OBJECTIVETo investigate the interaction between hydrogen sulfide (H2S)/cystathionine gamma-lyase (CSE) system and nitric oxide (NO)/nitric oxide synthase (NOS) system on cardiac protection in metabolic syndrome (MS) rats.

METHODSForty one male Sprague-Dawley rats were randomly divided into 6 groups: control group, MS group, H2S donor group, CSE inhibitor group, NOS inhibitor group, and NO donor group. The MS rat model was established by a high-fat diet of 16 weeks. Rats in control and MS groups were subjected to normal saline and the other four groups were respectively subjected to sodium hydrosulfide (NaHS, 56 μmol/kg), D,L-propargylglycine (PPG, 37.5 mg/kg), Nψ-nitro-L-arginine methyl ester (L-NAME, 18 mg/kg), L-Arginine (500 mg/kg) every day. Four weeks later, the obesity indices, blood sugar of oral glucose tolerance test in each time point (0,30,60, and 120 minutes) and blood lipids (cholesterol, triglyceride, high density lipoprotein, low density lipoprotein) were measured. The computer-based electrophysiological recorder system was used to measure the changes of the left ventricular systolic pressure (LVSP), the left ventricular end diastolic pressure (LVEDP), the maximal rate of pressure increase in the contraction phase (+dP/dtmax), and the maximal rate of pressure decrease in the diastole phase (-dP/dtmax). H2S and NO concentration in plasma and myocardium, as well as CSE, constitutive NOS (cNOS), and inducible NOS (iNOS) activities in myocardium were measured with colorimetric method. Reverse transcription-polymerase chain reaction was used to assess the gene expression of CSE and endothelial NOS (eNOS) mRNAs.

RESULTSCompared with control group, the obesity indices, blood sugar at each time point, and blood lipids significantly increased in MS group (P<0.05). H2S and NO concentration in plasma and myocardium, CSE and cNOS activities in myocardium, the expressions of CSE mRNA and eNOS mRNA, and the myocardial function significantly decreased in MS group (P<0.05). Compared with MS group, NO concentration in plasma and myocardium, cNOS and iNOS activities in myocardium, and the expression of eNOS mRNA significantly increased in CSE inhibitor group (P<0.05). However, activities of cNOS and iNOS in myocardium and the expression of eNOS mRNA were significantly decreased in H2S donor group (P<0.01), while the myocardial function significantly increased (P<0.05). H2S concentration in plasma and myocardium, and the expression of CSE mRNA significantly increased in NOS inhibitor group (P<0.05). However, in NO donor group, the CSE activity in myocardium and the expression of CSE mRNA significantly decreased (P<0.05). And the myocardial function was improved significantly (P<0.05).

CONCLUSIONSBoth the H2S/CSE and NO/NOS systems appear to have a mutual down-regulation effect on myocardium in MS rats. Meanwhile, exogenous H2S and NO supplement is cardioprotective in rat model of MS.

Animals ; Cystathionine gamma-Lyase ; metabolism ; physiology ; Disease Models, Animal ; Heart ; physiopathology ; Hydrogen Sulfide ; metabolism ; Male ; Metabolic Syndrome ; metabolism ; physiopathology ; Myocardium ; metabolism ; Nitric Oxide ; metabolism ; physiology ; Nitric Oxide Synthase ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the mechanism of occupational medicamentosa-like dermatitis (OMDT) induced by trichloroethylene (TCE) and some immunity indexes in workers occupationally exposed to TCE.

METHODSThe blood samples from 8 cases with medicamentosa-like dermatitis in 1st, 2nd, 3rd, 4th and 5th weeks after admitting to hospital were examined for liver function, immunoglobulin and some complement indexes. Thirty nine workers occupationally exposed to TCE were investigated for urinary TCE and some immuno-complement indexes. The TCE concentrations of air in workplaces were monitored.

RESULTSC3d-CIC and C3 of patients before admission were (92.86 ± 44.80) mg/L and 0.91 ± 0.19 mg/L, respectively. C3d-CIC and C3 of patients before discharge were (52.41 ± 17.75) mg/L and (1.14 ± 0.22) mg/L, respectively. There were significant differences between admission and discharge (P < 0.05). The average TCE concentration in 4 workplaces was (351.96 ± 36.72) mg/m(3), which was higher than the occupational exposure limits (OELs). The number of workers exposed to the TCE concentration-time weighted and TCA in urine over OELs were 28.21% and 56.41% of total subjects, respectively. The serum IgG and CIC levels of patients before discharge were (10.03 ± 1.21) mg/L and 103.50 ± 29.17 mU/L, which were significantly lower than those (17.21 ± 1.85) mg/L and (227.46 ± 111.67) mU/L of patients before admission (P < 0.01).

CONCLUSIONThe type II and III hypersensitivity may be associated with OMDT and the organ injure induced by TCE.

