[The efficacy and safety of insulin degludec versus insulin glargine in insulin-naive subjects with type 2 diabetes: results of a Chinese cohort from a multinational randomized controlled trial].

Objective: To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM). Methods: This was a 26-week, randomized, open-label, parallel-group, treat-to-target trial in 560 Chinese subjects with T2DM (men/women: 274/263, mean age 56 years, mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs). Subjects were randomized 2∶1 to once-daily IDeg (373 subjects) or IGlar(187 subjects), both in combination with metformin. The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks. Results: Mean HbA1c decreased from 8.2% in both groups to 6.9% in IDeg and 7.0% in IGlar, respectively. Estimated treatment difference (ETD) of IDeg-IGlar in change from baseline was -0.10% points (95%CI-0.25-0.05). The proportion of subjects achieving HbA1c<7.0% was 56.3%and 49.7% with IDeg and IGlar, respectively [estimated odds ratio of IDeg/IGlar: 1.26(95%CI 0.88-1.82)]. Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar, respectively [estimated rateratio of IDeg/IGlar 0.69(95%CI 0.46-1.03), and 0.43(95%CI 0.19-0.97)]. No differences in other safety parameters were found between the two groups. Conclusions: IDeg was non-inferior to IGlar in terms of glycaemic control, and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia. IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment. Clinical trail registration: Clinicaltrials.gov, NCT01849289.

Association between adiponectin gene T45G polymorphism and nonalcoholic fatty liver disease risk: a meta-analysis.

Numerous epidemiological investigations have evaluated the association between adiponectin gene T45G polymorphism and risk of nonalcoholic fatty liver disease (NAFLD). However, the results of these studies have proven to be inconsistent. Therefore, we conducted a meta-analysis to obtain a more accurate estimation of this association. Published articles were retrieved from PubMed and Web of Science databases and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effect models. Five case-control studies incorporating 597 cases and 701 controls were included in this meta-analysis. No association between adiponectin gene T45G polymorphism and NAFLD was established (TT vs GG: OR = 0.83, 95%CI = 0.37-1.86; TG vs GG: OR = 0.76, 95%CI = 0.33-1.79; dominant model: OR = 0.83, 95%CI = 0.37-1.84; recessive model: OR = 1.10, 95%CI = 0.69-1.76). Moreover, in a subgroup analysis, no significant correlation was found among Asian subjects. In conclusion, the T45G polymorphism of the adiponectin gene may not constitute an NAFLD risk factor. However, this needs to be further validated in single large well-designed future studies.

Changes and clinical significance of serum vaspin levels in patients with type 2 diabetes.

We investigated serum visceral adipose tissue-derived serpin (vaspin) levels in patients with normal glucose regulation and recently diagnosed type 2 diabetes (T2DM) and explored the association between vaspin and body mass index, age, gender, glucose, lipid metabolism, and insulin sensitivity. Fasting serum vaspin levels in 66 patients with T2DM and 48 normal subjects were detected using enzyme-linked immunosorbent assay. We found that serum vaspin levels in the DM group were 0.65 ± 0.13 mg/L in non-obese patients and 1.13 ± 0.25 mg/L in obese patients. Serum vaspin levels in the control group were 0.38 ± 0.18 mg/L in non-obese patients and 0.95 ± 0.11 mg/L in obese patients. Average serum vaspin levels were significantly higher in obese patients than in non-obese patients in both the DM group and control group. In the DM group, the serum vaspin level was 0.76 ± 0.22 mg/L in males and 0.92 ± 0.35 mg/L in females. In the control group, the serum vaspin level was 0.48 ± 0.14 mg/L in males and 1.05 ± 0.21 mg/L in females. Association analysis showed that serum vaspin levels were significantly associated with body mass index, waist-to-rip ratio (WHR), fat percentage, triglyceride, fasting plasma insulin, and insulin sensitivity index. Stepwise multiple regression analysis showed that gender, insulin sensitivity index, and WHR were the most significant independent factors affecting vaspin. Therefore, serum vaspin levels were significantly elevated in obese people and were independently associated with WHR, gender, and index sensitivity index.

