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Programmed death-1 receptor ligand 1 (PD-L1) is a promising therapeutic target in aggressive cancers. However, immune landscapes and cancer hallmarks of human PD-L1(+) tumors as well as their roles in determining therapeutic efficacies are unknown. Here, we showed, in detailed studies of gene data regarding 9769 patients of 32 types of human cancers, that PD-L1 could not exclusively represent the IFN-γ signature and potentially signified proinflammatory myeloid responses in a tumor. PD-L1 heterogeneity endowed by local immune landscapes controlled cancer hallmarks and clinical outcomes of patients. Mechanically, NF-κB signal elicited by macrophage inflammatory responses generated PD-L1(+) cancer cells exhibiting capabilities to aggressively survive, support angiogenesis, and metastasize, whereas STAT1 signal triggered by activated T cells induced PD-L1(+) cancer cells susceptive to apoptosis. Importantly, PD-L1(+) cancer cells generated by macrophages established great resistance to conventional chemotherapy, cytotoxicity of tumor-specific effector T cells, and therapy of immune-checkpoint blockade. Therapeutic strategy combining immune-checkpoint blockade with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited cancer regression. Our results provide insight into the functional features of PD-L1(+) tumors and suggest that strategies to influence functional activities of inflammatory cells may benefit immune-checkpoint blockade therapy.

Myocardial contrast echocardiography (MCE) and two-dimensional speckle tracking echocardiography (2D-STE) were used to detect left ventricular myocardial microcirculation perfusion and myocardial systolic function in dilated cardiomyopathy (DCM) and to explore the relationship between the two.Conventional ultrasound, MCE, and 2D-STE examinations were performed on 30 patients and 30 controls. Left ventricular microcirculation perfusion, left ventricular longitudinal strain (GLS), and circumferential strain (GCS) were analyzed to further compare the correlation between left ventricular perfusion and myocardial strain parameters.Regional myocardial perfusion was reduced in patients with DCM, manifesting as a decrease in the rising slope (A) of the mid-segment of the posterior septum, the peak intensity (PI) of the mid-segment of the anterior septum and the posterior septum, the apical segment of the lateral wall, the area under the curve (AUC) of the posterior septum, the basal segment of the posterior wall, the anterior septum, posterior septum, posterior wall, mid-segment of the lateral wall, and apical segment of the lateral wall and the overall average PI and AUC of the mid-segment, compared with that in the controls (P < 0.05). The left ventricular systolic function and the strain parameters GLS and GCS of DCM patients were lower than those of the controls (P < 0.001). Correlation analysis revealed a positive correlation between the A of the mitral valve and GCS (r = 0.372, P = 0.043), and MV-E/e' had a positive correlation with the AUC of the basal and intermediate segments (r = 0.379, P = 0.039; r = 0.404, P = 0.027).In patients with DCM, regional myocardial microcirculation perfusion is reduced, and myocardial strain is impaired. Myocardial perfusion has a good positive correlation with myocardial mechanics.

Insulinoma is a rare pancreatic neuroendocrine tumor that can spontaneously produce excess endogenous insulin, resulting in recurrent and serious hypoglycemia. Patients with insulinoma always have intermittent neuroglycopenia, which has been frequently reported as being misdiagnosed as epilepsy. In this report, we analyzed the clinical data of patients with confirmed insulinoma who had ever been misdiagnosed to have epilepsy.The retrospective review was performed on 266 patients with confirmed insulinoma at the First Medical Center of Chinese PLA General Hospital between January 2000 and July 2020.1. The diagnosis of insulinoma was confirmed in 266 patients. Forty-four patients [male/female=1/1.8, aged (41.25±12.30) years old] were misdiagnosed to have epilepsy, with a misdiagnosis rate of 16.5%. 2. Thirty-eight patients presented with consciousness disorder. Eleven patients presented with palpitation, sweating, and anxiety. Five patients presented with convulsion and 6 patients presented with abnormal behavior and delirium. 3. Twenty-two patients underwent EEG examination. EEG showed spike wave or spike-slow complex wave in 5 patients, decreased α wave and increased slow wave in θ and δ band in 7 patients, and was normal in 10 patients. 4. Thirty-five patients were incorrectly prescribed with AEDs and 22 patients were even misdiagnosed to have refractory epilepsy. 5. All these 44 patients underwent successful surgery, and hypoglycemia symptoms were relieved after insulinoma resection.Patients with insulinoma sometimes share common clinical characteristics with epilepsy. To patients with epilepsy or suspected epilepsy, especially with poor response to ADEs, hypoglycemia caused by insulinoma should be emphasized in the differential diagnosis.

Objectives. To assess the effectiveness and safety of ARW for vascular recanalization in CTO patients. Background. Chronic total occlusion (CTO) of coronary artery accompanied with large branch distal to the occluded segment (

The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Infusion of mesenchymal stem cells (MSCs) has been identified in the rapid alleviation in hyperglycemia of diabetic individuals, but the mechanism involved has not been adequately explained by these cells' potential role in modulating system insulin sensitivity and islet regeneration. In this study, we demonstrated adipose-derived mesenchymal stem cells (ASCs) produced significantly lower blood glucose via promoting hepatic glycogen synthesis and inhibiting hepatic glucose production within 24 h after infusion in T2DM rats. In vitro, HepG2 cells treated with palmitate (PA) were used as a model of hepatic glucose metabolism disorder to confirm that ASCs stimulates the phosphorylation of hepatic AMP-activated protein kinase (AMPK) to restores hepatic glucose metabolism in type 2 diabetes. In summary, this study indicated that ASCs improve hyperglycemia via regulating hepatic glucose metabolism. Additionally, the effect of ASCs on hepatic glucose metabolism depended on the AMPK signaling pathway. Thus, this is the new research of the molecular mechanisms of MSCs administration to improve glucose metabolism, and it may indicate a new treatment target of MSCs in T2DM.

