related genes in CNC. Fourteen of 21 lncRNAs were confirmed to be significantly differentially expressed was detected by qPCR between the T2D and control validation cohorts. We also identified a panel of 4 lncRNAs showing significant differences in expression between T1D and T2D. Collectively, hundreds of novel DE-lncRNAs we identified in leukocytes from T2D patients will aid in epigenetic mechanism studies. Fourteen confirmed DE-lncRNAs can be regarded as diagnostic markers or regulators of T2D, including 4 lncRNAs that chould distinguish T1D and T2D in clinical practice to avoid misdiagnosis.

ObjectivePrimary adrenal lymphoma (PAL) is a rare form of adrenal mass. We summarize our experience in its clinical presentation, biochemical indexes, radiological features, pathological information, therapy regimens, and outcomes.MethodsThis was an institutional review board-approved retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of PAL at the Chinese People’s Liberation Army General Hospital and the First Affiliate Hospital of Xiamen University between July 2007 and July 2017.ResultsTwenty-six patients were identified. The mean age at presentation was 60.84 ± 13.14 years with a male-to-female ratio of 2.25:1 (18:8). The most common presenting symptoms were loss of appetite (65%, 17/26), weight loss (62%, 16/26), abdominal pain (58%, 15/26), and fatigue (58%, 15/26). The levels of lactate dehydrogenase (75%, 15/20), β2-microglobulin (100%, 10/10), C-reactive protein (82%, 14/17), and ferritin (88%, 7/8) and the erythrocyte sedimentation rate (83%, 10/12) were elevated. Bilateral involvement was seen in 21 of 26 patients (81%); 12 of 19 evaluated patients with bilateral lesions (63%) were confirmed to have adrenal insufficiency. On computed tomography (CT), the mean tumor diameter was 7.31 ± 3.35 cm and the median Hounsfield density was 37.0 HU (range: 31.0–45.0 HU); 67% (10/15) and 27% (4/15) of lesions presented with mild and moderate enhancement after injection of contrast medium. 18F-fluorodeoxyglucose positron emission tomography (FDG PET)-CT revealed not only an adrenal tumor but also extra-adrenal lesions. Diffuse large B-cell lymphoma (DLBCL) was the most common phenotype (92%, 24/26). Ninety-two percent (24/26) of patients received chemotherapy while 8% (2/26) received unilateral adrenalectomy plus chemotherapy. The prognosis of PAL was poor, with a general survival time of 7.20 ± 5.18 months.ConclusionPAL is a rare disease. The clinical characteristics of PAL include loss of appetite and weight loss. Endocrine evaluation should be performed to determine whether patients have adrenal insufficiency, especially patients with bilateral lesions. FDG-PET appears to be more accurate than other imaging modalities in revealing extra-adrenal sites. Better therapy is required to improve the poor prognosis of PAL.

Ectopic ACTH syndrome (EAS) accounts for 10–20% of endogenous Cushing’s syndrome (CS). Hardly any cases of adrenal medullary hyperplasia have been reported to ectopically secrete adrenocorticotropic hormone (ACTH). Here we describe a series of three patients with hypercortisolism secondary to ectopic production of ACTH from adrenal medulla. Cushingoid features were absent in case 1 but evident in the other two cases. Marked hypokalemia was found in all three patients, but hyperglycemia and osteoporosis were present only in case 2. All three patients showed significantly elevated serum cortisol and 24-h urinary cortisol levels. The ACTH levels ranged from 19.8 to 103.0pmol/L, favoring ACTH-dependent Cushing’s syndrome. Results of bilateral inferior petrosal sinus sampling (BIPSS) for case 1 and case 3 confirmed ectopic origin of ACTH. The extremely high level of ACTH and failure to suppress cortisol with high dose dexamethasone suppression test (HDDST) suggested EAS for patient 2. However, image studies failed to identify the source of ACTH secretion. Bilateral adrenalectomy was performed for rapid control of hypercortisolism. After surgery, cushingoid features gradually disappeared for case 2 and case 3. Blood pressure, blood glucose and potassium levels returned to normal ranges without medication for case 2. The level of serum potassium also normalized without any supplementation for case 1 and case 3. The ACTH levels of all three patients significantly decreased 3-6 months after surgery. Histopathology revealed bilateral adrenal medullary hyperplasia and immunostaining showed positive ACTH staining located in adrenal medulla cells. In summary, our case series reveals the adrenal medulla to be a site of ectopic ACTH secretion. Adrenal medulla-originated EAS makes the differential diagnosis of ACTH-dependent Cushing’s syndrome much more difficult. Control of the hypercortisolism is mandatory for such patients.