Association of serum adipose triglyceride lipase levels with obesity and diabetes.

The aim of this study was to detect the serum adipose triglyceride lipase (ATGL) levels in obesity and newly diagnosed type 2 diabetes patients, and to explore the association between ATGL with glucose and lipid metabolism. We enrolled 66 patients with type 2 diabetes and 48 patients with normal glucose regulation, who were divided into an overweight or obese subgroup and a normal weight subgroup according to body mass index (BMI) ≥ 25 kg/m(2). The enzyme-linked immunosorbent assay was used to detect fasting blood glucose, blood lipids, fasting insulin, and ATGL levels. The serum ATGL level in the overweight or obese group was lower than that in the non-obese group including patients with type 2 diabetes and normal glucose regulation: 239 ± 61 vs 355 ± 54 mg/L and 242 ± 60 vs 383 ± 58 mg/L, respectively (t = 22.53, t = 8.23, P < 0.05). The Pearson correlation analysis showed that fasting serum ATGL was negatively correlated with body fat content, BMI, waist-to-hip ratio, triglycerides, and the homeostatic model assessment-insulin resistance level (r = -0.271, r = -0.238, r = -0.375, r = -0.313, and r = -0.164, respectively, P < 0.05). The stepwise regression analysis showed that the waist-to-hip ratio and body fat content were independently associated with the serum ATGL level. Our results indicated that the ATGL level may be closely related to obesity.

Plasma chemerin level in metabolic syndrome.

To investigate the chemerin level in the Chinese Han population with metabolic syndrome and its relationship with each metabolic syndrome component [body mass index (BMI), blood pressure, blood lipids, and blood glucose], we selected 30 patients with metabolic syndrome and 30 healthy control subjects. The chemerin level was measured by enzyme immunoassay in these 2 groups. The subjects' weight, blood pressure, BMI, waist circumference, fasting blood glucose, fasting insulin, lipids, and glycated hemoglobin were simultaneously detected. The t-test, correlation analysis, and multiple regression analysis were used to perform statistical analysis. We found that plasma chemerin level was higher in the metabolic syndrome group than that in the control group (97.61 ± 6.49 vs 70.26 ± 6.97, t = 15.73, P < 0.05). The plasma chemerin level was positively correlated with systolic blood pressure, waist circumference, BMI, waist-to-hip ratio, fasting blood glucose, fasting insulin, and glycated hemoglobin (r = 0.548, 0.442, 0.359, 0.556, 0.613, 0.581, and 0.572, respectively; all P < 0.05). However, it was negatively correlated with high-density lipoprotein cholesterol (r = -0.378, P < 0.05). Therefore, we concluded that plasma chemerin level was correlated with obesity, blood pressure, and high-density lipoprotein cholesterol, suggesting that it may play a role in the pathogenesis of metabolic syndrome.

Determination of glycyrrhetic acid in human plasma by HPLC-MS method and investigation of its pharmacokinetics.

OBJECTIVE: To develop a high performance liquid chromatography mass spectrometry (HPLC-MS) method for the determination of the glycyrrhetic acid (GA) in human plasma and for the investigation of its pharmacokinetics after the oral administration of 150 mg diammonium glycyrrhizinate test and reference capsule formulations. METHODS: The GA in plasma was extracted with ethyl acetate, separated on a C(18) column with a mobile phase of methanol (5 mmol/L ammonium acetate)-water (85 : 15, V/V) and analysed using a MS detector. Ursolic acid (UA) was used as internal standard. The target ions were m/z 469.5 for GA and m/z 455.6 for UA, the fragment voltages were 200 V and 100 V for GA and UA respectively. RESULTS: The calibration curve was linear over the range of 0.5-200 ng/mL (r = 0.9974). The limit of quantification for GA in plasma was 0.5 ng/mL, the recovery was 76.0-80.0%, and the inter- and intra-day relative standard deviations (RSD) were <12%. The pharmacokinetic parameters of GA after a single dose of 150 mg diammonium glycyrrhizinate test and reference were as follows: the half life (t(1/2)) 9.65 +/- 3.54 h and 9.46 +/- 2.85 h, the time to peak concentration (T(max)) 10.95 +/- 1.32 h and 11.00 +/- 1.30 h, the peak concentration (C(max)) 95.57 +/- 43.06 ng/mL and 103.89 +/- 49.24 ng/mL; the area under time-concentration curve (AUC(0-48) and AUC(0-infinity)) 1281.84 +/- 527.11 ng.h/mL and 1367.74 +/- 563.27 ng.h/mL, 1314.32 +/- 566.40 ng.h/mL and 1396.97 +/- 630.06 ng.h/mL. The relative bioavailability of diammonium glycyrrhizinate capsule was 98.88 +/- 12.98%. CONCLUSION: The assay was sensitive, accurate and convenient, and can be used for the determination of GA in human plasma. Comparison of the bioavailability and pharmacokinetic profile of GA indicated that the test and reference capsules were bioequivalent.

