Methodologies and key considerations for implementing the International Classification of Diseases-11th revision morbidity coding: insights from a national pilot study in China.

OBJECTIVE: The aim of this study was to disseminate insights from a nationwide pilot of the International Classification of Diseases-11th revision (ICD-11). MATERIALS AND METHODS: The strategies and methodologies employed to implement the ICD-11 morbidity coding in 59 hospitals in China are described. The key considerations for the ICD-11 implementation were summarized based on feedback obtained from the pilot hospitals. Coding accuracy and Krippendorff's alpha reliability were computed based on the coding results in the ICD-11 exam. RESULTS: Among the 59 pilot hospitals, 58 integrated ICD-11 Coding Software into their health information management systems and 56 implemented the ICD-11 in morbidity coding, resulting in 3 723 959 diagnoses for 873 425 patients being coded over a 2-month pilot coding phase. The key considerations in the transition to the ICD-11 in morbidity coding encompassed the enrichment of ICD-11 content, refinement of tools, provision of systematic and tailored training, improvement of clinical documentation, promotion of downstream data utilization, and the establishment of a national process and mechanism for implementation. The overall coding accuracy was 82.9% when considering the entire coding field (including postcoordination) and 92.2% when only one stem code was considered. Krippendorff's alpha was 0.792 (95% CI, 0.788-0.796) and 0.799 (95% CI, 0.795-0.803) with and without consideration of the code sequence, respectively. CONCLUSION: This nationwide pilot study has enhanced national technical readiness for the ICD-11 implementation in morbidity, elucidating key factors warranting careful consideration in future endeavors. The good accuracy and intercoder reliability of the ICD-11 coding achieved following a brief training program underscore the potential for the ICD-11 to reduce training costs and provide high-quality health data. Experiences and lessons learned from this study have contributed to WHO's work on the ICD-11 and can inform other countries when formulating their transition plan.

The potential value of ultrasound in predicting local refractory/relapse events in primary thyroid lymphoma patients.

BACKGROUND: Primary thyroid lymphoma (PTL) is a rare malignant disorder, and ultrasound plays an important role in PTL diagnosis and follow-up surveillance. Prediction of refractory/relapse events in PTL patients is an essential issue, yet no ultrasonic PTL features have been discovered to be related to refractory/local relapse events. METHODS: From January 2008 to September 2022, newly diagnosed PTL patients in our center who underwent standard first-line treatment and received an ultrasound examination before treatment were enrolled. Data regarding patients' clinical and sonographic features, as well as their therapeutic responses were collected. Subjects with an ideal prognosis were compared to those with refractory/relapse events. RESULTS: In total, 37 PTL patients were analyzed, including 26 with diffuse large B-cell lymphoma, 2 with follicular lymphoma and 9 with mucosa-associated lymphoid tissue lymphoma. During the median follow-up of 25 months, 30 patients obtained a complete response, 4 were refractory patients, and 3 experienced local relapse. No significant difference was detected in the baseline clinical characteristics between patients with an ideal prognosis and those with refractory/local relapse events. In terms of sonographic features, however, an event-free survival (EFS) curve comparison revealed that patients with bilobar enlargement (defined as an anterior-posterior diameter > 2.5 cm on both sides of thyroid lobes) had a poorer EFS than those without (P < 0.0001), and patients with diffuse type had a poorer EFS than those with mixed/nodular types (P = 0.043). No significant difference was observed in EFS between patients with or without signs of suspicious cervical lymph node metastasis, rich blood signal distribution or symptoms of trachea compression. CONCLUSIONS: PTL patients with an anterior-posterior diameter > 2.5 cm for both thyroid lobes or PTL patients of the diffuse ultrasound type could be prone to refractory/local relapse events.

Impaired Sensitivity to Thyroid Hormones Is Associated With Decreased Vitamin D Levels in the Euthyroid Population.

