Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is no...Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body metabolism.Exosomes are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms.However,the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated.In this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders.Moreover,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.展开更多
BACKGROUND The measurement of triceps skinfold(TSF)thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution.Despite its clinical utility,the TSF thickness trajectories and their correlatio...BACKGROUND The measurement of triceps skinfold(TSF)thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution.Despite its clinical utility,the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated.AIM To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality.METHODS This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey.Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness.Subjects were classified into subgroups reflective of their respective TSF thickness trajectory.We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality,including contributory factors.RESULTS Upon adjustment for multiple confounding factors,we discerned that males in the‘Class 2:Thin-stable’and‘Class 3:Thin-moderate’TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the‘Class 1:Extremely thin’subgroup.In the mediation analyses,the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality.For females,a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort.CONCLUSION In males and non-elderly females,lower TSF thickness trajectories are significantly predictive of heightened mortality risk,independent of single-point TSF thickness,body mass index,and waist circumference.展开更多
BACKGROUND Since adverse events during treatment affect adherence and subsequent glycemic control,understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus(T2DM)therapy.AI...BACKGROUND Since adverse events during treatment affect adherence and subsequent glycemic control,understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus(T2DM)therapy.AIM To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4(DPP-4)inhibitors.METHODS Electronic databases were searched.The selection criteria included randomized controlled trials focused on cardiovascular outcomes.In these studies,the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo.Six trials involving 53616 patients were deemed eligible.We calculated aggregate relative risks employing both random-effects and fixed-effects approaches,contingent upon the context.RESULTS The application of DPP-4 inhibitors showed no significant link to the overall infection risk[0.98(0.95,1.02)]or the risk of serious infections[0.96(0.85,1.08)],additionally,no significant associations were found with opportunistic infections[0.69(0.46,1.04)],site-specific infections[respiratory infection 0.99(0.96,1.03),urinary tract infections 1.02(0.95,1.10),abdominal and gastrointestinal infections 1.02(0.83,1.25),skin structure and soft tissue infections 0.81(0.60,1.09),bone infections 0.96(0.68,1.36),and bloodstream infections 0.97(0.80,1.18)].CONCLUSION This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.展开更多
The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity(MVPA)time and sedentary(SED)time with a history of cardiovascular disease(CVD)and multifactorial(i.e.,blood pre...The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity(MVPA)time and sedentary(SED)time with a history of cardiovascular disease(CVD)and multifactorial(i.e.,blood pressure(BP),body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),and glycated hemoglobin A1c(HbA1c))control status among type 2 diabetes mellitus(T2DM)patients in China.A cross-sectional analysis of 9152 people with type 2 diabetes from the Multifactorial Intervention on Type 2 Diabetes(MIDiab)study was performed.Patients were grouped according to their self-reported MVPA time(low,<150 min·week−1;moderate,150 to<450 min·week−1;high,≥450 min·week−1)and SED time(low,<4 h·d–1;moderate,4 to<8 h·d–1;high,≥8 h·d–1).Participants who self-reported a history of CVD were identified as having a CVD risk.Odds ratios(ORs)and 95%confidence intervals(CIs)of CVD risk and multifactorial control status associated with MVPA time and SED time were estimated using mixed-effect logistic regression models,adjusting for China’s geographical region characteristics.The participants had a mean±standard deviation(SD)age of(60.87±8.44)years,44.5%were women,and 25.1%had CVD.After adjustment for potential confounding factors,an inverse association between high MVPA time and CVD risk that was independent of SED time was found,whereas this association was not observed in the moderate-MVPA group.A higher MVPA time was more likely to have a positive effect on the control of BMI.Compared with the reference group(i.e.,those with MVPA time≥450 min·week−1 and SED time<4 h·d–1),CVD risk was higher in the low-MVPA group:The OR associated with an SED time<4 h·d–1 was 1.270(95%CI,1.040–1.553)and that associated with an SED time≥8 h·d–1 was 1.499(95%CI,1.149–1.955).We found that a high MVPA time(i.e.,≥450 min·week−1)was associated with lower odds of CVD risk regardless of SED time among patients with T2DM.展开更多
BACKGROUND Although conservative treatment is typically recommended for pregnant patients with pituitary adenoma(PA),surgical treatment is occasionally necessary for those with acute symptoms.Currently,surgical interv...BACKGROUND Although conservative treatment is typically recommended for pregnant patients with pituitary adenoma(PA),surgical treatment is occasionally necessary for those with acute symptoms.Currently,surgical interventions utilized among these patients is poorly studied.AIM To evaluate the surgical indications,timing,perioperative precautions and postoperative complications of PAs during pregnancy and to provide comprehensive guidance.METHODS Six patients with PAs who underwent surgical treatment during pregnancy at Peking Union Medical College Hospital between January 1990 and June 2021 were recruited for this study.Another 35 pregnant patients who were profiled in the literature were included in our analysis.RESULTS The 41 enrolled patients had acute symptoms including visual field defects,severe headaches or vision loss that required emergency pituitary surgeries.PA apoplexies were found in 23 patients.The majority of patients(55.9%)underwent surgery in the second trimester of pregnancy.A multidisciplinary team was involved in patient care from the preoperative period through the postpartum period.With the exception of 1 patient who underwent an induced abortion and 1 fetus that died due to a nuchal cord,39 patients delivered successfully.Among them,37 fetuses were healthy until the most recent follow-up.CONCLUSION PA surgery during pregnancy is effective and safe during the second and third trimesters.Pregnant patients requiring emergency PA surgery require multidisciplinary evaluation and healthcare management.展开更多
