Objective To explore the clinical characteristics of immune-related adverse events (irAEs) involving the pituitary gland in malignant tumor patients following the administration of immune checkpoint inhibitors (ICIs), and to compare characteristics of pituitary irAEs with primary hypophysitis. Methods A total of 753 malignant tumor patients who were hospitalized at Sir Run Run Shaw Hospital School of Medicine, Zhejiang University from January 2019 to November 2022 and received ICIs treatment were retrospectively included. The incidence of endocrine irAEs were statistically analyzed. The clinical characteristics of patients with pituitary irAEs were analyzed and compared with those of patients with primary hypophysitis (n＝18). Results Among the 753 patients treated with ICIs, the majority (742, 98.5%) received PD-1/PD-L1 inhibitors. The incidence of endocrine irAEs was 32.0% (241/753), with primary thyroid dysfunction being most common (212, 28.2%), followed by pituitary dysfunction (35, 4.6%). The median time to onset of pituitary irAEs was 5.8 months, with the majority presenting as secondary hypoadrenocorticism (33, 94.3%). Surgery was a protective factor for preventing pituitary irAEs (P＝0.002), whereas higher body mass index (BMI) and dual ICIs combination therapy were recognized as risk factors (P＜0.05). Compared to patients with primary hypophysitis, patients with pituitary irAEs had a higher proportion of males, lower BMI, lower rates of visual field defects and diabetes insipidus, higher rate of secondary hypoadrenocorticism and lower positive rate on MRI (P＜0.05). Conclusions Malignant tumor patients treated with ICIs exhibit a relatively high incidence of endocrine irAEs, with thyroid involvement being most common, followed by the pituitary gland. Pituitary irAEs primarily manifest as secondary hypoadrenocorticism, lacking specific clinical symptoms and exhibiting a low positive rate on MRI. These factors contribute to a high risk of misdiagnosis or missed diagnosis, necessitating heightened clinical vigilance.

Objective:To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling.Methods:A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN.Results:DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A 1c (HbA 1c) ( OR=1.159, 95% CI 1.039-1.292), systolic blood pressure ( OR=1.041, 95% CI 1.031-1.051), serum creatinine (Scr) ( OR=1.011, 95% CI 1.004-1.017), serum globulin (GLOB) ( OR=1.072, 95% CI 1.039-1.105), diabetic retinopathy (DR) ( OR=1.463, 95% CI 1.073-1.996), education level of more than junior high school ( OR=2.018, 95% CI 1.466-2.777), and moderate-intensity exercise ( OR=0.751, 95% CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95% CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions:HbA 1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.

Objective:To analysis the correlation of eating speed with obesity.Methods:A total of 644 people aged 40-65 from Caihe Community in Hangzhou were enrolled to collect clinical and demographic data, undergo extensive physical examination and laboratory tests. Participants were divided into two groups according to their eating speed (non-fast and fast). Obesity-related parameters were compared between two groups. Multivariable logistic regression was conducted to explore the relationship between eating speed and obesity after adjusting confounders.Results:Body mass index, waist circumference, and visceral fat area were greater in the fast eating group than non-fast eating group(all P<0.01). After adjusting for age, gender, smoking, alcohol drinking, physical activity level per week, and principal food intake, logistic regression analysis showed that eating fast was correlated with abdominal obesity( OR=1.66, 95% CI 1.11-2.48, P=0.014) and visceral obesity( OR=1.65, 95% CI 1.14-2.39, P=0.007). After stratified by gender, in the group of men, eating fast was correlated with abdominal obesity( OR=2.04, 95% CI 1.07-4.04, P=0.032) and visceral obesity( OR=1.85, 95% CI 1.04-3.31, P=0.037); In the group of women, eating fast was correlated with overweight and obesity( OR=1.59, 95% CI 1.04-2.42, P=0.031). Conclusion:Eating fast is positively associated with obesity. Interventions for reducing eating speed may be effective for weight control.

