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Blunt snout bream (Megalobrama amblycephala) were randomly assigned into three diets: normal-carbohydrate diet (NCD, 30% carbohydrate, w/w), high-carbohydrate diet (HCD, 43% carbohydrate), and HCB (HCD supplemented with 50 mg/kg berberine (BBR)). After 10 weeks' feeding trial, the results showed that higher levels of plasma glucose, triglyceride, and total cholesterol were observed in HCD-fed fish than in NCD-fed fish, while HCB feeding significantly ameliorated this effect. Moreover, HCB feeding remarkably reversed HCD-induced hepatic glycogen and lipid contents. In insulin signaling, BBR inclusion restored HCD-induced suppression of insulin receptor substrate mRNA expression and elevation of forkhead transcription factor 1 mRNA expression. In glucose metabolism, upregulated glucose transporter 2 and glycogen synthase mRNA expressions in the HCD group were observed compared to the NCD group. However, BBR adding reduced the mRNA expressions of glycogen synthase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase and increased the transcriptional levels of glucose transporter 2 and pyruvate kinase. In lipid metabolism, BBR supplementation could reverse downregulated hepatic carnitine palmitoyl transferase I mRNA expression and upregulated hepatic acetyl-CoA carboxylase and fatty acid synthetase mRNA expressions in the HCD group. Taken together, it demonstrates that BBR could improve glucose metabolism of this species via enhancing liver's glycolysis and insulin signaling, while inhibiting liver's glycogen synthesis and gluconeogenesis. It also indicates that BBR could reduce the metabolic burden of the liver by inhibiting fat synthesis and promoting lipid decomposition, and then enhance fat uptake in peripheral tissues.

Deficits in information processing speed (IPS) are among the earliest and most prominent cognitive manifestations in mild traumatic brain injury (mTBI). We investigated the impact of white matter fiber location on IPS outcome in an individual basis assessment. A total of 112 acute mild TBI with all CT negative underwent brain DTI and blood sampling for inflammation cytokines within 7 days postinjury and 72 age‐ and sex matched healthy controls with same assessments were enrolled. IPS outcome was assessed by the trail making test at 6–12 month postinjury in mild TBI. Fractional anisotropy (FA) features were extracted using a novel lesion‐load analytical strategy to capture spatially heterogeneous white matter injuries and minimize implicit assumptions of uniform injury across diverse clinical presentations. Acute mild TBI exhibited a general pattern of increased and decreased FA in specific white matter tracts. The power of acute FA measures to identify patients developing IPS deficits with 92% accuracy and further improved to 96% accuracy by adding inflammation cytokines. The classifiers predicted individual's IPS and working memory ratings (r = .74 and .80, respectively, p, Combination of inflammation cytokine and fibers projecting to frontal cortex as predictors can identify long‐term information processing speed deficits in mild TBI patients with negative CT.

Neutrophil gelatinase-associated lipocalin (NGAL) is not only a biomarker of kidney injury but also a bone-derived factor involved in metabolism. We aimed to explore relationships between plasma NGAL and chronic kidney disease-mineral bone disorder (CKD-MBD) parameters in maintenance hemodialysis (MHD) patients. First, a cross sectional observational study, including 105 MHD patients, was conducted to explore relationships between plasma NGAL levels and CKD–MBD parameters. Second, impact of parathyroidectomy and auto-transplantation (PTX + AT) on plasma NGAL was investigated in 12 MHD patients with severe secondary hyperparathyroidism (SHPT). According to Spearman correlation analysis, plasma NGAL levels were positively correlated with female (r = 0.243, P = 0.012), vintage (r = 0.290, P = 0.003), Klotho (r = 0.234, P = 0.016), calcium(Ca) (r = 0.332, P = 0.001), alkaline phosphatase (ALP) (r = 0.401, P