The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activati...The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.展开更多
Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituit...Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma （21 invasive and 14 non-invasive） patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. Results Flow cytometric analyses showed that the percentage of CXCR4- and CXCL12-positive cells from invasive pituitary adenomas （IPA） was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas （nlPA） （P〈O.05）. Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas （P〈O.05）. In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. Conclusion Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.展开更多
BACKGROUND Patients with hypothalamic-pituitary disease have the feature of central obesity,insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fa...BACKGROUND Patients with hypothalamic-pituitary disease have the feature of central obesity,insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease(NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients.AIM To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients.METHODS Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospitalbetween August 2012 and April 2018. According to abdominal ultrasonography,these patients were divided into an NAFLD(-) group and an NAFLD(+) group,and the latter was further divided into an NAFLD group and a cirrhotic group.The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed.RESULTS A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43(87.0%) of these patients exhibited growth hormone(GH) deficiency, and 39(78.3%) had diabetes insipidus. A total of 27(54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2 O and 151.0 mmol/L,respectively, which were significantly higher than those of the NAFLD patients(P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index(BMI)and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD(P = 0.011 and0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI(r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD.CONCLUSION NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.展开更多
Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with typ...Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.展开更多
Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Meth...Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNA^Lcu（UUR） A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980（P=0.02）. Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNA^Lcu（UUR） A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNA^Lcu（UUR） A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.展开更多
Objective To investigate the effect of interleukin-6(IL-6)on the human growth hormone(hGH)gene expression in a rat somatotropic pituitary cell line MtT/S.Methods The plasmids containing various lengths of hGH gene 5&#...Objective To investigate the effect of interleukin-6(IL-6)on the human growth hormone(hGH)gene expression in a rat somatotropic pituitary cell line MtT/S.Methods The plasmids containing various lengths of hGH gene 5'-promoter fragments were constructed.Stably transfected MtT/S cells were created by cotransfecting the above plasmids and pcDNA3.1(+)with DMRIE-C transfection reagent.After the administration of these cells with IL-6 and/or various inhibitors of signaling transduction pathways,the luciferase activities in MtT/S cells lysis were assayed to demonstrate the effects of IL-6 on hGH gene promoter activity and possibly involved mechanism.Results The 103 U/mL IL-6 stimulated GH secretion and synthesis,and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.69 times above the control.Among inhibitors of signaling transduction pathways,mitogen-activated protein kinase kinase(MAPKK/MEK)inhibitor PD98059(40 μmol/L)and p38 mitogen-activated protein kinase(MAPK)inhibitor SB203580(5 μmol/L)completely blocked the stimulatory effect of IL-6.Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells.Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected IL-6 induction of hGH promoter activity.A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-6.The results showed that the stimulatory effect of IL-6 was abolished following deletion of the-196 to-132 bp fragment.Conclusions IL-6 promotes GH secretion and synthesis by rat MtT/S somatotroph cells.The stimulatory effect of IL-6 on hGH gene promoter appears to require the activation of MEK and p38 MAPK,and a fragment of promoter sequence that spans the-196 to-132 bp of the gene,but may be unlinked with Pit-1 protein.展开更多
Objective To elucidate the effect of interleukin-1β （IL- 1β） on human growth hormone （hGH） gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly es...Objective To elucidate the effect of interleukin-1β （IL- 1β） on human growth hormone （hGH） gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Lucl plasmid which contained hGH gene promoter --484 to ＋30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 10^3 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5＇-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase （MAPKK/MEK） inhibitor PD98059 （40 μmol/L） and p38 mitogen-activated protein kinase （MAPK） inhibitor SB203580 （5 μmol/L） completely blocked the stimulatory effect of IL-1μ, and phosphatidylinositol-3-kinase （PI3-K） inhibitor LY294002 partly abolished the effect of IL-1μ. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit- 1 nor inhibition of Pit- 1 expression affected induction of hGH promoter activity by IL-1μ. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the --196 to -- 132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.展开更多
Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2(SGLT2) inhibitor—SGLT2 inhibitors,in combination with insulin for type 1 diabetes mellitus(T1DM). Methods We searched Medline,E...Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2(SGLT2) inhibitor—SGLT2 inhibitors,in combination with insulin for type 1 diabetes mellitus(T1DM). Methods We searched Medline,Embase,and the Cochrane Collaboration Library to identify the eligible studies published between January 2010 and July 2016 without restriction of language. The Food and Drug Administration(FDA) data and Clinical Trials(http://www.clinicaltrials.gov) were also searched. The included studies met the following criteria:randomized controlled trials; T1DM patients aged between 18 and 65 years old; patients were treated with insulin plus SGLT2 inhibitors for more than 2 weeks; patients' glycosylated hemoglobin(HbA1c) levels were between 7% and 12%. The SGLT2 inhibitors group was treated with SGLT2 inhibitors plus insulin,and the placebo group received placebo plus insulin treatment. The outcomes should include one of the following items:fasting blood glucose,HbA1c,glycosuria,or adverse effects. Data were analyzed by two physicians independently. The risk of bias was evaluated by using the Cochrane Collaboration's Risk of Bias tool and heterogeneity among studies was assessed using Chi-square test. Random effect model was used to analyze the treatment effects with Revman 5.3. Results Three trials including 178 patients were enrolled. As compared to the placebo group,SGLT2 inhibitor absolutely decreased fasting blood glucose [mean differences(MD)-2.47 mmol/L,95% confidence interval(CI)-3.65 to-1.28,P<0.001] and insulin dosage(standardized MD-0.75 U,95%CI-1.17 to-0.33,P<0.001). SGLT2 inhibitors could also increase the excretion of urine glucose(MD 131.09 g/24 h,95%CI 91.79 to 170.39,P<0.001). There were no significant differences in the incidences of hyperglycemia [odds ratio(OR) 1.82,95%CI 0.63 to 5.29,P=0.27],urinary tract infection(OR 0.95,95%CI 0.19 to 4.85,P=0.95),genital tract infection(OR 0.27,95%CI 0.01 to 7.19,P=0.43),and diabetic ketoacidosis(OR 6.03,95%CI 0.27 to 135.99,P=0.26) between the two groups. Conclusion SGLT2 inhibitors combined with insulin might be an efficient and safe treatment modality for T1DM patients.展开更多
Objective To investigate the clinical and genetic features of a Chinese family with yon Hippel- Lindau （VHL） disease revealed by bilateral pheochromocytoma. Methods The proband and other members in a Chinese family...Objective To investigate the clinical and genetic features of a Chinese family with yon Hippel- Lindau （VHL） disease revealed by bilateral pheochromocytoma. Methods The proband and other members in a Chinese family with familial pheochromocytoma were clinically evaluated and followed up. Genomic DNA extracted from the peripheral blood of 8 family members （including 3 patients） was amplified by polymerase chain reaction （PCR） and the PCR products were directly sequenced. Results The first presentation in the proband, his mother, and his sister was bilateral pheochromocytoma, and the missense mutation of 695G-A （Arg161Gln） in exon 3 of VHL gene was detected in the three patients. In the follow-up study, the proband and his mother were found to have other VHL tumors, induding retinal and cerebellar hemangioblastomas and pancreatic tumor. Neither clinical presentation of VHL disease nor gene mutation was found in other family members. Conclusion VHL disease should be suspected in some patients with familial pheochromocytoma, and VHL gene screening helps to achieve early diagnosis of the disease.展开更多
INSULINOMA is the most common cause of hypoglycemia. Although it is a rare disease, there has been a significant progress in its diagnosis along with the technology development. A set of
In 2017,American College of Cardiology(ACC)/American Heart Association(AHA)et al.jointly released the latest guidelines for adult hypertension,exactly including prevention,diagnosis,assess and treatment,in which blood...In 2017,American College of Cardiology(ACC)/American Heart Association(AHA)et al.jointly released the latest guidelines for adult hypertension,exactly including prevention,diagnosis,assess and treatment,in which blood pressure levels greater than 130/80 mm Hg were defined as hypertension[1].Based on these modified guidelines,the morbidity of hypertension in US increased from 32%to 46%.展开更多
Type II autosomal dominant osteopetrosis(ADO2), which is the most common form of osteopetrosis, is caused by heterozygous mutations in the chloride channel 7(CLCN7) gene. The osteopetrosis of ADO2 has been attributed ...Type II autosomal dominant osteopetrosis(ADO2), which is the most common form of osteopetrosis, is caused by heterozygous mutations in the chloride channel 7(CLCN7) gene. The osteopetrosis of ADO2 has been attributed to hypofunctional osteoclasts. The mechanism underlying the abnormality in osteoclast function remains largely unknown. This study was designed to investigate gene mutations and osteoclast function in a case that was clinically diagnosed as ADO2. Genomic DNA was extracted from blood samples of this patient, and the 25 exons of CLCN7 were amplified. Peripheral blood from the ADO2 subject and a healthy age- and sex-matched control was used to evaluate osteoclastogenesis, osteoclast morphology, and bone resorption. Analysis of DNA from the patient showed a germline heterozygous missense mutation,c.1856C>T(p.P619L), in exon 20 of CLCN7. A similar homozygous mutation at this site was previously reported in a patient with autosomal recessive osteopetrosis. When cultured, the peripheral blood mononuclear cells(PBMCs) from the ADO2 patient spontaneously differentiated into mature osteoclasts in vitro. The ADO2 patient’s PBMCs formed enhanced, but heterogeneous, osteoclasts in both the presence and absence of macrophage-colony stimulating factor, and nuclear factor-?B ligand. Bone resorption was reduced in the ADO2 patient’s osteoclasts, which exhibited aberrant morphology and abnormal distribution of integrin avβ3. Gene analysis found increased c-fos expression and reduced Rho A and integrin beta 3expression in ADO2 cells. In conclusion, our data suggest that enhanced, heterogeneous osteoclast induction may be an intrinsic characteristic of ADO2.展开更多