Aims Currently, available Doppler echocardiographic reference values are derived mainly from North American and European population studies, which may not applicable to the Chinese population. We aimed to establish normal reference values of Doppler echocardiographic parameters in a nationwide, population-based cohort of healthy Han Chinese adults. Methods and results A total of 1394 qualified healthy subjects (mean age 47.3 ± 16.0 years, 678 men) were enrolled at 43 collaborating laboratories, 37 transvalvular flow and tissue Doppler parameters were obtained, and the impacts of gender and age on each parameter were analysed. Significant differences were found between men and women in 48.6% (18/37) of the parameters analysed, and among different age groups in 83.8% (31/37) of the parameters in men and in 86.5% (32/37) of the parameters in women. Conclusions Normal reference values of Doppler echocardiographic parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Since most of these parameters differed by gender and/or age, reference values specified for gender and age should be recommended in clinical practice. [10.1093/ehjci/jev353][1] [1]: /lookup/doi/10.1093/ehjci/jev353

Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 (LRP16) is correlated with the progression of estrogen-related tumors, but the regulatory mechanism between LRP16 and prolactinoma remain unclear. This study demonstrates a variation in LRP16 with estrogen receptor α (ERα) in prolactinoma models and the up and downregulation effects of LRP16 on prolactin secretion of pituitary adenomas cells (GH3 cells). In our study, 50 male SD rats (30-day-old) were randomly divided into five groups of 10 rats each. After 120 days of treatment, the rats were sacrificed, and the expression of LRP16 and ERα were examined by Western blot and immunohistochemistry to explore the changes in ERα, LRP16, and prolactin. After siRNA transfection of the respective genes, the GH3 cells were cultured, and their secretory function as well as the expression of ERα mRNA and prolactin were analyzed by enzyme-linked immunosorbent assay and real-time-polymerase chain reaction analysis. The results show that secretion of prolactin by GH3 cells can be affected by up and downregulating LRP16 expression, which may provide a novel medical therapy in clinical trials.

Background The aim of this study is to evaluate the safety and feasibility of laparoscopic common bile duct exploration and primary closure of choledochotomy for the patients with common bile duct stones (CBDS) who failed in endoscopic sphincterotomy (EST). Methods Between January 2007 and June 2012, a total of 78 patients who subjected to endoscopic retrograde cholangiopancreatography (ERCP) and EST, but failed in endoscopic stone extraction, were referred to us. The following day, laparoscopic cholecystectomy, laparoscopic common bile duct exploration (LCBDE) and primary closure of choledochotomy were performed in all patients. Results No intraoperative complications were experienced in the patients. 6 patients required conversion to open cholecystectomy due to impacted stones. The mean operative time was 145 min. The mean postoperative hospital stay was 6d. All the patients achieved successful stone clearance. 13 cases had slight bile leaks, which resolved spontaneously. None of the patients experienced biliary peritonitis, biliary fistula, pancreatitis, or cholangitis. Conclusion If it is performed by experienced laparoscopic surgeons, primary closure following immediate laparoscopic common bile duct exploration (LCBDE) is safe and feasible for patients with CBDS who fail in endoscopic stone extraction.

KMT5A (known as PR-Set7/9, SETD8 and SET8), a member of the SET domain containing methyltransferase family specifically targeting H4K20 for methylation, has been implicated in multiple biological processes. In the present study, we identified that KMT5A was elevated in 50 pairs of papillary thyroid cancer tissue samples and in cell lines K1 and TPC-1 by qRT-PCR and western blotting, as well as by immunohistochemical staining. CCK-8 assay and flow cytometric analysis revealed that inhibition of KMT5A attenuated proliferation and induced apoptosis. Transwell assays revealed that cell migration and invasion were suppressed in KMT5A-knockdown cells. Moreover, the inhibition of KMT5A arrested the cell cycle in the G1/S phase of papillary thyroid cancer cells. The TCGA data revealed that elevated KMT5A expression was significantly correlated with extrathyroidal extension, lymph node metastasis and advanced pathological stage of papillary thyroid cancer. Furthermore, we observed that inhibition of KMT5A suppressed the expression of SREBP1, SCD, FASN and ACC, key molecules involved in lipid metabolism and decreased the level of malondialdehyde in papillary thyroid cancer cells. In conclusion, KMT5A may be a novel oncogenic factor, specifically a regulator for lipid metabolism in papillary thyroid carcinoma.

Objective To analyze the clinical characteristics of pituitary stalk interruption syndrome(PSIS). Methods The clinical data including clinical manifestations,laboratory tests,and imaging findings of 114 PSIS patients in our hospital were retrospectively analyzed. Results Of these 114 PSIS patients,102 cases (89.4%) were male. The average age was 21.1?6.1 years. A history of breech delivery was documented in 91 cases (91.9%). Short stature was found in 89 cases (71.8%) and bone age delayed (6.1?5.1) years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone,gonadotropins,corticotropin,and thyrotropin were 100.0%,94.0%,84.2%,and 74.6%,respectively. Hyperprolactinemia was found in 28.1% of patients. Three or more pituitary hormone abnormalities were found in 105 cases(92.1%). Compared with the 5 cases with history of cephalic delivery,no difference were found in the aspects of height(t=0.297,P=0.634),penile length(t=1.205,P=0.882),testicular volume (U=99.000,P=0.348),growth hormone peak (U=89.000,P=0.186),adrenocorticotropic hormone peak(U=131.000,P=0.967),luteinizing hormone peak(U=98.500,P=0.582),thyroid-stimulating hormone (U=82.000,P=0.162),and the height of anterior pituitary (t=1.676,P=0.107) in the 53 cases with history of breech delivery. Conclusions The clinical manifestations,symptoms,hormone deficiencies were severe in our series. The condition severities were not remarkably different in patients with different delivery ways.

Patients with malignant insulinoma always present with symptoms of severe hypoglycemia and have poor life expectancy. In addition, inoperable metastatic malignant insulinomas are very difficult to manage. The aim of this report is to present our successful experiences in diagnosis and treatment of this disease in 6 patients.Six patients (male 2, female 4) with malignant insulinomas were admitted into our hospital. Their clinical histories, including clinical presentations, endocrine evaluations, radiological images, pathological examination and treatments, were reviewed.The diagnosis of malignant insulinoma combined with liver metastases was confirmed in all patients by endocrine evaluation and radiological images. Patients 1-3 underwent surgical management. The primary and metastasized tumors were completely resected. After successful surgery, no hypoglycemia recurred. Patients 4-6 did not undergo surgery because of systemic disease and poor health. Instead, they were administrated with diazoxide 50 mg Three Times a Day (TID), with final doses up to 200-300 mg TID. These 3 patients had good responses to diazoxide administration. After treatment, the frequency and severity of hypoglycemia were improved significantly. All 6 patients had better life quality than previously expected.Combination of surgical and medical approaches can improve life quality and prolong survival of patients with malignant insulinomas.