CONTEXT: The relationship between vitamin D and thyroid profiles lacks consensus despite extensive investigations. Whether vitamin D levels correlate with thyroid hormone sensitivity remains largely unexplored. OBJECTIVE: To explore the relationship between vitamin D levels and thyroid hormone sensitivity among euthyroid individuals. METHODS: This study involved 6452 euthyroid participants. Clinical parameters, including TSH, free thyroxine, 25-hydroxyvitamin D [25(OH)D], and other relevant indicators were extracted from the National Health and Nutrition Examination Survey 2007-2012. To quantify thyroid hormone sensitivity, we calculated the Thyroid Feedback Quantile-based Index (TFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI). RESULTS: Subjects with impaired thyroid hormone sensitivity have decreased 25(OH)D levels (TFQI, TT4RI: P < 0.05; TSHI: P = .05574) following adjustment of confounding variables. Age-specific analysis found negative correlations between thyroid hormone sensitivity indices and 25(OH)D within the 20 to 60 years subgroup, turning positive in the 60 to 80 years subgroup. In females, thyroid hormone sensitivity indices and vitamin D levels were negatively linked, while in males, vitamin D's relationships with TFQI, TT4RI, and TSHI shifted from negative to positive when 25(OH)D levels exceeded 63.5 nmol/L, 56.7 nmol/L, and 56.7 nmol/L, respectively. Stratification by race revealed U-shaped curvilinear patterns resembling those found in the males. In body mass index (BMI) subanalysis, vitamin D had differing associations with thyroid hormone sensitivity indices: negative in the <25 kg/m2 and ≥30 kg/m2 subgroups and U-shaped in the 25-30 kg/m2 subgroup. CONCLUSION: Impaired thyroid hormone sensitivity correlates with decreased vitamin D levels among euthyroid subjects, with associations varying by age, sex, race, and BMI.

Familial dysalbuminemic hyperthyroxinemia combined with Graves' disease: a rare case report.

BACKGROUND: Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disease characterised by an abnormally increased affinity of albumin for serum thyroxine. Assay interference and differential diagnosis remain challenging for FDH. The condition is more complicated when FDH is combined with primary thyroid diseases. Co-occurrence of FDH and Graves' disease is rare. CASE PRESENTATION: We report the case of a 28-year-old woman with complex FDH and coexisting Graves' disease. Initially, the existence of FDH was not recognised. Graves' disease was relieved after treatment with antithyroid drugs and two administrations of radioactive iodine therapy. She subsequently developed primary hypothyroidism and was prescribed levothyroxine replacement. However, thyroid function failed to normalise despite frequent levothyroxine dose adjustments. Ultimately, syndromes involving the inappropriate secretion of thyroid-stimulating hormone (IST) were considered, and FDH was successfully differentiated from other causes of IST. CONCLUSIONS: A greater focus on FDH when investigating the causes of IST is critical to correctly evaluate thyroid function status and avoid inappropriate treatment, especially in complicated cases with concurrent FDH and primary thyroid diseases.

A Scientometric Analysis and Visualization of Scientific Research and Technology Innovation in Needle-free Insulin Injection From 1974 to 2022.

PURPOSE: Needle-free jet injection has to some extent improved the quality of life of patients with diabetes, but it has not been widely used. Therefore, we analyzed articles, clinical trials, and patents of needle-free insulin injection to (1) perform a systematic and comprehensive analysis of scientific research and technology innovation in needle-free insulin injection during the past 49 years (1974 to 2022) and (2) identify the status of scientific research and technology innovation, their limitations, and future trends. METHODS: With a new perspective, we use scientometric tools, including co-word and word frequency analyses, text mining, and cluster network analysis, to provide a scientometric analysis and visualization of articles, clinical trials, and patents related to needle-free insulin injection delivery applications. FINDINGS: Patent innovation in this field was more active than clinical research, and clinical research prevailed over basic research. Basic research and clinical trials in this field mainly involved therapy, penetration, tolerability, absorption, and pharmacokinetic properties. Drive mechanisms and needle-free injection devices were the core patent technologies in this field. IMPLICATIONS: Although needle-free insulin injection has been under development for decades, its full potential has not yet been reached; needle-free injection technology is still in the growth stage. The field of needleless insulin injection is dominated by patent technology innovation.

Using preoperative ultrasound vascularity characteristics to estimate medullary thyroid cancer.

