Clinical characterization and genetic analysis of 5 Chinese families with glucokinase gene mutations / 中华内分泌代谢杂志

Objective:To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2 (MODY2) caused by glucokinase (GCK) gene mutations.Methods:Clinical data and biochemical results of probands were collected. Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing. After comparing against the database, the suspected pathogenic sites were selected for Sanger sequencing verification.Results:All the 5 probands presented with mild fasting hyperglycemia, HbA 1C<7.5%, and no symptoms of thirst, polydipsia or polyuria. There were 6 mutants in 5 families, including M1: c.555delT (P.leu186CysFS Ter19) and M3: c. 263T>A (p.Met88Lys) which haven′t been reported before. During the follow-up, all probands received life-style intervention, except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes. Conclusion:Among patients who meet the diagnostic criteria for MODY, MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history. GCK gene detection is the gold standard for diagnosis, and accurate diagnosis will be conducive to the selection of appropriate treatment.

Approach to the patient with pituitary metastases initially manifested as central diabetes insipidus / 中华内分泌代谢杂志

The data of 10 patients with pituitary metastases were retrospectively analyzed, including tumor origin, clinical features, imaging characteristics, diagnosis and differential diagnosis, treatment and prognosis. The results showed that the average age of 10 patients at the time of consultation was 62.0 years. Nine metastases were originated from lung cancer and one from breast cancer. All patients started with central diabetes insipidus, and some of them accompanied with hypopituitarism, as well as occupancy manifestations such as headache, blurred vision, etc. MRI showed abnormalities in the pituitary stalk and posterior pituitary, four of which showed characteristic " dumbbell-shaped" changes. Three patients with epidermal growth factor receptor(EGFR)-mutated lung adenocarcinoma revealed improvement in both primary lesion and pituitary metastases after targeted therapy.

Risk factors in predicting lymph node metastases in intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the risk factors of lymph node metastases in patients with intrahepatic cholangiocarcinoma (ICC) and to establish a risk prediction model of lymph node metastases in ICC.Methods:The clinicopathological data of 587 ICC patients who underwent radical hepatectomy and lymph node dissection at Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) from January 2007 to December 2011 were retrospectively analyzed. There were 395 males and 192 females with ages which ranged from 20 to 82 (54.7±10.8) years. Independent risk factors of lymph node metastases were studied using univariate and multivariate logistic regression analysis, and a risk prediction model was established. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of this model.Results:Of 587 patients, 158 (26.9%) had lymph node metastases. Multivariate logistic regression analysis showed that platelet count >300×10 9/L ( OR=1.985, 95% CI: 1.030-3.824, P=0.041), carbohydrate antigen 19-9 >37 U/ml ( OR=2.978, 95% CI: 1.994-4.448, P<0.001), tumor situated in left hemiliver ( OR=1.579, 95% CI: 1.065-2.341, P=0.023), multiple tumors ( OR=1.846, 95% CI: 1.225-2.783, P=0.003), and absence of cirrhosis ( OR=2.125, 95% CI: 1.192-3.783, P=0.011) were independent risk factors for lymph node metastases in ICC. The area under the ROC curve was 0.714, with a cutoff value of 0.215, and the sensitivity and specificity being 75.9% and 58.3%, respectively. Conclusions:The risk prediction model of ICC lymph node metastases was established using readily available clinical data obtained before operation. This model has good predictive values and can provide a reference for treatment decision on patients with ICC.