Asia bears the world's greatest burden of type 2 diabetes (T2DM) and prevalence is increasing rapidly. Compared to other races, Asians develop T2DM younger, at a lower degree of obesity, suffer longer from its complications and die earlier. Curbing this epidemic requires an integrated, risk-based, and multidisciplinary approach. Inadequately managed T2DM has macrovascular and microvascular sequelae, Asians with T2DM being particularly susceptible to diabetic nephropathy. Earlier and more intensive monitoring and management of risk factors are required, especially for patients with, or at risk of, renal impairment. Particular challenges of T2DM management in Asia include: lack of access to specialist healthcare, insufficient clinical evaluation and delayed diagnosis. As in Caucasians, conventional treatment modalities are limited by deteriorating glycaemic control with disease progression and there is an unmet need for efficacious, safe, cost-effective and convenient pharmacotherapies for treating different stages of T2DM and preventing its complications, particularly in high-risk patients. There is a trend towards increasing use of DPP-IV inhibitors, which are no less efficacious and safe in Asians than Caucasians and may have some advantages over existing oral antidiabetic agents, particularly for certain high-risk groups. Such agents may play a significant future role in the management of T2DM.

Laparoscopic approach has been increasingly used in the treatment of pancreatic benign diseases. This report evaluates our experience with laparoscopic surgery for pancreatic insulinomas.Between July 2000 and December 2007, laparoscopic pancreatectomy was attempted in 29 consecutive patients with insulinomas. The localization of tumors, operating characteristics, and clinical outcomes were analyzed.Tumors were precisely localized in 28 of 29 (96.6%) patients by a combination of preoperative imaging techniques and intraoperative ultrasonography. Laparoscopic pancreatectomy was successfully performed in 26 patients, including enucleation (n = 14), hand-assisted enucleation (n = 2), and distal pancreatectomy with (n = 9) or without (n = 1) spleen preservation. Two conversions to open procedure were required because of unfavorable locations of the tumors. The pancreatic fistula occurred in four patients who underwent tumor enucleation. The median hospital stay was 5.5 days (range, 3-18 days) after laparoscopic procedure. Twenty-eight patients with pancreatic resection were free of symptoms and remained normoglycemic after a median follow-up period of 19 months (range, 10-36 months).Laparoscopic pancreatic resection is a feasible and safe procedure for patients with insulinomas. Further studies are required to evaluate the potential application of the hand-assisted approach for tumors located at anatomically unfavorable positions.

This paper describes a simple, sensitive, efficient, and rapid method for simultaneous analysis of biologically active amines and acids by capillary electrophoresis in conjunction with laser-induced native fluorescence detection (CE-LINF) using a diode pumped solid state nanolaser at 266 nm. In order to optimize resolution of the amines that were prepared in 10.0 mM formate-Tris (FT) solutions, 10.0 mM FT solutions with and without containing halides were used to fill the capillary and reservoirs, respectively. The electrophoretic mobilities of tryptamine (TA) and serotonin (5-HT) at pH 4.0 decrease with the increase in halide concentration (0-10.0 mM). Taken together with a great effect of iodide than other halides, we suggest that the formation of ion pairs is a main contributor for altering the migration of the amines. In order to simultaneously analyze the amines and their metabolites (acids) at low pH, a high bulk EOF is required. The analysis of 10 anlytes including amines and acids was completed within 12 min by CE-LINF using a capillary treated with 0.5M NaOH and then filled with 10.0 mM FT solutions (pH 4.0) containing 10.0 mM KCl prior to analysis. The limits of detection for TA and 5-hydroxyindole-3-acetic acid (5-HIAA) are 0.12 and 6.0 nM, respectively. The present method has been further validated by analyzing urine samples, with an RSD less than 3.1% (migration times) and 3.9% (concentration).

White blood cell (WBC) count has been associated with diabetic risk, but whether the correlation is independent of other risk factors has hardly been studied. Moreover, very few such studies with large sample sizes have been conducted in Chinese. Therefore, we investigated the relationship between WBC count and glucose metabolism in China. We also examined the relevant variables of WBC count. A total of 9,697 subjects (mean age, 58.0 ± 9.1 years) were recruited. The subjects were classified into four groups, including subjects with normal glucose tolerance, isolated impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). We found that WBC count increased as glucose metabolism disorders exacerbated. WBC count was also positively correlated with waist hip ratio, body mass index, smoking, triglycerides, glycosylated haemoglobin A1c (HbA1c) and 2-h postprandial glucose. In addition, high density lipoprotein and the female gender were inversely correlated with WBC levels. In patients with previously diagnosed T2DM, the course of T2DM was not correlated with WBC count. Our findings indicate that elevated WBC count is independently associated with worsening of glucose metabolism in middle-aged and elderly Chinese. In addition, loss of weight, smoking cessation, lipid-modifying therapies, and control of postprandial plasma glucose and HbA1c may ameliorate the chronic low-grade inflammation.

Background Currently available echocardiographic reference values are derived mainly from North American and European population studies, and no echocardiographic reference values are available for the Chinese population. The aim of this study was to establish normal values of echocardiographic measurements of the cardiac chambers and great arteries in a nationwide, population-based cohort of healthy Han Chinese adults. Methods A total of 1,586 healthy Han Chinese volunteers aged 18 to 79 years were screened at 43 collaborating laboratories throughout China. Standard M-mode and two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries. The impacts of gender and age on all echocardiographic measurements were analyzed. Results A total of 1,394 qualified healthy subjects (mean age, 47.3 ± 16.0 years; 678 men) were ultimately enrolled. Except for left ventricular ejection fraction, values of cardiac chamber and great arterial dimensions were significantly higher in men than in women. Most measurements of the atrial and great arterial dimensions, left ventricular wall thickness, and left ventricular mass increased with age in both men and women. Conclusions Normal reference values of cardiac dimensional parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Because most of these parameters were found to vary with gender and age, reference values stratified for gender and age should be used in clinical practice.

To explore the imaging features of congenital adrenal cortex hyperplasia (CAH).A total of 45 patients clinically confirmed as CAH were retrospectively analyzed to investigate the imaging features and strengthening way of the multi-detector-row Computed tomography.The imaging features of all the cases presented as following: 25 with bilateral adrenal hyperplasia, 6 with unilateral adrenal hyperplasia, 6 with adrenal nodular hyperplasia, 2 with adrenal hyperplasia and unilateral solid cystic lesion, 2 with adrenal hyperplasia and double side real cystic lesion, 1 with adrenal hyperplasia and unilateral cystic changes and 3 with normal adrenal. The unilateral or bilateral hyperplasia adrenal could be homogeneously enhanced, while the enhanced performance of other cases was inequitable.The adrenal imaging features of CAH by multi-detector-row CT are variable, with the bilateral adrenal hyperplasia as the main form, which could be restored to normal morphology after hormone replacement therapy.No regression of the tumor size is observed in cases with adrenal mass. CT scanning combined with clinical manifestation and biochemical examination could facilitate the diagnosis of CAH.

