Adjunctive vagus nerve stimulation for treatment-resistant depression: a preliminary study.

BACKGROUND: This study is the first to assess the safety and therapeutic efficacy of vagus nerve stimulation (VNS) as an adjunctive treatment for Chinese patients suffering from treatment-resistant depression (TRD). METHODS: A total of seven patients with TRD underwent surgical implantation of a VNS device were followed over a 9-month period. The 24-item Hamilton Rating Scale for Depression (HAMD-24) and the 14-item Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms, respectively. Neurocognitive function was measured with the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale (WMS). RESULTS: After 3 months of treatment with VNS, the antidepressant response and remission rates were 42.9% and 28.6%, respectively. After 9 months of treatment with VNS, the response and remission rates increased to 85.7% and 57.1%, respectively. Significant time main effects were identified for HAMD-24 scores, HAMA scores, the WMS memory quotient, and the full intelligence quotients measured with the WAIS (all ps < 0.05). The most frequent adverse effects of VNS treatment were voice alteration (100%) and cough frequency increase (71.4%). CONCLUSION: This preliminary study indicated that adjunctive VNS was effective and safe in treating Chinese patients who were suffering from TRD, and its efficacy increased with time.Key pointsThere is positive evidence to support the role of VNS as an adjunctive treatment in Chinese patients with TRD.The antidepressant efficacy of adjunctive VNS for Chinese patients with TRD increased with time.The most frequent adverse effects of VNS treatment were voice alteration and cough frequency increase.

Adjunctive Vagus Nerve Stimulation for Treatment-Resistant Depression: a Quantitative Analysis.

Vagus nerve stimulation (VNS) has been increasingly studied in treating treatment-resistant depression (TRD), but the findings have been mixed. This updated meta-analysis was conducted to examine the efficacy and safety of adjunctive VNS for TRD. Controlled studies reporting on the efficacy and safety of adjunctive VNS for TRD were screened, identified and analyzed. Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were analyzed using RevMan version 5.3. Three controlled studies with a total of 1048 patients with TRD compared VNS (n = 622) with control (n = 426) groups. Only one study was rated as 'high quality' using the Jadad scale. Adjunctive VNS was significantly superior to the control group regarding study-defined response [SMD:1.96 (95%CI:1.60, 2.40), P < 0.00001, I2 = 0%]. Patient-reported voice alteration occurred more frequently with adjunctive VNS for patients with TRD. No significant group differences were found regarding discontinuation due to any reason [RR:0.50 (95%CI:0.12, 2.09), P = 0.34, I2 = 85%]. Adjunctive VNS appeared to be effective and relatively safe treatment for TRD. Further randomized controlled trials are needed to confirm the efficacy and safety of VNS for TRD.

[Effect of vasoactive agents on the prognosis of children in the third stage of hand-foot-mouth disease].

OBJECTIVE: To study the effect of the application timing of vasoactive agents on the prognosis of children in the third stage of hand-foot-mouth disease (HFMD). METHODS: A retrospective analysis was performed on the medical data of children in the third stage of HFMD between April 2012 and September 2016. According to the application time of vasoactive agents (milrinone combined with phentolamine) after admission, the children were divided into an early stage (within 2 hours after admission) group with 32 children, a middle stage (within 2-6 hours after admission) group with 28 children, and a late stage (more than 6 hours after admission) group with 26 children. Venous blood samples were collected before vasoactive agent treatment and after 24 hours of vasoactive agent treatment to measure the levels of creatine kinase-MB (CK-MB), troponin (TnI), and brain natriuretic peptide (BNP). The recovery time of left ventricular ejection fraction (LVEF), respiratory rate, blood pressure, and heart rate were recorded. The response rate to the treatment within 72 hours of treatment was evaluated. RESULTS: The early stage group had a significantly higher overall response rate to the treatment than the middle stage and late stage groups (P<0.0167). After 24 hours of treatment, there were significant differences in heart rate, blood pressure, respiratory rate, and LVEF among the three groups (P<0.05). The early stage group showed the most significant improvement in these parameters (P<0.0167). Compared with the middle stage and late stage groups, the early stage group had significantly shorter recovery time of LVEF, respiratory rate, heart rate, and blood pressure (P<0.0167). After 24 hours of treatment, the early stage group had a significantly lower level of BNP than the middle stage and late stage groups (P<0.05). CONCLUSIONS: Vasoactive agents should be given to children with critical HFMD as early as possible to improve cardiovascular function, reduce the risk of disease progression, and improve prognosis.

