Objective:To explore the relationship between serum retinol binding protein(RBP)and metabolic-associated fatty liver disease(MAFLD)in elderly patients with type 2 diabetes mellitus(T2DM)and possible underlying metabolic mechanisms.Methods:A total of 3384 elderly T2DM patients hospitalized and with complete clinical records at the Department of Endocrinology and Metabolism, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University between January 2003 and December 2012 were recruited in this retrospective study.Patients were divided into four groups according to the quartiles of serum RBP levels: the first quartile of serum RBP levels(<35 mg/L, 844 cases), the second quartile of serum RBP levels(35 mg/L≤ RBP ≤41 mg/L, 773 cases), the third quartile of serum RBP levels(42 mg/L≤ RBP ≤51 mg/L, 902 cases), and the fourth quartile of serum RBP levels(RBP>51 mg/L, 865 cases). Clinical data and laboratory test results were collected.Differences in the prevalence of MAFLD were compared between the four groups.The association between RBP and MAFLD was analyzed via binary logistic regression.Results:After adjusting for age and sex, the proportion of obesity( χ2=15.222, P<0.01), the percentage using lipid-lowering drugs( χ2=88.552, P<0.01), systolic blood pressure( F=12.002, P<0.01), diastolic blood pressure( F=6.872, P<0.01), waist circumference( F=9.563, P<0.01), waist-hip ratio( F=7.972, P<0.01), body mass index( F=9.057, P<0.01), serum creatinine( χ2=185.445, P<0.01), serum uric acid( χ2=314.691, P<0.01), 24-hour urinary albumin( χ2=91.012, P<0.01), alanine aminotransferase( χ2=17.049, P=0.003), γ-glutamyl transpeptidase( χ2=50.514, P<0.01), total cholesterol( F=45.669, P<0.01), triglycerides( χ2=361.269, P<0.01), low-density lipoprotein( F=8.772, P<0.01), fasting C-peptide( χ2=165.756, P<0.01), 2h postprandial C-peptide( χ2=120.690, P<0.01), and the homeostasis model assessment of insulin resistance(HOMA2-IR)( χ2=148.884, P<0.01)in elderly patients with T2DM all showed a clear upward trend.The prevalence of MAFLD also gradually increased across the quartiles of serum RBP levels[26.5%(224/844), 30.1%(233/773), 36.6%(330/902), and 41.8%(362/865)], respectively( χ2=52.526, P<0.01). Elderly T2DM patients with MAFLD had a significantly higher value of HOMA2-IR than those without MAFLD[2.0(1.31-2.8) vs.1.39(0.86-2.06), F=220.826, P<0.01]. After correcting for other confounding factors, binary logistic regression showed that serum RBP was strongly associated with the presence of MAFLD in elderly patients with T2DM( β=0.209, 95% CI: 1.079-1.408, OR=1.232, χ2=9.441, P<0.01). Conclusions:Elevated serum RBP levels are an independent risk factor for the development of MAFLD in elderly T2DM patients, possibly through increased insulin resistance induced by RBP.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. METHODS: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. RESULTS: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. CONCLUSION: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Brain Neoplasms/genetics*