Influence of different options of preoperative biliary drainage on perioperative complications of patients with periampullary carcinoma undergoing pancreaticoduodenectomy / 中华肝胆外科杂志

Objective:To evaluate the effect of different options of preoperative biliary drainage (PBD) on perioperative complications of patients undergoing pancreaticoduodenectomy (PD).Methods:The clinical data of patients undergoing PD for periampullary carcinoma from January 2016 to November 2021 at Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) were retrospectively analyzed. The 303 patients including 199 males and 104 females, aged (64.2±8.8) years. According to PBD, the patients were divided into two groups: percutaneous transhepatic biliary drainage (PTBD) group ( n=228) and endoscopic retrograde cholangiopancreatography (ERCP) group ( n=75). PBD operation-related complications (including bleeding, biliary leakage, etc.), postoperative complications of PD (including pancreatic fistula, biliary leakage, surgical site infection, etc.) and perioperative complications (PBD operation-related complications + postoperative complications of PD) were compared between the two groups. Univariate and multivariate logistic regression analysis were used to analyze factors influencing perioperative complications of PD. Results:The incidence of PBD operation-related complications in PTBD group was 10.1% (23/228), lower than that in ERCP group 25.3%(19/228), and the difference was statistically significant (χ 2=10.99, P=0.001). The incidence of postoperative complications of PD in PTBD group was 38.2%(87/228), lower than that in ERCP group 69.3%(52/75), the difference was statistically significant (χ 2=22.09, P<0.001). The incidence of total perioperative complications in PTBD group was 44.3% (101/228), lower than that in ERCP group 73.3%(55/75), the difference was statistically significant (χ 2=19.05, P<0.001). Multivariate logistic regression analysis showed that patients with periampullary carcinoma undergoing ERCP biliary drainage and PD had increased risk of surgical site infection ( OR=2.86, 95% CI: 1.59-5.16, P<0.001) and pancreatic fistula ( OR=3.06, 95% CI: 1.21-7.74, P=0.018). Conclusion:ERCP biliary drainage is a risk factor for postoperative pancreatic fistula and surgical site infection in patients with periampullary carcinoma undergoing PD. PTBD should be recommended as the first choice for the patients underwent PD.

Clinical characteristics of congenital nephrogenic diabetes insipidus / 中华内科杂志

The purpose of this study was to improve the ability to visualize and diagnose congenital nephrogenic diabetes insipidus (CNDI). The clinical manifestations, laboratory examination findings, imaging features and treatment outcomes of 22 patients with CNDI admitted to the First Affiliated Hospital of Zhengzhou University from May 2013 to May 2020 were retrospectively analyzed. Among the 22 patients with CNDI, 86.4% (19 cases) were male. The age of the 22 patients ranged from 2 months to 47 years old, in which 20 cases were younger than 30 years old and 2 cases were older than 30 years old. The clinical manifestations were polydipsia and polyuria, accompanied with various degrees of fever, defects in growth and development, and increased serum creatinine in some patients. Fifteen patients (68.2%) had different degrees of bilateral kidney and ureteral hydronephrosis, and increased residual urine volume in the bladder. Pituitary magnetic resonance imaging (MRI) enhanced scan showed that the high signal intensity in the posterior pituitary lobe was not detectable in 5 cases (22.7%), and blurred in 6 cases (27.3%). Seven tested patients were all found AVPR2 gene mutation. For patients with suspected CNDI, water-inhibiting vasopressin test and genetic testing should be performed in time so as to confirm diagnosis and treat as early as possible.

25-hydroxyvitamin D, sex hormone levels and cardiovascular risk among men in northeast area of Henan province / 中华内科杂志

