OBJECTIVE To determine the functional role of hydrogen sulfide (H2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca2 +/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) using wild type and CSE knockout mouse models. METHODS Continuous subcutaneous injection isoprenaline (7.5 mg·kg-1·d-1), once a day for 4 weeks to induce heart failure in Male C57BL/6 (6-8 weeks old) mice and CSE-/- mice. 150 μmol·L-1 H2O2 was used to induce oxidative stress in H9c2 cells. Echocardiograph was used to detect cardiac parameters. H&E stain and Masson stain was to observation histopathological changes. Western blot was used to detect protein expression and activity. The siRNA was used to silence protein expression. HPLC was used to detect H2S level. Biotin assay was used to detect the level of S- sulfhydration protein. RESULTS Treatment with S-propyl-L-cysteine (SPRC) or sodium hydrosulfide (NaHS), modulators of blood H2S levels, attenuated the development of heart failure in animals, reduced lipid peroxidation, and preserved mitochondrial function. The inhibition CaMKⅡ phosphorylation by SPRC and NaHS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds. Interestingly, CaMKⅡ activity was found to be elevated in CSE-/- mice as compared to wild type animals and the phosphorylation status of CaMKⅡ appeared to relate to the severity of heart failure. Importantly, in wild type mice SPRC was found to promote S-sulfhydration of CaMKII leading to reduced activity of this protein however, in CSE-/- mice S-sulfhydration was abolished following SPRC treatment. CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of CaMKⅡ is presented. SPRC mediated S-sulfhydration of CaMKII was found to inhibit CaMKⅡ activity and to preserve cardiovascular homeostasis.

OBJECTIVE To determine the functional role of hydrogen sulfide (H2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca2 +/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) using wild type and CSE knockout mouse models. METHODS Continuous subcutaneous injection isoprenaline (7.5 mg·kg-1 per day), once a day for 4 weeks to induce heart failure in male C57BL/6 (6-8 weeks old) mice and CSE-/- mice. 150 μmol·L-1 H2O2 was used to induce oxidative stress in H9c2 cells. Echocardiograph was used to detect cardiac parameters. H&E stain and Masson stain was to observation histopathological changes. Western blot was used to detect protein expression and activity. The siRNA was used to silence protein expression. HPLC was used to detect H2S level. Biotin assay was used to detect the level of S-sulfhydration protein. RESULTS Treatment with S-propyl-L-cysteine (SPRC) or sodium hydrosulfide (NaHS), modulators of blood H2S levels, attenuated the development of heart failure in animals, reduced lipid peroxidation, and preserved mitochondrial function. The inhibition CaMKⅡ phosphorylation by SPRC and NaHS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds. Interestingly, CaMKⅡ activity was found to be elevated in CSE-/- mice as compared to wild type animals and the phosphorylation status of CaMK Ⅱ appeared to relate to the severity of heart failure. Importantly, in wild type mice SPRC was found to promote S-sulfhydration of CaMKⅡ leading to reduced activity of this protein however, in CSE-/- mice S-sulfhydration was abolished following SPRC treatment. CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of CaMKⅡ is presented. SPRC mediated S-sulfhydration of CaMKⅡ was found to inhibit CaMKⅡ activity and to preserve cardiovascular homeostasis.

Animals ; Cell Differentiation ; Female ; Hematopoietic Stem Cells ; cytology ; Hepatocytes ; cytology ; Male ; Mice ; Mice, Inbred BALB C