Description of Sphingomonas mesophila sp. nov., isolated from Gastrodia elata Blume.

A Gram-staining-negative, strictly aerobic, non-motile strain, SYSUP0001T, was isolated from tubers of Gastrodia elata Blume. The 16S rRNA gene sequence result indicated that SYSUP0001T represents a member of the genus Sphingomonas, with the highest sequence similarity (97.7 %) to the type strain of Sphingomonasginsengisoli. SYSUP0001T grew at 14-37 °C and pH 6-8, with optimum growth at 28 °C and pH 7. Tolerance to NaCl was up to 3 % (w/v) with optimum growth in the absence of NaCl. The respiratory quinone was Q-10. The major fatty acids were C18 : 1ω7c, Summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), and C16 : 0. The polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), sphingoglycolipid (SGL), phosphatidylcholine (PC) and four unidentified polar lipids (L). The DNA G+C content was 67.5 %. The average nucleotide identity (ANI) values between SYSUP0001T and closely related members of the genus Sphingomonas were below the cut-off level (95-96 %) for species delineation. On the basis of the phenotypic, phylogenetic and chemotaxonomic characterizations, SYSUP0001T represents a novel species of the genus Sphingomonas, for which the name Sphingomonasmesophila sp. nov. is proposed. The type strain is SYSUP0001T (=KCTC 62179 T=CGMCC 1.16462T).

Sarcocystis eothenomysi n. sp. (Apicomplexa: Sarcocystidae) from the large oriental vole Eothenomys miletus (Thomas) (Cricetidae: Microtinae) from Anning, China.

Fifty-six oriental voles, Eothenomys miletus (Thomas), were collected in Anning prefecture of Yunnan Province (China) between March 2012 and December 2013 and examined for the presence of sarcocysts. Sarcosysts of a new species, Sarcocystis eothenomysi n. sp., were found in 14 out of 56 E. miletus (25%); they possessed a striated cyst wall, c.1-2 µm thick. Under transmission electron microscopy the cysts of S. eothenomysi exhibited numerous small, irregular protrusions, which may appear T-shaped in some sections. A phylogenetic analysis based on 18S rRNA gene sequences indicated that S. eothenomysi shares closest affinity with those species of Sarcocystis Lankester, 1982, which use cobra or viperid snakes as definitive hosts. We therefore, hypothesise that a venomous snake may serve as the definitive host for S. eothenomysi. This is the first species of Sarcocystis reported from Eothenomys spp.

[Capillaria hepatica infection in rodents from Anning Prefecture of Yunnan Province and experimental research on host animals].

OBJECTIVE: To investigate the prevalence of Capillaria hepatica in rodents from Anning Prefecture, Yunnan, and observe the susceptibility of C. hepatica to SD rats and KM mice. METHODS: Rodents were trapped in a cultivated filed of Wenquan Town, Annning from March 2010 to March 2012. The species of rodents were identified. The liver was examined and a microscopic examination of tissue was performed by the tissue press technique for the presence of the typical bipolar eggs, adults or larval stages. The prevalence of C. hepatica in rodents was calculated. C. hepatica eggs were collected and cultured in vitro. Each SD rat or KM mouse was orally infected with approximately 1 000 C. hepatica eggs. The control groups with 4 SD rats or 4 KM mice received only normal saline. The experimental animals were euthanized at the 30th and 80th day post infection. Collected liver samples were processed for gross pathological and histological section examination. RESULTS: A total of 115 rodents were captured and examined. C. hepatica eggs were found in 26 (22.6%) rodents. There was no significant difference in the prevalence between female (22.5%, 18/80) and males (22.9%, 26/115) (P > 0.05). The highest prevalence was found in Rattus norvegicus (10/11). Pathologi cal findings showed numerous white-yellow small nodules ranged from 0.1-0.2 cm in diameter. Under light microscope, C. hepatica eggs were ovoid [(50-65) microm x (25-30) microm]. At the 30th day post-infection, there were several adult worms and their eggs delimited by a fibrous capsule, and septal fibrosis formations occurred in the liver of SD rat. No worm or eggs were found in the mouse liver, but the liver presented inflammatory cell infiltration. At the 80th day post-infection, live worms disappeared from the focal lesions in the liver of SD rat, being replaced by partially calcified worm debris. Mature worms and eggs were seen in the KM mouse liver, however, septal fibrosis was absent. CONCLUSION: This study has documented a high prevalence of C. hepaticum in R. norvegicus from Anning Prefecture. SD rat and KM mouse are the susceptible hosts of C. hepatica.

Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza: a randomized trial.

BACKGROUND: Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE: To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING: Eleven hospitals from 4 provinces in China. PATIENTS: 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION: Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE: Beijing Science and Technology Project and Beijing Nova Program.

Methylation of the glutathione-S-transferase M3 gene promoter is associated with oxidative stress in acute-on-chronic hepatitis B liver failure.

Chronic hepatitis B (CHB) is a major cause for liver disease worldwide, ranking as the first cause for liver cirrhosis and hepatocellular carcinoma. Acute-on-chronic hepatitis B liver failure (ACHBLF) is most commonly caused by acute severe exacerbation during CHB virus infection. The pathophysiology of ACHBLF is still poorly understood. Glutathione-S-transferase (GST) M3 belongs to GSTs superfamily and it has been demonstrated to contribute to oxidative stress-mediated liver damage. The present study was aimed to determine the potential association between GSTM3 promoter methylation and oxidative stress in ACHBLF patients. Thirty ACHBLF patients, 30 CHB patients and 10 healthy controls were included in this study. Methylation of GSTM3 promoter was determined using methylation-specific PCR (MSP) method. Plasma biomarkers for oxidative stress including malondialdehyde (MDA) and GST were detected by enzyme-linked immunosorbent assay (ELISA). Model for end-stage liver disease (MELD) scoring system was used for predicting the severity and prognosis of liver failure. ACHBLF patients had significant higher GSTM3 promoter methylation rate than CHB patients (30% versus 6.7%, χ(2) = 5.455, P = 0.020). Plasma MDA and GST levels were significantly increased in ACHBLF patients compared with CHB patients. Meanwhile, MDA, MELD scores and mortality rate were significantly higher in methylated group than those in unmethylated group of ACHBLF patients. Furthermore, plasma MDA levels were positively correlated with MELD scores of ACHBLF (r = 0.588, P = 0.001). In conclusion, the methylation of GSTM3 promoter may contribute to oxidative stress-associated liver damage and correlate with the disease severity in ACHBLF.

(3,6-Dimethyl-1,2,4,5-tetra-zine-1,4-di-yl)bis-[(morpholin-4-yl)methanone].

In the title mol-ecule, C(14)H(22)N(6)O(4), the amide-substituted N atoms of the tetra-zine ring deviate from the approximate plane of the four other atoms in the ring by 0.160 (2) and 0.243 (2) Å, forming a slight boat conformation. The morpholine rings are in chair conformations.

3,6-Dimethyl-N,N-bis-(pyridin-2-yl)-1,2,4,5-tetra-zine-1,4-dicarboxamide.

In the title mol-ecule, C(16)H(16)N(8)O(2), four atoms of the tetra-zine ring are coplanar, with the largest deviation from the plane being 0.0236 (12) Å; the other two atoms of the tetra-zine ring deviate on the same side from this plane by 0.320 (4) and 0.335 (4) Å. Therefore, the central tetra-zine ring exhibits a boat conformation. The dihedral angles between the mean plane of the four coplanar atoms of the tetrazine ring and the two pyridine rings are 26.22 (10) and 6.97 (5)°. The two pyridine rings form a dihedral angle of 31.27 (8)°. In the molecule, there are a number of short C-H⋯O interactions. In the crystal, molecules are linked via a C-H⋯O interaction to form zigzag chains propagating along the [010] direction.

Clinicopathological and prognostic significance of EGFR over-expression in esophageal squamous cell carcinoma: a meta-analysis.