Objective@#To examine associations of 25-hydroxyvitamin D [25(OH)D] concentrations with sex hormone levels and cardiovascular risk factors.@*Methods@#A total of 697 male subjects were obtained from the thyroid disorders, lodine status and diabetes: a national epidemiological survey-2014 (TIDE) research--Henan sub-center survey through multistage stratified cluster random sampling from December 2015 to March 2016. The associations between 25(OH)D and sex hormones or cardiovascular risk factors were analyzed by linear regression analyses.@*Results@#The age of the subjects was (46.6±15.9) years (19-85 years). Proportions of vitamin D deficient, vitamin D intermediate and vitamin D optimal were 9.3%, 13.1% and 77.6%, respectively. More subjects with vitamin D deficient were in urban area than in rural area (13.3% vs. 5.7%, P=0.001). After fully adjusting for age, residence area, economic status, education, body mass index, waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), hypertension, diabetes, triglyceride, high-density lipoproteincholesterol, total cholesterol, low-density lipoprotein cholesterol and uric acid, linear regression analyses showed that every 25 nmol/L increase in 25(OH)D levels increased lg FT(FT=free testosterone) by 0.013ng/L (β=0.013, P=0.036), lg DHT (DHT=dihydrotestosterone) by 0.030 ng/L (β=0.030, P=0.019), and lg AD (AD=androstenedione) by 0.019 μg/L (β=0.019, P=0.008). After fully adjusting for age, residence area, economic status and education, every 25 nmol/L increase in 25(OH)D levels lowered glycosylated hemoglobin A1c (HbA1c) by 0.051% (β=-0.051, P=0.027).@*Conclusions@#Higher 25(OH)D concentrations in men were associated with higher FT, DHT, AD and lower HbA1c levels.

25?hydroxyvitamin D, sex hormone levels and cardiovascular risk among men in northeast area of Henan province / 中华内科杂志

To examine associations of 25?hydroxyvitamin D [25(OH)D] concentrations with sex hormone levels and cardiovascular risk factors. Methods A total of 697 male subjects were obtained from the thyroid disorders, lodine status and diabetes: a national epidemiological survey?2014 (TIDE) research??Henan sub?center survey through multistage stratified cluster random sampling from December 2015 to March 2016. The associations between 25(OH)D and sex hormones or cardiovascular risk factors were analyzed by linear regression analyses. Results The age of the subjects was (46.6 ± 15.9) years (19?85 years). Proportions of vitamin D deficient, vitamin D intermediate and vitamin D optimal were 9.3%, 13.1% and 77.6%, respectively. More subjects with vitamin D deficient were in urban area than in rural area (13.3% vs. 5.7%, P=0.001). After fully adjusting for age, residence area, economic status, education, body mass index, waist circumference, homeostasis model assessment of insulin resistance (HOMA?IR), hypertension, diabetes, triglyceride, high?density lipoproteincholesterol, total cholesterol, low?density lipoprotein cholesterol and uric acid, linear regression analyses showed that every 25 nmol/L increase in 25(OH)D levels increased lg FT(FT=free testosterone) by 0.013ng/L (β=0.013, P=0.036), lg DHT (DHT=dihydrotestosterone) by 0.030 ng/L (β=0.030, P=0.019), and lg AD (AD=androstenedione) by 0.019 μg/L (β=0.019, P=0.008). After fully adjusting for age, residence area, economic status and education, every 25 nmol/L increase in 25(OH)D levels lowered glycosylated hemoglobin A1c (HbA1c) by 0.051% (β=-0.051, P=0.027). Conclusions Higher 25(OH)D concentrations in men were associated with higher FT, DHT, AD and lower HbA1c levels.

SALL4 and its clinical application value in non-germ cell tumors / 国际肿瘤学杂志

Sal-like 4 (SALL4) plays an important role in promoting the cellular proliferation and maintaining the pluripotency of embryonic stem cells and tumor cells.In fully differentiated cells,the expression of SALL4 is silenced or down-regulated.However,the expression of SALL4 is found to be restored or up-regulated in a variety of non-germ cell tumors.Besides,the expression of SALL4 is often associated with disease progression,treatment effect and prognosis.Therefore,examining the expression level of SALL4 will be of great importance in the diagnosis of disease and monitoring the disease progression for non-germ cell tumors.

