Objective To study the mechanism of monophosphoryl lipid A (MPLA) protecting liver ischemia-reperfusion injury in rats, and explore the hemeoxygenase-1-carbon monoxide-cyclic guanosine monophosphate (HO-1-CO-cGMP) pathway whether involved in MPLA enhance calcitonin gene-related peptides (CGRP) releasing or not. Methods Male SD rats were randomly divided into control group, sham-operated group, hepatic ischemia-reperfusion group, MPLA low, medium and high dose groups (hepatic ischemia-reperfusion + MPLA0. 2,0. 5,1.0 mg/ kg). Hepatic isehemia-reperfusion model was constructed, followed by observation of cell ultrastructure through electron microscope. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and liver tissue levels of CO were determined. HO-1 expression in liver tissue was detected by immunohistochemic, CGRP, eGMP concentration in liver tissue was detected by RIA assay. Results Compared with hepatic isehemia-reperfusion group, the cell damage in MPLA group were relatively minor, and ALT, AST, LDH were significantly decreased (P <0.05), while HO-1, CO, cGMP, CGRP levels were signifi-cantly increased (P < 0.05). HO-1 and CO, CO and cGMP, cGMP and CGRP were obviously positive correlated (P <0.05). Conclu-sion MPLA enhanced CGRP synthesis and release through HO-1-CO-cGMP pathway in liver ischemia / reperfusion, which may be one of the mechanisms of MPLA reducing hepatic ischemia-reperfusion injury in rat.

0 05), but HR was significantly higher (P

Objective To evaluate the blond-saving effect of low central venous pressure(CVP) combined with acute hypervolemic hemedilution(AHHD)in patients undergoing hepatic lobectomy.Methods sixty ASA I orⅡpatients of both sexes aged 32-48 yr weighing 47-72 kg undergoing hepatic lobectomy for primary malignant hepatonm under epidural combined with general anesthesia were randomly divided into 3 groups(n=20 each);group I control(C);group 1I AHHD and group Ⅲ low CVP+AHHD.Group C received crystalloid and coloid in a ratio of 1.5:1 during operation.In groupⅡ4% suecinylated gelatin was infused at 50 ml·kg-1·h-1 for 30 min after tracheal intubation (AHHD);while inⅢ group low CVP was induced and maintained by epidural administration of a mixture of 1.5% lidnoaine +O.2% bupivacaine 6-8 ml combined with intravenous infmion of propofol at 6 mg·kg-1·h-1 until 10 min after hepatic lobectomy was completed.then 4% succinylated gelatin was infused at 50 ml·kg-1·h-1 for 30 min.Blood glucose,Hb,Hct, WBC count,blood coagulation (PT,AVIT,Fib),shtmic-pyruvic transaminase (GPT) and renal function (BUN,Cr) were determined before operation (baseline),immediately before skin incision,immediately before and 10 min after liver lobe was removed,at the end of operation and 7 d after operation.Urine output,intraoperative blood loss and blood transfusion and complications were recorded.Results The glood glucose concentration.WBC count and GPT levd were significantly lower;the amount of fluid infused and urinary output before hepatic lobe resection and the percentage of the patients with allogeneic blood transfusion during operation were less;Hb,Hct and the amounl of fluid infused and urinary output after hepatic lobe resection were uigher in grolp Ⅲ than in group I and ⅡⅡⅡ.There were no significant differences in blood coagulation,renal function,the total amount of fluid infused and urine output among the 3 groups.No patient developed any complication.Conclusion The low CVP hefor combined with AHHD after hepatic resection can decrease intraoperative blood loss and allogeneic blood transfusior and is safe.

OBJECTIVE To investigate the inhibitory effect and mechanism of lead(Pb2+)on γ-amino-butyric acid(GABA)A receptor-mediated currents(IGABA)and GABAergic synaptic transmission in rat cortical neurons.METHODS ①The cortical neurons from 0 d Sprague Dawley(SD)rats were cultured for experiments.The cultured cells(7-14 d)were recorded using the patch-clamp technique to analyze the effects of Pb2+ at different concentrations(1,5,10,50 and 100 μmol·L-1)on IGABA induced by GABA 100 μmol·L-1.② The effects of Pb2+ 50 μmol·L-1 on IGABA induced by GABA at different concentrations(1,10,50,100,500 and 100 μmol·L-1)were detected.③Brain slices(350 μm)were prepared from SD rats(15-19 d).The spontaneous inhibitory post-synaptic currents(sIPSCs),miniature inhibitory post-synaptic currents(mIPSCs)and current injection-induced action potential(AP)were recorded to detect the effects of Pb2+ 10 μmol·L-1 on the amplitude and frequency of sIPSCs and mIPSCs,and the frequency of AP.RESULTS ①Pb2+ inhibited IGABA in a concentration-dependent manner,and IC50 was(68±20)μmol·L-1.②Pb2+ also suppressed the maximum current induced by GABA(P<0.01),with a significant increase of the GABA′s EC50 from(20±6)μmol·L-1 to(87±39)μmol·L-1,indicating that Pb2+ might inhibit IGABA in a non-competitive mechanism.③Pb2+ 10 μmol·L-1 inhibited the frequency(P<0.01)rather than the ampli-tude of sIPSCs reversibly,but had no effect on eigher the frequency or amplitude of mIPSCs.In addi-tion,Pb2+ decreased the frequency of evoked AP by current injection(P<0.01)and reduced the overall excitability of rat cortical neurons.CONCLUSION Pb2+ can significantly inhibit IGABA in primary cultured neurons.In the brain slice experiment,Pb2+ may affect sIPSCs frequency by inhibiting the AP of cortical neurons,suggesting that there are different intrinsic mechanisms through which Pb2+ inhibits both IGABA in primary cultured neurons and the frequency of sIPSCs in brain slice neurons,which points to the complexity of the mechanism of Pb2+ poisoning.

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.