Background. Previous studies have shown that the ratio of triglyceride to high-density lipoprotein cholesterol level (TG/HDL-C) is a risk factor for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the nonlinear relationship between TG/HDL-C and the incidence of T2DM in a Chinese population. Methods. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the incidence of T2DM among 7,791 participants from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) cohort study at baseline. Results. After adjusting for age, sex, body mass index, smoking status, alcohol intake, low-density lipoprotein cholesterol level, strenuous activity, education level, family histories of T2DM and tumors, and the presence of hypertension, tumor, stroke, and coronary heart disease, we showed that TG/HDL-C was positively associated with the incidence of T2DM at the 4-year follow-up (OR=1.49, 95%CI=1.26–1.78). TG/HDL-C and incidence of T2DM showed a nonlinear relationship; the inflection point of TG/HDL-C was 1.50. The ORs (95% CI) on the left and right sides of the inflection point were 2.50 (1.70–3.67) and 0.96 (0.67–1.37), respectively. After adjusting for age, sex, and body mass index (BMI) in the linear relationship, the OR of the incidence of T2DM was 1.60 (95%CI=1.37–1.87). When the TG/HDL-C was less than 1.50 or greater than 1.76, the ORs (95% CI) were 2.41 (1.82–3.18) or 0.81 (0.53–1.25), respectively. Subgroup analysis showed no relationships of T2DM incidence with sex, BMI, family history of T2DM, or TG/HDL-C. Conclusion. TG/HDL-C is positively associated with diabetes risk. In our study, with each increasing quintile, the risk of T2DM after 4 years was 1.60 or 1.49 depending on the variables adjusted. In addition, our cohort study showed a nonlinear relationship between TG/HDL-C and T2DM incidence, with an inflection point of 1.76 or 1.50, depending on the variables adjusted. When the TG/HDL was less than 1.50, the ORs (95% CI) were 2.41 (1.82–3.18) and 2.50 (1.70–3.67). When the TG/HDL-C was greater than 1.76 or 1.50, there was no significant difference in the change in OR.

Objective Autoimmune hypothalamitis (AHT) is a rare inflammatory disorder that involves the hypothalamus. It remains unclear whether autoimmune hypophysitis (AH) and AHT represent different diseases or different aspects of the same disease. Thus, further investigation of AHT is required. Methods A retrospective review of medical and pathological records of AHT patients from the Chinese PLA General Hospital were examined from January 1, 2005 to May 1, 2017. Clinical data, treatments, and outcomes were investigated. Results Five female patients were identified (median age, 42.6 years). Symptoms included central diabetes insipidus, hypopituitarism, hyperprolactinemia, headache, and hypothalamic syndrome. The following hormonal deficits were noted: follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, thyroid stimulating hormone, and growth hormone. One patient underwent high-dose methylprednisolone pulse treatment (HDMPT) and azathioprine plus intensity modulated radiation therapy (IMRT), and two patients underwent HDMPT and two rounds of replacement therapy. During follow-up, one patient died because of non-compliance with therapy and the others were in remission or they recovered. Conclusions AHT had similar MRI results, pathology, and treatment compared with AH. Thus, it may be a subtype of AH, and AHT patients may also show hypothalamic syndrome.