BACKGROUND: The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. METHODS: Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as "ultrasound-high suspicious" (h-MTC) and "ultrasound-low suspicious" (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. RESULTS: We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P < 0.001). We also showed that more CHAMMAS IV patterns (central blood flow greater than perinodular flow) (87.1% vs. 32.3%, P < 0.001)) and CHEN IV patterns (penetrating vascularity) (100% vs. 25.8%, P < 0.001) were found in l-MTC than benign nodules. CONCLUSIONS: Vascularity features can help differentiate l-MTC from benign nodules; moreover, we report a novel sonographic vascularity pattern of l-MTC disease, penetrating branching vascularity. The utilization of vascularity features will help to identify MTC among nodules with low-intermediate suspicion by ultrasound risk classification to ensure appropriate clinical management.

Extracellular volume fraction of the pancreas predicts glucose intolerance in patients undergoing major pancreatic surgeries.

PURPOSE: Pancreatic T1 value and extracellular volume fraction (ECV) are potential imaging biomarkers for pancreatic exocrine and endocrine function. This study aims to evaluate the ability of native T1 value and ECV of the pancreas in predicting postoperative new-onset diabetes (NODM) and worsened glucose tolerance in patients undergoing major pancreatic surgeries. METHODS: This retrospective study involved 73 patients who underwent 3 T pancreatic MRI with pre- and postcontrast T1 mapping before major pancreatic surgeries. Patients were divided into non-diabetic, pre-diabetic and diabetic groups based on their glycated hemoglobin (HbA1c) value. Preoperative native T1 value and ECV of the pancreas were compared among the three groups. The correlation of pancreatic T1 value and ECV with HbA1c was assessed by linear regression analysis, and the ability of pancreatic T1 value and ECV for predicting postoperative NODM and worsened glucose tolerance was assessed using Cox Proportional hazards regression analysis. RESULTS: Native pancreatic T1 value and ECV were both significantly higher in diabetic patients compared to pre-diabetic/non-diabetic patients, and ECV was also significantly higher in pre-diabetic patients compared to non-diabetic patients (all p < 0.05). Both native pancreatic T1 value and ECV showed positive correlation with preoperative HbA1c value (r = 0.50 and 0.55, respectively, both p < 0.001). ECV > 30.7% was the only independent predictor for NODM (HR = 5.687, 95% CI: 1.557, 13.468, p = 0.012) and worsened glucose tolerance (HR = 6.783, 95% CI:, 1.753, 15.842, p = 0.010) after surgery. CONCLUSIONS: Pancreatic ECV predicts the risk of postoperative NODM and worsened glucose tolerance in patients undergoing major pancreatic surgeries.

Thyroid dysfunction after immune checkpoint inhibitor treatment in a single-center Chinese cohort: a retrospective study.

BACKGROUND: Thyroid dysfunction is a common adverse event after immune checkpoint inhibitor (ICI) therapy. The clinical manifestations of thyroid immune-related adverse events (irAEs) are variable and the underlying mechanisms remain unclear. PURPOSE: To identify the clinical and biochemical characteristics of Chinese patients with ICI-related thyroid dysfunction. METHODS: We retrospectively reviewed patients with carcinoma who received ICI therapy and underwent evaluation of thyroid function during hospitalization at Peking Union Medical College Hospital between January 1, 2017 and December 31, 2020. Clinical and biochemical features were analyzed in patients who developed ICI-related thyroid dysfunction. Survival analyses were performed to determine the effect of thyroid autoantibodies on thyroid abnormalities and the impact of thyroid irAEs on clinical outcomes. RESULTS: The cohort included 270 patients with a median follow-up of 17.7 months; 120 (44%) of these patients developed thyroid dysfunction on immunotherapy. The most common thyroid irAE was overt hypothyroidism (with/without transient thyrotoxicosis), which occurred in 38% of patients (n = 45), followed by subclinical thyrotoxicosis (n = 42), subclinical hypothyroidism (n = 27), and isolated overt thyrotoxicosis (n = 6). The median time to first clinical presentation was 49 days (interquartile range 23, 93) for thyrotoxicosis and 98 days (interquartile range 51, 172) for hypothyroidism. In patients treated with PD-1 inhibitors, hypothyroidism was strongly associated with younger age (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.67; P < 0.001), previous thyroid disease (OR 4.30, 95% CI 1.54-11.99; P = 0.005), and a higher baseline thyroid-stimulating hormone level (OR 2.76, 95% CI 1.80-4.23; P < 0.001). Thyrotoxicosis was only associated with the baseline thyroid-stimulating hormone (TSH) level (OR 0.59, 95% CI 0.37-0.94; P = 0.025). Thyroid dysfunction after initiation of ICI therapy was associated with better progression-free survival (hazard ratio [HR] 0.61, 95% CI 0.44-0.86; P = 0.005) and overall survival (hazard ratio 0.67, 95% CI 0.45-0.99; P = 0.046). Anti-thyroglobulin antibody positivity increased the risk of thyroid irAEs. CONCLUSIONS: The occurrence of thyroid irAEs with diverse phenotypes is common. Distinct clinical and biochemical characteristics suggest heterogeneity among different subgroups of thyroid dysfunction, which requires further research to explore the under mechanism.