Background Mild traumatic brain injury (mTBI) has a higher prevalence (more than 50%) of developing chronic posttraumatic headache (CPTH) compared with moderate or severe TBI. However, the underlying neural mechanism for CPTH remains unclear. This study aimed to investigate the inflammation level and cortical volume changes in patients with acute PTH (APTH) and further examine their potential in identifying patients who finally developed CPTH at follow-up. Methods Seventy-seven mTBI patients initially underwent neuropsychological measurements, 9-plex panel of serum cytokines and MRI scans within 7 days post-injury (T-1) and 54 (70.1%) of patients completed the same protocol at a 3-month follow-up (T-2). Forty-two matched healthy controls completed the same protocol at T-1 once. Results At baseline, mTBI patients with APTH presented significantly increased GM volume mainly in the right dorsal anterior cingulate cortex (dACC) and dorsal posterior cingulate cortex (dPCC), of which the dPCC volume can predict much worse impact of headache on patients’ lives by HIT-6 (β = 0.389, P = 0.007) in acute stage. Serum levels of C-C motif chemokine ligand 2 (CCL2) were also elevated in these patients, and its effect on the impact of headache on quality of life was partially mediated by the dPCC volume (mean [SE] indirect effect, 0.088 [0.0462], 95% CI, 0.01–0.164). Longitudinal analysis showed that the dACC and dPCC volumes as well as CCL2 levels had persistently increased in patients developing CPTH 3 months postinjury. Conclusion The findings suggested that structural remodelling of DMN brain regions were involved in the progression from acute to chronic PTH following mTBI, which also mediated the effect of inflammation processes on pain modulation. Trial registration ClinicalTrial.gov ID: NCT02868684; registered 16 August 2016.

Key roles of the gut–brain axis in brain injury development have been suggested in various mouse models; however, little is known about its functional significance in human mild traumatic brain injury (TBI). Here, we decipher this axis by profiling the gut microbiota in 98 acute mild TBI patients and 62 matched controls, and subgroup of them also measured circulating mediators and applied neuroimaging. Mild TBI patients had increased α-diversity and different overall microbial compositions compared with controls. 25-microbial genus classifiers distinguish patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.889, while adding serum mediators and neuroimaging features further improved performance even in a small sample size (AUC = 0.969). Numerous correlations existed between gut bacteria, aberrant cortical thickness and cerebrovascular injury. Co-occurrence network analysis revealed two unique gut–brain axes in patients: 1) altered intestinalLachnospiraceae_NK4A136_groupandEubacterium_ruminantium_group-increased serum GDNF-subcallosal hypertrophy and cerebrovascular injury; 2) decreased intestinalEubacterium_xylanophilum_group–upregulated IL-6–thinned anterior insula. Our findings provide a new integrated mechanistic understanding and diagnostic model of mild TBI.

Objective Total parathyroidectomy with autotransplantation(TPTX+AT) and subtotal parathyroidectomy(SPTX) have been recommended to patients with renal hyperparathyroidism(RHPT).But which one is the best surgical method remains controversial. The aim of the present study was to compare the two surgical procedures with respect to long-term outcomes. Methods A literature search was undertaken using Medline, EMBASE, CNKI and CBM from inception to May 2015. Study quality was assessed using the Newcastle-Ottawa Scale. Data were analyzed using Review Manager version 5.1.0. Results A total of 13 studies comprising 1589 patients with renal failure were identified. There was no statistically significant difference in the rate of symptomatic improvement(OR 0.77; 95%CI 0.22 to 2.69; P = 0.68), radiological success (OR 0.17; 95%CI 0.02 to 1.56; P = 0.90), hyperparathyroidism recurrence or persistence(OR 1.31; 95%CI 0.65 to 2.65; P = 0.45) and reoperation(OR 1.55; 95%CI 0.62 to 3.86;P = 0.35) between TPTX + AT and SPTX. The effects on serum calcium and parathyroid hormone(PTH) were similar between two surgical protocols. Conclusions Both the TPTX + AT and SPTX were effective in treating RHPT and preventing recurrence. The difference between the two surgeries in recurrence or persistence and reoperation rate was insignificant. Further prospective, randomized controlled trials with high statistic power are necessary to comparative the two surgeries on the long term safety.