Aims. To investigate the effect of preoperative HbA1c levels on the postoperative outcomes of coronary artery disease surgery in diabetic and nondiabetic patients. Methods and Results. The MEDLINE (via PubMed), Cochrane Library, Web of Science, Embase, Wanfang Data, China National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) databases were used to search the effects of different preoperative HbA1c levels on the postoperative outcomes of coronary artery disease surgical treatment in diabetic and nondiabetic patients from inception to December 2018. Two review authors worked in an independent and duplicate manner to select eligible studies, extract data, and assess the risk of bias of the included studies. We used a meta-analysis to synthesize data and analyze subgroups, sensitivity, and publication bias as well as the GRADE methodology if appropriate. The literature search retrieved 886 records initially, and 23 cohort studies were included in the meta-analysis. In this meta-analysis, we found that there was a reduced incidence of surgical site infections (OR=2.94, 95% CI 2.18-3.98), renal failure events (OR=1.63, 95% CI 1.13-2.33), and myocardial infarction events (OR=1.69, 95% CI 1.16-2.47), as well as a shortened hospital stay (MD=1.08, 95% CI 0.46-1.71), in diabetic patients after coronary artery disease surgical treatment with lower preoperative HbA1c levels. For nondiabetic patients, a higher preoperative HbA1c level resulted in an increase in the incidence of mortality (OR=2.23, 95% CI 1.01-4.90) and renal failure (OR=2.33, 95% CI 1.32-4.12). No significant difference was found between higher and lower preoperative HbA1c levels in the incidence of mortality (OR=1.06, 95% CI 0.88-1.26), stroke (OR=1.49, 95% CI 0.94-2.37), or atrial fibrillation (OR=0.94, 95% CI 0.67-1.33); the length of ICU stay (MD=0.20, 95% CI -0.14-0.55); or sepsis incidence (OR=2.49, 95% CI 0.99-6.25) for diabetic patients or for myocardial infarction events (OR=1.32, 95% CI 0.27-6.31) or atrial fibrillation events (OR=0.99, 95% CI 0.74-1.33) for nondiabetic patients. The certainty of evidence was judged to be moderate or low. Conclusion. This meta-analysis showed that higher preoperative HbA1c levels may potentially increase the risk of surgical site infections, renal failure, and myocardial infarction and reduce the length of hospital stay in diabetic subjects after coronary artery disease surgical treatment and increase the risk of mortality and renal failure in nondiabetic patients. However, there was great inconsistency in defining higher preoperative HbA1c levels in the studies included; we still need high-quality RCTs with a sufficiently large sample size to further investigate this issue in the future. This trial is registered with CRD42019121531.

Long noncoding RNAs (lncRNAs) regulate gene expression at different levels in various diseases, including type 1 diabetes (T1D). However, the expression of circulating lncRNAs in leukocytes in T1D has not been well documented. To identify differentially expressed lncRNAs between T1D patients and healthy controls, RNA sequencing was performed on samples of leukocytes collected from both healthy persons and T1D patients. The categories, enriched pathways, coexpression networks, and the characteristics of novel lncRNAs were analyzed to provide an extensive profile. qPCR was adopted to validate the differential expression of lncRNAs in the validation cohort. A total of 14,930 lncRNAs and 16,063 mRNAs were identified in the peripheral blood leukocyte of T1D patients. After optimization using an adjusted p value (threshold of