Objective: The study was aimed to investigate the prevalence and causes of hyponatremia in hospitalized patients, and to analyze the relationship between hyponatremia and mortality. Methods: A retrospective analysis was carried out in 525 patients with hyponatremia, who were older than 14 years old and hospitalized in the Zhoushan Hospital from Jan. 2014 to Apr. 2014. Based on the severity of the hyponatremia the patients were divided into three groups: the mild, moderate and severe hyponatremia groups. The underlying causes of hyponatremia were analyzed, and the association between hyponatremia and mortality was explored using logistic regression analyses. Results: (1) The prevalence of hyponatremia was 5.26% in whole hospitalized patients (n=9 989) during the study period. It was 6.1% in the elderly population (≥60 years old). (2) Malignant tumors and infectious diseases were the main primary diseases of hyponatremia in all three groups. Among them, lung cancer was the most common malignant tumor, and pneumonia was the most common infectious disease associated with hyponatremia. Cerebral hemorrhage was common in patients with moderate and severe hyponatremia, in which subarachnoid hemorrhage was the major primary disease associated with moderate to severe hyponatremia. In the subgroup of elderly patients, malignant tumor and infectious diseases were the major basic diseases. (3) Among the 525 cases, 13.7% and 3.8% of them were diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt-wasting syndrome (CSWS), respectively. The proportions of SIADH and CSWS increased to 17.4% and 4.2%, respectively, in the elderly hyponatremic patients (n=264). (4) More patients were prescribed with sodium-excretion drugs in the moderate and severe hyponatremia groups than those in the mild one(42.2% vs.21.4%, 43.2% vs.21.4%, all P<0.05). (5) Patients with moderate or severe hyponatremia had a higher mortality compared to those with mild hyponatremia (moderate vs. mild group: OR 6.92, 95%CI 2.53-18.92, P<0.001; severe vs. mild group: OR 4.54, 95%CI 1.05-19.58, P=0.043). Conclusions Hyponatremia was common in hospitalized patients. The major primary diseases were malignant tumor (lung cancer), infectious diseases (pneumonia) and cerebral hemorrhage complicated with SIADH and CSWS. Use of sodium-excretion drugs increased the risk of moderate to severe hyponatremia. Patients with moderate to severe hyponatremia had a higher risk of death in hospitals.

Objective To investigate the correlation between serum uric acid (SUA) level and early-phase insulin secretion in subjects with normal glucose regulation (NGR).Methods Totally 367 community NGR residents confirmed by a 75g oral glucose tolerance test were enrolled.The insulin resistance index (HOMA-IR) and the early-phase insulin secretion index after a glucose load (ΔI30/ΔG30) were used to estimate the insulin sensitivity and the early-phase insulin secretion, respectively.The subjects were divided into 4 groups according to the SUA level quartiles.Differences in early-phase insulin levels, ΔI30/ΔG30, and HOMA-IR were compared among the 4 groups.Results Age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting insulin (FINS), 30 minutes postprandial insulin (30 minINS), 2 hours postprandial insulin(2hlNS), HOMA-IR and TG levels increased across the rising categories of SUA levels, while the HDL-C was decreased across the SUA groups (P ＜ 0.01).The SUA level was positively correlated with age (r =0.157, P ＜ 0.01), BMI (r =0.262, P ＜ 0.01), waist circumference(r =0.372, P ＜ 0.01), systolic blood pressure (r =0.200, P ＜ 0.01), diastolic blood pressure(r =0.254,P ＜ 0.01) , 30 minutes postprandial plasma glucose(r =0.118 ,P =0.023), FINS(r =0.249, P ＜ 0.01), 30minlNS (r =0.189, P ＜ 0.01) ,2hlNS (r =0.206, P ＜ 0.01), glycosylated hemoglobin (HbAlc, r=0.106,P =0.042), HOMA-IR(r =0.244,P ＜0.01), TG(r =0.350,P ＜0.01), ΔI30/ΔG30 (r =0.144, P ＜ 0.01), and negatively correlated with HDL-C level (r =-0.321, P ＜ 0.01).Multiple stepwise regression analysis showed that SUA (β =0.292, P ＜ 0.01) and HOMA-IR (β3 =29.821, P ＜ 0.01)were positively associated with ΔI30/ΔG30.Conclusion SUA level is closely related with the early-phase insulin secretion in NGR subjects.