BACKGROUND/AIMS: To elucidate the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) over-expression in esophageal squamous cell carcinoma (ESCC). METHODOLOGY: A meta-analysis of previous studies was performed to assess the effects of EGFR over-expression on clinicopathological parameters and overall survival (OS) in patients with ESCC, using pooled odds ratio (OR) with its 95% confidence interval (CI) and pooled hazard ratio (HR) with its 95% CI, respectively. RESULTS: A total of nine studies including 802 patients were subjected to the final analysis. The overall results suggested that over-expression of EGFR was significantly correlated with, not only the lymph node status and tumour differentiation grade, with a pooled OR of 0.64 (95% CI: 0.46-0.89; Z=2.62; p=0.009) and 1.60 (95% CI: 1.09-2.37; Z=2.37; p=0.018), respectively, but also the poorer OS with a pooled HR of 1.60 (95% CI: 1.05-2.43; Z=2.19 p=0.028). CONCLUSIONS: This meta-analysis suggests that over-expression of EGFR might play an important role in the progression of ESCC, and it might be useful as a predictive biomarker in clinical practice, yet the predictive value of EGFR in ESCC still needs further confirmation by prospective trials.

Enhanced demethylation of interferon-γ gene promoter in peripheral blood mononuclear cells is associated with acute-on-chronic hepatitis B liver failure.

Acute-on-chronic hepatitis B liver failure (ACHBLF) refers to liver failure occurring in patients with chronic hepatitis B (CHB) related liver diseases. Interferon-γ (IFN-γ) plays an important role in the exacerbation of liver function. However, the exact mechanism, by which IFN-γ mediates ACHBLF, is not fully understood. Forty patients with ACHBLF, fifteen patients with CHB and ten healthy controls were included in this present study. ELISA was performed to measure the level of serum IFN-γ. The methylation status of IFN-γ promoter in peripheral blood mononuclear cells (PBMCs) was determined using methylation-specific PCR. Model for End-stage Liver Disease (MELD) scoring was performed for evaluating the severity of liver failure. The serum level of IFN-γ in patients with ACHBLF or CHB was significantly lower than that in healthy controls, while the serum IFN-γ level in ACHBLF patients was significantly higher than that in CHB patients. In ACHBLF patients, the level of IFN-γ was positively correlated with total bilirubin and MELD score, but negatively correlated with prothrombin time activity. These results suggest the involvement of IFN-γ in the pathogenesis of ACHBLF. Importantly, the degree of methylation of the IFN-γ gene promoter in ACHBLF patients (60%, 24/40) was significantly lower than that in CHB patients (93%, 14/15), but was higher than that in the control group (20%, 2/10). Furthermore, in ACHBLF patients, the serum IFN-γ level was significantly higher in unmethylation group than that in methylation group. In conclusion, enhanced demethylation of IFN-γ gene promoter in PBMCs may be associated with the onset of ACHBLF.

Identification of differentially expressed proteins in the locoregional recurrent esophageal squamous cell carcinoma by quantitative proteomics.

BACKGROUND: This study aimed to identify potential biomarkers associated with locoregional recurrence in patients with esophageal squamous cell carcinoma (ESCC) after radical resection. METHODS: We performed a quantitative proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ) with reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) to identify differential expression proteins (DEPs) between a locoregional recurrence group and good prognosis group of ESCC after radical esophagectomy. The bioinformatics analysis was performed with ingenuity pathway analysis software (IPA) and Gene Ontology (GO) database using the software of MAS 3.0. Kaplan-Meier (KM) Plotter Online Tool (http://www.kmplot.com) was used to evaluate the relationship between the differential expression of proteins and survival in patients with ESCC. RESULTS: More than 400 proteins were quantitated of which 27 proteins had upregulated expression and 55 proteins had downregulated expression in the locoregional recurrence group compared to the good prognosis group. These 82 DEPs were associated with biological procession of cancer development including cellular movement, cellular assembly and organization, cellular function and maintenance, cellular growth and proliferation, cell death and survival, DNA replication recombination and repair, and so on. Of these DEPs, SPTAN1 and AGT proteins were identified to be associated with RFS in ESCC. SPTAN1 was positively associated with RFS and AGT was negatively associated with RFS. Expression of SPTAN1 tended to have favorable OS while expression of AGT tended to have poor OS. CONCLUSIONS: Our results demonstrated that quantitative proteomics is an effective discovery tool to identify biomarkers for prognosis prediction in ESCC. However, it needs more studies with large populations of ESCC to validate these potential biomarkers.