Familial hypocalciuric hypercalcemia （FHH） is caused by inactivating mutations in the calcium-sensing receptor （CaSR） gene. The loss of function of CaSR presents with rickets as the predominant skeletal abnormalit...Familial hypocalciuric hypercalcemia （FHH） is caused by inactivating mutations in the calcium-sensing receptor （CaSR） gene. The loss of function of CaSR presents with rickets as the predominant skeletal abnormality in mice, but is rarely reported in humans. Here we report a case of a 16-year-old boy with FHH who presented with skeletal manifestations of rickets. To identify the possible pathogenic mutation, the patient was evaluated clinically, biochemically, and radiographicaUy. The patient and his family members were screened for genetic mutations. Physical examination revealed a pigeon breast deformity and X-ray examinations showed epiphyseal broadening, both of which indicate rickets. Biochemical tests also showed increased parathyroid hormone （PTH）, 1,25-dihydroxyvitamin D, and elevated ionized calcium. Based on these results, a diagnosis of FHH was suspected. Sequence analysis of the patient＇s CaSR gene revealed a new missense mutation （c.2279T 〉 A） in exon 7, leading to the damaging amino change （p.I760N） in the mature CaSR protein, confirming the diagnosis of ~H. Moreover, the skeletal abnormities may be related to but not limited to vitamin D abnormity. Elevated ~H levels and a rapid skeletal growth period in adolescence may have also contributed. Our study revealed that rickets-like features have a tendency to present atypically in FHH patients who have a mild vitamin D deficiency, and that CaSR mutations may have a partial role in the pathogenesis of skeletal deformities.展开更多
BACKGROUND A number of recent studies indicate a transformation in the natural course of chronic kidney disease(CKD)in type 2 diabetes(T2D)patients:an increasing prevalence of declined renal function without proceedin...BACKGROUND A number of recent studies indicate a transformation in the natural course of chronic kidney disease(CKD)in type 2 diabetes(T2D)patients:an increasing prevalence of declined renal function without proceeding to the accompanying elevation of albuminuria.It has been suggested that albuminuric and nonalbuminuric CKD patterns could be different in their phenotypes and pathogenic mechanisms.AIM To identify the risk factors and biomarkers of albuminuric and non-albuminuric patterns of CKD in patients with T2D.METHODS Three hundred sixty patients with T2D duration≥10 years were included in this observational cross-sectional study.The associations of a panel of demographic and clinical characteristics,complications,comorbidities,and metabolic and hematology parameters with albuminuric and non-albuminuric CKD patterns were analyzed.The urinary excretion of nephrin and podocin,two podocytespecific markers,and WAP-four-disulfide core domain protein 2(WFDC-2),a marker of tubulointerstitial fibrosis,was determined by ELISA in comparison with healthy controls.RESULTS Non-albuminuric CKD was associated with age≥65 years(P=0.0001),female sex(P=0.04),diabetes duration≥15 years(P=0.0009),and the use of diuretics(P=0.0005).Male sex(P=0.01),smoking(P=0.01),waist-to-hip ratio>1.0(P=0.01)and hemoglobin A1c(HbA1c)>8.0%(P=0.005)were risk factors for elevated albuminuria not accompanied by a decrease in estimated glomerular filtration rate(eGFR).Duration of diabetes≥15 years and the use of calcium channel blockers were risk factors for albuminuria with decreased eGFR(both P=0.01).In multivariate logistic regression analysis,age,HbA1c,female sex and diuretics were significant predictors for reduced eGFR,while waist-to-hip ratio,HbA1c and male sex were associated with elevated urinary albumin-to-creatinine ratio(UACR).Excretion of nephrin and podocin was increased in patients with albuminuria,regardless of decline in renal function(P<0.001),correlating positively with UACR.The urinary excretion of WFDC-2 was markedly higher in men than in women(P<0.000001).Men with T2D demonstrated increased WFDC-2 levels independently of the CKD pattern(all P<0.05).In T2D women,WFDC-2 excretion was increased in those with reduced renal function(P≤0.01),correlating negatively with eGFR.CONCLUSION The data provide further evidence that albuminuric and non-albuminuric CKD phenotypes correspond to different pathways of diabetic kidney disease progression.展开更多
Objective: To study the effects of low-dose and long-term hormone replacement therapy (HRT) on blood lipids in postmenopausal women.Methods: (1) 141 postmenopausal female medical staffs aged from 50 to 87 years with a...Objective: To study the effects of low-dose and long-term hormone replacement therapy (HRT) on blood lipids in postmenopausal women.Methods: (1) 141 postmenopausal female medical staffs aged from 50 to 87 years with average 68 years were from Peking Union Medical college Hospital, among them 63 were treated with low-dose HRT for 5-31 years as HRT group, and other 78 postmenopausal women matched with age as the control group. (2) withdrew vein blood from objects on fasting for 12-14 h and serum was separated for determining serum concentration of lipid, lipoprotein and apolipoprotein. (3)data were analyzed with SPSS statistical software for statistical significance by P＜0.05.Results:In comparison with control, the levels of TG, HDL-C, LDL-C, apoA I , Lp(a) of HRT group had no statistical significance,but the levels of TC, TC/HDL-C, ApoE, ApoCⅢ and ApoB were significantly lower.Conclusion: The levels of TC, LDL-C, ApoB, ApoC Ⅲ, ApoE decreased significantly in postmenopausal women receiving low-dose and long-term HRT. The decrease in the levels of blood lipids may provide cardiovascular protection and reduce the risk of cardiovascular events.展开更多
基金supported by the National Natural Science Foundation of China(No.82070859).