Objective To investigate the relationship between serum uric acid (UA) level and abdominal obesity or metabolic syndrome (MS).Methods A total of 875 subjects,with 350 males and 525 females,aged 40-65 years old,were enrolled in this study.The clinical and biochemical data were collected and MRI was used to assess the visceral and subcutaneous adipose tissues.The relationships between UA level and abdominal obesity or MS were analyzed,and the cut-off values of UA for abdominal obesity and MS were determined.Results Raised risks of abdominal obesity (OR =4.35,95％ CI 1.91-9.90 in males; OR =5.44,95％ CI 2.41-12.31 in females) and MS (OR =4.47,95 ％ CI 2.08-9.62 in males; OR =11.62,95％ CI 3.43-39.37 in females) were observed with the increase of UA level.The multiple logistic regression analysis showed that UA was an independent risk factor for hypertriglyceridemia (OR =2.23,95％ CI 1.02-4.87 in males ; OR =3.04,95％ CI 1.49-6.23 in females) in all subjects and for abdominal obesity(OR =3.23,95％ CI 1.32-7.91) and hypertension (OR =2.35,95％ CI 1.37-4.05)in the females.Among the females,the regression line analyzed by simple correlation indicated that the UA level of 244.0 μmol/L was corresponded to the visceral adipose tissue area of 80 cm2.The optimal cut-off point of UA for the diagnosis of MS was 258.8 μmol/L determined by the receiver operating characteristic curve.Conclusions The level of UA is closely correlated with abdominal obesity and MS in the middleaged Chinese.The elevated UA level is an independent risk factor for abdominal obesity and MS in the female.

Objective To evaluate the clinical effectiveness in screening asymptomatic diabetic peripheral neuropathy(ADPN) by the Michigan neuropathy screening instrument (MNSI) and the Toronto clinical scoring system(TCSS).Methods MNSI,TCSS and neural electrophysiological test (NET) were conducted in 232 neurologically asymptomatic type 2 diabetes patients.By using the results of NET as the golden criteria for diagnosis of ADPN,we evaluated the effectiveness of the two different scoring system by the receiver operator characteristic curve.The sensitivity,specificity,positive and negative predictive values,accuracy,Youden indexes and kappa values on different diagnostic cut-off points of MNSI and TCSS were analyzed.The correlation between the two different scoring system and the risk factors of diabetic peripheral neuropathy (DPN) were also analyzed.Results The area under the ROC curve of MNSI and TCSS were 0.792,0.704,respectively.The sensitivity,specificity,accuracy,Youden indexes and kappa values of MNSI over 2 and TCSS over 2 were 66.2％ vs 73.3％,90.4％ vs 63.7％,78.3％ vs 68.5％,0.566 vs 0.370,and 0.588 vs 0.345,respectively.MNSI was better than TCSS in the effectiveness of diagnosing ADPN and consistence with the result of NET.Moreover,MNSI was associated with the most related risk factors of DPN including age,glycosylated hemoglobin (HbA1c),HbA1c × disease duration,islet function and HDL-C.Conclusions MNSI could be used as a relatively simple and reliable method for clinical and epidemiological screening and assessment of ADPN.

OBJECTIVETo investigate effects of glucose excursion on the oxidative/antioxidative system in subjects with different types of glucose regulation.

METHODSA total of 30 individuals with normal glucose regulation (NGR), 27 subjects with impaired glucose regulation (IGR) and 27 subjects with newly diagnosed type 2 diabetes mellitus (T2DM) were selected and recruited for 3 days' continuous glucose monitor system (CGMS) assessment. The data from CGMS was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), area under the ROC curve when the blood glucose >5.6 mmol/L within 24 h (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE). In all groups, the content or activity of malondialdehyde (MDA), total antioxidation capacity (TAOC) and glutathione peroxidase (GSH-Px) were detected.

