Objective The present study was designed to investigate the efficiency of simvastatin therapy for experimental pul‐monary hypertension (PH) in rat ,and the effects on the number and function of circulating endothelial progenitor cells (EPC) . Methods Twenty four Sprague Dawley rats were divided into 3 groups randomly :model group ,treatment group and control group , 8 rats in each group .Rats were treated with a single subcutaneous injection of monocrotaline to induce PH (PBS used as control) . The rats in the experimental group were administrated with simvastatin 3 days following subcutaneous injection of monocrotaline .In the 21st day ,the number of circulating EPC ,the right ventricle systolic pressure of rat ,pulmonary vascular structural changes and the quantity of cultured EPC were measured .At the same time ,EPC in each group were cultured in vitro ,then the ability of prolif‐eration and function were analyzed and compared .Results The number of circulating EPC in model group was decreased signifi‐cantly compared to both control and model groups (P< 0 .01) .Compared with model group ,simvastatin treatment markedly de‐creased the RVSP and the ratio of media thickness to eternal diameter (P<0 .01) ,but the ratio of vessel area to total arterial area (VA/TAA) was definitively increased(P<0 .01) .After 7 days of culture in vitro ,both the output of EPC and the ability of prolif‐eration ,conglutination and migration of EPC in treatment group were up -regulated compared with those in model group (P<0 .01) .Conclusion This study confirmed that simvastatin effectively treat experimental PH through improving quantity and func‐tion of circulating EPC .

Introduction:Transcatheter arterial chemoembolization (TACE) plus thermal ablation has been widely used recently in the treatment of hepatocellular carcinoma (HCC). In this study, we aimed to compare results of the combination of TACE and percutaneous thermal ablation with those of hepatectomy in patients with HCC. Methods:The clinical data of 137 HCC patients who sequentially received TACE and computed tomography (CT)-guided percutaneous thermal ablation as an initial curative treatment (combination group) and 148 matched HCC patients who received hepatectomy (surgery group) between 2004 and 2011 were collected and analyzed. After TACE, multiphase contrast-enhanced CT was performed to identify the total number of tumors as well as lipiodol deposition in the liver. Survival was calculated by using the Kaplan-Meier method and compared by using the log-rank test. The prognostic factors were assessed with multivariate Cox proportional hazards regression analysis. Results:Of all 285 patients, 225 (79.0%) had cancerous lesions≤5 cm in diameter. In preoperative contrast-enhanced CT or magnetic resonance imaging, the number of tumors was 1–4 for each patient. The 1-, 3-, and 5-year overal survival rates were 95, 74%, and 67%in the combination group and 88, 66, and 47%in the surgery group, respectively (P=0.004);the corresponding recurrence-free survival rates for the two groups were 92, 69, and 61%and 75, 58, and 44%, respectively (P=0.001). In the multivariate analysis, treatment al ocation was an independent prognostic factor for survival. Only 60 patients in the combination group had sufficient imaging data, and 135 new lesions with lipiodol deposition were diagnosed as malignancies in 22 of 60 patients, whereas 20 new lesions were found in 11 of 148 patients in the surgery group. Conclusion:The combination of TACE and CT-guided percutaneous thermal ablation for HCC improves survival of HCC patients compared with hepatectomy.