The Uygur in Hotan (Xinjiang, China) are reported to have a long life expectancy. The purpose of this study was to clarify the relationship between variations in blood pressure (BP) and longevity. Cross-sectional surveillance was carried out in both Hotan and Barkol. The subjects were divided into five groups: 1. Uygur longevity subjects in Hotan (103 subjects, age >90 yr); 2. Uygur elderly subjects in Hotan (107 subjects, age 65-70 yr); 3. Han elderly subjects in Hotan (41 subjects, age 65-70 yr); 4. Kazakh elderly subjects in Barkol (117 subjects, age 65-70 yr); 5. Han elderly subjects in Barkol (50 subjects, age 65-70 yr). BP was monitored and analyzed using the fourteen devices of ambulatory BP monitoring. The prevalence of hypertension was lowest in the Uygur (16.2% in Uygur elderly subjects in Hotan; 23.7% in Uygur longevity subjects in Hotan; 27.0% in Han elderly subjects in Hotan; 42.0% in Han elderly subjects in Barkol; 50.0% in Kazakh elderly subjects in Barkol). The ratio of dips in BP was largest in the Han (57% in Han elderly subjects in Barkol; 50% in Han elderly subjects in Hotan; 50% in Uygur longevity subjects in Hotan, 49% in Uygur elderly subjects in Hotan; 17% in Kazakh elderly subjects in Barkol). The 24-h mean systolic BP in Uygur longevity subjects in Hotan was not different from those in Uygur elderly subjects and Han elderly subjects in Hotan, nor did the 24-h mean diastolic BP differ from those in Uygur elderly subjects and Han elderly subjects in Hotan respectively. In conclusion, Uygur subjects seem to be less hypertensive, compared to Kazakh subjects. Uygur longevity subjects had more dipping in their BP variation than did the Kazakh subjects in Xinjiang, China.

Thyroid nodules (TNs) have annual increasing trends worldwide, and large-scale investigations on the prevalence of TNs in Beijing communities have not been conducted since the introduction of salt iodization in 1995. We performed a cross-sectional study to determine the prevalence of TNs, their epidemiological characteristics, and their correlation with lifestyle factors. A total of 6324 permanent residents aged 18 years or older (mean age, 52.15 ± 11.58 years) from seven representative communities in Beijing were included in the analyses. Once informed consent was obtained, the subjects were asked to complete questionnaires, a physical examination, and thyroid ultrasound. A total of 3100 cases had TNs. The overall prevalence rate was 49.0%, and the age-standardized prevalence was 40.1%, which increased significantly as age increased (p < 0.001). The prevalence was significantly higher in females compared to males (p < 0.001), and it was significantly higher among female current smokers and former smokers compared to non-smokers (p = 0.007). There was no correlation between alcohol consumption and TNs, and there were no significant differences in the prevalence among different groups of taste preference. The prevalence decreased with an increased frequency of seafood intake (p = 0.015) and with higher literacy levels (p < 0.001). The Cochran–Armitage trend test showed that the prevalence significantly increased with decreased physical labor and exercise intensity (p < 0.001, p = 0.009). Logistic regression analysis showed that age (Odds ratio (OR) = 1.039 (1.034–1.044), p < 0.001), the female sex (OR = 1.789 (1.527–2.097)), Body mass index (BMI) (OR = 1.019 (1.005–1.034)), and current smoking habits (OR = 1.246 (1.046–1.483)) were independent risk factors for TNs. Our findings indicate that there is a high prevalence of TNs in Beijing, with a higher prevalence in females than in males. Moreover, the prevalence increases as age increases. Smoking and BMI are independent risk factors for TNs. Therefore, intervention against smoking and weight loss might help reduce the risk of TN occurrence.

To analyze the clinical and laboratory characteristics of Gitelman syndrome.Seventeen patients with Gitelman syndrome (male/female: 11/6) were analyzed for their clinical symptoms, laboratory test results, imaging findings, treatments and outcomes.Fifteen of the 17 patients presented with varying degrees of lower limb weakness, and 8 experienced flaccid paralysis. The laboratory tests showed hypokalemia (17/17), hypomagnesemia (17/17) and hypocalcemia (17/17). Blood renin activity (17/17), angiotensin II (14/17) and aldosterone levels (7/17) were significantly higher in the patients than in normal subjects. The symptoms were relieved by potassium alone or in combination with indomethacin, spironolactone and other potassium magnesium asparaginate, but the serum potassium and magnesium failed to recover the normal levels after the treatments.The primary clinical manifestations of Gitelman syndrome are lower extremity weakness with hypokalemia and hypomagnesemia. Combined drug therapies including potassium, magnesium, aldosterone antagonists and other drugs are recommended. The prognosis of the patients is favorable.

Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma.Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed.In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher, but nadir GH levels were all still1 µg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission.When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.

The accurate and comprehensive assessment of glycemic control in patients with diabetes is important for optimizing glycemic management and for formulating personalized diabetic treatment schemes. This study aimed to analyze the correlation between 1,5-anhydroglucitol (1,5-AG) and glycemic excursions in type 2 diabetic patients.Seventy-one outpatients with type 2 diabetes mellitus were randomly recruited from Chinese People's Liberation Army General Hospital. Using a continuous glucose monitoring system (CGMS), these patients' blood glucose levels were monitored for three consecutive days to obtain mean blood glucose (MBG) data. Intraday glycemic excursions were evaluated using the mean amplitude of glycemic excursions (MAGE), the largest amplitude of glycemic excursions (LAGE), standard deviation of blood glucose (SDBG) and the M-value. Interday glycemic excursion was assessed by absolute mean of daily difference (MODD). Postprandial glycemic fluctuations were evaluated using postprandial glucose excursions (PPGE) and postprandial incremental area under the curve (iAUC). Fasting venous blood samples were collected to measure serum 1,5-AG, whole-blood hemoglobin A1c (HbA1c) and serum glycated albumin (GA). Clinical markers of glycemia and parameters of glycemic excursions from CGMS were analyzed using the Pearson correlation coefficient and multivariate stepwise regression.Pearson correlation analysis revealed that 1,5-AG was significantly correlated with MAGE, SDBG, M-value, LAGE, PPGE and iAUC (r values were -0.509, -0.430, -0.530, -0.462, -0.416 and -0.435, respectively, P0.01), especially in moderately and well-controlled patients, based on defined HbA1c levels. Multivariate stepwise regression analysis revealed a negative correlation between 1,5-AG and the above parameters, but not HbA1c and GA. Finally, HbA1c and GA were positively correlated with MBG and fasting blood glucose (FBG).1,5-AG was much better than HbA1c and GA as a marker of glycemic excursions in type 2 diabetic patients. Based on these results 1,5-AG is the best metric for assessing postprandial glucose levels in moderately and well-controlled patients, while HbA1c and GA were superior to 1,5-AG for monitoring MBG and FBG.

Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3 cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.

To retrospectively evaluate the diagnostic accuracy of ultrasonographic (US) features for the pre-operative differentiation of benign and malignant thyroid nodules by using pathological diagnosis as the reference standard.A total of 1501 patients with 2123 thyroid nodules (1864 malignant, 259 benign) diagnosed intra-operatively and undergoing pre-operative ultrasonography at our hospital were recruited. The following characteristics of US images were evaluated: nodule size, shape, margin, echotexture, echogenicity, presence and type of calcification, blood flow inside or around nodules and the presence of ipsilateral cervical lymphadenectasis.(1) The risk of malignancy was higher in a solitary nodule than in a non-solitary nodule [16.7% (109/653) vs 10.2% (150/1470), P=0.000]. The mean diameter of benign nodules was larger than that of malignant nodules [(2.4±1.4) vs (2.1±1.9) cm, P=0.009]. (2) Microcalcification, irregular shape, ill-defined border, solid and hypoechogenicity were more common in malignant nodules. Irregular shape had the highest sensitivity and positive predictive value while microcalcification had the highest diagnostic accuracy. (3) Nodules with a rich blood flow inside tended to have a higher risk of malignancy. The distribution pattern of blood flow around the nodules was not associated with the differentiation of benign and malignant thyroid nodules. Nodules with the presence of ipsilateral cervical lymphadenectasis had a higher risk of malignancy than those without lymphadenectasis [28.3% (80/283) vs 9.6% (92/963), P0.01]. (4) If microcalcification, irregular shape, ill-defined border, solid, hypoechogenicity and the presence of ipsilateral cervical lymphadenectasis were treated as the characteristics of malignancy, a higher frequency of these characteristics was correlated with a higher risk of malignancy.Despite a lack of specific US imaging characteristics in malignant thyroid nodules, microcalcification and irregular shape appear closely correlated with malignancy. A combined use of conventional US characteristics may improve the accuracy of differential diagnosis.

The objective of the present study was to evaluate whether left ventricular (LV) pressure changes influence left atrial (LA) function during acute LV ischemia by strain rate imaging. In 11 healthy dogs, the left anterior descending coronary artery was occluded to cause regional acute ischemia. The peak strain rate (PSR) values of the LA walls during the reservoir, conduit, and contractile phases of the LA cycle, as well as the LV pressures, were measured before and after ischemia. All PSR values increased significantly after ischemia (P < 0.001). Left ventricular end-diastolic pressure (LVEDP) increased after ischemia (P < 0.0001) and its percent change was positively correlated with the LA contractile phase and conduit phase percent changes of PSR for the anterior and lateral walls of the atrium (r = 0.72, 0.72, 0.83, and 0.73; P = 0.05, 0.05, 0.002, and 0.01, respectively). LA function is influenced by the change of LVEDP during regional LV ischemia. There is a compensatory increase in wall motion after regional acute LV ischemia.

To study the cerebrospinal fluid (CSF) and serum level of human chorionic gonadotropin (HCG) in patients with intracranial germinoma and to evaluate its diagnostic and therapeutic value.Thirty-one patients with intracranial germinoma receiving estimation of HCG in CSF and serum in our hospital were retrospectively analyzed in terms of HCG level, its influencing factors and the relationship of HCG with clinical features.HCG levels in CSF of the 31 cases ranged from 0.17 IU/L to 5316.98 IU/L with a median value of 3.44 IU/L. The sensitivity of diagnosis increased from 80.6% to 90.3%, when the cut point of HCG in CSF changed from 0.60 IU/L to 0.50 IU/L. The sensitivity increased from 83.9% to 93.5% when the cut point of the ratio of CSF/serum HCG decreased from 1.8 to 1.7. HCG level of germinoma located in pineal region was higher than that in basal ganglia region, while it is lowest in sellar region. The ratio of CSF/serum HCG in different parts showed no difference. Multiple risk factors analysis revealed that serum HCG (r = 0.886, P = 0.0001) and tumor size (r = 0.748, P = 0.0211) were positively correlated with the HCG level in CSF, while course of the disease, age and gender were not correlated. After radiation therapy, HCG in CSF and serum decreased dramatically as compared with those before radiation.The HCG level and its dynamic change were sensitive marker of intracranial germinomas. Based on our analysis, HCG in CSF over 0.50 IU/L and the its ratio in CSF/serum over 1.7 were highly indicative of the possibility of intracranial germinomas.

A rare case with ectopic adrenocorticotrophic hormone syndrome (EAS) caused by medullar thyroid carcinoma (MTC) in mediastinum was reported. This 49 year-old male patient initially presented with serious and intractable hypokalemia. Endocrine evaluations showed increased levels of adrenocorticotrophic hormone (ACTH) and urinary free cortisol, which could not be suppressed more than 50% by high-dose dexamethasone suppression test. Computed tomography (CT) scan detected a 5×5×5 cm mass at the bottom of thyroid in anterior mediastinum. The patient underwent total thyroidectomy with central compartment and ipsilateral modified radical neck dissection. Pathological examination showed an infiltrating thyroid medullary carcinoma with abundant amyloid deposition, meanwhile immunohistochemical positive for ACTH. After surgery, serum levels of kalium, as well as cortisol and ACTH returned to normal range. During follow-up, the patient's clinical manifestation of Cushing syndrome relieved.

