Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To elucidate the regulatory mechanism of hepatocyte nuclear factor 1α(HNF1A)in inducing human embryonic stem cells(hESCs)towards insulin producing cells(IPCs)differentiation.Methods An optimized stepwise protocol was implemented to generate definitive endoderm-derived IPCs.Dynamic HNF1A expression patterns were systematically monitered by qRT-PCR and Western blot.In the third stage(S3)of differentiation,cells were subjected to lentiviral-mediated interventions:respectively HNF1A knockdown(si-HNF1A)with scramble control(si-NC),and HNF1A over expression(oe-HNF1A)with empty vector control(oe-NC).Quantitative analysis of pancreatic lineage markers was performed by qRT-PCR.Glucose stimulated insulin secretion(GSIS)was assessed using ELISA under low glucose(LG)and high glucose(HG)conditions.Results Both HNF1A mRNA and protein levels demonstrated stage-dependent elevation,reaching peak expression at S3 relative to S1(P<0.05).Genetic silencing of HNF1A significantly suppressed key β-cell markers such as Pancreatoduodenal homeobox protein 1,GluT2,Ins compared to controls(P<0.05).Conversely,HNF1A overexpression enhanced transcriptional activation of these markers.Ins secretion increased stimulated by HG than LG in si-NC group.Functional analysis revealed impaired GSIS in si-HNF1A compared with si-NC group(P<0.05),whereas oe-HNF1A cells exhibited augmented GSIS capacity.Conclusions HNF1A positively regulates the IPC differentiation in hESCs,which may play a vital role in potentiating glucose-responsive insulin secretion.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To elucidate the regulatory mechanism of hepatocyte nuclear factor 1α(HNF1A)in inducing human embryonic stem cells(hESCs)towards insulin producing cells(IPCs)differentiation.Methods An optimized stepwise protocol was implemented to generate definitive endoderm-derived IPCs.Dynamic HNF1A expression patterns were systematically monitered by qRT-PCR and Western blot.In the third stage(S3)of differentiation,cells were subjected to lentiviral-mediated interventions:respectively HNF1A knockdown(si-HNF1A)with scramble control(si-NC),and HNF1A over expression(oe-HNF1A)with empty vector control(oe-NC).Quantitative analysis of pancreatic lineage markers was performed by qRT-PCR.Glucose stimulated insulin secretion(GSIS)was assessed using ELISA under low glucose(LG)and high glucose(HG)conditions.Results Both HNF1A mRNA and protein levels demonstrated stage-dependent elevation,reaching peak expression at S3 relative to S1(P<0.05).Genetic silencing of HNF1A significantly suppressed key β-cell markers such as Pancreatoduodenal homeobox protein 1,GluT2,Ins compared to controls(P<0.05).Conversely,HNF1A overexpression enhanced transcriptional activation of these markers.Ins secretion increased stimulated by HG than LG in si-NC group.Functional analysis revealed impaired GSIS in si-HNF1A compared with si-NC group(P<0.05),whereas oe-HNF1A cells exhibited augmented GSIS capacity.Conclusions HNF1A positively regulates the IPC differentiation in hESCs,which may play a vital role in potentiating glucose-responsive insulin secretion.

The use of bariatric and metabolic surgery as a central treatment for obesity has been steadily increasing. BMI, as a widely used metric for assessing obesity, has considerable relevance in the field of metabolic research. However, its limitations, such as its inability to account for variations in fat distribution, remain a subject of considerable controversy. In recent years, there has been a surge of interest in the relationship between changes in body composition and the risk of metabolic disease. Consequently, the study of the effects of bariatric and metabolic surgery on changes in body composition has become a major focus of bariatric and metabolic surgery research. As a potential replacement for BMI, body composition measurements are expected to improve and standardize the assessment of the effectiveness of bariatric and metabolic surgery. This underscores the urgent need for the development of methods and standards for body composition measurement. This paper undertakes a comprehensive review of the existing evidence on the application of body composition measurement techniques for the efficacy evaluation of bariatric and metabolic surgery. The intent is to provide new insights and pave the way for the exploration of future research directions in this area.

The use of bariatric and metabolic surgery as a central treatment for obesity has been steadily increasing. BMI, as a widely used metric for assessing obesity, has considerable relevance in the field of metabolic research. However, its limitations, such as its inability to account for variations in fat distribution, remain a subject of considerable controversy. In recent years, there has been a surge of interest in the relationship between changes in body composition and the risk of metabolic disease. Consequently, the study of the effects of bariatric and metabolic surgery on changes in body composition has become a major focus of bariatric and metabolic surgery research. As a potential replacement for BMI, body composition measurements are expected to improve and standardize the assessment of the effectiveness of bariatric and metabolic surgery. This underscores the urgent need for the development of methods and standards for body composition measurement. This paper undertakes a comprehensive review of the existing evidence on the application of body composition measurement techniques for the efficacy evaluation of bariatric and metabolic surgery. The intent is to provide new insights and pave the way for the exploration of future research directions in this area.