High body mass index (BMI) is the most common parameter to assess excess adiposity, and has been linked to glomerular hyperfiltration (GH). However, BMI may be misleading in the estimation of body fat content due to its inability to discriminate between body fat and lean mass. In recent years, the convenient biological impedance analysis has made prediction of certain diseases somewhat feasible and accessible using body composition (BC). Accordingly, we conducted a cross-sectional study to explore the association between BC and GH among Chinese adult population. A total of 6902 adults (aged 38.6 ± 8.3 years, 70.1% males) who consecutively visited the Health Checkup Clinic were enrolled. BC including fat mass and lean body mass (LBM) was evaluated by biological impedance analysis. The upper quartile of eGFR which exceeded 117.3 mL/min/1.73 m2 was defined as GH, in comparison with the lower three quartiles (control group). As a categorical outcome, GH subjects had higher fat/LBM than the control group, which was 34.7 ± 10.9 (%) vs. 34.0 ± 10.5 (%), P = 0.01; however, the BMI in GH group was lower than in the control group, which was 24.5 ± 3.7 (%) vs. 24.9 ± 3.6 (%), P < 0.001. Fat/height and Fat/BSA were not significantly different between the two groups. Moreover, after adjusting for potential confounders, fat/LBM significantly correlated with GH (OR = 2.09, 95% CI, 1.11 to 3.93). The study revealed that fat/LBM significantly correlated with GH among Chinese adult population, which highlights that adiposity might be an important and potentially modifiable determinant of GH.

We investigated the effects of icariin (ICA) on growth performance, antioxidant capacity and non-specific immunity in Chinese mitten crab (Eriocheir sinensis). A total of 200 healthy crabs (average weight: 33.58 ± 0.05 g) were randomly assigned to four treatments with five replicates, each with ten individuals per pool. There were four dietary treatments: the control group (fed with the basal diet), the ICA 50 group, the ICA100 group, and the ICA 200 group (fed with the basal diet supplemented with 50, 100, and 200 mg/kg ICA, respectively). These diets were provided for 8 weeks. Results indicated that ICA100 crabs had higher weight gain (WG), specific growth rate (SGR) and survival rate (SR) than the controls. Protein carbonyl content (PCC) and malondialdehyde (MDA) concentrations in the haemolymph and hepatopancreas of ICA100 crabs were significantly lower than in the control group, while the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were significantly higher. The activities of PO, LZM, ACP and AKP were significantly enhanced with ICA supplementation at 50 and 100 mg/kg, yet decreased subsequently at 200 mg/kg. Furthermore, supplementation of 100 mg/kg ICA up-regulated the mRNA expression of prophenoloxidase (proPO), catalase (CAT), mitochondrial manganese superoxide dismutase (mtMnSOD), thioredoxin-1 (Trx1) and peroxiredoxin 6 (Prx6), while the mRNA expression of toll like receptors (TLRs), NF-κB-like transcription factor Relish and lipopolysaccharide-induced TNF-α factor (LITAF) were down-regulated in the hepatopancreas (P 0.05). These findings indicate that dietary ICA supplementation at an optimum dose of 100 mg/kg may be effective in improving growth performance, antioxidant capability and non-specific immunity of Chinese mitten crab.

// Zuguang Xia 1, * , Xiaoyan Jia 3, * , Kai Chen 2 , Dapeng Li 2 , Jing Xie 2 , Hong Xu 2 , Yixiang Mao 2, 3 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 2 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China 3 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA * These authors contributed equally to this work Correspondence to: Zuguang Xia, email: zuguang_xia@163.com Hong Xu, email: 13301549066@163.com Yixiang Mao, email: maoyix@gmail.com Keywords: pancreatic adenocarcinoma, postoperative radiation therapy, lymph node metastasis, survival Received: March 10, 2016 Accepted: April 16, 2016 Published: May 26, 2016 ABSTRACT The benefit of combining postoperative radiation therapy (PORT) with chemotherapy for resected patients with pancreatic adenocarcinoma is controversial. We sought to determine the effects of PORT on survival in patients with pancreatic adenocarcinoma who underwent primary site surgery. Patients with pancreatic adenocarcinoma receiving primary tumor surgery between 1988 and 2012 were identified from the Surveillance, Epidemiology and End Results (SEER) database. We estimated the association between PORT and other clinicopathologic factors and survival. In total, 5304 patients were identified who underwent pancreatic resection including 2093 patients who had PORT and 3211 patients who had no PORT. Median overall, cancer-specific, and other-cause survival were 19.0, 20.0, and 196.0 months, respectively, with PORT versus 14.0, 15.0, and 163.0 months, respectively, without PORT (all P < 0.001). Subset analysis revealed that the benefit of PORT was limited to patients with N1 disease. Median overall, cancer-specific, and other-cause survival for patients with N1 disease were 18.0, 18.0, and NA months, respectively, with PORT versus 12.0, 13.0, and 154.0 months, respectively, without PORT (all P < 0.001). Regardless the number of positive lymph node count (PLN) and lymph node ratio (LNR), PORT was always associated with increased survival on multivariate analysis in patients with N1 disease (all P < 0.001). In summary, survival benefits might be obtained from PORT on lymph node positive patients with pancreatic adenocarcinoma.