To improve the diagnostic and therapeutic ability of ectopic ACTH syndrome by analysing its clinical features.Sixteen cases of ectopic ACTH syndrome diagnosed in Chinese PLA General Hospital from 2000 to 2009 were analyzed retrospectively.(1) The main causes of ectopic ACTH syndrome were lung tumor and thymic carcinoid; (2) Abnormal glucose metabolism, hypertension, hypokalemia and edema of both lower limbs were the most common clinical symptoms; (3) Laboratory examination showed a significant increase of serum cortisol, adrenocorticotropic hormone (ACTH) and 24 h urinary free cortisol (24hUFC) together with severe hypokalemia and alkalosis; (4) High dose dexamethasone suppressing test, corticotrophin-releasing hormone (CRH) stimulating test and petrosal sinus sampling were the most meaningful diagnostic methods; (5) Most of the primary lesions might be detected with chest film and CT; (6) Resection of the primary lesion was the treatment of first choice.The diagnosis of ectopic ACTH syndrome is very hard. Resection of the primary lesion is the best treatment.

To observe the effects of candesartan on the expressions of JAK2 and protein tyrosine phosphatase-1B (PTP-1B) in adipose tissue of obese rats induced by high-fat diet.A total of 45 male Wistar rats were randomly assigned into 3 groups of normal control (NC group), high fat diet (HF group) and high-fat diet with daily Candesartan treatment (FC group). The rats of FC group were treated with orally taken Candesartan at a dose of 8 mg/kg body weight per day. Blood chemistry and insulin were assayed at Week 16. Euglycemic-hyperinsulinemic clamp technique was performed to evaluate the peripheral insulin resistance. The expressions of JAK2 and PTP-1B in adipose tissue were confirmed by both reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.(1) The body weight and peri-renal fat weight of HF group were significantly higher than those of FC and NC groups (all P0.05). (2) total cholesterol (TC) and fasting insulin (FINS) of FC group were lower than those of HF group [TC, FC group: (1.37 ± 0.39) mmol/L vs HF group: (2.01 ± 0.26) mmol/L, P0.05; FINS, FC group: (3.03 ± 1.37) mU/L vs HF group: (4.76 ± 2.75) mU/L, P0.05] while insulin sensitive index (ISI) and angiotensin II (AngII) of FC group were much higher than those of HF group [ISI, FC group: (58 ± 12) × 10(-3) vs HF group: (29 ± 9) × 10(-3), P0.05; AngII, FC group: (61 ± 11) mmol/L vs HF group: (52 ± 10) mmol/L, P0.05]. (3) The steady-state glucose infusion rate (SSGIR) of FC group was significantly higher than that of HF group [FC group: (22 ± 5) mg×kg(-1)×min(-1) vs HF group:(14 ± 4) mg×kg(-1)min(-1), P0.05]. (4) Both the mRNA and protein expressions of JAK2 and PTP-1B in FC group were significantly lower than those in HF group respectively.There are insulin resistance and a high expression of JAK2 and PTP-1B in adipose tissue of obese rats induced by high-fat diet. And both are related with the elevated AngII level. Candesartan can reverse these effects.

To evaluate the clinical significance of glycated albumin (GA) measured by enzymatic method and to compare its effect with glycosylated hemoglobin A1c (HbA1c) in type 2 diabetes mellitus (DM).128 type 2 DM patients and 84 normal subjects from the Chinese PLA General Hospital were enrolled for the study. The levels of GA, HbA1c, FBG, PBG in DM patient were detected at baseline and followed visit at 2, 4, 8 weeks after blood glucose management. The levels of GA, HbA1c, FBG, PBG and 75 g OGTT were also detected in above normal subjects.Intra CV and inter CV of enzymatic were (0.74-0.9)% and (0.94-1.49)% respectively. In normal subjects GA was in the range of (9-14)%. At baseline, the GA level was significantly correlated with HbA1c (r = 0.8326, P0.01), FBG and 2 hour PBG. After 2, 4, 8 weeks treatment, GA level in DM patients was concomitantly decreased with the improvement of FBG, PBG and HbA1c. At early 2 weeks visit, GA, but not HbA1c, showed significant decrease from its baseline (P0.05).Enzymatic measuring GA was highly correlated with HbA1c, and changing concomitantly with the decrease of HbA1c, FBG, PBG during the 8 weeks treatment. GA was more sensitive than HbA1c for short-term variations of glycemic control during treatment of diabetic patients. GA can be used as a better index of short term mean level of blood glucose in diabetic patients.

To investigate the characteristics of glycemic excursion of different subtypes of glucose tolerance.Assessed by oral glucose tolerance test (OGTT) repeated twice, 81 individuals were divided into 4 groups: normal glucose tolerance (NGT, n = 18), isolated impaired fasting glycemia (IFG, n = 12), isolated impaired glucose tolerance (IGT, n = 19), combined IFG/IGT (n = 11), and newly diagnosed type 2 diabetes mellitus (T2DM, n = 21). And then continuous glucose monitoring system (CGMS) was used for 72 hours to monitor the blood glucose (BG) level before drug intervention.(1) The levels of largest amplitude of glycemic excursions (LAGE), mean blood glucose (MBG), and standard deviation of mean level of blood glucose fluctuation (SDBG) increased gradually with the deterioration of glucose tolerance. The mean amplitude of glucose excursion (MAGE) readout of the IGT group was (3.2 +/- 1.2) mmol/L, significantly higher than that of the NGT group [(1.6 +/- 0.5) mmol/L, P0.05], and significantly lower than that of the T2DM group [(5.2 +/- 1.9) mmol/L, P0.05]. The level of frequency of glucose excursion (FGE) decreased along with the decrease of glucose tolerance: NGT group [(6.1 +/- 3.4)]IGT/IFG group [(5.5 +/- 2.5)]T2DM group [(4.8 +/- 1.8)]. Among the three components of IGR, the IGT group showed highest MAGE (3.2 +/- 1.2) mmol/L and lowest FGE level (4.9 +/- 1.8). (2) The level of absolute mean of daily difference (MODD) increased in the following order: NGT group [(0.8 +/- 0.3) mmol/L], IGT group [(1.1 +/- 0.4) mmol/L], IFG/IGT group [(1.2 +/- 0.4) mmol/L], and T2DM group [(2.0 +/- 1.0) mmol/L] (all P0.05). (3) The fasting glucose level deteriorated the most rapidly in the IFG group, while it reached the highest postprandial peak in the IFG/IGT group. The blood glucose curve increased along the order of NGT, I-IGT, IFG/IGT, IFG, and T2DM. (4) When the level of glycosylated hemoglobin (HbA1c) level was less than 7%, the fasting phase of curve virtually coincided with each other among individual groups with different HbA1c levels; however, the postprandial peak separated slightly. When the HbA1C level was between 7.0% and 7.9%, the postprandial peaks of individual groups with different HbA1c levels dispersed markedly. When the HbA1c level was higher than 8%, the fasting blood glucose curve moved upwards significantly with increasing postprandial excursion.(1) With the deterioration of glucose regulation, the intraday and day-to-day blood glucose excursions become increasingly fluctuant. (2) The amplitude of glycemic excursion is lower in the NGT group than in the T2DM group, however, the frequency of glycemic excursion is higher in the NGT subject than in the T2DM subjects. The glucose excursion profile of the IGR subjects is between the NGR and T2DM subjects. (3) The characteristics of glucose excursion of the IGT group are similar to those of the T2DM group, and the characteristics of the IFG group are similar to those of the NGT group. (4) The loss of postprandial glycemic control precedes evident deterioration in fasting phase of IGR.