Tumour necrosis factor 308 polymorphisms and hepatocellular carcinoma risk: a meta-analysis.

BACKGROUND/AIMS: To investigate the association of the common polymorphisms comprehensively defining the genetic variability of the TNFA-308G > A with HCC risk. METHODOLOGY: We performed a meta-analysis of 9 published studies that included 1362 cancer cases and 2426 controls. We used random-effect (RE) or fixed-effect (FE) odds ratios (ORs) and 95% confidence intervals (CIs) according to the studies' heterogeneity to assess the strength of the associations. RESULTS: The overall results suggested that the TNFA-308 AA and AG variant genotypes were associated with a significantly increased risk of HCC in different genetic models (homozygote comparison: OR = 2.51,95% CI: 1.11-5.67, p heterogeneity = 0.905; heterozygote comparison: OR = 1.58, 95% CI: 1.00-2.50, p heterogeneity = 0.001; dominant model comparison: OR = 1.59, 95% CI: 1.00-2.53, p heterogeneity = 0.000; recessive model comparison: OR = 2.27, 95% CI: 1.01-5.12, p heterogeneity = 0.962; complete overdominant model comparison: OR = 1.57, 95% CI: 1.00-2.45. P heterogeneity = 0.001; and allele comparison: OR = 1.52, 95% CI: 1.01-2.28, p heterogeneity = 0.002. There was at some extent heterogeneity when analyses were performed in some models, and there was no publication bias. CONCLUSIONS: This meta-analysis supported that the TNFA-308 A allele is a risk factor for HCC development.

Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males.

AIM: To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1*c1/*c2, ALDH2*1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited. RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with >30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with >30 drink-years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P=0.014; P=0.094; P=0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2*1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2+*2/*2) and CYP2E1 (*c1/*c2+*c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1)+ADH1B (*1/*2+*2/*2), ALDH2 (*1/*1)+CYP2E1 (*c1/*c2+*c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction. CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.

Effect of Hyperglycemia on Purinergic and Nitrergic Inhibitory Neuromuscular Transmission in the Antrum of the Stomach: Implications for Fast Gastric Emptying.

BACKGROUND: Hyperglycemia has been reported to enhance vagovagal reflex that causes the release of inhibitory neurotransmitter, nitric oxide (NO), at the neuromuscular junction in the antrum to relax the antrum and slow gastric emptying by stimulating glucose-sensitive afferent neurons. However, hyperglycemia has also been reported to cause fast gastric emptying that may be due to suppression of the inhibitory motor neurons. AIMS: The purpose of the present study was to investigate changes in inhibitory neuromuscular transmission in the gastric antrum due to hyperglycemia. METHODS: Inhibitory electrical junction potentials were recorded from gastric antral muscle strips, using intracellular electrodes under non-adrenergic, non-cholinergic conditions. Studies were performed in non-hyperglycemic NOD (NH-NOD), NOD mice as they develop hyperglycemia (H-NOD) and their age-matched controls. The purinergic inhibitory junction potential (pIJP) and nitrergic IJP (nIJP) were isolated pharmacologically. RESULTS: The control pIJP was large, around -18 mV and nIJP was small, around -9 mV. In NH-NOD the IJPs were not affected, but in H-NOD pIJP was nearly abolished and nIJP was significantly reduced. In H-NOD mice, membrane hyperpolarization caused by exogenous α,ß-MeATP or diethylenetriamine NO adduct was similar to that in wild-type controls (P > 0.05). H-NOD smooth muscles were significantly depolarized as compared to NH-NOD smooth muscles. CONCLUSION: These observations show that hyperglycemia causes suppression of purinergic and nitrergic transmission by acting on the motor neurons that form the last neuron in the vagovagal circuit. Moreover, the loss the neurotransmission is due to a defect in neurotransmitter release rather than a defect in signal transduction. Hyperglycemia also causes depolarization of smooth muscles that may increase their excitability.

Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study.