文摘Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body metabolism.Exosomes are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms.However,the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated.In this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders.Moreover,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.
基金Supported by National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015CAMS Innovation Fund for Medical Sciences,No.2021-1-12M-002+1 种基金CAMS Innovation Fund for Medical Sciences,No.2023-I2M-C&T-B-043Beijing Municipal Natural Science Foundation,No.M22014.
文摘BACKGROUND The measurement of triceps skinfold(TSF)thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution.Despite its clinical utility,the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated.AIM To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality.METHODS This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey.Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness.Subjects were classified into subgroups reflective of their respective TSF thickness trajectory.We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality,including contributory factors.RESULTS Upon adjustment for multiple confounding factors,we discerned that males in the‘Class 2:Thin-stable’and‘Class 3:Thin-moderate’TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the‘Class 1:Extremely thin’subgroup.In the mediation analyses,the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality.For females,a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort.CONCLUSION In males and non-elderly females,lower TSF thickness trajectories are significantly predictive of heightened mortality risk,independent of single-point TSF thickness,body mass index,and waist circumference.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2023-I2M-C&T-B-043 and No.2021-I2M-1-002National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015+1 种基金Beijing Municipal Natural Science Foundation,No.M22014National Natural Science Foundation of China,No.91846106.
文摘BACKGROUND Since adverse events during treatment affect adherence and subsequent glycemic control,understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus(T2DM)therapy.AIM To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4(DPP-4)inhibitors.METHODS Electronic databases were searched.The selection criteria included randomized controlled trials focused on cardiovascular outcomes.In these studies,the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo.Six trials involving 53616 patients were deemed eligible.We calculated aggregate relative risks employing both random-effects and fixed-effects approaches,contingent upon the context.RESULTS The application of DPP-4 inhibitors showed no significant link to the overall infection risk[0.98(0.95,1.02)]or the risk of serious infections[0.96(0.85,1.08)],additionally,no significant associations were found with opportunistic infections[0.69(0.46,1.04)],site-specific infections[respiratory infection 0.99(0.96,1.03),urinary tract infections 1.02(0.95,1.10),abdominal and gastrointestinal infections 1.02(0.83,1.25),skin structure and soft tissue infections 0.81(0.60,1.09),bone infections 0.96(0.68,1.36),and bloodstream infections 0.97(0.80,1.18)].CONCLUSION This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.
基金supported by the National Key Research and Development Program of China(2017YFC1309800)the“Outstanding University Driven by Talents”Program and Academic Promotion Program of Shandong First Medical University(2019LJ007)the Key Research and Development Program of Shandong Province(2017CXGC1214).
文摘The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity(MVPA)time and sedentary(SED)time with a history of cardiovascular disease(CVD)and multifactorial(i.e.,blood pressure(BP),body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),and glycated hemoglobin A1c(HbA1c))control status among type 2 diabetes mellitus(T2DM)patients in China.A cross-sectional analysis of 9152 people with type 2 diabetes from the Multifactorial Intervention on Type 2 Diabetes(MIDiab)study was performed.Patients were grouped according to their self-reported MVPA time(low,<150 min·week−1;moderate,150 to<450 min·week−1;high,≥450 min·week−1)and SED time(low,<4 h·d–1;moderate,4 to<8 h·d–1;high,≥8 h·d–1).Participants who self-reported a history of CVD were identified as having a CVD risk.Odds ratios(ORs)and 95%confidence intervals(CIs)of CVD risk and multifactorial control status associated with MVPA time and SED time were estimated using mixed-effect logistic regression models,adjusting for China’s geographical region characteristics.The participants had a mean±standard deviation(SD)age of(60.87±8.44)years,44.5%were women,and 25.1%had CVD.After adjustment for potential confounding factors,an inverse association between high MVPA time and CVD risk that was independent of SED time was found,whereas this association was not observed in the moderate-MVPA group.A higher MVPA time was more likely to have a positive effect on the control of BMI.Compared with the reference group(i.e.,those with MVPA time≥450 min·week−1 and SED time<4 h·d–1),CVD risk was higher in the low-MVPA group:The OR associated with an SED time<4 h·d–1 was 1.270(95%CI,1.040–1.553)and that associated with an SED time≥8 h·d–1 was 1.499(95%CI,1.149–1.955).We found that a high MVPA time(i.e.,≥450 min·week−1)was associated with lower odds of CVD risk regardless of SED time among patients with T2DM.