Objective To ohserve the rat myocardial damage induced by citreoviridin(CIT)in the status of combined selenium and protein deficiency.Methods According to 2×2 factorial design,forty 4-week-old healthy Wistar rats were randomly divided into four groups.i.e.combined selenium and protein adequate with no CIT and with some CIT groups(Se+Pro+CIT-.Se+Pro+CiT+),combined selenium and protein deficiency with no CIT and with some CIT groups(Se-Pro-CIT-,Se-Pro-CIT+).The numbers of male and female were fifty-fifty.Theserats were fed with combined selenium and protein adequate and combined selenium and protein deficiency fodder until the 16th week. Cardiac toxicity of CIT was evaluated by general state of health, heart weight index, myocardial pathological change, the levels of selenium and the activities of glutathion peroxidase (GSH-Px) and creatine kinase (CK) in serum, and the activity of superoxide dismutase(SOD) of myocardium. Results The interaction effects of combined selenium and protein deficiency and adequate CIT on body weight, serum levels of selenium and albumin, heart weight index, the activities of CK and GSH-Px in serum and SOD of myocardium were statistically not significant(F= 0.000, 1.210, 0.625, 0.981, 2.785, 0.074, 0.001, all P> 0.05). The main effects of combined selenium and protein on the levels of serum selenium and albumin, heart weight index and the activity of GSH-Px in serum were statistically significant(F = 507.698, 87.734, 4.201, 109.389, all P < 0.05). The main effects of CIT on body weight, the levels of serum selenium and albumin, heart weight index and the activity of CK in serum were statistically significant(F = 10.929, 4.371, 26.108, 24.844, 4.439, all P < 0.05). The mean levels of serum selenium of Se-Pro- groups [(70.4 ± 40.0), (87.7 ± 59.6 )μg/L] were lower than those of Se+Pro+ groups [(446.1 ± 74.8),(502.1 ± 39.2)μg/L, all P < 0.05]. The mean levels of serum albumin of Se-Pro- groups [(34.36 ± 1.28 ), (33.38 ±2.48)g/L] were lower than those of Se+Pro+ groups[(40.69 ± 1.30), (38.71 ± 2.15)g/L, all P < 0.05]. The mean levels of heart weight index of CIT+ groups[(4.14 ± 0.36) × 10-3, (4.39 ± 0.53) x 10-3] were higher than those of CIT-groups[(3.56 ± 0.26) x 10-3, (3.80 ± 0.28) x 10-3, all P < 0.05] respectively at the same levels of selenium and protein. The mean levels of CK in serum of Se-Pro-CIT+ group[(2.54 ± 0.56)kU/L] was lower than that of Se-Pro-CIT- group [(3.37 ± 0.67 )kU/L, P < 0.05]. The mean levels of activity of GSH-Px in serum of Se-Progroups[(408.1 ± 412.6), (510.5 ± 392.0)U/L] were lower than those of Se+Pro+ groups[(1667.8 ± 102.2),(1731.5 ± 144.4)U/L, all P < 0.05]. In Se+Pro+CIT+ group, there was part of intercalary disc of cardiac myocytes fragmented;the conjunctions between myoeytes were broken;in some region, cardiac myocytes became edematous,even dissolved. In Se-Pro-CIT- group, the change of cardiac myocytes membrane structures was not obvious;filament structure was disappeared around nucleus;deposition of mass floccule could be seen. In Se-Pro-CIT+ group,the structure of sarcomeres was not obvious;mitochondrial cristae was loosened;cavities in myocytes could be seen occasionally;there were lots of disseminated sareoplasmic reticulum extending. Conclusions .CIT is the main risk factor in inducing myocardial damage. The deficiency of combined selenium and protein can aggravate the damage,but its independent pathogenic effect is weak.

BACKGROUNDDue to the floating of the guideline, there is no evidence-based evaluation index on when to start the blood transfusion for patients with hemoglobin (Hb) level between 7 and 10 g/dl. As a result, the trigger point of blood transfusion may be different in the emergency use of the existing transfusion guidelines. The present study was designed to evaluate whether the scheme can be safely and effectively used for emergency patients, so as to be supported by multicenter and large sample data in the future.

METHODSFrom June 2013 to June 2014, patients were randomly divided into the experimental group (Peri-operative Transfusion Trigger Score of Emergency [POTTS-E] group) and the control group (control group). The between-group differences in the patients' demography and baseline information, mortality and blood transfusion-related complications, heart rate, resting arterial pressure, body temperature, and Hb values were compared. The consistency of red blood cell (RBC) transfusion standards of the two groups of patients with the current blood transfusion guideline, namely the compliance of the guidelines, utilization rate, and per-capita consumption of autologous RBC were analyzed.