Association between Air Pollution and Type 2 Diabetes Mellitus in Developing Countries: A Systematic Review and Meta-Analysis.

Objective In recent years, many studies have reported that air pollution is a risk factor for type 2 diabetes mellitus (T2DM). The aim of this systematic review and meta-analysis is to summarize the evidence about the association between exposure to air pollution and T2DM in developing countries. Methods The databases, including PubMed, EMBASE and Web of Science, were systematically searched for studies published up to 31 March 2022. Studies about the association between air pollution and T2DM prevalence or incidence in developing countries were included. The odds ratio (OR) was used as effect estimate. We synthesized the included studies in the meta-analysis. Results We included 8 cross-sectional studies and 8 cohort studies, all conducted in developing countries. Meta-analysis of 8 studies on PM2.5 (particulate matter ≤ 2.5 µm in diameter) showed that T2DM prevalence was significantly associated with PM2.5 exposure (OR=1.12; 95% CI: 1.07, 1.17; P<0.001). The association between air pollutants and T2DM incidence was not estimated due to the limited relevant studies. Conclusions The exposure to PM2.5 would be positively associated with an increased prevalence of T2DM in developing countries. Some effective measures should be taken to reduce air pollutant exposure in people who are vulnerable to diabetes.

Non-islet cell tumor hypoglycemia concurrent with acromegalic features: A case report and literature review.

Background: Non-islet cell tumor hypoglycemia (NICTH) is a rare cause of hypoglycemia due to the overproduction of high molecular weight insulin-like growth factor (big-IGF2), which activates the insulin receptor and subsequently caused hypoglycemia. But NICTH with acromegaly had rarely been reported. We firstly reported a rare case of NICTH concurrent with acromegalic facial features induced by a retroperitoneal hemangiopericytoma and reviewed similar cases in the literature. Case presentation: A 30-year old man was admitted to hospital because of recurrent unconscious, which usually occurred in the late afternoon or early morning before supper or breakfast. On one unconscious occasion, his blood glucose was 2.4 mmol/L. His consciousness recovered rapidly with intravenous 50% glucose administration. Physical examination showed that he had coarse oily facial features with acne, prominent forehead and brow, broad nose, prominent nasolabial folds. At the time of hypoglycemia, suppressed serum insulin, GH and IGF-1 levels was found. Computed Tomography further revealed a large left retroperitoneal mass measuring 7.0 cm × 12.3 cm × 13.0 cm. He underwent complete surgical resection of the mass. Surgical pathology demonstrated a hemangiopericytoma and strong positive for IGF-2. He did not experience further episodes of hypoglycemia after the operation during the 2.5 years follow-up. Conclusions: Fibrous origin is the most common tumor type for NICTH with acromegaly features. NICTH should be considered in non-diabetic patients who have recurrent hypoglycemia along with suppressed serum insulin and IGF-1 levels.

Analysis of thyroid involvement in children and adult Langerhans cell histiocytosis: An underestimated endocrine manifestation.