Adolescent ; Adult ; Complement System Proteins ; immunology ; Dermatitis, Occupational ; immunology ; Female ; Humans ; Male ; Occupational Exposure ; Trichloroethylene ; toxicity ; Young Adult

Non-alcoholic fatty liver disease(NAFLD)is a series of diseases characterized by hepatic steatosis and is also a metabolism-associated disease and an important factor for liver fibrosis,liver cirrhosis,and hepatocellular carcinoma.Endoplasmic reticulum is a core organelle for the regulation of lipid metabolism,and unfolded protein response is an important process of endoplasmic reticulum stress(ERS).Based on the important stress role of endoplasmic reticulum in metabolism-associated diseases,this article explores the influencing mechanism between ERS and NAFLD and reviews the research advances in lipid metabolism,inflammatory response,hepatocyte death,fibrosis,and ERS-targeted therapies in the pathological development of NAFLD.

OBJECTIVETo compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver.

METHODSOne hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis.

RESULTSCompared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT.

CONCLUSIONSRhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

Animals ; Anthraquinones ; adverse effects ; pharmacology ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; drug therapy ; pathology ; Dose-Response Relationship, Drug ; Female ; Liver ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Tannins ; adverse effects ; pharmacology

Severe liver dysfunction in pregnancy (SLDP) is rare but serious complications with high mortality rate. This study compared the effectiveness and safety of double-balloon catheter versus intra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy in patients with SLD. A total of 55 patients with indications of labor induction were enrolled and analyzed by retrospective control analysis method. Twenty-three cases adopted Cook double balloon dilation as Cook group, and 32 cases received intra-amniotic injection of ethacridine lactate as EL group. The primary outcome was evaluated by successful abortion rate and the difference in the induction-to-abortion interval. Secondary outcomes included liver function recovery and the frequency of adverse events. Both Cook and EL regimens were effective, with successful abortion rate of 87.0% and 93.8%, respectively (P=0.639). The induction-to-delivery interval was similar between Cook group and EL group (38.1 ± 21.5 vs. 41.3 ± 17.4, P=0.543). The liver disease status was more severe in Cook group than in EL group, but it did not show any significant difference after pregnancy termination between the two groups and the improvement rate also did not show any significant difference. Both treatments were safe and there was no significant difference in bleeding and cervical laceration adverse events between the two groups. Our study firstly compared double-balloon catheter and ethacridine lactate for the induction of labor in women with SLD during second trimester pregnancy.
Abortion, Induced ; Catheters ; Ethacridine ; administration & dosage ; Female ; Humans ; Liver Diseases ; physiopathology ; Pregnancy ; Pregnancy Trimester, Second

OBJECTIVETo evaluate the efficacy and safety of dose-reduced intravenous busulfan, cyclophosphamide and etoposide (BCV) as conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM).

METHODSFrom September 2007 to September 2010, thirty-two ASCT-eligible patients with MM received high dose melphalan (HDM) as conditioning in our center. Median age was 53.5 (30-63) years. From October 2010 to October 2012, thirty-eight patients conditioned by BCV regimen (intravenous busulfan, total doses 9.6 mg/kg), whose median age was 54(35-64) years.

RESULTSThere were no statistical differences in clinical characteristics between the two groups, including myeloma isotype, Durie-Salmon staging, international staging system(ISS), and patients received the first line, second line or more than third line therapy. The median time to neutrophil and platelet engraftment were 10.5 vs 11 days (P=0.057) and 11 vs 12 days (P=0.100) in the BCV and HDM groups, respectively. The toxicity of two conditioning regimens had no significant difference. None of hepatic veno-occlusive disease and early transplant related mortality was observed. Although overall response rates showed no significant difference between two groups (P>0.05), the CR rates increased from 44.74% pre-ASCT to 63.18% post-ASCT in the BCV group, while 37.50% to 59.38% in the HDM group. During the median follow-up of 16 months (range 2-27) in BCV group, ten patients (26.32%) developed progressive disease and PFS at 12 months were 71.37%.

CONCLUSIONSIn this study, the dose-reduced intravenous busulfan, cyclophosphamide and etoposide (BCV) conditioning was demonstrated an effective and safety regimen for ASCT-eligible patients with MM. However, the long term observation is needed.

Adult ; Busulfan ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Etoposide ; therapeutic use ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Melphalan ; therapeutic use ; Middle Aged ; Multiple Myeloma ; therapy ; Transplantation Conditioning ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma (MM), who previously responded to bortezomib.

METHODSRetrospective analysis of 76 MM patients, who had achieved at least a partial response (PR) on initial bortezomib therapy in our hospital from May 2006 to August 2011, received bortezomib retreatment when they relapsed or progressed.

RESULTSThe overall response rate (ORR) was 60.5%, among them 6.5% patients achieved CR, 5.8% patients achieved very good partial response (VGPR), 38.2% patients achieved PR. Then we further stratified all patients into 3 groups according to the response of initial bortezomib therapy, including CR group, VGPR group and PR group. After bortezomib retreatment, the ORR of the 3 groups was 84.6%, 73.1% and 43.2%, respectively. According to the response of bortezomib retreatment, the patients were divided into 2 groups: group 1 who at least achieved PR, group 2 who showed no response. The median progression-free survival (PFS) after bortezomib retreatment for group 1 and 2 was 7(1-39) and 5(1-14) months, respectively (P>0.05), while the median overall survival (OS) after bortezomib retreatment was 16(2-64) and 8(1-28) months, respectively (P<0.05). Adverse events (AE) were identified in 88% patients during bortezomib retreatment, including neutropenia, diarrhea and thrombocytopenia, only 9.2%(7 patients) reached Ⅲ-Ⅳ grade of AE. Severe peripheral neuropathy occurred in only one patient.