Objective To examine neuroinflammation,oxidative damage and neuron loss in the contralateral parie-tal lobecortex of TBI model mice, and to investigate effects of berberine chloride on such secondary damage.Methods TBI model was established by a weight-drop hitting device and mice in berberine group were administered intragastrically with berberine chloride (50mg/kg.day) for 21 days.Immunofluorescence staining was used to assess activity of microglia and astrocyte.Immunohistochemistry was used to assess DNA oxidative damage, neuron loss and expression of COX-2 and iN-OS.Results Activation of microglia and astrocyte, expressions of COX-2 and iNOS and DNA oxidative damage were ob-viously increased by TBI,(19.82 ±1.88)and(16.96 ±1.69)、(13.79 ±4.32)and(8.67 ±0.96)、(27.86 ±5.38) and (16.00 ±7.59)、(31.92 ±6.57)and(24.79 ±2.78)respectively (P<0.01 or P<0.05).Activation of microglia and ex-pressions of COX-2 and iNOS were significantly suppressed by berberine ,(15.49 ±1.88)and(19.82 ±1.88)、(16.83 ± 7.89)and(27.86 ±5.38)、(26.25 ±2.41)and(31.92 ±6.57) respectively(P<0.01 or P<0.05).There was no differ-ence in neuron loss among three groups, (49.05 ±4.38),(48.56 ±3.56)and (47.75 ±4.14) respectively (P>0.05). Conclusions TBI can cause neuroinflammation and oxidative damage but not neuron loss in the contralateral parietal lobe cortex.Berberine chloride can significantly suppress neuroinflammtion in the contralateral parietal lobe cortex after TBI.

Objective To study the effects of granisetron hydrochloride on vasovagal syncope(VVS) in rabbits.Methods Twenty-four healthy New Zealand rabbits were divided stochastically into control group and intervention group,12 in each group. The control group was injected intravenously with normal saline. The intervention group was injected intravenously with granisetron hydrchloiride.Rabbit VVS models were established,each was taken at 4 points in time in the bloodletting process:T1,T2,T3,T4,to compare the bloodletting time,the concentration of 5-hydroxytryptamine(5-HT) in T2,T3,T4 and the total blood volume between the groups,and monitor the heart rate, blood pressure during the entire process.Results 1.The time of intervention group in T2,T3,T4 was longer than the time of control group obviously(P

Interleukin-1 receptor antagonist (IL-1ra), a member of IL-1 family, is a naturally occurring IL-1 inhibitor as "receptor antagonist", which blocks biological responses mediated by IL-1. Recombinant human IL-1ra (rhIL-1ra, Kineret) was introduced in clinical trials involving patients with RA. Between 2001 to approximately 2002, rhIL-1 ra was approved by the US Food and Drug Administration and the European Agency for the Evaluation of Medicine Procedure. Unfortunately, 10,000 to 100,000-fold excess amounts of IL-1ra are needed to relieve disease because minimal IL-1 can induce complete biological responses, and the dosage of 100 to approximately 150mg/day in a RA patient is so big that it greatly influence patients' physical, psychological and economical situation. In this study, IL-1ra mutants were established by site-specific mutagenesis to improve its stability. The sites of mutagenesis included R6 K7-AA,R93 K94-AA and K97 R98-AA. IL-1ra and its mutants were expressed in E. coli BL21 (DE3) using pTIG-Trx expressing system with the induction of IPTG. The recombinant proteins were purified by Ni2+ chelate chromatography and Sephadex G75 gel filtration chromatography. The activity of mutants is as high as IL-1ra. We characterized the pharmacokinetic profile of IL-1ra and its mutants. The third mutant's half life is 2.26 times than wt IL-1ra. The study has provided some approaches and experience for further research to improve the metabolism stability of IL-1ra.
Animals ; Escherichia coli ; genetics ; metabolism ; Female ; Humans ; Interleukin 1 Receptor Antagonist Protein ; biosynthesis ; genetics ; pharmacokinetics ; Mutagenesis, Site-Directed ; methods ; Mutant Proteins ; biosynthesis ; pharmacokinetics ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacokinetics

Calcitonin gene-related peptide (CGRP) play a key role in some physiological and pathological progresses. The latest studies indicate that CGRP might involve in some disease progress and has a close relation with wound healing. It is significant to further investigate and then apply it to clinical diagnosis and therapy as well as forensic pathology.
Animals ; Calcitonin Gene-Related Peptide/physiology* ; Forensic Medicine ; Humans ; Receptors, Calcitonin Gene-Related Peptide/physiology* ; Wound Healing