Background. Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pathologic complete response rate than do diabetic patients not receiving metformin, but findings on salvage treatment have been inconsistent. We performed a meta-analysis to assess the effect of adding metformin to standard therapy on the prognosis of breast cancer patients with diabetes. Methods. We searched PubMed, Embase, Web of Science (Thomson Scientific), China Knowledge Resource Integrated Database, VIP journal integration platform, and Chinese BioMedical Literature Database from inception to January 10, 2015, without language restrictions, including references related to metformin, breast cancer, and prognosis. We performed the meta-analysis using a random-effects model, with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures. Results. A total of 11 studies consisting of 5,464 breast cancer patients with diabetes were included, comprising 2,760 patients who had received metformin and 2,704 patients who had not. The meta-analysis showed that metformin was associated with better overall survival times (HR: 0.53; 95% CI: 0.39-0.71) and cancer-specific survival times (HR: 0.89; 95% CI: 0.79-1.00). Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression (HR: 0.35; 95% CI: 0.15–0.84). Taking metformin after the diagnosis of breast cancer was still associated with prolonged overall survival. Conclusion. The use of metformin in standard cancer therapy might improve both overall and cancer-specific survivals of diabetic patients with breast cancer. Implications for Practice: Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pathologic complete response rate than diabetic patients not receiving metformin, but findings on salvage treatment have been inconsistent. The meta-analysis showed that metformin was associated with better overall survival times and cancer-specific survival times. Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression. Taking metformin after the diagnosis of breast cancer was still associated with prolonged overall survival. The findings of this study highlight the potential usage of metformin in diabetic patients with breast cancer.

The aim of the present study was to compare total parathyroidectomy without autotransplantation (TPTX) versus total parathyroidectomy with autotransplantation (TPTX + AT) for renal hyperparathyroidism (RHPT) with respect to long-term outcomes. A literature search was undertaken using Medline and EMBASE from inception to December 2013. Data were analyzed using Review Manager version 5.0. A total of seven cohort studies comprising 931 patients were identified. Compared with TPTX + AT, patients in the TPTX group have lower "recurrence" (odds ratio (OR) 0.08, confidence interval (CI) 0.03 to 0.21; P

Few studies have examined the relationships between the prevalence of chronic kidney disease (CKD) and the metabolic risk factors in a developing country such as China, where genetic and environmental backgrounds differ from those in Western countries.The subjects of this cross-sectional study were the individuals from 18 to 92y. The metabolic syndrome (MetS) was defined based on the criteria of Adult Treatment Panel Third Report (ATP III), but using body mass index (BMI) instead of waist circumference. CKD was defined as decreased estimated glomerular filtration rate (eGFR60mL/min/1.73mA total of 26,601 subjects (average age of 48.7y) were analyzed. Among them, the prevalence of the MetS and CKD was 36.4% and 3.0%, respectively. After adjustment for age, gender, cigarette smoking and alcohol drinking, the prevalence of CKD was significantly greater in subjects with than without MetS (OR 1.99, 95% CI 1.57-2.53, p0.001). Multivariate-adjusted odd ratios for CKD in subjects with 3, 4 or 5 MetS components were 1.82 (95% CI 1.31-2.52, p0.001), 2.92 (95% CI 2.09-4.09, p0.001), and 3.07 (95% CI 1.67-5.67, p0.001), respectively. After further adjustments were made for the other components of MetS, only high fasting glucose (OR 1.52, 95% CI 1.12-2.05) were significant risk factors for reduced renal function(eGFR60mL/min/1.73mMetS was highly prevalent in the middle-aged and elderly Chinese population in the city of Jinan. There was a graded relationship between the number of MetS components and risk of CKD. High fasting blood glucose levels were the main risk factor of reduced renal function. High blood pressure, high fasting blood glucose levels and high triglycerides were main risk factors for proteinuria.