To investigate the clinical characteristics of multiple endocrine neoplasia type 1 (MEN1) patients presenting with hypoglycemic coma as chief manifestation and the related clinical experience in diagnosis and therapy.We analyzed the clinical data of 4 patients who were hospitalized because of recurrent hypoglycemic coma and diagnosed as having MEN1 by endocrinological, radiological and pathological examinations.In the 4 cases of Whipple trilogy, radiological examination showed occupying lesion in the pancreas and pathological examination confirmed the diagnosis of insulinoma. In 2 cases the insulinomas were multiple. In this series, one case was complicated with pituitary adenoma, parathyroidoma (recurrent after operation) and adrenocortical adenoma, one case with pituitary adenoma, parathyroidoma (2 tumors) and adrenal nodular hyperplasia, one case with pituitary adenoma and parathyroidoma, and the remaining one with pituitary adenoma and suspectible parathyroidoma.For patients with insulinoma, MEN1 should be considered. In patients with MEN1, the presence of multiple or ectopic parathyroid adenomas (or hyperplasia) and insulinomas should be inspected during operation. After operation, examinations should be regularly performed to identify whether the diseases relapse or new endocrine neoplasias occur.

BACKGROUND Since the size of ischemic myocardium is closely related with both global and regional function of the myocardium, it is of great significance to measure the size of ischemic myocardium with non-invasive methods. METHODS Eleven mongrel dogs were subjected to occlusion of the left anterior descending coronary artery for acute ischemia. Strain rate imaging had M-mode of strain-rate (CAMM) curve pointed from the basal segment of the anterior wall to the basal segment of the inferior wall to detect the border of ischemia size. The strain rate (SR) defined the cut-off value of ischemic myocardium in a two-chamber apical view, and marked by the anterior and inferior wall on two-dimensional images respectively. Along the endocardium and epicardium, the ischemic size was curved on two-dimensional images by the trackball method and then compared with the pathologically ischemic size. And then longitudinal strain rates were compared in the cut-off value, adjacent non-ischemic and ischemic segments at which the cut-off point was defined by changing the curve M-mode of strain rate after ischemia. RESULTS Linear correlation existed between pathology and strain rate ischemic size (r = 0.884, P < 0.001). The SR parameters were lower in ischemia and cut-off point than in non-ischemic segments. The peak SRs of systole (S(SR)), early diastole (E(SR)), late diastole (A(SR)), strain during ejection time (epsilon(et)), and the maximum length change during the entire heart cycle (epsilon(max)) in ischemic segments lowered (P < 0.05). Time to onset of regional relaxation (T(R)) was prolonged (P = 0.012). CONCLUSION SR imaging can accurately assess the size of ischemic myocardium.

To investigate the effects of candesartan, an angiotension II type I receptor antagonist, in improvement of insulin resistance (IR) induced by high-fat diet and the possible mechanism thereof.45 male Wistar rats were randomly divided into 3 groups: normal chow group (NC, n = 15) fed with normal diet, high fat diet group (HF, n = 15) fed with high fat diet, and high-fat diet with daily candesartan treatment group (HF + C, n = 15) fed with high fat diet and given orally with candesartan 8 mg/kg per day. Body weight was measured regularly. Four weeks later, oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp technique were performed to estimate the insulin sensitivity. After 12 h fasting blood samples were collected from the abdominal aorta to test the contents of blood glucose, and serum triglyceride (TG), total cholesterol (TC), LDL, HDL, and free fatty acid (FFA). Radioimmunoassay was used to detect the serum insulin. Viscera were taken out. Immunohistochemistry was used to examine the expression of peroxisome proliferation activated receptor (PPAR)-gamma in hepatic and adipose tissues.The body weight 16 weeks later of the HF group was significantly higher than that of the HF + C group (P0.01). The liver weight and epididymal and peri-renal fat weights of the HF group were all significantly higher than those of the HF + C group and NC group (all P0.01). There was no significant difference in fasting blood sugar among these 3 groups (P0.05). The glucose levels 2 h after OGTT in the HF + C group was (6.3 +/- 0.5) mmol/L, significantly lower than that of the HF group [(7.3 +/- 1.2) mmol/L, P0.01]. The glucose infusion rate (GIR) of the HF + C group was (22 +/- 5) mmol/L, significantly higher than that of the HF group [(14 +/- 4) mmol/L, P0.01]. The PPARgamma expression levels in liver and adipose tissue of the HF + C group were up-regulated significantly compared with those of the HF group.Candesartan may improve insulin resistance through promoting the expression of PPARgamma in liver and adipose tissue.

This paper tackles a simple and efficient method for the simultaneous separation and stacking of neurotransmitters in capillary electrophoresis with UV detection. By using poly(diallyldimethylammonium chloride) (PDDAC) as a buffer additive, the high and reversed EOF are observed. Moreover, the mobility of indolamines and catecholamines decreases as the PDDAC concentration increases. Based on the difference in mobility in the presence and absence of PDDAC, the analytes were simply stacked between the boundary of the sample zone and the background electrolyte containing PDDAC. The separation of 14 analytes including indolamines, catecholamines, and metanephrines was accomplished within 33 min under optimal conditions (1.2% PDDAC and 5 mM formic acid at pH 4.0), and the values of relative standard deviation of their migration time were less than 3.1%. By applying stacking methods for fourteen analytes, we observed: (a) the sample injection volume of sample is up to 216 nL, (b) the limits of detection at signal-to-noise of 3 range from 15.4 to 122.1 nM, and (c) the sensitivity enhancements, compared to normal injection (12 nL), range from 110- to 220-fold. Under the optimal stacking conditions, the present method has been applied to analyze of vanillomandelic acid, 5-hydroxyindole-3-acetic acid, dopamine, tryptamine, and 3-indoxyl sulfate in urine samples.