Background: Langerhans cell histiocytosis (LCH) is a rare disease caused by the clonal expansion of CD1a+/CD207+ LCH cells. The thyroid involvement in LCH has mostly been described in case reports. Methods: We retrospectively evaluated the clinical characteristics, diagnosis, and treatment of 27 children and adult patients with thyroid LCH in our center between 2010 and 2021. Results: The incidence of thyroid LCH was 14.00% (7/50) in children and 10.10% (20/198) in adults, respectively. Among patients with thyroid involvement, 81.5% presented with diabetes insipidus (DI) as the first symptom, and 51.9% complained of neck swelling or mass. Children and adults with thyroid LCH had higher frequencies of the hypothalamic-pituitary axis (HPA) (children: 100% vs. 62.8%, P=0.05; adult: 95% vs. 42.1%, P<0.001), the lung (children: 85.7% vs. 25.6%, P=0.004; adult: 70% vs. 50.6%, P=0.099), and a lower frequency of bone (children: 14.3% vs. 55.8%, P=0.049; adult: 45% vs. 73.6%, P=0.008) involvement than patients without thyroid involvement. Patients with thyroid LCH had a higher frequency of primary hypothyroidism and a lower frequency of euthyroidism than patients without it. The two major types of ultrasound imaging were diffuse (55%) and nodular type (45%). The standardized uptake value of thyroid on 18-F-fluorodeoxyglucose positron emission tomography/computed tomography was 5.3-12.8. The diagnoses were confirmed using thyroid aspiration (54.5%) or surgery (45.5%). In addition, thyroid LCH combined with papillary thyroid carcinoma was not rare (2/27). Conclusion: Thyroid involvement in LCH is not rare. Furthermore, identifying thyroid involvement can facilitate the pathological diagnosis of LCH. Therefore, the possibility of thyroid LCH should be fully investigated in patients with DI, primary hypothyroidism, abnormal thyroid ultrasound results, and multi-system disease. In addition, thyroid aspiration can confirm suspected thyroid LCH. Finally, special attention should be paid to evaluating HPA and pulmonary involvement in thyroid LCH.

Design of Diselenide-Bridged Hyaluronic Acid Nano-antioxidant for Efficient ROS Scavenging to Relieve Colitis.

Overproduction of reactive oxygen species (ROS), a key characteristic of inflammatory bowel disease (IBD), is responsible for dysregulation of signal transduction, inflammatory response, and DNA damage, which ultimately leads to disease progression and deterioration. Thus, ROS scavenging has become a promising strategy to navigate IBD. Inspired by the targeting capability of hyaluronic acid (HA) to CD44-overexpressed inflammatory cells together with the redox regulation capacity of diselenide compounds, we developed an oral nanoformulation, i.e., diselenide-bridged hyaluronic acid nanogel (SeNG), with a view to treat colitis through a ROS scavenging mechanism. Our data demonstrated that SeNG specifically accumulated in colitis tissue that was mediated by highly efficient CD44-HA interaction. This has allowed us to demonstrate a significant anti-inflammatory effect in an acute colitis mouse model induced by dextran sulfate sodium and trinitrobenzenesulfonic acid. Mechanistically, we continued to show SeNG reduced the ROS level via both direct elimination and up-regulation of the Nrf2/HO-1 signal pathway. Collectively, our work provides proof-of-principle evidence for a SeNG-mediated nano-antioxidant strategy, by which colitis could be effectively managed.

Identification of core genes associated with type 2 diabetes mellitus and gastric cancer by bioinformatics analysis.

Background: Gastric cancer (GC) is the most common type of malignant neoplasm of the digestive system. Diabetes mellitus (DM) or hyperglycemia may increase the incidence or mortality of GC. We aimed to investigate the possible genetic relationship between GC, DM, and type 2 diabetes mellitus (T2DM), and to identify core genes that are associated with T2DM and GC. Methods: The GeneCards database was used to screen DM-, T2DM-, and GC-related genes, and a protein-protein interaction (PPI) network of the genes/proteins associated with overlapping genes between DM, T2DM, and GC was constructed. Molecular Complex Detection (MCODE) was used to identify the significant module. CytoHubba (U.S. National Institute of General Medical Sciences) was utilized to detect hub genes in the PPI. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) resources were used to analyze selected module genes, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment of PPI networks. The Kaplan-Meier plotter database, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN and western blot were used to identify the prognostic value of hub genes and their expression in GC and normal tissue. Results: One thousand one hundred and fifty-two DM-related genes, 466 GC-related genes, and 531 T2DM-related genes were obtained. Subsequently, 401 genes/proteins associated with 59 overlapping genes were screened. Two significant modules, which had higher scores, and 10 hub genes were chosen. Finally, caspase 3 (CASP3), and tumor protein P53 (TP53) were identified as core genes. Conclusions: We identified two genes that may play key roles in T2DM and GC: CASP3, TP53. Our study will contribute to further understanding the possible mechanism of diabetes progression to GC and provide useful information to identify new biomarkers for GC, and provided theoretical basis for the prevention of the occurrence and development of GC.