Previous studies have indicated that complex interactions among viral, environmental and genetic factors lead to hepatocellular carcinoma (HCC). To identify susceptibility alleles for hepatitis B virus (HBV)-related HCC, the present study conducted a pilot two-phase genome-wide association study (GWAS) in 660 Han Chinese individuals. In phase 1, a total of 500,447 single-nucleotide polymorphisms (SNPs) were genotyped in 50 HCC cases and 50 controls using Affymetrix GeneChip 500k Array Set. In phase 2, 1,152 SNPs were selected from phase 1 and genotyped in 282 cases and 278 controls using the Illumina GoldenGate platform. The prior probability of HCC in control subjects was assigned at 0.01, and false-positive report probability (FPRP) was utilized to evaluate the statistical significance. In phase 1, one SNP (rs2212522) showed a significant association with HCC (Pallele=5.23×10-8; ORallele=4.96; 95% CI, 2.72-9.03). In phase 2, among 27 SNPs with unadjusted Pallele<0.05, 9 SNPs were associated with HCC based on FPRP criteria (FPRP <0.20). The strongest statistical evidence for an association signal was with rs2120243 (combined ORallele=1.76; 95% CI, 1.39-2.22; P=2.00×10-6), which maps within the fourth intron of VEPH1. The second strongest statistical evidence for an association was identified for rs1350171 (combined ORallele=1.66; 95% CI, 1.33-2.07; P=6.48×10-6), which maps to the region downstream of the FZD4 gene. The other potential susceptibility genes included PCDH9, PRMT6, LHX1, KIF2B and L3MBTL4. In conclusion, this pilot two-phase GWAS provides the evidence for the existence of common susceptibility loci for HCC. These genes involved various signaling pathways, including those associated with transforming growth factor ß, insulin/phosphoinositide 3 kinase, Wnt and epidermal growth factor receptor. These associations must be replicated and validated in larger studies.

Prognostic significance of thymidylate synthase expression in pancreatic adenocarcinoma: A meta-analysis.

The prognostic significance of thymidylate synthase (TS) overexpression in pancreatic adenocarcinoma has been extensively investigated; however, data on the survival of patients with pancreatic adenocarcinoma remain equivocal. We performed a meta-analysis of previous studies to assess the effects of TS overexpression on the overall survival (OS) of patients with pancreatic adenocarcinoma, using hazard ratio (HR) with its 95% confidence interval (CI). A total of 5 studies, including 425 patients, were subjected to the final analysis. The pooled HR was 0.72 (95% CI: 0.41-1.25; Z=1.18, P=0.238), indicating that TS expression exerted no significant survival effect on patients with pancreatic adenocarcinoma. The combined HR was 0.46 (95% CI: 0.31-0.68; Z=3.95, P<0.001), limiting the analysis to the studies assessing R0 resection patients, which indicated that a high expression of TS was significantly correlated with better OS in patients with pancreatic adenocarcinoma who underwent R0 resection. This meta-analysis identified TS as an independent factor predicting favourable outcome following R0 curative resection in patients with pancreatic adenocarcinoma.

Benefits from adjuvant intraoperative radiotherapy treatment for gastric cancer: A meta-analysis.

The benefits of adjuvant intraoperative radiotherapy (IORT) for resectable gastric cancer have been extensively studied, but data on the survival rate remains equivocal. A meta-analysis was performed of the studies involving the use of IORT for resectable gastric cancer using web-based databases. Hazard ratios (HRs) describing the impact of adjuvant IORT on the overall survival (OS) rate and locoregional control were extracted directly from the original studies or calculated from survival curves. A meta-analysis of four studies that provided OS data revealed that IORT had no significant impact on OS [HR, 0.97; 95% confidence interval (CI), 0.75-1.26; P=0.837]. In the three studies testing the efficacy of IORT for OS in the subgroup of patients with stage III disease, there was a significantly improved OS (HR, 0.60; 95% CI, 0.40-0.89; P=0.011). Significant locoregional control improvement was observed in the four studies that provided locoregional control data (HR 0.40; 95% CI, 0.26-0.62; P<0.001). This meta-analysis showed a statistically significant locoregional control benefit with the addition of IORT in patients with resectable gastric cancer. In addition, the available data revealed that adjuvant IORT may provide promising results on the survival rate for the subgroup of patients with stage III disease. Further study is required to optimize the implementation of adjuvant IORT for gastric cancer with regard to patient selection and integration with systemic therapy.