To investigate the molecular diagnosis method and possible molecular mechanism of the etiology of a hereditary genetic hypercholesterolemia family by scanning and analyzing the related genes of hereditary hypercholesterolemia in a clinically diagnosed proband and his family members.Molecular diagnosis was performed with PCR and then DNA sequencing of the promoter and 18 exons of low-density lipoprotein receptor (LDLR) gene and 3500 - 3531 fragment of apolipoprotein B-100 gene was carried out. The sequencing results were compared with the normal nucleotide sequence queried from the GeneBank database to discover the mutations.Familial defective apolipoprotein B-100 was excluded, as no mutation was detected in the apolipoprotein B 3500 - 3531 fragment. Two new point mutations were detected in the exon 4 of the proband's LDLR gene, they were heterozygous 685delA (Del A at 685) and 386AG. The sequencing in his parents and other family members showed that the two mutations were paternal origin (685delA) and maternal origin (386AG) respectively and should be located in different alleles of the proband.Molecular diagnosis in the family shows that the proband is a compound heterozygote and the newly detected LDLR gene mutations of 685delA and 386AG are the possible molecular etiological basis of the disease in this family.

To investigate the effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells.The rat Leydig cells (LC-540) were incubated with 0 to 80 nmol/L TBT and TPT for 24 to approximately 96 h, and then the cell viability was determined by MTT. DNA fragmentation ladder formation of cell apoptosis was examined by agarose electrophoresis. Effects of chelator of intracellular Ca2+ (BAPTA) and the inhibitors of PKA, PKC and TPK on cell apoptosis induced by TBT were observed. Effects of TBT on testosterone production in primary cultured rat Leydig cells treated with or without hCG were detected.TBT and TPT suppressed Leydig cell survival in a time- and dose-dependent manner. The suppressive effects of TBT and TPT on the cell survival was caused by apoptosis which was determined by DNA ladder formation. The apoptotic effect of TBT was possibly mediated by the rise in intracellular Ca2+ because it could be blocked by BAPTA, the chelator of intracellular Ca2+; PKA, PKC and TPK inhibitors did not prevent the apoptotic effects induced by TBT. TBT markedly suppressed testosterone production of primary cultured rat Leydig cells with or without hCG stimulation.TBT and TPT induced apoptosis in rat testicular Leydig cells possibly through increasing intracellular Ca2+. TBT reduced the testosterone production of rat Leydig cells.

To evaluate the superiority of insulin glargine as basal insulin replacement by continuous glucose monitoring system (CGMS). Twenty-four patients with type 2 diabetes mellitus (T2DM) whose blood glucose was not well controlled with sulphanylureas were enrolled. At first, they were treated with extended-release glipizide (glucotrol XL) 5mg/d before breakfast for 2 weeks, then randomized to combination treatment with glargine (16 patients) or NPH (8 patients) and treated for 12 weeks. CGMS were carried in the second week after treatment with glucotrol XL, and in the 12th week after combination treatment. The data of CGMS showed: (1) When FPG were well controlled in both groups (glargine group versus NPH group: 6.0+/-1.0 mmol/L versus 5.8+/-1.3 mmol/L), the blood glucose level at 3:00 a.m. (5.1+/-0.9 mmol/L versus 4.2+/-0.8 mmol/L) were higher (P

To study the expression of matrix metalloproteinase-9 (MMP-9) in diabetic nephropathy of Kkay mice with hyperhomocysteinemia.Sixteen Kkay mice were divided into two groups with 8 in each:diabetes group (KA) and methionine-diet group (KB). C57BL/6 mice were used as normal control (C57). Four months after being treated with two different diets, the mice were sacrificed and serum homocysteine (Hcy) was assayed with fluorescence polarization immunoassay. Renal pathological change was examined with periodic acid Schiff (PAS). The expression of MMP-9 protein and mRNA was detected with immunohistochemical staining and reverse transcriptase-PCR respectively.It was shown that induction of hyperhomocysteinemia in Kkay mice (KB) with a diet enriched in methionine aggravated diabetic nephropathy as compared with the KA group (P0.05). The expression of MMP-9 protein and mRNA in KB group was also enhanced and the mean positive area of MMP-9 in KB group was higher than that in KA group (15.90% vs 11.14%, P0.05).The increased level of Hcy could worsen the nephropathy; this may be related to a higher expression of MMP-9.

In men, obesity has generally been associated with reduced plasma testosterone levels and with elevation of the plasma free fatty acids (FFAs). In this study, we investigated the effects of saturated FFAs including palmitic acid (PA) and stearic acid (SA), and polyunsaturated FFA arachidonic acid (AA) on the survival of rat testicular Leydig cell cultured in vitro. PA and SA markedly suppressed Leydig cell survival in a time- and dose-dependent manner. In contrast, AA stimulated the cell proliferation at 5-10 times of physiological concentration. The suppressive effect of PA and SA on cell survival was caused by apoptosis evidenced by DNA ladder formation and Annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effect of PA was possibly mediated by ceramide generation because it could be completely blocked by ceramide synthase inhibitor fumonisin B1 and exogenous ceramide itself could directly induce apoptosis in vitro. Surprisingly, the apoptosis induced by PA could be partly prevented by AA. These results indicate that PA and SA induce apoptosis in testicular Leydig cells by ceramide production and these apoptotic effects may be a possible mechanism for reproductive abnormalities in obese men, and AA can partly prevent the apoptotic effect induced by saturated FFA.

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species.

We report concentration methods for the analysis of small solutes by capillary electrophoresis in conjunction with laser-induced native fluorescence using a Nd:YAG laser. After injecting samples, poly(ethylene oxide) (PEO) in the anode reservoir entered a capillary filled with Tris-borate buffer. When migrating in PEO solution, the analytes slowed down and stacked at the interface between the sample zone and PEO solution. As a result, the limits of detection (LODs) down to 8 p M for 2-naphthalenesulfonic acid and 70 p M for L-tryptophan have been achieved when injecting at 30 cm height for 120 s and 230 s, respectively. Such low LODs are partially due to the effects of NaCl in the samples and PEO on the fluorescence characteristics of the analytes. In addition, the concentrations of NaCl and PEO have great impacts on the migration of the analytes and electroosmotic flow, thereby affecting resolution and speed. Without pretreatment, the determinations of five important markers in urine samples and two acids in a cerebrospinal fluid sample have been performed separately, with the relative standard deviations of the concentrations less than 3.6%. Furthermore, by applying a short plug of low-pH buffer after injection, the analysis of greater volumes of the urine sample has been carried out, resulting in detecting more peaks.