RESULTSDuring the study period, a total of 72 patients were recorded, and 65 of them met the inclusion criteria, which included 33 males and 32 females with a mean age of (34.8 ± 14.6) years. 50 underwent abdomen surgery, 4 underwent chest surgery, 11 underwent arms and legs surgery. There was no statistical difference between the two groups for demography and baseline information. There was also no statistical differences between the two groups in anesthesia time, intraoperative rehydration, staying time in postanesthetic care unit, emergency hospitalization, postoperative 72 h Acute Physiologic Assessment and Chronic Health Evaluation II scores, blood transfusion-related complications and mortality. Only the POTTS-E group on the 1 st postoperative day Hb was lower than group control, P < 0.05. POTTS-E group was totally (100%) conformed to the requirements of the transfusion guideline to RBC infusion, which was higher than that of the control group (81.25%), P < 0.01.There were no statistical differences in utilization rates of autologous blood of the two groups; the utilization rates of allogeneic RBC, total allogeneic RBC and total RBC were 48.48%, 51.5%, and 75.7% in POTTS-E group, which were lower than those of the control group (84.3%, 84.3%, and 96.8%) P < 0.05 or P < 0.01. Per capita consumption of intraoperative allogeneic RBC, total allogeneic RBC and total RBC were 0 (0, 3.0), 2.0 (0, 4.0), and 3.1 (0.81, 6.0) in POTTS-E groups were all lower than those of control group (4.0 [2.0, 4.0], 4.0 [2.0, 6.0] and 5.8 [2.7, 8.2]), P < 0.05 or P < 0.001.

CONCLUSIONSPeri-operative Transfusion Trigger Score-E evaluation scheme is used to guide the application of RBC. There are no differences in the recent prognosis of patients with the traditional transfusion guidelines. This scheme is safe; Compared with doctor experience-based subjective assessment, the scoring scheme was closer to patient physiological needs for transfusion and more reasonable; Utilization rate and the per capita consumption of RBC are obviously declined, which has clinical significance and is feasible. Based on the abovementioned three points, POTTS-E scores scheme is safe, reasonable, and practicable and has the value for carrying out multicenter and large sample clinical researches.

Adolescent ; Adult ; Emergency Medical Services ; statistics & numerical data ; Female ; Humans ; Male ; Transfusion Reaction ; Young Adult

OBJECTIVEThe Medical Outcome Study of 36-item Short-Form Health Survey (SF-36) is a well-validated generic questionnaire widely used to assess health-related quality of life (HRQOL), and the Chronic Liver Disease Questionnaire (CLDQ) is a specific HRQOL assessment designed for patients with liver diseases. The aim of our study is to evaluate the HRQOL based on SF-36 and CLDQ (Chinese version) in patients with chronic hepatitis B and liver cirrhosis, especially in the status of minimal hepatic encephalopathy (MHE).

METHODSThe SF-36 and CLDQ were answered by 160 healthy volunteers, 20 patients with chronic hepatitis B and 106 patients with cirrhosis. HRQOL scores of the groups with different liver disease severities and with or without MHE were compared. The SF-36 includes one multi-item scale that assesses eight health categories: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotion, and mental health. CLDQ assesses 6 categories: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry.

RESULTSCompared with the healthy controls, patients with chronic hepatitis B and liver cirrhosis at baseline had a lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increased severity of liver cirrhosis (based on the Child-Pugh score but with MHE or without) was associated with a decrease in most components, both in SF-36 and in CLDQ. However, patients with Child-Pugh B and C disease had similar HRQOL scores on both the SF-36 and CLDQ (P > 0.05), except role-physical and vitality on SF-36. There was a significant difference between patients with and without MHE on the SF-36 score (P < 0.01), and no significant difference (P > 0.05) on CLDQ scores except in abdominal symptoms.

CONCLUSIONThe Chinese version of SF-36 along with CLDQ are valid and reliable methods for testing MHE in patients with liver cirrhosis.