25-hydroxyvitamin D levels are inversely related to metabolic syndrome risk profile in northern Chinese subjects without vitamin D supplementation.

BACKGROUND: The comparatively low 25 hydroxyvitamin D [25(OH)D] levels have been reported in patients with metabolic syndrome (MetS). Herein we investigated the cross-sectional and longitudinal relationships between serum 25(OH)D levels and MetS risk profile in northern middle-aged Chinese subjects without vitamin D supplementation. METHODS: A cohort of 211 participants including 151 MetS patients and 60 controls at 20-69 years of age were enrolled from suburban Beijing, China. The recruited MetS patients were subjected to diet and exercise counselling for 1-year. All subjects at baseline and MetS patients after intervention underwent clinical evaluations. RESULTS: Serum 25(OH)D levels were significantly decreased in MetS patients. 25(OH)D levels were inversely related to MetS score, fasting blood glucose (FBG) and triglyceride-glucose index (TyG) after adjusting for cofounders (all P < 0.05). Participants in the lowest tertile of 25(OH)D levels had increased odds for MetS (P = 0.045), elevated FBG (P = 0.004) in all subjects, and one MetS score gain in MetS patients (P = 0.005). Longitudinally, the metabolic statuses as well as 25(OH)D levels of MetS patients were significantly improved (all P < 0.05), and the increase of 25(OH)D levels were inversely related to MetS scores, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), FBG, and TyG, while positively related to high-density lipoprotein cholesterol (HDL-C) after adjusting for confounders. CONCLUSIONS: 25(OH)D levels were significantly decreased in MetS patients, and it was negatively associated with metabolic dysfunctions at baseline and 1-year after. Metabolic aberrations of MetS patients were significantly ameliorated with 1-year follow-up counselling accompanying by notably elevated 25(OH)D levels.

Acute high intensity interval exercise is similarly effective as moderate intensity continuous exercise on plasma glucose control in type 2 diabetic men aged 30 to 50 years: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the acute effects of high-intensity interval exercise (HIIE) versus moderate-intensity continuous exercise (MICE) on postprandial plasma glucose and insulin concentrations in men aged 30-50 years with type 2 diabetes (T2D), hoping to provide empirical evidence for the effects of different exercise types on glucose management in T2D patients. METHODS: Fourteen men with type 2 diabetes (T2D) underwent a randomized three crossover intervention: HIIE with cycling; energy expenditure matched MICE with cycling; and a sedentary control [CON]) in postprandial state. Plasma glucose and insulin levels were measured at pre-exercise, postexercise, 1 h postexercise, prelunch and 1 h postlunch, respectively. Responses of areas under the curve (AUC) during 4 h from pre-exercise to 1 h postlunch were also calculated. RESULTS: Both HIIE and MICE decreased plasma glucose and insulin levels during 4 h experimental period compared to CON, with significant intervention × time interaction effects for glucose (P=0.001) and insulin (P=0.006) values evolution. Area under curve (AUCs) for glucose and insulin were reduced in HIIE and MICE compared to CON (P<0.05), whereas no differences were found between HIIE and MICE. CONCLUSIONS: Acute HIIE and the matched MICE improve plasma glucose control in the same magnitude in type 2 diabetic men aged 30-50 years.

Molecular Characterization of an Aquaporin-2 Mutation Causing Nephrogenic Diabetes Insipidus.

