Objective To study the effects of mild hypothermia (MH) on blood coagulation and cerebral microcirculation in rabbits after cardiopulmonary resuscitation (CPR). Method A total of 24 New Zealand rabbits were randomly (random number) divided equally into normothermic group (NT) and MH group. CPR model was established by ventricular fibrillation induced by using alternating current. The rabbits of NT group were observed for 12 h in room temperature after restoration of spontaneous circulation (ROSC). The mild hypothermia was induced in the rabbits of group MH by surface cooling after ROSC, and maintained for 12 h after the aimed low temperature reached. The PT (prothrombin time), APTT (activated partial thromboplastin time), INR (international normalized ratio of prothrombin), D-dimmer (DD) , blood platelet count (BPC) , anti-thrombin Ⅲ activity (AT-Ⅲ) and protein C activity (PC) were measured before CPR and 4 h, 8 h and 12 h after ROSC, and at the same time the cerebral microcirculation was measured by using PERIMED Multichannel Laser Doppler system. One-way ANOVA or Mann-Whitney rank was used to determine the statistical significance between two groups. LSD-t test was used for multiple comparisons,t test for comparisons of means between two independent samples, and Pearson correlation test for correlation analysis. Results The PT, APTT and INR showed a trend of gradually shortening during the course. The APTT in 12 h after ROSC was significantly shorter than that before CPR (23.32 ±5.19 vs. 29.53 ±5.10,P = 0.025), and the activity of AT- Ⅲ and PC were decreased significantly. Compared with the group NT,the PT, APTT and INR in group MH were increased significantly, while there were no differences in the activity of AT- Ⅲ, PC and D-D between two groups. The rates of cerebral microcirculation in group NT before CPR and 4 h, 8 h and 12 h after ROSC were 401.60 ± 11.76 mL/min, 258.86 ± 34. 58 mL/min,317.59 ± 23.36 mL/min and 371.98 ± 5.79 mL/min, respectively, and those in group MT were 398.18 ±12.91 mL/min, 336.19 ± 19.27 mL/min, 347.76 ± 13.80 mL/min and 383.78 ± 3.29 mL/min, respectively. There were significant differences between two groups at each interval after ROSC (4 h: t = - 6.025,df=16, P=0.000;8 h: t= -2.942, df=12, P=0.012;12 h: t= -3.959, df=8, P=0.004). The Pearson correlation test showed that the rate of cerebral microcirculation was positive correlated with APTT after ROSC (4 h:R =0.503,P=0.033;8 h:R=0. 565,P=0. 035;12 h:R=0. 774,P=0. 009), and was not correlated with the other blood coagulants. Conclusions The mild hypothermia led to the inhibition of blood coagulation and improved the cerebral microcirculation concomitantly, which may be one of the mechanism of cerebral protection.

Objective To explore the safety and rate of intraperitoneal cooling in rabbits after cardiopulmonary resuscitation(CPR). Method There were two experiments. In the experiment one: 15 healthy adult NewZealand rabbits were divided into five groups as per the various amounts, 30, 40, 60, 80, and 100 mL/kg, of priming volume of 4 ℃ cold balanced salts solution injected into peritoneal cavity of rabbits. After injection of priming cold solution, the tympanic temperature between 33 ℃～ 35 ℃. For the maintenance of this mild hypothermia, a intraperitoneal infusion device(patent number ZL200820201265) was connected to the rabbits. The rabbits were rewarmed by using the same device after 12-hour hypothermia. The biochemical parameters were assayed during the experiment. After the rabbits were sacrificed, the liver, ileocecal junction of intestine and kidneys were removed to fix them in 3 % formalin, and examined by using H.E. staining. In the experiment two, another 12 healthy adult New Zealand rabbits were induced into ventricular fibrillation by alternating electric current and then gave CPR for 2 minutes. After return of spontaneous circulation(ROSC), the priming volume of 4 ℃ cold liquid was infused into peritoneal cavity of rabbits, and then the rabbits were connected to the intraperitoneal cooling device to maintain hypothermia for 12 hours. Matched-pairs t test was used for the comparison of biomarkers before and after intraperitoneal cooling. A two-tailed value of P < 0.05 was considered statistically significant. Results In the experiment one, the tympanic temperature of rabbits with priming volume of 80 mL/kg cold solution was decreased quickly reaching the target temperature in(30±2.00) minutes. During the induction of hypothermia, the intraperitoneal temperature reached the target temperature in less than 10 minutes, and was 1 -2℃ lower than the tympanic temperature during the maintenance of hypothermia. The intraperitoneal cooling did not cause damage in the liver, ileocecal junction of intestine and kidney, and did not alter the biomarkers. In the experiment two, the tympanic temperature of rabbits after ROSC was decreased quickly after intraperitoneal infusion of 80 mL/kg 4 ℃ cold solution, and reached the target temperature in(26.00±6.99) minutes, and the intraperitoneal temperature was lowered to reach the target temperature in less than 10 minutes. This cooling method after CPR didn' t disturbance water-electrolyte and acid-base balance. Conclusions The intraperitoneal cooling can safely and quickly induce hypothermia after CPR in rabbits.