RATIONALE Fibroma of tendon sheath is a rare entity that is typically attached to the tendon sheath. PATIENT CONCERNS A 43-year-old man presented with a painful mass in his right wrist, which was initially misdiagnosed as an enchondroma. DIAGNOSIS Fibroma embedded into carpal bones, which exhibited lytic radiographic features similar to those of enchondroma. Excisional biopsy demonstrated spindle-shaped cells and collagen-like stroma. INTERVENTIONS The patient underwent lesion resection surgery. OUTCOMES The patient recovered well and showed no signs of recurrence at 6-month follow-up. LESSONS This case provides valuable insights for hand surgeons. While radiograph is helpful in multiple diseases, histological examination is indispensable for establishment of final diagnosis.

Aim: Hyperphosphataemia is almost inevitable in end stage renal disease (ESRD) patients and is associated with increased morbidity and mortality. In this study we examined whether oral activated charcoal (oAC) reduces serum phosphate level in haemodialysis patients. Methods: This was an open-label, prospective, uncontrolled study. One hundred and thirty-five haemodialysis patients were included in this study, with cessation of treatment with any phosphate binders during a 2 week washout period. Patients with serum phosphate levels greater than 5.5 mg/dL during the washout period were included for treatment with oAC. oAC was started at a dose of 600 mg three times per day with meals and was administered for 24 weeks. oAC dose was titrated up during the 24 week period to achieve phosphate control (3.5–5.5 mg/dL). A second 2 week washout period followed the end of oAC treatment. Results: In the 114 patients who successfully completed the trial, the mean dose of activated charcoal was 3190 ± 806 mg/day. oAC reduced mean phosphate levels to below 5.5 mg/dL, with mean decreases of 2.60 ± 0.11 mg/dL (P

Objective. To study the influence of strengthening the all-round quality control of the department on the quality of terminal medical records of the nephrology department of our hospital. Methods. A total of 2,547 terminal medical records of 2013, from the nephrology department of our hospital, are chosen as an experimental group, and a total of 2,373 terminal medical records of 2012 are used as a control group. The experimental group strengthens the quality control of the departments in an all-round manner. The control group performs the routine quality control. The defect numbers of medical records, the average admission medical record scores and the A-level medical record rates of the two groups are compared. Results. The defect number of admission medical records in the experimental group is obviously lower than that in the control group, the average admission medical record scores and the A-level medical record rates in the experimental group are obviously higher than those in the control gro...

Concurrent diabetes has been linked with an increased risk of death in many cancers, but findings in pancreatic cancer have been inconsistent. We performed a systematic review and meta-analysis to assess the effect of diabetes on survival in patients with pancreatic cancer. Of 4, 463 original articles, 41 were included in the review; 29 studies with 33 risk estimates were included in the meta-analysis. In the overall comparison of patients with pancreatic cancer and diabetes with their nondiabetic counterparts, the former had significantly higher all-cause mortality (pooled HR: 1.13; 95% CI: 1.04–1.22). Subgroup analyses showed that diabetes was associated with poor survival in patients with resectable disease (HR: 1.37; 95% CI: 1.15–1.63) but not in those with unresectable disease (HR: 1.07; 95% CI: 0.89–1.29). The HR (95% CI) was 1.52 (1.20–1.93) for patients with new-onset diabetes (≤2 years of diabetes duration) and 1.22 (0.83–1.80) for those with longstanding diabetes (>2 years). Diabetes was associated with higher mortality overall in patients with pancreatic cancer. The effect of diabetes on overall survival was associated with the stages of tumor and the duration of diabetes.