Background. Functional pancreatic neuroendocrine neoplasms (PanNENs) are very rare disorders but have complex spectrum, including insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma. Patients with PanNENs usually present with characteristic symptoms caused by corresponding hormone hypersecretion. It has always been challenging in dealing with such rare but complicated disorders. In this report, we analyzed the clinical characteristics of functional PanNENs in a large cohort of Chinese patients and summarized our clinical experience in diagnosis and treatment. Methods. The retrospective analysis was performed in patients with a definite diagnosis of functional PanNENs hospitalized in Chinese PLA General Hospital between 2000 and 2020. The clinical characteristics, surgical information, and pathological findings were extracted from their medical records and were analyzed. Results. Totally, 286 patients (gender: male 103 and female 183; age: 45.55 ± 15.23 years old) were diagnosed with definite functional PanNENs. The most frequent functional PanNENs were insulinoma (266/286) followed by glucagonoma (10/286), somatostatinoma (3/286), adrenocorticotropic hormone- (ACTH-) producing tumor (3/286), gastrinoma (2/286), and VIPoma (2/286). Nine patients were diagnosed with multiple endocrine neoplasia type 1 (MEN1) in which all the associated functional PanNENs were insulinomas. The duration from symptoms’ onset to confirmed diagnosis was 3.67 ± 4.28 years. Two hundred and eighty patients with tumor localized in pancreatic or with limited metastasis underwent surgery. The symptoms associated with hormonal oversecretion were improved significantly after surgery. Five patients with unresectable metastases or tumor recurrence after surgery were administrated with systemic chemotherapy or other targeted therapies. With these various therapies, the symptoms were also partially relieved. According to findings in pathological and immunochemical examination, all the functional PanNENs were categorized into NEN-G1 (41.95%), NEN-G2 (54.90%), NEN-G3 (3.15%), and NEC-G3 (0%). Conclusion. Patients with suspected functional PanNENs should have a systematic endocrine examination at diagnosis. Multidisciplinary collaborations are essential for precise diagnosis and tumor localization. A successful surgery or other targeted therapies can improve the prognosis of patients with such rare but complex disorders.

Background/Aims: Chronic inflammation contributes to the development of type 2 diabetes mellitus by targeting the insulin receptor substrate protein-1 (IRS-1) signaling pathway. Previous studies showed that Leukemia related protein 16 (LRP16) reduced insulin stimulated glucose uptake in adipocytes by impairing the IRS-1 signaling pathway. We explored the mechanism by which LRP16 promotes the inflammatory response. Methods: We screened LRP16 induced proteins in the lipopolysaccharide (LPS)-stimulated inflammatory response using liquid chromatography-mass spectrometry (LC-MS) and analyzed the potential biological functions of these proteins using online bioinformatics tools. mRNA expression and protein expression of target genes were measured by real time PCR and Western blot, respectively. Results: A total of 390 differentially expressed proteins were identified. The mitogen-activated protein kinase (MAPK) signaling pathway was the primary activated pathway in LRP16-expressing cells. Overexpression of LRP16 activated ERK1/2 and Rac1, which are two key players related to the MAPK signaling pathway. Furthermore, knock down of endogenous LRP16 by RNA interference (RNAi) reduced Rac1 expression, ERK activation, and inflammatory cytokine expression in human adipocytes stimulated by LPS. The stimulatory effect of LRP16 was diminished by suppressing Rac1 expression and treating the cells with the ERK specific inhibitor, PD98059. Conclusion: These findings revealed the functions of LRP16 in promoting the inflammatory response through activating the Rac1-MAPK1/ERK pathway in human adipocytes.

Objective: To investigate the role of PSMA in the differential diagnosis of adrenocortical carcinoma samples (ACCs) and adrenocortical adenoma samples (ACAs), to validate the prognostic role of PSMA in patients with ACCs, and to explore the possibility that this marker can differentiate localized ACCs from adrenal metastases from other sites.Methods: PSMA protein expression in tissue samples from 50 ACCs, 90 ACAs (including 20 from patients who presented with Cushing's syndrome, 20 aldosterone-producing adenomas and 50 non-functional tumors) and 10 tissues that were metastases from other primary sites was assessed by immunohistochemistry. The clinical and pathological characteristics were compared, the intensity and density were analyzed, and the prognostic role was evaluated.Results: The analysis of clinical and pathological features revealed that the size of ACCs was greater than that of benign tissues and the ACC patients were older than the ACA patients (p < 0.01). The percentage of PSMA-positive vessels, the mean intensity and the degree of staining density were found to be significantly lower in ACAs than in ACCs (p < 0.01). In these 140 samples, 60% of the ACCs were grouped in the positive category. The samples were negative for metastases that were from other primary sites. The ENSAT stage and Ki-67 were correlated with PSMA expression. The survival distribution revealed that high PSMA expression did not show any prognostic relevance in the current ACCs series. Those samples with a score of > 3.5 were 75 times more likely to be malignant (OR = 75). We established a cut-off score of 3.5 (p < 0.05), which had 46% sensitivity and 99% specificity. Paralleling PSMA and Ki-67 maximized the area under the curve, with 72% sensitivity and 100% specificity.Conclusions: Our results strongly confirm that PSMA is helpful for distinguishing benign from malignant tumors and that its high expression levels correlate with a high ENSAT stage and high proliferation. The combination of PSMA and Ki-67 can be particularly useful. Furthermore, PSMA might be a useful tool for the identification of localized adrenal carcinoma and metastatic carcinoma.