Objective To investigate the association of uric acid excretion(UUAE)with obesity and abdominal obesity in newly diagnosed patients with type 2 diabetes mellitus(T2DM).Methods A total of 1175 newly diagnosed T2DM patients hospitalized in the Department of Endocrinology and Metabolism of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from January 2006 to December 2012.According to the quartile of UUAE,they were divided into Q1 group(UUAE＜2383 μmol/24 h,n=295),Q2 group(2383≤UUAE＜2953 μmol/24 h,n=292),Q3 group(2954≤UUAE＜3680 μmol/24 h,n=292)and Q4 group(UUAE＞3680 μmol/24 h,n=293).Clinical data and laboratory examination results were collected,and the prevalence of obesity and abdominal obesity was compared among the four groups.The associations of UUAE with obesity and abdominal obesity were analyzed.Results The prevalence of obesity was 47.9%,while the prevalence of abdominal obesity was 61.9%in the whole study population.After adjusting for age,the prevalence of abdominal obesity was higher in women than in men(P＜0.05).After adjusting for age and gender,the prevalence of obesity and MS was higher in Q4 group than in Q1,Q2,and Q3 groups(P＜0.05),and the prevalence of abdominal obesity was higher in Q4 group than in Q1 and Q2 groups(P＜0.05).Compared with Q1 group,the proportion of men,BMI,WC,DBP,FIns,2 hIns,HOMA-IR,TG,ALT,γ-GT,SUA,UAlb in Q4 group increased(P＜0.05),age,HbA1c,HDL-C decreased(P＜0.05).Logistic regression analysis showed that after adjusting for confounding factors,UUAE was a factor affecting obesity and abdominal obesity.Conclusion UUAE increases the risk of obesity,abdominal obesity and MS in newly diagnosed T2DM patients.UUAE may be used as a simple indicator to assess the risk of metabolic disorders such as obesity and MS in T2DM patients.

Objective:To investigate the association of the difference between 2-hour postprandial blood glucose and fasting blood glucose with non-alcoholic fatty liver disease(NAFLD)in elderly patients with type 2 diabetes(T2DM).Methods:A total of 953 patients aged≥65 years with T2DM hospitalized in the Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital from January 2007 to June 2009, with complete clinical data, were selected in this retrospective study.The absolute value of the difference between 2-hour postprandial blood glucose and fasting blood glucose was recorded as the blood glucose difference.According to the tertiles of the blood glucose difference, patients were divided into three groups including the first tertile(n=317, blood glucose difference<4.12 mmol/L), the second tertile(n=320, blood glucose difference between 4.12-7.69 mmol/L), and the third tertile(n=316, blood glucose difference≥7.69 mmol/L). Detailed clinical data of the patients were collected, and clinical characteristics and the prevalence of NAFLD were compared among the three groups.The correlation between the blood glucose difference and NAFLD was analyzed.Results:From the first tertile to the third tertile, there appeared to be increased proportions of patients using metformin( χ2=9.581, P=0.008), higher waist-to-hip ratios( F=3.663, P=0.026), increased 24 h uric acid excretion( χ2=6.241, P=0.044), increased alanine aminotransferase levels( χ2=22.361, P<0.001), increased γ-glutamyl transpeptidase levels( χ2=17.681, P<0.001)and increased 2h postprandial blood glucose levels( χ2=579.315, P<0.001), with significant statistical differences in the waist circumference( F=4.723, P=0.009), body mass index( F=5.811, P=0.003), fasting C-peptide levels( χ2=9.442, P=0.009), 2h postprandial C-peptide levels( χ2=17.599, P<0.001)and glycosylated hemoglobin A1c( F=30.836, P<0.001)between the three groups and the prevalence of NAFLD also grew steadily(24.0%, n=76 vs. 33.1%, n=107 vs. 36.7%, n=116, χ2=12.712, P<0.01). After adjusting for other variables, multivariate logistic regression analysis showed that the blood glucose difference was correlated with NAFLD in elderly patients with T2DM( OR=1.396, Wald χ2=0.002, P<0.01). Conclusions:Elderly T2DM patients with greater blood glucose differences have more severe metabolic disorders and a higher prevalence of NAFLD.An increase in blood glucose differences is an independent risk factor for NAFLD in elderly T2DM patients.