association between long-term diabetes and poor overall survival among patients with diabetes and pancreatic cancer in three longitudinal studies. The authors reported a 40% to 50% increased risk of death for patients with long-term diabetes (duration of 4 years) compared with those without diabetes (P .05) in two prospective cohort studies 2,3 and a clinic-based study. 1 In contrast, no statistically significant association between short-term diabetes (duration of 4 years) and survival was observed. Thus, the authors concluded that there is a link between chronic glucose intolerance and pancreatic cancersurvival,whereasshort-termdiabetesdoesnotportendaworse prognosis among patients with pancreatic adenocarcinoma. We have a concern about the authors’ conclusion regarding the association between short-term diabetes and survival. Because the information on diabetes was collected via a biennial questionnaire in the cohort studies, it is possible that the number of patients with short-term diabetes was greatly underestimated, which may have biased the risk estimate toward null. The prevalence of patients with short-term diabetes was 4.67% (47 of 1,006) and 18.65% (72 of 386), whereas the prevalence of patients with any type of diabetes was 17.99% (181 of 1,006) and 31.35% (121 of 386) in the cohort and the clinic-based studies, respectively. The prevalence of diabetes in the clinic-based study was quite similar to the numbers previously reported by other studies. Short-term diabetes was associated with a nonsignificant but increased risk of death in this clinic series (hazard ratio [HR], 1.22; 95% CI, 0.89 to 1.67). In our recently completed studyof1,328patientswithpathologicallyconfirmedpancreaticductal adenocarcinoma of all stages at MD Anderson Cancer Center, we foundthatshort-termdiabetes(durationof3years)wasassociated with a significantly increased risk of death (HR, 1.23; 95% CI, 1.09 to 1.40).Wehavealsoconductedameta-analysisof29studiesondiabetesandoverallsurvivalofpatientswithpancreaticcancerandfounda reduced survival of patients with diabetes in 25 clinic-based studies (pooled HR, 1.13; 95% CI, 1.02 to 1.25), but not in four cohort studies 4-7 (pooled HR, 1.12; 95% CI, 0.95 to 1.32). The prevalence of patients with diabetes was 28.61% (4,133 of 14,446) and 20.92% (1,124 of 5,372) in the clinic and cohort studies, respectively. These observations suggest that short-term diabetes is associated with a higher risk of death in patients with pancreatic cancer. The inconsistentobservationswithrespecttotheassociationbetweendiabetesand

Many people with epilepsy suffer from poorly controlled seizures, despite current antiepileptic treatments. Due to high rates of treatment resistance, there is interest in new pharmacological treatment options such as pregabalin. However, it remains unclear whether existing evidence of pregabalin is rigorous enough to support its monotherapy.To determine the efficacy and tolerability of pregabalin in people with epilepsy.We searched the Cochrane Epilepsy Group's Specialized Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7 ), MEDLINE (1946 to August week 1, 2012), EMBASE (1974 to August 2012) and the Chinese Biomedical Literature Database (CBM) (1978 to August 2012). No language restrictions were imposed.Randomised controlled trials (RCTs) comparing pregabalin with placebo or another antiepileptic drug monotherapy for epilepsy.Two review authors (QZ and LY) independently extracted trial data and assessed trial quality. We assessed the following outcomes: (1) time to withdrawal after randomisation; (2) time to achieve six-, 12- or 24-month remission; (3) the proportion of participants who remained seizure-free for six or more continuous months; (4) time to first seizure after randomisation; (5) validated quality of life measures; (6) health economic outcomes; (7) adverse effects. We expressed time-to-event outcomes as hazard ratios (HRs) with 95% confidence interval (CI), where an HR1 indicates an event is more likely to occur earlier on pregabalin than the comparator.Two short-term studies involving 753 participants met the inclusion criteria. Only one study investigated the effects of pregabalin compared with lamotrigine in patients with newly diagnosed partial seizures, and the other study investigated the effects of pregabalin compared with gabapentin in hospitalised patients with refractory partial epilepsy. There were no studies on generalised-onset tonic-clonic seizures (with or without other generalised seizure types).We found that pregabalin was inferior in comparison to lamotrigine when measuring time to withdrawal due to inadequate seizure control after dose stabilisation from randomisation: hazard ratio (HR) 4.52; 95% confidence interval (CI) 1.93 to 10.60; time to achieve six-month remission after dose stabilisation from randomisation: HR 0.56; 95% CI 0.41 to 0.76; the proportion of participants who remained seizure-free for six or more continuous months: RR 0.76, 95% CI 0.67 to 0.87 (Europe: 0.83, 95% CI 0.69 to 0.99; Asia: RR 0.70, 95% CI 0.57 to 0.86; the Americas: RR 0.62, 95% CI 0.33 to 1.19); and time to first seizure after dose stabilisation from randomisation: HR 1.74; 95% CI 1.26 to 2.39. There was no significant difference in safety-related outcomes between pregabalin and lamotrigine, but more participants in the pregabalin group developed somnolence, weight increase and convulsion. Pregabalin was better than gabapentin when measuring time to withdrawal due to all reasons after randomisation: HR 0.25; 95% CI 0.11 to 0.57; and time to withdrawal due to inadequate seizure control after randomisation: HR 0.41; 95% CI 0.18 to 0.92. No significant difference was found in safety-related outcomes between pregabalin and gabapentin. But we found some limitations in the study design which may have had an influence on the results.Pregabalin seems to have similar tolerability but inferior efficacy in comparison to lamotrigine for newly diagnosed partial seizures. However, considering the limitations in the study design (such as the short-term follow-up and the low initial target dose selection), the results should be interpreted with caution. The available data were too limited to draw any conclusions between pregabalin and gabapentin. The result indicated that the treatment effects were influenced by the study regions. The clinical disadvantage of pregabalin was more prominent in Asia when compared with lamotrigine. We should determine whether pregabalin has ethnic differences in the treatment of epilepsy in the future. This review does not inform any treatment policy for patients with generalized onset tonic-clonic seizures. Further long-term trials are needed to investigate the genuine effectiveness of pregabalin as monotherapy.