Objective: To investigate the characteristics and prognostic factor of central nervous system (CNS) involvement in patients with hemophagocytic lymphohistiocytosis (HLH) . Methods: From January 2006 to October 2015, 152 patients with HLH, 88 patients had CNS involvement, their clinical data were collected, and survival was analyzed using the Kaplan-Meier life table method, univariate and multivariate Cox regression model analyses were applied to identify the risk factors of prognosis. Results: ①57.9% patients complicated with neurological symptoms, cerebrospinal fluid abnormalities were observed in 37.0% patients, 57.5% patients had abnormal neuroradiology. ②36 patients survived well, 3 patients lost to follow-up, 49 dead, 1 survival patient had epilepsy. ③The 3-year overall survival rate of 88 patients was 44%. ④abnormal CSF and unreceived IT bore a significant, independent adverse prognostic value (P<0.05) . Conclusion CNS involvement in HLH has a high frequency and poor prognosis, few patients remained neurologic sequelae; abnormal CSF related to poor prognosis, positive intrathecal injections could improve the prognosis.

AIMTo investigate the inhibitory effect of ginkgolide B on angiogenesis in chronic inflammation and the possible mechanisms.

METHODSThe murine chronic granulomatous air pouch model was used to observe the anti-angiogenesis effect of ginkgolide B. The vascular index was determined by colorimetry of carminic acid, and angiogenesis was observed by histology method. The interleukin-1beta (IL-1beta) levels in mice serum and in supernatants of U937 cell culture stimulated by phorbol 12-myristate 13-acetate (PMA) were detected by radioimmunoassay (RIA). The tumor necrosis factor-alpha (TNF-alpha) levels in mice serum and in supernatant of U937 cell culture were measured by cytotoxicity bioassay. The mRNA expression of IL-1beta and TNF-alpha of U937 cell culture was investigated by RT-PCR.

RESULTSOral administration of ginkgolide B 25 and 100 mg x kg(-1) was shown to significantly inhibit the vascular index of murine chronic granulomatous air pouch model with the inhibitory rate of 22.52% and 25.29%, respectively. This result was supported by histological observation. Concomitantly, the IL-1beta levels in mice serums were also significantly decreased with the inhibitory rate of 50.61% and 58.66%; so were the TNF-alpha levels with the inhibitory rate of 28.91% and 52.41%. Ginkgolide B at concentration of 1 x 10(-5) to 1 x 10(-8) mol x L(-1) could also reduce both the IL-1beta and TNF-alpha contents in the supernatants of U937 cell culture stimulated by PMA, but the scopes of changes were much different. For IL-1beta the IC50 was 1.93 x 10(-8) mol x L(-1), while ginkgolide B at concentration of 1 x 10(-5) mol x L(-1) only decreased the release of TNF-alpha by 25.99%. Furthermore, ginkgolide B at concentrations of 1 x 10(-5) to 1 x 10(-7) mol x L(-1) was shown to significantly inhibit TNF-alpha mRNA expression of U937 cells; and at concentrations of 1 x 10(-5) and 1 x 10(-6) mol x L(-1) could inhibit IL-1beta mRNA expression.