文摘BACKGROUND Although conservative treatment is typically recommended for pregnant patients with pituitary adenoma(PA),surgical treatment is occasionally necessary for those with acute symptoms.Currently,surgical interventions utilized among these patients is poorly studied.AIM To evaluate the surgical indications,timing,perioperative precautions and postoperative complications of PAs during pregnancy and to provide comprehensive guidance.METHODS Six patients with PAs who underwent surgical treatment during pregnancy at Peking Union Medical College Hospital between January 1990 and June 2021 were recruited for this study.Another 35 pregnant patients who were profiled in the literature were included in our analysis.RESULTS The 41 enrolled patients had acute symptoms including visual field defects,severe headaches or vision loss that required emergency pituitary surgeries.PA apoplexies were found in 23 patients.The majority of patients(55.9%)underwent surgery in the second trimester of pregnancy.A multidisciplinary team was involved in patient care from the preoperative period through the postpartum period.With the exception of 1 patient who underwent an induced abortion and 1 fetus that died due to a nuchal cord,39 patients delivered successfully.Among them,37 fetuses were healthy until the most recent follow-up.CONCLUSION PA surgery during pregnancy is effective and safe during the second and third trimesters.Pregnant patients requiring emergency PA surgery require multidisciplinary evaluation and healthcare management.
基金supported by the European Union Grant Alehoop(H2020-BBIJTI-2019-887259)And from the Xunta de Galicia(Centro singular de Investigación de Galicia accreditation 2016-2019),ED431 G/02(to FM)。
文摘The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.
基金supported by the key program for clinical research foundation of PUMC Hospital(Grant No.200611)
文摘Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma （21 invasive and 14 non-invasive） patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. Results Flow cytometric analyses showed that the percentage of CXCR4- and CXCL12-positive cells from invasive pituitary adenomas （IPA） was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas （nlPA） （P〈O.05）. Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas （P〈O.05）. In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. Conclusion Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.
基金Supported by the National Key Program of Clinical Science,No.WBYZ 2011-873the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,No.2016YFC0901500the Special Research Fund for Central Universities,Peking Union Medical College,No.2017PT31004
文摘BACKGROUND Patients with hypothalamic-pituitary disease have the feature of central obesity,insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease(NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients.AIM To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients.METHODS Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospitalbetween August 2012 and April 2018. According to abdominal ultrasonography,these patients were divided into an NAFLD(-) group and an NAFLD(+) group,and the latter was further divided into an NAFLD group and a cirrhotic group.The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed.RESULTS A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43(87.0%) of these patients exhibited growth hormone(GH) deficiency, and 39(78.3%) had diabetes insipidus. A total of 27(54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2 O and 151.0 mmol/L,respectively, which were significantly higher than those of the NAFLD patients(P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index(BMI)and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD(P = 0.011 and0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI(r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD.CONCLUSION NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.
文摘Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.
文摘Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNA^Lcu（UUR） A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980（P=0.02）. Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNA^Lcu（UUR） A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNA^Lcu（UUR） A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.
文摘Objective To investigate the effect of interleukin-6(IL-6)on the human growth hormone(hGH)gene expression in a rat somatotropic pituitary cell line MtT/S.Methods The plasmids containing various lengths of hGH gene 5'-promoter fragments were constructed.Stably transfected MtT/S cells were created by cotransfecting the above plasmids and pcDNA3.1(+)with DMRIE-C transfection reagent.After the administration of these cells with IL-6 and/or various inhibitors of signaling transduction pathways,the luciferase activities in MtT/S cells lysis were assayed to demonstrate the effects of IL-6 on hGH gene promoter activity and possibly involved mechanism.Results The 103 U/mL IL-6 stimulated GH secretion and synthesis,and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.69 times above the control.Among inhibitors of signaling transduction pathways,mitogen-activated protein kinase kinase(MAPKK/MEK)inhibitor PD98059(40 μmol/L)and p38 mitogen-activated protein kinase(MAPK)inhibitor SB203580(5 μmol/L)completely blocked the stimulatory effect of IL-6.Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells.Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected IL-6 induction of hGH promoter activity.A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-6.The results showed that the stimulatory effect of IL-6 was abolished following deletion of the-196 to-132 bp fragment.Conclusions IL-6 promotes GH secretion and synthesis by rat MtT/S somatotroph cells.The stimulatory effect of IL-6 on hGH gene promoter appears to require the activation of MEK and p38 MAPK,and a fragment of promoter sequence that spans the-196 to-132 bp of the gene,but may be unlinked with Pit-1 protein.
文摘Objective To elucidate the effect of interleukin-1β （IL- 1β） on human growth hormone （hGH） gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Lucl plasmid which contained hGH gene promoter --484 to ＋30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 10^3 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5＇-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase （MAPKK/MEK） inhibitor PD98059 （40 μmol/L） and p38 mitogen-activated protein kinase （MAPK） inhibitor SB203580 （5 μmol/L） completely blocked the stimulatory effect of IL-1μ, and phosphatidylinositol-3-kinase （PI3-K） inhibitor LY294002 partly abolished the effect of IL-1μ. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit- 1 nor inhibition of Pit- 1 expression affected induction of hGH promoter activity by IL-1μ. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the --196 to -- 132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.