BACKGROUND: The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved. However, few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk. This study aimed to determine whether the polymorphisms in the IRAK-4 gene are associated with susceptibility to and prognosis of severe sepsis in the Chinese Han ethnic population.METHODS: In this case-control study, 192 patients with severe sepsis hospitalized in the emergency department of Zhongshan Hospital from February 2006 to December 2009 and 192 healthy volunteers were enrolled. Exclusion criteria included metastatic tumors, autoimmune diseases, AIDS or treatment with immunosuppressive drugs. This study was approved by the ethical committee of Zhongshan Hospital, Fudan University. Sepsis patients were divided into a survival group (n=124) and a non-survival group (n=68) according to the 30-day mortality. Primer 3 software was used to design PCR and sequencing primers. Genomic DNA was extracted from peripheral blood mononuclear cells. Seven tagSNPs in IRAK-4 were selected according to the data of the Chinese Han population in Beijing from the Hapmap project and genotyped by direct sequencing. The chi-square test was used to evaluate the differences in genotype and allele frequencies between the two groups.RESULTS: The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium. The allele and genotype frequencies of rs4251545 (G/A) were significantly different between the severe sepsis and healthy control groups (P=0.015, P=0.035, respectively). Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G (OR=1.69, 95％ CI: 1.10-2.58). The allele and genotype frequencies of all SNPs were not significantly different between the survival group and non-survival group.CONCLUSION: These findings indicate that the variants in IRAK-4 are significantly associated with susceptibility to severe sepsis in the Chinese Han ethnic population.

OBJECTIVETo determine the difference of post-operative mortality between ORIF (open reduction internal fixation) and hip replacement for the treatment of intertrochanteric fracture in elderly by using survival analysis.

METHODSThe clinical data of 110 patients above 60 years old who underwent surgical treatment (ORIF or hip replacement) for the intertrochanteric fracture between April 2003 and May 2013 were retrospectively analyzed. Among the patients, 83 cases were treated with ORIF (ORIF group), there were 32 males and 51 females, aged from 61.44 to 98.75 years old with an average of (78.52 ± 7.98) years old; and 27 cases were treated with hip replacement (arthroplasty group), there were 8 males and 19 females, aged from 71.82 to 96.54 years old with an average of (79.99 ± 6.11) years old. A survival analysis was performed on the clinical data by using SPSS 110 software. The survival rate of 1-year,2-year, 5-year and the mean survival time for the total patients, the mortality rate of 1-year, 2-year in each group, the survival rate of 1-year, 2-year and mean survival time and survival curve in each group were included.

RESULTSAll wounds achieved primary healing and no deaths were found in stay hospital. All patients were followed up from 1 to 125 months with an average of (46.93 ± 29.53) months. Among all 110 cases, 31 were dead and 79 survived. The survival rate of 1-year, 2-year and 5-year was (90.7 ± 2.8)%, (82.5 ± 3.9)% and (57.6 ± 6.5)%, respectively,while the ensemble mean survival time was (84.137 ± 5.902) months. The mortality rate of 1-year, 2-year in ORIF group was 7.2% and 12.0%, respectively; and in arthroplasty group, there was 14.8% and 25.9%, respectively. There was no significant difference in mortality rate of 1-year and 2-year between two groups. According to the survival analysis of the ORIF group, the survival rate of 1-year, 2-year was (92.6 ± 2.9)%, and (85.8 ± 4.3)%, respectively, and the mean survival time was (87.508 ± 6.063) months. In arthroplasty group, the survival rate of 1-year, 2-year was (85.2 ± 6.8)% and (73.9 ± 8.5)%,and the mean survival time was (67.294 ± 11.180) months. There was significant difference in mean survival time between two groups (P < 0.05).