CONCLUSIONGinkgolide B was shown to significantly inhibit angiogenesis of the murine chronic granulomatous air pouch model, reduce the IL-1beta and TNF-alpha levels in mice serums, and significantly inhibit IL-1beta and TNF-alpha mRNA expression and protein secretion in supernatants of U937 cell culture. It was suggested that reduction of proangiogenic cytokines IL-1beta and TNF-alpha secretion may contribute to the anti-angiogenesis effect of ginkgolide B in the murine chronic granulomatous air pouch model.

Animals ; Cell Line ; Diterpenes ; pharmacology ; Female ; Fibrinolytic Agents ; pharmacology ; Fibroblasts ; cytology ; metabolism ; Ginkgolides ; Granuloma ; metabolism ; pathology ; Humans ; Inflammation ; metabolism ; pathology ; Interleukin-1 ; biosynthesis ; genetics ; Lactones ; pharmacology ; Mice ; Mice, Inbred BALB C ; Neovascularization, Pathologic ; pathology ; Platelet Activating Factor ; antagonists & inhibitors ; RNA, Messenger ; biosynthesis ; genetics ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics ; U937 Cells ; metabolism

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

OBJECTIVEAge, body weight and dose have been shown as important influencing factors for sodium valproate plasma concentrations. However it is unclear whether there is interaction among them and whether the interaction could influence sodium valproate plasma concentrations. This study aimed to evaluate the influence of age, body weight and dose on plasma concentrations of sodium valproate and the interaction among them.

METHODSOne hundred and thirty-two children with epilepsy (age: 4 months-6 years, weight: 5-25 kg) were enrolled. Sodium valproate was administered at the dosage of 10-30 mg/kg/d. Plasma concentrations of sodium valproate were measured by high-performance liquid chromatography 3-5 days after administration. The relationship of sodium valproate plasma concentrations with age, body weight, and dose of sodium valproate was examined using variance analysis, pearson correlation analysis and stepwise regression analysis.

RESULTSAge (F=8.630, P<0.01), body weight (F=3.650, P<0.05) and dose of sodium valproate (F=11.720, P<0.01) were influencing factors for sodium valproate plasma concentrations. The interaction between age and oral dose (F=2.484, P<0.05) and the interaction of age and body weight with oral dose (F=4.923, P<0.01) had significant effects on sodium valproate plasma concentrations. Stepwise regression analysis showed that dose of sodium valproate and body weight were entered to the regression equation.

CONCLUSIONSAge, body weight and dose of sodium valproate as well as the interactions between age and dose and between age, body weight and dose were influencing factors for valproate plasma concentrations.

Age Factors ; Anticonvulsants ; blood ; Body Weight ; Child ; Child, Preschool ; Epilepsy ; drug therapy ; Female ; Humans ; Infant ; Male ; Regression Analysis ; Valproic Acid ; administration & dosage ; adverse effects ; blood

Objective To analyze the current status of studies related to home enteral nutrition (HEN) in China,and provide scientific basis for the research and management of HEN in China.Methods We searched CNKI and WanFang Data since it built to January 1st,2018.The included studies were screened and categorized by publication information,study type,subjects of the study,topic,interventions and outcomes.Descriptive analysis was conducted after extraction of information.Results A total of 153 studies were included,of which 37 were observational studies,102 were experimental studies,12 were case report,and 2 were exploring articles.Since 2012,the number of studies has been increasing.Most of the subjects were elderly people who were diagnosed with diseases of digestive system,head and neck tumors and diseases of nervous system.These studies were featured as small sample size and short intervention time,follow-ups by telephone and home visit,less than 1/4 providing professional nutrition support team,and outcomes mainly as complication,nutritional biochemical indices,anthropometric indices and prognosis.Conclusion HEN in China is still in its infancy.The number of relative studies is still small and quality of literatures is very low,but it has been increasing.At present,there are some problems in the implementation of HEN in China,such as lack of standardized management model and professional team,short-term intervention,and single follow-up mode.The elderly and patients with digestive disease,head and neck tumors and nervous disease are the key subjects;more professional nutrition support team and scientific management model should be established in the future.