文摘Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2(SGLT2) inhibitor—SGLT2 inhibitors,in combination with insulin for type 1 diabetes mellitus(T1DM). Methods We searched Medline,Embase,and the Cochrane Collaboration Library to identify the eligible studies published between January 2010 and July 2016 without restriction of language. The Food and Drug Administration(FDA) data and Clinical Trials(http://www.clinicaltrials.gov) were also searched. The included studies met the following criteria:randomized controlled trials; T1DM patients aged between 18 and 65 years old; patients were treated with insulin plus SGLT2 inhibitors for more than 2 weeks; patients' glycosylated hemoglobin(HbA1c) levels were between 7% and 12%. The SGLT2 inhibitors group was treated with SGLT2 inhibitors plus insulin,and the placebo group received placebo plus insulin treatment. The outcomes should include one of the following items:fasting blood glucose,HbA1c,glycosuria,or adverse effects. Data were analyzed by two physicians independently. The risk of bias was evaluated by using the Cochrane Collaboration's Risk of Bias tool and heterogeneity among studies was assessed using Chi-square test. Random effect model was used to analyze the treatment effects with Revman 5.3. Results Three trials including 178 patients were enrolled. As compared to the placebo group,SGLT2 inhibitor absolutely decreased fasting blood glucose [mean differences(MD)-2.47 mmol/L,95% confidence interval(CI)-3.65 to-1.28,P<0.001] and insulin dosage(standardized MD-0.75 U,95%CI-1.17 to-0.33,P<0.001). SGLT2 inhibitors could also increase the excretion of urine glucose(MD 131.09 g/24 h,95%CI 91.79 to 170.39,P<0.001). There were no significant differences in the incidences of hyperglycemia [odds ratio(OR) 1.82,95%CI 0.63 to 5.29,P=0.27],urinary tract infection(OR 0.95,95%CI 0.19 to 4.85,P=0.95),genital tract infection(OR 0.27,95%CI 0.01 to 7.19,P=0.43),and diabetic ketoacidosis(OR 6.03,95%CI 0.27 to 135.99,P=0.26) between the two groups. Conclusion SGLT2 inhibitors combined with insulin might be an efficient and safe treatment modality for T1DM patients.
基金Supported by the "tenth five-years " National Science and Technology Tackle Key Project (2004BA720A29)
文摘Objective To investigate the clinical and genetic features of a Chinese family with yon Hippel- Lindau （VHL） disease revealed by bilateral pheochromocytoma. Methods The proband and other members in a Chinese family with familial pheochromocytoma were clinically evaluated and followed up. Genomic DNA extracted from the peripheral blood of 8 family members （including 3 patients） was amplified by polymerase chain reaction （PCR） and the PCR products were directly sequenced. Results The first presentation in the proband, his mother, and his sister was bilateral pheochromocytoma, and the missense mutation of 695G-A （Arg161Gln） in exon 3 of VHL gene was detected in the three patients. In the follow-up study, the proband and his mother were found to have other VHL tumors, induding retinal and cerebellar hemangioblastomas and pancreatic tumor. Neither clinical presentation of VHL disease nor gene mutation was found in other family members. Conclusion VHL disease should be suspected in some patients with familial pheochromocytoma, and VHL gene screening helps to achieve early diagnosis of the disease.
文摘INSULINOMA is the most common cause of hypoglycemia. Although it is a rare disease, there has been a significant progress in its diagnosis along with the technology development. A set of
基金supported by the National Natural Science Foundation of China[81670706&81800736]Natural Science Foundation of Shandong Province[ZR2019PH078].
文摘In 2017,American College of Cardiology(ACC)/American Heart Association(AHA)et al.jointly released the latest guidelines for adult hypertension,exactly including prevention,diagnosis,assess and treatment,in which blood pressure levels greater than 130/80 mm Hg were defined as hypertension[1].Based on these modified guidelines,the morbidity of hypertension in US increased from 32%to 46%.
基金supported by grants from the National Natural Science Foundation of China(Nos.81572639,81370969 and 81072190 to X Yu)the Ministry of Education of the People's Republic of China(No.20130181110066 to X Yu)the Chengdu Bureau of Science and Technology(No.2014-HM01-00382-SF to X Yu)
文摘Type II autosomal dominant osteopetrosis(ADO2), which is the most common form of osteopetrosis, is caused by heterozygous mutations in the chloride channel 7(CLCN7) gene. The osteopetrosis of ADO2 has been attributed to hypofunctional osteoclasts. The mechanism underlying the abnormality in osteoclast function remains largely unknown. This study was designed to investigate gene mutations and osteoclast function in a case that was clinically diagnosed as ADO2. Genomic DNA was extracted from blood samples of this patient, and the 25 exons of CLCN7 were amplified. Peripheral blood from the ADO2 subject and a healthy age- and sex-matched control was used to evaluate osteoclastogenesis, osteoclast morphology, and bone resorption. Analysis of DNA from the patient showed a germline heterozygous missense mutation,c.1856C>T(p.P619L), in exon 20 of CLCN7. A similar homozygous mutation at this site was previously reported in a patient with autosomal recessive osteopetrosis. When cultured, the peripheral blood mononuclear cells(PBMCs) from the ADO2 patient spontaneously differentiated into mature osteoclasts in vitro. The ADO2 patient’s PBMCs formed enhanced, but heterogeneous, osteoclasts in both the presence and absence of macrophage-colony stimulating factor, and nuclear factor-?B ligand. Bone resorption was reduced in the ADO2 patient’s osteoclasts, which exhibited aberrant morphology and abnormal distribution of integrin avβ3. Gene analysis found increased c-fos expression and reduced Rho A and integrin beta 3expression in ADO2 cells. In conclusion, our data suggest that enhanced, heterogeneous osteoclast induction may be an intrinsic characteristic of ADO2.