Predictive value of liver enzymes and alcohol consumption for risk of type 2 diabetes / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the predictive value of liver enzymes and alcohol consumption for determining risk of type 2 diabetes (T2DM).</p><p><b>METHODS</b>A cross-sectional study was conducted in Zhengzhou with a total of 2, 693 men.Participants' height, weight, and histories of smoking and drinking were recorded. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and blood glucose, as well as related metabolic indexes were detected.</p><p><b>RESULTS</b>Moderate daily alcohol consumption (more than 35 g ethanol/week and less than 140 g ethanol/week) decreased the risk of type 2 diabetes (OR =0.376, 95% CI:0.306 -0.463, P less than 0.05) but increased risk for higher levels of GGT and ALT (OR GGT =3.012, 95% CI:2.357-3.849, Pless than 0.01; ORALT =1.473, 95% CI:1.043-2.081, Pless than 0.05). In joint analyses of alcohol consumption and liver enzymes, the group of nondrinkers/light drinkers (less than or equal to 35 g ethanol/week) in the fourth quartile of GGT levels had the highest risk for type 2 diabetes (OR =12.219, 95% CI:6.217-24.016, P less than 0.01). The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT (nondrinkers/light drinkers in the fourth quartile of ALT levels (OR =5.357, 95% CI:3.070-9.350, P less than 0.0 1).</p><p><b>CONCLUSION</b>GGT, ALT and daily alcohol consumption were independently associated with risk of type 2 diabetes. Nondrinkers/light drinkers with the highest levels ofGGT orALT were at high risk of type 2 diabetes.</p>

Clinical analyses of 11 cases with pituitary stalk interruption syndrome / 中华全科医师杂志

Eleven male patients with pituitary stalk interruption syndrome (PSIS) at our hospital were retrospectively analyzed with respects to clinical features,endocrine status and imaging characteristics.The clinical manifestations included growth retardation and delayed puberty.All of them were deficient in growth hormone and pituitary gonadotropin secretion.Secondary hypothyroidism and hypocortisolism occurred in 8 patients and one had concurrent central diabetes insipidus.MRI with gadolinium contrast revealed no pituitary stalk or slim and anterior pituitary hypoplasia with ectopic posterior pituitary.The clinical characteristics of PSIS are growth retardation and delayed puberty,partial or complete adenohypophyseal dysfunction.The detection of hypothalamic pituitary region by MRI is an important diagnostic tool.

The association between Graves disease with hypokalemic periodic paralysis or thymus hyperplasia / 中国综合临床

Objective To explore the relationship between Graves disease and hypokalemic periodic paralysis or thymus hyperplasia.Methods Sixty-two patients with Graves disease were enrolled in this study.Thirty-three patients without thymus hyperplasia were selected as group A and other 29 patients were group B.In addition,30 healthy volunteers served as control group.Results There were no significant difference between group A and group B in terms of sex,age,illness course,thyroid enlargement,exophthalmos,periodic paralysis and the levels of free triiodothyronine (FT3),free thyroxin (FT4),thyroid stimulating hormone (TSH) (P ＞ 0.05).The incidence rate of hypokalemic periodic paralysis in male Graves disease with thymus hyperplasia was 62％ (8/13),higher than that in female patients (6％ (1/16),x2 =10.24,P ＜ 0.05).The incidence rate of hypokalemic periodic paralysis in male Graves patients was 62％ (16/26),higher than in female Graves patients (6％ (2/36),x2 =22.96,P ＜ 0.05).There was no significant relationship between Graves disease patients combined with thymus hyperplasia and sex,age,illness course,thyroid enlargement,exophthalmos,periodic paralysis and the levels of FY3,FT4,TSH.Conclusion The incidence rate of hypokalemic periodic paralysis in male Graves disease patients combind with thymus hyperplasia is higher than in female,and therefore it should pay more attention of male Graves patients in case misdiagnosis.