The aquaporin 2 (AQP2) plays a critical role in water reabsorption to maintain water homeostasis. AQP2 mutation leads to nephrogenic diabetes insipidus (NDI), characterized by polyuria, polydipsia, and hypernatremia. We previously reported that a novel AQP2 mutation (G215S) caused NDI in a boy. In this study, we aimed to elucidate the cell biological consequences of this mutation on AQP2 function and clarify the molecular pathogenic mechanism for NDI in this patient. First, we analyzed AQP2 expression in Madin-Darby canine kidney (MDCK) cells by AQP2-G215S or AQP2-WT plasmid transfection and found significantly decreased AQP2-G215S expression in cytoplasmic membrane compared with AQP2-WT, independent of forskolin treatment. Further, we found co-localization of endoplasmic reticulum (ER) marker (Calnexin) with AQP2-G215S rather than AQP2-WT in MDCK cells by immunocytochemistry. The functional analysis showed that MDCK cells transfected with AQP2-G215S displayed reduced water permeability compared with AQP2-WT. Visualization of AQP2 structure implied that AQP2-G215S mutation might interrupt the folding of the sixth transmembrane α-helix and/or the packing of α-helices, resulting in the misfolding of monomer and further impaired formation of tetramer. Taken together, these findings suggested that AQP2-G215S was misfolded and retained in the ER and could not be translocated to the apical membrane to function as a water channel, which revealed the molecular pathogenic mechanism of AQP2-G215S mutation and explained for the phenotype of NDI in this patient.

Clinical management and treatment of obesity in China.

China has one of the largest populations with obesity in the world, and obesity has become a major challenge for the country's health-care system. Current guidelines for obesity management are not adequately supported by evidence from clinical studies in Chinese populations. Effective lifestyle interventions suitable for Chinese populations are scarce, insufficient weight-loss medications have been approved by regulatory bodies, and there is low acceptance of non-lifestyle interventions (ie, medications and surgery) among both health-care providers and the general public. Large, well designed, and well implemented clinical trials are needed to strengthen the evidence base for the clinical management of obesity in China. Obesity management can be improved through use of a tiered system involving health management centres, integrated lifestyle interventions and medical treatments, strengthened obesity education and training, and use of advanced electronic health technologies. Resource mobilisation, support from major stakeholders for people with overweight or obesity, and education and changes to social norms among the wider public are also needed. National health policies should prioritise both obesity prevention and improvement of the treatment and management of obesity.

Plasma levels of acylated ghrelin in patients with insulinoma and expression of ghrelin and its receptor in insulinomas.

BACKGROUND: Insulinoma is a subtype of pancreatic neuroendocrine tumors. Many patients with insulinoma are obese due to frequent food intake. Ghrelin is associated with obesity and blood levels of insulin. It is not clear if plasma levels of ghrelin in insulinoma patients correlate with hyperinsulinemia and obesity. Expression of ghrelin and its receptor has not been well demonstrated in insulinoma. OBJECTIVE: To study if plasma levels of ghrelin is associated with obesity and hyperinsulinemia or hyperproinsulinemia in patients with insulinoma, and to detect the expression of ghrelin and its receptor in insulinoma. METHODS: Plasma levels of acylated ghrelin, insulin, and proinsulin were measured in 37 patients with insulinoma and 25 controls by ELISA. Expression of ghrelin and its receptor GHS-R1A was examined in 20 insulinoma and paired pancreatic specimens by immunostaining. P ≤ 0.05 was considered significant. RESULTS: The plasma levels of acylated ghrelin in patients with insulinoma were significantly lower than that in the controls (median 15 pg/ml vs. 19 pg/ml, respectively, P = 0.016). The reduced plasma levels of acylated ghrelin in patients were significantly correlated with obesity, hyperinsulinemia, and hyperproinsulinemia (P = 0.029 and P = 0.028, respectively). Expression of ghrelin and its receptor GHS-R1A was shown in the majority of insulinoma specimens. The expression of GHS-R1A was positively correlated with ghrelin expression in insulinoma (P = 0.014). CONCLUSIONS: Plasma levels of acylated ghrelin decreased in patients with insulinoma, probably due to the hyperinsulinemia and obesity in the patients. Expression of both ghrelin and its receptor is common in insulinoma.