[Study on the expression of T, B lymphocyte antigen and platelet antibodies in patients with platelet transfusion refractoriness].

OBJECTIVE: To explore whether T lymphocytes subgroup, B lymphocytes, platelet antigen CD41a, CD61 or platelet antibodies are involved in the platelet transfusion refractoriness. METHODS: Forty-seven patients diagnosed as platelet transfusion refractoriness and 32 patients that achieved effective platelet therapy were ennolled in this study. Flow cytometry was performed to detect the proportion of cytotoxic T cell (CD3(+)CD4(-)CD8(+)), helper T cell (CD3(+)CD4(+)CD8(-)) and B lymphocytes (CD19 (+) ), and the expression of platelet glycoproteins, including CD41a and CD61, while platelet antibodies were also measured by solid-phase agglutination. RESULTS: The significant lower level of helper T cell (36.60% vs 48.53%), higher level of cytotoxic T cell (53.26% vs 44.02%) and lower cytotoxic/helper T cell ratio (0.85 vs 1.31) were observed in platelet refractoriness group when compared with effective platelet therapy group (P<0.05). However, the significant difference was not observed in B lymphocytes between the two group (3.02% vs 2.85%, P>0.05). Platelet glycoproteins CD41a and CD61 and antibodies were both expressed at high levels in platelet refractoriness group (88.10% vs 51.69%, 88.36% vs 51.83%, 85.37% vs 14.82%, respectively, P<0.05). CONCLUSIONS: Activation of cytotoxic T cells, suppression of helper T cells, higher expression level of platelet glycoproteins CD41a and CD61 as well as the development of anti-platelet antibodies are involved in the immunologic mechanism of platelet refractoriness.

The use of transcallosal-interforniceal approach for microsurgical removal of the third ventricle tumors.

AIM: The third ventricle is located deep in the brain and is adjacent to important neurovascular structures. This makes tumor resection in this region difficult and causes more postoperative complications than surgeries in other regions of the brain. The objective of this study was to investigate the feasibility and clinical effects of transcallosal-interforniceal approach for microsurgical removal of the third ventricle tumors. METHODS: After preoperative evaluation, 23 patients with the third ventricle tumors were microsurgically operated using the transcallosal-interforniceal approach. RESULTS: Of these 23 patients, 12 (52.2%) underwent total excision, 9 (39.1%) had subtotal resection, and the remaining 2 (8.7%) underwent partial excision. After surgery, the following complications were observed: diabetes insipidus (11 patients), hemorrhages of the upper digestive tract (2 patients), central fever (1 patient), and memory impairment (1 patient). No mortality in the perioperative period was reported. CONCLUSION: The surgical procedure using the transcallosal-interforniceal approach is direct and provides good surgical field exposure and fewer post operational compilations. This approach should be considered as the method of choice for surgical removal of the third ventricle tumors.

Pharmacokinetic study of icariside II after a single dose administration of YiGu capsule in healthy Chinese volunteers.