Objective To investigate the association between serum estradiol levels and macrovascular complication of atherosclerosis in mid-aged and elderly male patients with type 2 diabetes mellitus(T2DM).Methods One hundred and twenty nine male diabetic patients aged over 45 years were recruited in this study.Serum estriol(E2), testosterone(T)and lipid levels were detected using chemiluminescent immunoassay.Carotid ultrasonography was taken to evaluate macrovascular complication of atherosclerosis.The demographic characteristics, clinical features including duration of diabetes and prevalence of carotid atherosclerosis and biochemical features were compared among patients with different serum E2levels.Correlation analysis was also performed using binary logistic analysis.Results There were 43 patients with low serum E2level(<134.1 pmol/L), 44 with intermediate E2level(134.1 -198.2 pmol/L)and 42 with high E2level(>198.2 pmol/L).Among 129 patients the carotid artery lesions were detected in 64 cases.There were significant differences in body weight[(61.0 ±10.4), (67.4 ±13.0)and(76.8 ±10.5)kg,t=3.40,P=0.00], waist circumference[(81.5 ±7.9),(86.6 ± 10.7)and(90.0 ±8.0)cm,t=3.57,P=0.00],body mass index(BMI)[(21.6 ±3.2),(23.5 ±3.8) and(26.2 ±3.0)kg/m2,t=3.72, P=0.00], systolic pressure[(140.2 ±14.8),(143.9 ±18.1)and (155.0 ±13.1)mmHg(1 mmHg=0.133 kPa),t=3.18, P=0.04]and TG[(1.46 ±0.88),(2.23 ± 1.08)and(3.35 ±0.9)mmol/L, t =2.66, P=0.04]among patients with low, intermediate and high serum E2levels.The age-adjusted incidence of carotid atherosclerotic plaque in patients with low, intermediate and high E2levels were 25.6%(11/43),56.8%(25/44)and 66.7%(28/42), respectively (χ2=15.73,P=0.00).Compared to low E2level,the risk ratio of carotid atherosclerosis in intermediate and high E2levels was 1.60(95%CI:1.04-2.46, P<0.05)and 1.80(95%CI:1.17 -2.76, P<0.05),respectively.Conclusion Serum E2level is closely associated with carotid atherosclerotic plaque in middle-aged and elderly male type 2 diabetic patients.

Objective Metabolites produced by metabolic imbalance such as free fatty acids and lipopolysaccharides can result in a state of chronic low-grade inflammation, or metabolic inflammation, which plays an important role in the pathogenesis of atherosclerosis, type 2 diabetes, non-alcoholic fatty liver disease, and obesity. The above metabolic disorders are closely related with the metabolic inflammation, which always coexist. Therefore, we proposed the concept ofmetabolic inflammatory syndrome ( MIS). According to our study, patients with two or more metabolic disorders above could be diagnosed as MIS. The current research is aimed to investigate the prevalence of MIS and its components, and to compare the clinical values of MIS and metabolic syndrome ( MS) . Methods 2 001 in patients with type 2 diabetes from 6 hospitals in Shanghai were recruited in the current multi-center cross-sectional study. The diagnostic rates of MIS and MS and their components of both syndromes were compared. Results In the patients with type 2 diabetes, the detective rate of MIS was 96. 2%, which was higher than that of MS (71. 3%). Among 4 components of MIS, atherosclerosis showed the highest detective rate (75.6%). MIS[OR=2.252(95%CI1.026-4.942),P=0.043],atherosclerosis[OR=2.726(95% CI1.953-3. 804),P<0. 001], and MS[OR=1. 915 (95%CI 1. 444-2. 540),P<0. 01] were the risk factors of coronary heart disease. Conclusion With atherosclerosis, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and obesity as its 4 components, MIS has a high detective rate in patients with metabolic disorders, and seems to be more sensitive than MS to distinguish inflammation-related metabolic diseases. The concept of MIS will promote the screening and prevention of atherosclerosis in its early stage.