Adolescent ; Adult ; Case-Control Studies ; Female ; Hepatic Encephalopathy ; Humans ; Liver Cirrhosis ; Male ; Middle Aged ; Quality of Life ; Surveys and Questionnaires ; Young Adult

Acute Disease ; Adolescent ; Adult ; Aged ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Pesticides ; poisoning ; Poisoning ; epidemiology

OBJECTIVETo study the relationship between pretransplantation host thymic recent output function and prognosis in HLA-matched sibling bone marrow transplantation (MSD-BMT) and determine whether pretransplantation host thymic recent output function can act as a marker for predication of prognosis after HSCT.

METHODST-cell receptor excision circle (TREC) in DNA of pretransplantation peripheral blood mononuclear cells from 64 patients underwent MSD-BMT was detected by real-time quantitative PCR. The content of TREC in 70 normal donors was detected as well. All clinical data of patients after HSCT were collected and studied. Survival rates of patients after HSCT were estimated with Log-rank test. Univariate and multivariate analysis of prognostic factors were carried out by COX's proportional hazard regression model.

RESULTSThe mean value of TREC in normal donors was (3351 +/- 3711) copies/10(5) cells. There was an inverse correlation between TREC and age in the donor groups. Before transplantation, all patients were detected TREC, with a mean TREC number of (180 +/-332) copies/10(5) cells being significantly lower than that of normal donors. The results of univariate analysis showed that the counts of pre-HSCT TREC were closely, correlated with long term survival and chronic graft versus host disease (cGVHD) (P < 0.05) and with CMV infection (P = 0.084) but not with acute graft versus host disease (aGVHD). The results of multivariate analysis showed the same thing as that of univariate analysis.

CONCLUSIONPretransplantation host thymic recent output function is closely correlated with prognosis in MSD-BMT and can be a factor for predicting the outcome of HSCT.

Adolescent ; Adult ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Middle Aged ; Prognosis ; Receptors, Antigen, T-Cell ; genetics ; Retrospective Studies ; Siblings ; Thymus Gland ; immunology ; Transplantation, Homologous ; immunology ; methods

Biphasic Insulins ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; administration & dosage ; analogs & derivatives ; Insulin Aspart ; Insulin, Isophane ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo explore the effect of CMV gB genotypes on viral load and treatment time in patients with CMV infection after hematopoietic stem cell transplantation (HSCT).

METHODSViral load was detected by real-time (RT) quantitative polymerase chain reaction (PCR) (Q-PCR), CMV gB genotypes by PCR restriction fragment length polymorphism (RFLP) (PCR-RFLP) in 115 patients with CMV infection (CMV-DNA positive) after HSCT during July 2004 and May 2010.

RESULTS(1) The distribution of CMV gB genotypes in HSCT recipients were as following: gB1, 42/115 (36.52%); gB2, 3/115 (2.61%); gB3, 43/115 (37.39%); gB4, 2/115 (1.74%). 20 patients (17.39%) had a combination of 2 different CMV genotypes and 5 patients (4.35%) had a CMV variant that lacked an RsaI digestion site, herein named gB5. (2) The median viral load were 2.7×10(3)(1.81×10(3) ∼ 6.03×10(4)) in gB1, 4.0×10(3) (1.32×10(3) ∼ 6.39×10(4)) in gB3 and 1.2×10(4)(2.28×10(3) ∼ 6.50×10(5)) in mixed gB. There was no statistical difference in viral load between gB1 and gB3 (P > 0.050). There was significantly statistical difference in viral load between single-gB (gB1 or gB3) and mixed-gB (P < 0.05). (3) The median treatment time was 17 days in mixed-gB and 14 days in single-gB. There was significantly statistical difference between two groups (P < 0.05). Conclusion gB genotype may have an impact on CMV DNA load and treatment time in HSCT recipients with CMV infection.

Adolescent ; Adult ; Cytomegalovirus ; genetics ; Cytomegalovirus Infections ; virology ; DNA, Viral ; isolation & purification ; Female ; Genotype ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Viral Envelope Proteins ; genetics ; Viral Load ; Young Adult