CONCLUSIONORIF can achieve a better postoperative survival compare with hip replacement in treating intertrochanteric fracture in elderly.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; Female ; Fracture Fixation, Internal ; Hip Fractures ; mortality ; surgery ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

OBJECTIVETo evaluate the alterations in coagulation in patients during conditioning with modified busulfan plus cyclophosphamide (BU/CY) +/- antithymocyte globulin (ATG) regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to assess the effect of ATG on coagulation system.

METHODSThirty-five patients with various hematological malignancies undergoing allo-HSCT were assessed. Of them, 19 patients with HLA-matched sibling donors (group A) were conditioned with modified BU/CY regimen, 16 with HLA-mismatched family members or HLA-matched unrelated donors (group B) were conditioned with modified BU/CY + ATG regimen. Blood samples were collected before the beginning of conditioning till d + 1 after allo-HSCT. The following parameters were measured: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fg), antithrombin (AT), D-Dimer, fibrin degradation product (FDP), platelet (BPC), liver enzymes and bilirubin. FVIII: C, FIX: C, FXI: C and FXII: C in prolonged APTT blood samples were also determined. Clinical hemorrhagic symptoms were monitored.

RESULTSDuring conditioning, temporary lengthening of APTT, persistent rising in Fg and declining of BPC were observed in the two groups. Alterations of Fg and BPC were more significant in group B than in group A. Transient D-Dimer increase occurred only in group B on administration of ATG. Among intrinsic pathway coagulation factors, FXII: C and FXI: C were commonly decreased while APTT prolonged. No difference between the two groups was found with regard to PT, FDP, AT and liver parameters which remained in normal ranges. Most of patients in the two groups did not have overt bleeding manifestations.

CONCLUSIONSModified BU/CY +/- ATG conditioning regimen can induce subclinical alterations in coagulation. The regimen containing ATG has more significant effect on coagulation parameters.

Adolescent ; Adult ; Antilymphocyte Serum ; therapeutic use ; Blood Coagulation ; drug effects ; Child ; Cyclophosphamide ; therapeutic use ; Female ; Hematologic Neoplasms ; physiopathology ; surgery ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Transplantation Conditioning ; Young Adult

OBJECTIVETo study the effects of perinatal recurrent infection on the brain development in immature mice.

METHODSSix pregnant C57BL6 mice were randomly assigned to three groups: intrauterine infection, perinatal recurrent infection and control. The intrauterine infection group was intraperitoneally injected with LPS (0.5 mg/kg) on the 18th day of pregnancy. The perinatal recurrent infection group was injected with LPS (0.5 mg/kg) on the 18th day of pregnancy and their offsprings were intraperitoneally injected with the same dose of LPS daily from postnatal day 3 to 12. The control group was administered with normal saline at the same time points as the recurrent infection group. The short-time neurobehaviors were assessed on postnatal day 13. The mice were then sacrificed to measure brain weights and neuropathological changes using cresyl violet staining. Western blot was used to evaluate the expression of TNF-α, Caspase-3 and myelin basic protein (MBP).

RESULTSThe brain weights of the recurrent infection group were significantly lower than the control and intrauterine infection groups (P<0.05) and the recurrent infection group displayed significant neuropathological changes. Perinatal recurrent infection resulted in increased expression levels of TNF-α and Caspase-3, and decreased expression level of MBP compared with the intrauterine infection and control groups (P<0.01). The neurobehavior test showed that the recurrent infection group used longer time in gait reflex, right reflex and geotaxis reflex compared with the control and intrauterine infection groups on postnatal day 13 (P<0.05).

CONCLUSIONSPerinatal recurrent infection may exacerbate inflammatory response and cell death in the immature brain, which may be one of the important factors for perinatal brain injury.

Animals ; Animals, Newborn ; Bacterial Infections ; physiopathology ; Body Weight ; Brain ; growth & development ; pathology ; Caspase 3 ; analysis ; Female ; Mice ; Mice, Inbred C57BL ; Myelin Basic Protein ; analysis ; Pregnancy ; Recurrence ; Reflex