Clinical value of triptorelin stimulation test in differential diagnosis of disorder due to delayed puberty: 128 cases report / 中华内分泌代谢杂志

Objective To evaluate the diagnostic value of triptorelin stimulation test in disorders due to delayed puberty.Methods Triptorelin stimulation test was carried out in 128 teenagers with delayed puberty,due to idiopathic hypogonadotropic hypogonadism(IHH) in 77 cases and constitutional delayed puberty(CDP) in 51.Blood samples were obtained 15 min before and 0,30,60,and 120 min after tripotorelin administration,and the levels of LH and FSH were determined.An extended GnRH stimulation test was carried out in 3 patients with IHH.Results Peak LH,peak FSH,and LH increment were parameters with high diagnostic value.A cut-off point at 8.2 IU/L of peak LH showed a sensitivity of 87％ and a specificity of 80.4％ in the differential diagnosis of IHH and CDP.Conclusion Peak LH cut-off point at 8.2 IU/L of triptorelin stimulation test seems to be sufficient to confirm diagnosis of IHH and CDP.An extended GnRH stimulation test may distinguish hypothalamic from the pituitary hypogonadotropic hypogonadism.

Association between serum 25-hydroxyvitamin D3 concentration, parathyroid hormone, and arterial stiffness in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective To evaluate the association between serum 25-hydroxyvitamin D3 [25 (OH) D3],parathyroid hormone,and arterial stiffness in patients with type 2 diabetes.Methods Serum 25 (OH) D3 and parathyroid hormone(PTH) were determined in a cross-sectional sample of 258 patients aged 30 years and over.Arterial stiffness was assessed by pulse wave velocity(PWV) obtained with a VP-1000 pulse wave unit.Fasting plasma HbA1c,lipid profile,calcium,and high sensitive-C reactive protein were determined.Results (1)The prevalence of vitamin D3 deficiency was high(79.84％) in patients with type 2 diabetes.(2) Those with lowered serum vitamin D3 levels had raised PWV [(1610.76 ± 142.70 vs 1527.95 ± 58.02) cm/s,P＜0.05].(3) Multiple stepwise regression analysis showed that 25 (OH) D3 was an impact factor of PWV risk score,which was independent of age,duration of diabetes,and systolic blood pressure(β =-0.256,P＜0.01).(4) Serum PTH was positively correlated with PWV (r =0.210,P ＜ 0.05) and systolic blood pressure (r =0.229,P ＜ 0.05),but negatively correlated with 25 (OH) D3 (r =-0.153,P ＜ 0.05).Conclusions 25 (OH) D3 deficiency is common in patients with type 2diabetes,and a low serum 25 (OH) D3 level is significantly associated with increased arterial stiffness in these patients.The association of serum PTH with arterial stiffness may result via changes in vitamin D and blood pressure.

Transdifferentiation of mouse pancreatic ductal epithelial cells into islet-like cells / 中国组织工程研究

BACKGROUND: Islet transplantation is an effective method for the treatment of type 1 diabetes mellitus and parts of type 2 diabetes mellitus. However, its application is hindered by insufficient sources and immunologic rejection. Though transdifferentiation of pancreatic stem cells is at the starting step, it is thought to be the hopeful source for islet cell transplantation.OBJECTIVE: To look for a suitable cells-transplantation source for the treatment of diabetes mellitus. METHODS: The pancreatic ductal epithelial cells were separated from Kunming mice and cultured in DMEM/F12 medium supplemented with keratinocyte growth factor, hepatocyte growth factor and nicotinamide, etc. Samples were taken at different time points for light microscopy and electron microscope. The changes of CK-19 and PDX-1 were detected by immunocytochemistry at 1 and 16 days. The expressions of insulin and glucagon gene were detected by RT-PCR at 1 and 16 days. The physiologic function of these islet-like clusters was determined by dithizone staining and glucose stimulation at 21 days. RESULTS AND CONCLUSION: A large number of epitheliod cells were CK-19 immunoreactive positive and few of them were PDX-1 positive at 1 day after isolation, then CK-19 positive cells proliferated quickly and formed substantial plaques of epithelial cells in cobblestone pattern. At 16 days later, these cells begin to form islet-like clusters gradually, while most of them were PDX-1 immunoreactive positive. The analysis of mRNA by RT-PCR showed very low levels of insulin and glucagon mRNA in the starting materials but increase was found as the process of transdifferentiation. At 21 day differentiated islet-like clusters were stained red by dithizone. In those samples exposed to a stimulatory 15 mmol/L glucose, there was a 1.6-fold increase in insulin compared with to 5.6 mmol/L glucose (P < 0.05). Pancreatic ductal cells of adult Kunming mice could proliferate quickly and have the potency of transdifferentiation into islet-like clusters when cultured in vitro under appropriate conditions.