Objective To determine the prognostic significance of non-thyroidal illness syndrome(NTIS) and FT3 on long-term all-cause and cardiovascular mortality in patients with coronary artery disease(CAD).Methods A total of 1 354 patients underwent coronary angiograhy and participated in the study.After screening,984 patients with CAD were enrolled finally and divided into NTIS group and euthyroid group.The admitted patients were also classified into Tertile 1-3 groups based on FT3 value.The relationship of long-term all-cause and cardiovascular mortality with FT3 was investigated by multivariate Cox regression analysis.Results 129 out of 984 patients had NTIS.As FT3 value decreased,both long-term all-cause mortality (Tertile 1 group 9.6％,Tertile 2 group 11.5％,Tertile 3 group 20.9％,P＜0.01) and cardiovascular mortality (Tertile 1 group 4.5 ％,Tertile 2 group 7.2％,Tertile 3 group 11.0％,P＜0.01) gradually increased.After adjusting for all factors,FT3 (HR =0.614,95％ CI 0.439-0.859)was independently associated with long-term all-cause mortality.FT3 (HR =0.605,95％ CI 0.370-0.986)was also a risk factor for cardiovascular mortality.Conclusion NTIS exists in patients with CAD without myocardial infarction.FT3 reduction is an independent risk factor for long-term all-cause and cardiovascular mortality in patients with CAD.

Objective To observe the impact of olmesartan and alprostadi on diabetic pa-tients with microalbuminuria.Methods 40 patients were divided into group A given olmesartan and B group given olmesartan and alprostadil.The two groups were treated for 2 weeks.The changes of microalbuminuria 、glomerular filtration rate,blood pressure,high-sensitivity C-reactive protein and blood clotting were observed.Results During the treament,there was statistically significant in the effect of microalbuminuria in group B than that in group A;There were signifi-cant difference in two groups of glomerular filtration rate,blood pressure,high-sensitivity C-reac-tive protein,and there was no significant difference in two groups of clotting change.Conclusion In group B,reduced microalbuminuria,glomerular filtration rate,blood pressure,high-sensitivity C-reactive protein was related with inhibition of the renin-angiotensin,and related to anti-kidney local hypercoagulable and micro-inflammatory state.

Objective To observe the impact of olmesartan and alprostadi on diabetic pa-tients with microalbuminuria.Methods 40 patients were divided into group A given olmesartan and B group given olmesartan and alprostadil.The two groups were treated for 2 weeks.The changes of microalbuminuria 、glomerular filtration rate,blood pressure,high-sensitivity C-reactive protein and blood clotting were observed.Results During the treament,there was statistically significant in the effect of microalbuminuria in group B than that in group A;There were signifi-cant difference in two groups of glomerular filtration rate,blood pressure,high-sensitivity C-reac-tive protein,and there was no significant difference in two groups of clotting change.Conclusion In group B,reduced microalbuminuria,glomerular filtration rate,blood pressure,high-sensitivity C-reactive protein was related with inhibition of the renin-angiotensin,and related to anti-kidney local hypercoagulable and micro-inflammatory state.

Objective To review the clinical features,diagnosis,management and prognosis of patients with nonfunctional malignant adrenal tumors. Methods 12 patients admitted with nonfunctional malignant adrenal tumors from 1990 to 2000 were reviewed.Among them 6 cases had symptoms of fever,ostealgia,etc.The tumor measured 3 cm in 1 case,5 to 10 cm in 9 cases and more than 10 cm in 2 cases.Ten cases developed local invasion and (or) matastasis. Results Five cases underwent tumor excision or enucleation and 5 underwent biopsy only.Of these 10 cases,4 were pathologically diagnosed as cortical adenocarcinoma,4 as metastatic carcinoma,1 as mucous liposarcoma and 1 as lymphoma.The remaining 2 cases had no operation.One case died during hospital stay.Ten cases died within 2 years.One case of adrenocortical carcinoma experienced relapse 3 years after initial operation and died next year. Conclusions Nonfunctional malignant adrenal tumor is rare and difficult to diagnosis in early stage,indicating an extremely poor prognosis.Tumor diameter is an important factor to be considered regarding surgical indication.