To investigate the pharmacokinetic characteristics of icariside II after a single oral dose administration of YiGu Capsule in healthy -Chinese volunteers. 8 (4 female) healthy Chinese volunteers were involved and administrated for 15 doses of YiGu Capsule after fasting overnight. 4 ml of blood samples were collected at scheduled time before and after administration. Icariside II in human plasma was separated on a Agela Venusil XBP-C18 column (250 mm×4.6 mm, 5 µm), and eluted using acetonitrile-water (containing 0.1% formic acid) (70:30, V/V) as mobile phase. The analytes were detected with a -triple quad HPLC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring mode were m/z 515.1 (precursor ion) to m/z 369.1 (product ion) for icariside II and m/z 321.0 (precursor ion) to m/z 275.0 (product ion) for lorazepam (internal standard).The plasma concentration of icariside II was determined by established HPLC-MS/MS method after disposition and its pharmacokinetic parameters were analyzed and evaluated by PK Solver Software (version 1.0). The Cmax, Tmax, t1/2, AUC0-24, AUC0-∞, MRT0-∞-1, 2.50±1.91 h, 7.61±2.81 h, 12.68±4.86 ng · mL-1 · h, 14.22±5.75 ng · mL-1 · h, 9.55±1.56 h, 12.81±7.94 L · h-1 and 121.70±32.70 L. The established HPLC-MS/MS method was sensitive, selective and rapid for icariside II pharmacokinetic study.

Bioequivalence of two misoprostol tablets in healthy Chinese female volunteers: a single-dose, two-period, double crossover study.

OBJECTIVE: To assess the bioequivalence of a new generic formulation of misoprostol (CAS 59122-46-2) 0.2 mg tablets (test) and the available branded tablet (reference) for the requirement of state regulatory criteria and the marketing of the test product in China. METHODS: A randomized-sequence, 2-period crossover study was conducted in 20 healthy Chinese female volunteers in the fasted state. Blood samples were collected at baseline and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 and 6 h after a single oral dose of 0.6 mg misoprostol test or reference, followed by a 7-day washout period. Misoprostol acid, the active metabolite of misoprostol, was determined by an HPLC-MS/MS method. Drug And Statistics 2.0 was used to calculate the pharmacokinetics parameters and assess bioequivalence of the 2 formulations. It was considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for Tmax, Cmax and AUC0-t were all within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. RESULTS: The main pharmacokinetics parameters for the test and reference were as follows: t1/2 was (0.680 ± 0.371) h and (0.650 ± 0.264) h; Tmax was (0.415 ± 0.087) h and (0.399 ± 0.097) h; Cmax was (1.941 ± 0.417) ng/mL and (2.047 ± 0.397) ng/mL; AUC0-t was (1.535 ± 0.419) ng·h/mL and (1.652 ± 0.400)ng·h/mL, and the AUC0-∞ was (1.576 ± 0.465) ng·h/mL and (1.686 ± 0.396) ng·h/mL. The mean ratios (test: reference) for Cmax, AUC0-t, and AUC0-∞ were 95.3% ±13.2%, 92.65% ± 17.31%, and 93.61%±18.97%, respectively. No significant (p>0.05) differences in pharmacokinetic parameters were found between preparations, treatments and periods. CONCLUSIONS: This single-dose study in healthy Chinese fasted volunteers was shown that the misoprostol test and reference met the requirement of US and China regulatory criterion, and the test and reference were bioequivalent.

A tunable radio-frequency magnetic probe.

A tunable center-tapped transformer is proposed to increase the output of a rf magnetic probe and improve the signal-to-noise ratio. The tuning is implemented by a variable capacitor connected parallel with the primary winding of the tunable center-tapped transformer. Undesirable common-to-differential conversion is reduced by installing a compensating capacitor. In addition, a planar Faraday shield is installed between the windings of the transformer to further suppress the electrostatic coupling. It is found that tuning the variable capacitor can result in a resonance in the output voltage of the rf magnetic probe. The largest output voltage, achieved with the tunable magnetic probe under the optimal condition, is higher than that with a conventional one by an order of magnitude. Effects of the compensating capacitance on the common-mode output voltage are studied and discussed. Influences of parameters such as cable length, the coupling coefficient, and the step-up ratio of the transformer on the output voltage are also presented. Analytical derivations and numerical calculations based on the equivalent circuit are performed to elucidate the characteristics of the differential mode.