The effects of glucose fluctuation on resistin / 中华内科杂志

Objective To explore the effect of glucose fluctuation on resistin. Methods The phorbol-12-myristate-13-acetate(PMA)-activated and differentiated U937 cells were exposed to experimental condition for 3 days, three groups of cells were formed, each one receiving the following fresh medium every 6 hours, respectively: (1) continuous 11.1 mmol/L glucose concentration medium (Con group), (2)continuous 22.2 mmol/L glucose concentration medium (CHG group), (3) alternating 11.1 mmol/L glucose concentration and 22. 2 mmol/L glucose concentration medium every 6 hours (IHG group). The supernatants of cell mediam at the last 6 hours were collected to test resistin concentration. Besides, 92 subjects were selected and classified into three groups according to the results of oral glucose tolerance test:normal glucose tolerance group ( NGT group, n =30), impaired glucose tolerance patients (IGT group, n =31) and newly diagnosed type 2 diabetes patients (T2DM group, n =31). Blood glucose and serum resistin levels were measured at 0 h and 1 h during oral glucose tolerance test ( OGTT) to compare the glucose fluctuation (△Glu1-0) and the change of serum resistin level (△lnRes1-0) among the three groups. Results Resistin concentration in the Con , CHG and IHG group was (73.62 ± 5.07)ng/L, (97.78 ±7.00)ng/L and(212.49 ± 28. 81 )ng/L respectively and in IHG group it was higher as compared with the other two groups (P<0.05). △Glu1-0 in NGT, IGT and T2DM group was(2.31 ±2.30)mmol/L,(5.70 ±2.08)mmol/L and (8.41 ±2.63)mmol/L respectively; △Glu1-0 increased gradually in all the three groups (P<0.05). Serum resistin level from 0 h to 1 h in the NGT group was 6.41 (1.52-15.76) μg/L to 6. 96( 1.52-22. 70) μg/L, in the IGT group 5.47( 1.49-24. 09)μg/L to 9. 12( 1.27-21.94)μg/L and in the T2DM group 5.77( 1.11-30.10) μg/L to 9. 27(1.02-48.15)μg/L In the IGT and T2DM group serum resistin level increased from 0 h to 1 h (P<0.05), but no difference was observed in the NGT group (P>0. 05).△lnRes1-0 in these 3 groups was (0.05 ± 0.05) μg/L, (0.25 ± 0.04) μg/L and (0.37 ± 0.03 )μg/L respectively and the change in the T2DM group was significant as compared with that in the NGT group,△lnRes1-0 was positively correlated with △Glu1-0 (r = 0.23, P = 0.02). Conclusion Glucose fluctuation induced monocyte/macrophage to secrete resistin, greater the glucose fluctuation, greater the change of amplitude of serum resistin.

Analysis on misdiagnosis of insulinoma / 中华内分泌代谢杂志

Retrospectively from February, 2006 to June, 2009 the clinical characteristics of 14 misdiagnosed cases of insulinoma in the First Affiliated Hospital of Zhengzhou University were analysed. The rate of misdiagnosis was 38% ( 14/37). The rate of IRI/G≤0. 3 was 33%. Insulinoma has often been misdiagnosised when IRI/G≤0. 3. Hence a diagnosis of insulinoma can not be excluded with this IRI/G rate.