Background: Basal and premixed insulin have been widely used for insulin therapy of type 2 diabetes mellitus (T2DM) in China. The aim of this study is to compare the sustained efficacy of basal and premixed insulin therapies in T2DM outpatients with insulin monotherapy.Materials and Methods: The survey was conducted in 602 hospitals across China from April to June in 2013. The participants included outpatients who were receiving basal or premixed insulin monotherapy for more than 3 months, and the outcome was attaining a glycated hemoglobin A1C (HbA1c) of

Craniopharyngiomas and germinomas are both rare cranial tumors that most commonly present during childhood or adolescence. Although these tumors have different origins, their clinical and radiological features may be similar. In this article, we report the case of a 35-year female patient with clinical and radiological findings and increased human chorionic gonadotrophin (HCG) levels in the cerebrospinal fluid (CSF) that were consistent with a germinoma. However, pathological analysis revealed a craniopharyngioma. This case report indicates that HCG, which is regarded as a specific tumor marker for germinomas in the differential diagnosis of intracranial lesions, is also detectable in other kinds of suprasellar tumors, such as craniopharyngiomas.

Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients’ diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI.

Background: Waist circumference has been correlated with the risk of hyperuricemia. Whether neck circumference is also associated with hyperuricemia has not been assessed. This study aimed to investigate whether neck circumference is associated with hyperuricemia.Methods: This study population from Beijing is part of the larger China-wide Risk Evaluation of Cancers in Chinese Diabetic Individuals: a lONgitudinal (REACTION) study. For this Beijing sub-center cross-sectional study, a total of 8971 subjects were recruited. Gender-specific multivariable-adjusted regression analyses were conducted to analyze the association of neck circumference and waist circumference with hyperuricemia and the association of neck circumference with serum uric acid levels in the non-hyperuricemia population.Results: After adjusting for confounding variables, regression analyses showed that neck circumference was positively associated with hyperuricemia [OR, 2.61 (1.86–3.67) for males and 3.27 (2.53–4.22) for females] in both genders; further, neck circumference was also positively associated with serum uric acid levels in non-hyperuricemia subjects [b, 2.58 (1.76–3.39) for males and 4.27 (3.70–4.84) for females] in both genders. Additionally, we demonstrated that neck circumference was similar to waist circumference in terms of the strength of association (OR, 3.03 for waist circumference vs. 2.61 for neck circumference in males, and 3.50 vs. 3.27 for females) with hyperuricemia and the ability to predict hyperuricemia (AUC, 0.63 for waist circumference vs. 0.61 for neck circumference in males, and 0.66 vs. 0.66 in females).Conclusion: Neck circumference is positively and independently associated with hyperuricemia in both genders and is also associated with serum uric acid levels in the non-hyperuricemia population.

Aim. To investigate the clinical and endocrinological characteristics of patients with adrenal incidentaloma (AI). Materials and Methods. This retrospective study enrolled 1941 AI patients hospitalized at the Department of Endocrinology, Chinese PLA General Hospital, Beijing, China, between January 1997 and December 2016. The patient gender, age at visits, imaging features, functional status, and histological results were analyzed. Results. Of the 1941 patients, 984 (50.70%) were men. The median age was 52 years (interquartile range: 44–69 years). 140 cases had bilateral AI. Endocrine evaluation showed that 1411 (72.69%) patients had nonfunctional tumor, 152 (7.83%) had subclinical Cushing syndrome (SCS), and 82 (4.33%) had primary hyperaldosteronism. A total of 925 patients underwent operation for removal of 496 cortical adenomas (53.62%), 15 adrenal cortical carcinomas (1.62%), and 172 pheochromocytomas (18.59%). The bilateral group had a higher proportion of SCS (18.57% versus 7.10%, P