RESULTSGlucose excursion parameters of subjects with T2DM or IGR were higher than those of NGR subjects (P<0.05 or 0.01). Moreover, Glucose excursion parameters of T2DM subjects were higher than those of IGR subjects (P<0.05 or 0.01). Subjects with T2DM or IGR had significant higher MDA levels and lower GSH-Px/MDA and TAOC/MDA levels compared to NGR subjects (P<0.01). T2DM subjects had even higher MDA levels and lower GSH-Px/MDA levels than IGR (P<0.05 or 0.01). According to the median of normal population for MAGE, T2DM and IGR subjects were divided into MAGE>2.6mmol/L Group and MAGE ≤ 2.6mmol/L Group. MAGE>2.6mmol/L Group had higher levels of MDA and lower levels of GSH-Px/MDA than MAGE ≤ 2.6mmol/L Group (P<0.05). There was no significant difference between the two groups (P>0.05) in terms of the levels of TAOC/MDA. Pearson correlation analysis showed that MDA was positively correlated with FPG, 2hPG, MAGE, and SBP. GSH-Px/MDA was negatively correlated with MAGE and TC. TAOC/MDA was negatively correlated with FPG. Partial correlation analysis showed that the relationship between MDA and MAGE, GSH-Px/MDA, and MAGE remained significant after adjustments for the other differences among groups.

CONCLUSIONGlucose excursion contributed significantly to promoting lipid peroxidation and decreasing antioxidation capacity than chronic sustained hyperglycemia did in the subjects with different types of glucose regulation.

Adult ; Antioxidants ; metabolism ; Blood Glucose ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Oxidation-Reduction

Objective To investigate the prevalence of renal insufficiency and its associated factors in type 2 diabetes mellitus with normoalbuminuria using estimated glomerular filtration rate ( eGFR) .Methods We retrospectively analyzed 10-year data of chronic complications in type 2 diabetics in-patient from the Chinese Diabetes Society.eGFR was estimated using the equation from Modification of Diet in Renal Disease(MDRD) study.The clinical characteristics as well as associated factors for low eGFR were analyzed among the normoalbuminuric type 2 diabetic patients.Results A total of 1351 type 2 diabetic patients were included, 755 patients with normoalbuminuria, 466 patients with microalbuminuria and 130 patients with macroalbuminuria respectively.Among the patients, 310 (22.9% ) had low eGFR (GFR <60 ml · min~(-1) · 1.73 m~(-2) ) , 19.7% (149/755) in the patients with normoalbuminuria, 21.9% (102/466) in microalbuminuria and 45.4% ( 59/130 ) in macroalbuminuria Patients with normoalbuminuria and low eGFR suffered more chronic complications than those with normoalbuminuria and normal eGFR, mainly retinopathy, cerebrovascular diseases and sensory neuropathy.Stepwise logistic regression analysis revealed that age ( OR = 1.042, P < 0.001), diabetic duration ( OR = 1.038, P = 0.045), systolic blood pressure (OR = 1.017, P < 0.001) were independently associated with renal impairment among the patients with normoalbuminuria.Body mass index ( OR = 0.868, P < 0.001) and HbAlc (OR =0.898, P =0.021) were also related with renal insufficiency.Conclusion A considerable proportion in type 2 diabetic patients without albuminuria may exist renal impairment, and eGFR estimation could benefit the evaluation of renal function in such patients.

Objective To investigate the effect of HIV-1 protease inhibitor saquinavir on insulin signaling and β-cell function in rat INS-1 cells. Methods INS-1 cells were preincubated with 0 or 10 μmol/L saquinavir for 48 h, stimulated with 100 nmol/L insulin for 2 min or 20 mmol/L glucose for 30 min. Insulin signaling parameters were analyzed by immunoprecipitation and Western blot on cell lysates. Insulin concentrations in the supernatant were measured by ELISA, and standardized by cellular DNA contents. Cell count with trypan blue stain and MTT test were determined to evaluate the effect of saquinavir on cell viability. Results Treatment with saquinavir for 48 h significantly decreased insulin-stimulated phosphorylation of IRS-1, IRS-2 and Thr~(308)-phosphorylation of Akt in INS-1 cells by 60%, 66% and 55%, decreased the rate of basal insulin secretion and glucose-stimulated insulin release by 39% and 49% compared with control cells, respectively. Conclusions Treatment with saquinavir impairs insulin signal transmission in pancreatic β cells and results in insulin resistance in β cells. This effect might influence the function of β cells.