Objective:To explore the clinical characteristics of patients with pituitary thyrotropin-secreting adenoma and evaluate the effect of preoperative short-acting octreotide treatment on hyperthyroidism.Methods:A retrospective analysis was performed in 40 patients with pituitary thyrotropin adenoma diagnosed in Beijing Tiantan Hospital from January 2008 to January 2018. The general data, laboratory examinations and imaging findings were reviewed and analyzed. The clinical effect of preoperative octreotide on hyperthyroidism was evaluated.Results:The age of onset year of the 40 patients (male: female = 24∶16) was (30.5±5.1) years. Among them, 35 patients (87.5%) were with macroadenoma. The most common symptoms were thyroid hypermetabolism syndrome, followed by headache, dizziness, visual field damage and hypogonadism. The thyroid function of 30 patients (75%) recovered to normal within 3-5 days after the octreotide treatment. The total effective rate of the octreotide was 90.0%. The level of free thyroxine (FT 4) before treatment in patients with more than 10 times of effective cumulative dose was significantly higher than that in patients with less than 10 doses. Conclusions:Thyroid hypermetabolism syndrome and pituitary occupying effect are the most common clinical manifestations of thyrotropin-secreting adenoma. Preoperative octreotide treatment can effectively control hyperthyroidism. The level of FT 4 is a crucial factor affecting the efficacy of octreotide.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To analyze the effect of long-acting somatostatin treatment on blood glucose, blood lipid, insulin resistance and islet function in patients with acromegaly after surgical treatment.Methods:Self-control study before and after treatment was used. A total of 30 subjects who were diagnosed as acromegalyand received surgical treatment in Beijing Tiantan Hospital from January 2016 to January 2018 were enrolled in this study. Because patients′ growth hormone (GH) level was notc ompletely controlled after surgery, all the patients were treated with long-acting octreotide for more than 1 year. Before and 1 year after treatment, oral glucose tolerance testing (OGTT) was performed at pretreatment and 1 year after initiation of treatment with long-acting octreotide. Homeostatic model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR) and β-cell function (HOMA-β). The HOMA-IR and HOMA-β were detected by 75 g glucose, insulin, C peptide release test and growth hormone suppression test to evaluate the therapy effects on insulin resistance and islet function.Results:The levels of GH, insulin-like growth factor 1(IGF-1), HOMA-IR, HOMA-β, and triacylglycerol(TG) were all decreased after 1 year of octreotide treatment compared with that before treatment: (2.8 ± 2.5) μg/L vs. (12.1 ± 10.5) μg/L, (356.8 ± 209.2) μg/L vs. (698.1 ± 207.3) μg/L, 1.56 ± 1.08 vs. 2.71 ± 1.52, 1.01 ± 0.97 vs. 4.87 ± 3.57, (1.12 ± 0.49) mmol/L vs. (1.76 ± 0.92) mmol/L, and the differences were statistically significant ( P<0.05). After treatment, the level of fasting blood glucose was increased compared with that before treatment: (5.83 ± 1.19) mmol/L vs.(5.11 ± 1.73) mmol/L, and the difference was statistically significant ( P<0.05). While there were no significant changes in postprandial 2 h blood glucose and glycosylated hemoglobin (GHb), total cholesterol (TC), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels before and after treatment ( P>0.05). Conclusions:Long-acting somatostatin therapy can effectively improve the insulin sensitivity of acromegaly patients, reduce β cell function, and slightly increase fasting blood glucose. It has no adverse effect on GHb, and can reduce the level of TG of the patients.

Objective:To summarize the clinical characteristics and treatment of pituitary thyrotropin mixed secreting adenoma.Methods:The clinical data of 9 patients with pituitary thyrotropin mixed secreting adenoma from January 2008 to December 2019 in Beijing Tiantan Hospital, Capital Medical University, were retrospectively analyzed.Results:Among 9 patients, male was in 7 cases, and female in 2 cases; age was (35.7 ± 13.5) years; course of disease was (3.8 ± 3.1) years; mixed thyrotropin and growth hormone secreting adenoma was in 6 cases; most of them were accompanied with different degrees of thyrotoxicosis, 6 with acromegaly and 2 with amenorrhea and lactation. All the tumors were pituitary macroadenoma, with aggressive growth. Only 1 patient was completely relieved after operation, and most patients needed combined treatment to control the disease.Conclusions:Mixed thyrotropin and growth hormone secreting adenoma is the most common type of the disease, the clinical manifestations are complex, and the tumor is aggressive growth, surgical treatment can not be completely relieved and radiotherapy and/or combination of medicine treatment can help to improve the condition.