OBJECTIVES: To explore the relationship between depressive symptoms and waist-to-hip ratio, dyslipidemia, glycemic levels or blood pressure among diabetic and non-diabetic Chinese women. METHODS: 11,908 women aged ≥40 years were enrolled in this cross-sectional study, including 2,511 with type 2 diabetes and 9,397 without. Depressive symptoms (defined as having mild-to-severe depressive symptoms) were assessed by the Patient Health Questionnaire-9 (PHQ-9) diagnostic algorithm. The prevalence and the odds ratios (ORs) with 95% confidence intervals (CIs) for having depressive symptoms were estimated using logistic regression analysis. RESULTS: The age-adjusted prevalence of depressive symptoms was significantly higher in non-diabetic subjects with waist-to-hip ratio (WHR) ≥0.9 (8.6%, age-adjusted OR 1.51 [95% CI 1.17, 1.95]), total cholesterol (TC)>6.22 mmol/L (8.8%, 1.58 [1.16, 2.15]), and Hemoglobin A1c (HbA1c) ≥6.00 mmol/L (7.7%, 1.69 [1.34, 2.14]), while it was significantly lower in non-diabetic subjects with diastolic blood pressure (DBP) between 80 to 89 mmHg (6.2%, 0.78 [0.64, 0.95]). These relationships remained significant even after controlling for multiple factors (WHR ≥0.9: multivariable-adjusted OR 1.39 [95% CI 1.07, 1.80]; TC>6.22 mmol/L: 1.56 [1.14, 2.12]; HbA1c ≥6.00 mmol/L: 1.64 [1.30, 2.08]; DBP 80-89 mmHg: 0.78 [0.64, 0.95]). However, no significant trend between depressive symptoms and WHC, TC, HbA1c, DBP was observed in diabetic women, and no significant trend relationship between depressive symptoms and BMI, WC, TG, or SBP was observed in both non-diabetic and diabetic women. Moreover, the prevalence of depressive symptoms was significantly higher in previously-diagnosed diabetes, compared with non-diabetic subjects, while no significant differences were observed between newly-diagnosed diabetes and non-diabetic subjects. CONCLUSION: The present study showed a relationship between WHR, TC, HbA1c, DBP and depressive symptoms among non-diabetic women, while no significant relationship between them was observed among diabetic women, even after controlling for multiple confounding factors.

OBJECTIVE: Pituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Due to the rarity of PSIS, clinical data are limited, especially in Chinese people. Herein, we analyzed the clinical characteristics of patients diagnosed with PSIS from our center over 10 years. PATIENTS AND METHODS: We retrospectively analyzed the clinical manifestations and laboratory and MRI findings in 55 patients with PSIS. RESULTS: Of the 55 patients with PSIS, 48 (87.3%) were male. The average age was 19.7±6.7 years and there was no familial case. A history of breech delivery was documented in 40 of 45 patients (88.9%) and 19 of 55 patients (34.5%) had a history of dystocia. Short stature was found in 47 of 55 patients (85.5%) and bone age delayed 7.26±5.37 years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone, gonadotropins, corticotropin, and thyrotropin were 100%, 95.8%, 81.8%, 76.3%, respectively. Hyperprolactinemia was found in 36.4% of patients. Three or more pituitary hormone deficiencies were found in 92.7% of the patients. All patients had normal posterior pituitary function and absent pituitary stalk on imaging. The average height of anterior pituitary was 28 mm, documented anterior pituitary hypoplasia. Midline abnormalities were presented in 9.1% of patients. CONCLUSIONS: The clinical features of our Chinese PSIS patients seem to be different from other reported patients in regarding to the higher degree of hypopituitarism and lower prevalence of midline defects. In addition, our patients were older at the time of case detection and the bone age was markedly delayed. We also had no cases of familial PSIS.