CONCLUSIONBortezomib retreatment regimen is demonstrated a higher response rate in patients who achieved deeper response in initial treatment, with no more adverse events.

Adult ; Aged ; Boronic Acids ; adverse effects ; therapeutic use ; Bortezomib ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; adverse effects ; therapeutic use ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate the effects of dexmedetomidine on renal microcirculatory perfusion in rabbits with renal ischemia/reperfusion (I/R) injury rabbit by quantitative analysis of contrast-enhanced ultrasound (CEUS).

METHODSTwenty- four New Zealand rabbits were randomly divided into 3 groups (8 in each), including a control group, renal I/R injury group and dexmedetomidine group. In the latter two groups, the right kidney of the rabbits was resected and I/R injury was induced in the left kidney. In dexmedetomidine group, the rabbits received an intraperitoneal dose of 10 µg/kg dexmedetomidine 30 min before renal ischemia, and 24 h after reperfusion, the renal size and renal artery resistance (RI) were measured, and renal cortex perfusion was observed by CEUS. The time-to-peak intensity (TTP), peak signal intensity (PSI), gradient between start frame to peak frame (Grad) and area under the curve (AUC) were quantitatively analyzed using the time-intensity curves. Pathological changes of the kidney were also observed.

RESULTSCompared with the control group, the rabbits in I/R and dexmedetomidine groups showed distinct changes of the renal size with obvious renal pathologies. RI, PPT and AUC all increased, and PSI and Grad decreased significantly in I/R and dexmedetomidine groups (P<0.05). Compared with I/R group, obvious improvement of the renal size and renal pathologies were observed in dexmedetomidine group, which showed significantly decreased RI, PPT and AUC and increased PSI and Grad (P<0.05).

CONCLUSIONCEUS combined with the time-intensity curve parameters allows quantitative and dynamic analysis of the protective effects of dexmedetomidine on microcirculatory perfusion in rabbits with renal I/R injury.

Animals ; Dexmedetomidine ; pharmacology ; Disease Models, Animal ; Kidney ; blood supply ; drug effects ; Kidney Diseases ; drug therapy ; Microcirculation ; drug effects ; Rabbits ; Renal Artery ; drug effects ; Reperfusion Injury ; drug therapy

Objective To study the epidemiological features of hantavirus in rodents in Wenzhou,Zhejiang province.Methods Rodents were captured in Wenzhou,where hemorrhagic fever with renal syndrome (HFRS) had been endemic. Hantavirus antigens in the rat lungs were detected by immunofluorescence assay (IFA).Partial S segment (nt 620-999) and partial M segment (nt 2001-2301)sequences were amplified by RT-PCR,and then sequenced.Neighbor-joining method was used to construct for phylogenetic analysis.Results A total of 96 rodents were trapped in the epidemic areas,and 6 hantavirus antigens were identified from these lung samples (6.3%).Partial S and partial M segment sequences were successfully recovered from 5 samples and determined. Phylogenetic analysis of these sequences indicated that all viruses belonged to Seoul virus (SEOV),regardless of the sources (Rattus norvegicus,Rattus tanezumi and Rattus rattoide) that they were derived. However,the clustering pattern in the partial S-tree was different from that in the partial M-tree,suggesting that the re-assortment between SEOVs had occurred.Conclusion All Rattus rats carried SEOV in Wenzhou and the genetic reassortment with SEOV had occurred naturally.

Objective: To compare the efficacy and safety of plasma exchange (PE) combined with double plasma absorption and simple PE in the treatment of acute-on-chronic liver failure. Methods: We retrospectively analyzed 251 cases of acute-on-chronic liver failure treated with artificial liver treatment since January 2015. Changes in clinical manifestations, laboratory tests, and complications of the patients before and after different modes of treatment were compared and short-term efficacy was tracked. In accordance with different data, t-test, Pearson's chi-squared test and Fisher's exact test were used for statistical analysis. Results: The effectiveness of low-volume PE combined with double plasma molecular adsorption system (DPMAS) and equal amount of PE combined with DPMAS was significantly better than simple PE (83.7%, 84.05% and 82.15 vs 55.6%, P < 0.05) in early stage of liver failure. In late-stage of liver failure, there was no significant difference in the treatment efficiency of each group (P > 0.05). Bilirubin and bile acid levels were significantly decreased in combined treatment groups than that to simple PE group (P < 0.05). PTA and albumin improvement rate of DPMAS PE groups were significantly lower than that of simple PE group (P < 0.05). There was no statistical difference in adverse reactions between each group. Conclusion PE combined with DPMAS improves the treatment efficiency of early hepatic failure and decrease dosage of plasma when compared with simple PE. A beforehand DPMAS treatment after PE treatment can improve the adverse effects of DPMAS on blood coagulation function and albumin levels.