基金supported by the National Natural Science Foundation of China(nos.81070687 and 81170805)Beijing Natural Science Foundation(no.7121012)+2 种基金Ministry of Science and Technology of the People’s Republic of China(National Science and Technology Major Projects for‘Major New Drugs Innovation and Development 2008ZX09312-016)Scientific Research Foundation of Beijing Medical Development(no.2007-3029)National Key Program of Clinical Science(WBYZ2011-873)
文摘Familial hypocalciuric hypercalcemia （FHH） is caused by inactivating mutations in the calcium-sensing receptor （CaSR） gene. The loss of function of CaSR presents with rickets as the predominant skeletal abnormality in mice, but is rarely reported in humans. Here we report a case of a 16-year-old boy with FHH who presented with skeletal manifestations of rickets. To identify the possible pathogenic mutation, the patient was evaluated clinically, biochemically, and radiographicaUy. The patient and his family members were screened for genetic mutations. Physical examination revealed a pigeon breast deformity and X-ray examinations showed epiphyseal broadening, both of which indicate rickets. Biochemical tests also showed increased parathyroid hormone （PTH）, 1,25-dihydroxyvitamin D, and elevated ionized calcium. Based on these results, a diagnosis of FHH was suspected. Sequence analysis of the patient＇s CaSR gene revealed a new missense mutation （c.2279T 〉 A） in exon 7, leading to the damaging amino change （p.I760N） in the mature CaSR protein, confirming the diagnosis of ~H. Moreover, the skeletal abnormities may be related to but not limited to vitamin D abnormity. Elevated ~H levels and a rapid skeletal growth period in adolescence may have also contributed. Our study revealed that rickets-like features have a tendency to present atypically in FHH patients who have a mild vitamin D deficiency, and that CaSR mutations may have a partial role in the pathogenesis of skeletal deformities.
文摘BACKGROUND A number of recent studies indicate a transformation in the natural course of chronic kidney disease(CKD)in type 2 diabetes(T2D)patients:an increasing prevalence of declined renal function without proceeding to the accompanying elevation of albuminuria.It has been suggested that albuminuric and nonalbuminuric CKD patterns could be different in their phenotypes and pathogenic mechanisms.AIM To identify the risk factors and biomarkers of albuminuric and non-albuminuric patterns of CKD in patients with T2D.METHODS Three hundred sixty patients with T2D duration≥10 years were included in this observational cross-sectional study.The associations of a panel of demographic and clinical characteristics,complications,comorbidities,and metabolic and hematology parameters with albuminuric and non-albuminuric CKD patterns were analyzed.The urinary excretion of nephrin and podocin,two podocytespecific markers,and WAP-four-disulfide core domain protein 2(WFDC-2),a marker of tubulointerstitial fibrosis,was determined by ELISA in comparison with healthy controls.RESULTS Non-albuminuric CKD was associated with age≥65 years(P=0.0001),female sex(P=0.04),diabetes duration≥15 years(P=0.0009),and the use of diuretics(P=0.0005).Male sex(P=0.01),smoking(P=0.01),waist-to-hip ratio>1.0(P=0.01)and hemoglobin A1c(HbA1c)>8.0%(P=0.005)were risk factors for elevated albuminuria not accompanied by a decrease in estimated glomerular filtration rate(eGFR).Duration of diabetes≥15 years and the use of calcium channel blockers were risk factors for albuminuria with decreased eGFR(both P=0.01).In multivariate logistic regression analysis,age,HbA1c,female sex and diuretics were significant predictors for reduced eGFR,while waist-to-hip ratio,HbA1c and male sex were associated with elevated urinary albumin-to-creatinine ratio(UACR).Excretion of nephrin and podocin was increased in patients with albuminuria,regardless of decline in renal function(P<0.001),correlating positively with UACR.The urinary excretion of WFDC-2 was markedly higher in men than in women(P<0.000001).Men with T2D demonstrated increased WFDC-2 levels independently of the CKD pattern(all P<0.05).In T2D women,WFDC-2 excretion was increased in those with reduced renal function(P≤0.01),correlating negatively with eGFR.CONCLUSION The data provide further evidence that albuminuric and non-albuminuric CKD phenotypes correspond to different pathways of diabetic kidney disease progression.
文摘Objective: To study the effects of low-dose and long-term hormone replacement therapy (HRT) on blood lipids in postmenopausal women.Methods: (1) 141 postmenopausal female medical staffs aged from 50 to 87 years with average 68 years were from Peking Union Medical college Hospital, among them 63 were treated with low-dose HRT for 5-31 years as HRT group, and other 78 postmenopausal women matched with age as the control group. (2) withdrew vein blood from objects on fasting for 12-14 h and serum was separated for determining serum concentration of lipid, lipoprotein and apolipoprotein. (3)data were analyzed with SPSS statistical software for statistical significance by P＜0.05.Results:In comparison with control, the levels of TG, HDL-C, LDL-C, apoA I , Lp(a) of HRT group had no statistical significance,but the levels of TC, TC/HDL-C, ApoE, ApoCⅢ and ApoB were significantly lower.Conclusion: The levels of TC, LDL-C, ApoB, ApoC Ⅲ, ApoE decreased significantly in postmenopausal women receiving low-dose and long-term HRT. The decrease in the levels of blood lipids may provide cardiovascular protection and reduce the risk of cardiovascular events.