Background Moderate to severe renal insufficiency and albuminuria have been shown to be independent risk factors for atherosclerosis. However, little is known about the direct association between subclinical atherosclerosis evaluated by carotid artery intima-media thickness (IMT) and microalbuminuria in elderly patients with normal renal function. Methods Subjects were 272 elderly patients (age ≥ 60 years) with normoalbuminuria (n = 238) and microalbuminuria (n = 34). Carotid IMT was measured by means of high-resolution B-mode ultrasonography. Estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 was defined as normal renal function. Those who had macroalbuminuria and atherosclerotic vascular disease were not included. Results Compared to subjects with normoalbuminuria, subjects with microalbuminuria had higher mean carotid IMT (1.02 ± 0.38 vs. 0.85 ± 0.28 mm; P Conclusions A slight elevation of albuminuria is a significant determinant of carotid IMT independent of traditional cardiovascular risk factors in our patients. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis when microalbuminuria is found in elderly patients, although with normal renal function.

In previous studies on the enteroinsular axis in Zucker rats, it was found that glucose-dependent insulinotropic polypeptide (GIP) levels were normal in obese animals, but the glucose threshold for the insulinotropic action of GIP in the perfused rat pancreas was reduced. Glucagonlike peptide I (GLP-I)(7–36) is also an important incretin, and in the current study, glucose, insulin, and immunoreactive (IR)–COOH-terminal GLP-I responses to oral glucose were compared in lean (Fa/?) and obese (fa/fa) rats. In addition, the concentration thresholds for stimulation and glucose dependence of perfused pancreases to GLP-I(7–36) were examined. Glucose responses to oral glucose were similar in fa/fa and Fa/? rats. Obese animals were hyperinsulinemic when fasting and after oral glucose. Significant increases in IR–GLP-I levels in response to glucose were only observed in fa/fa rats. Perfused pancreases from fa/fa rats hypersecreted insulin at all glucose concentrations. In the presence of 4.4 mmol/l glucose, GLP-I(7–36) increased insulin secretion in fa/fa pancreases ∼25-fold, whereas there was only a 5-fold increase in Fa/? Pancreases. Pancreases from fa/fa rats, perfused with a glucose gradient (2.8–11 mmol/l) in the presence of GLP-I(7–36), responded with an immediate increase in insulin secretion, i.e., at a glucose concentration of 2.8 mmol/l, whereas Fa/? pancreases required a minimum of 4.22 mmol/l glucose for stimulation. With high glucose (16.7 mmol/l), both fa/fa and Fa/? rat pancreases exhibited similar responsiveness to GLP-I(7–36), having thresholds of