Objective :To construct and identify a ScFv phage display library against human umbilical cord mesenchymal stem cells.Methods: BALB/c mice were immunized with cultured UC-MSCs.After the third immunization,the total RNA was extracted from the spleen cells of the immunized BALB/c mice and purified by affinity chromatography with mRNA Purification Kit.The heavy-chain and light-chain variable region genes(VH and VL) were amplified by PCR using relevant primers.PCR products of VH and VL genes were cloned into the phagemid vector pSEX81 and electroporated into the XL1-Blue strain of E.coli.The ScFv phage display library against human umbilical cord mesenchymal stem cells was constructed and the capacity of library was measured.The library was panned by three cycles and screened with purified UC-MSCs.The percentage of clones containing a full-length scFv-encoding insert and their diversity was determined for unselected and selected libraries.Results: The amplified fragments of VH and VL genes by RT-PCR were about 399bp and 357bp,respectively.VH and VL genes were all successfully cloned into the phagemid vector pSEX81,which were confirmed by the amplication of 786bp full-length scFv fragments by PCR.The ScFv phage display library had a capacity of approximately 2?107 cfu.After three cycles of panning,PCR of plasmid DNA prepared from 15 individual phage clones showed that the recombination rate increased from 93% to 100%.BstN1 fingerprinting of insert DNA showed that the diversity of clones decreased with increasing rounds of selection.After three rounds of selection,3 clones showed an identical restriction enzyme pattern.There was a 330-fold enrichment of library phage after 2 rounds of selection and after 3 rounds,a further 8-fold enrichment of library phage was obtained.Conclusion: The ScFv phage display library against human umbilical cord mesenchymal stem cells was successfully constructed.It can be used for succeeding screening of specific antibody against human umbilical cord mesenchymal stem cells and further studying of the cell surface molecules of mesenchymal stem cells.

Objective To summarize the ultrasonographic features and differential diagnosis of uterine cornual pregnancy.Methods Trans-abdominal and trans-vaginal ultrasound were performed in 93 uterine cornual pregnancy patients before surgery,ultrasonographic findings of uterine cornual pregnancy through different two approaches were analyzed and compared with surgical and pathologic findings.ResultsIn contrast with surgical and pathological diagnosis,66 cases(82.5%,66/80) of uterine cornual pregnancy were accurately diagnosed by ultrasonography before surgery,these cases were divided into gestational sac pattern (55 cases) and mixed mass pattern(11 cases); 11 cases were misdiagnosed as interstitial tubal pregnancy,2 cases were misdiagnosed as pregnancy in rudimentary horn,1 case was misdiagnosed as choriocarcinoma,misdiagnosed rate were 17.5%(14/80); uterine cornual pregnancy presented as adnexal mass in ultrasound in 13 cases,while ruptured uterine cornual mass were found in surgery,in which location and type of the masses couldn't be accurately diagnosed by ultrasound.Ultrasonographic features of uterine cornual pregnancy presented as a gestational sac located in extended cornual of uterus,surrounded by thin myometrium,and connected with endometrium.The misdiagnosed causes were: (1) Uterine cornual mass was not connected with endometrium or surrounded by thin myometrium,which were misdiagnosed as interstitial tubal pregnancy.(2) Uterine cornual pregnancy with thick lateral myometrium were misdiagnosed as pregnancy in rudimentary horn.(3)Uterine cornual pregnancy presented as cornual mass with abundant blood flow was misdiagnosed as choriocarcinoma.Conclusions Uterine cornual pregnancy can be accurately diagnosed by trans-abdominal and trans-vaginal ultrasound.Ultrasonographic features are helpful in differential diagnosis of uterine cornual pregnancy.