Objective:To study the effects of the Gekko gecko ethanol extract on granular cells apoptosis of rat ovaries.Methods :3 month and 6 month female Wistar rats were taken in this study, and 20 rats were in each age group.Each age group were randomly divided into two groups(experimental group and control tragastric administration in experimental group, corresponding volume of 0.9% sodium chloride was given in control group by the same way.Apoptosis of granular cells and distribution of cell cycle in rat ovary were measured by terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL) and propidi-um iodide(PI) staining, AnnexinV/PI double labelling staining by flow cytometry (FCM) after administration for 15 days.Re8utts:The apoptosis numbers of granular cells in 3 month and 6 month age experimental group were 34 ±7 and 53 ±11, in control group were 48±9 and 76±17 respectively by TUNEL.There was signrficantly statistic difference (P <0.01).The apoptosis rates in 3 month and 6 month age experimental group were(6.06 ±2.01)% and (12.16 ±3.26) % , in the control group were (8.23±2.13) % and (23.69 ±6.28)% respectively by PI staining.There was significantly statistic drfference (P <0.05).However, no significant difference was found between two groups in cellular cycle distribution (P > 0.05).Early apoptosis rates in 3 month and 6 month age experimental group were (6.71±3.11) % and (23.74±6.28) % , in the control group were (19.05 ±5.78) % and (36.55± 8.35) % respectively by AnnexinV/PI double labelling staining FCM.There was significantly statistic difference (P <0.01).The apoptosis of granular cells were sig-nificantly less in experimental groups comparing wrth control groups both in 3 month and 6 month age group (P<0.01 or P<0.05).Conclusions :The ethanol extract of gekko gecko can inhibit the apoptosis of granu-lar cells in rat ovary, then improves the ovary function and delay ageing of rat.

Principles of making an example include pertinency,type,instructiveness,science,morality,terseness,interesting,lifelikeness and verisimilitude.These may help to achieve satisfactory teaching effect and improve teaching quality.

Objective To evaluate the effect of hyperlipidemia on pulmonary uptake in the patients inhaling sevoflurane for anesthesia.Methods A total of 103 patients of both sexes,aged 20-50 yr,with body mass index of 18-25 kg/m2,of American.Society of Anesthesiologists physical status Ⅰ or Ⅱ,undergoing elective operation under general anesthesia,were enrolled in the study.Anesthesia was induced with iv midazolam 0.1 mg/kg,vecuronium 0.1 mg/kg,fentanyl 0.l mg/kg and etomidate 0.3 mg/kg.Patients were mechanically ventilated after endotracheal intubation.Patients inhaled 2％ sevoflurane for 30 min at an oxygen flow rate of 2 L/min.The inspired concentrations (Fi) and expired concentrations (Fe,Fe≈alveolar concentration [Fa]) of sevoflurane were recorded at 1,3,5,7,10,15,20 and 30 min of inhalation (T0-7).Patients were divided into either control group group C) or hyperlipidemia group (group H) according to the results of blood lipid levels after the end of observation.The ratio of Fa/Fi and time spent in reaching the titration value (Fa/Fi =0.8) were calculated in each group.Results There were 67 cases in group C and 36 cases in group H.Compared with group C,the Fa/Fi ratio was significantly decreased at 5,7 and 10 min of inhalation,and the time spent in reaching the titration value was prolonged in group H (P ＜ 0.05).Conclusion The pulmonary uptake of sevoflurane is increased,which may be associated with increased blood/gas partition coefficient.

Objective To examine whether Tim-3 plays a protective role in paraquat poisoning induced excessive immune response and tissue damage based on the critical roles of Tim-3 controlling inflammatory response.Methods A paraquat poisoning model was established in wild type and in Tim-3 transgenic C57BL/6 mice by intraperitoneal injection of paraquat (40 mg/kg) .In addition, C57BL/6 mice with paraquat poisoning were injected with Tim-3 soluble protein( sTim-3) or control protein to see the effect of Tim-3 blocking on the progression of paraquat poisoning.Samples were collected at 6 and 24 h after paraquat injection respectively and were examined for tissue damage, cytokine expression and paraquat metabolism.Results After paraquat poisoning, there was significantly attenuated tissue damage in the lungs and kidneys and decreased TNF-α,IL-6 and IL-1 beta expression in the PBMCs or in the serum from Tim-3 transgenic mice compared to wild type mice.The serum concentration of paraquat in Tim-3 transgenic mice was also significantly decreased.However, in sTim-3 treated paraquat poisoning mice, there was significantly increased cytokine expression and tissue damage compared to control protein treated mice.The in vitro data showed that Tim-3 signaling negatively regulated macrophages mediated inflammatory response.Conclusion Tim-3 plays a critical role in maintaining the homeostasis after paraquat poisoning. Further investigation on the regulatory roles of Tim-3 in inflammation will shed new light on the pathogenesis of paraquat poisoning and provide new therapeutic strategies.

OBJEVTIVETo investigate the expression of transient receptor potential lvanilloidreceptor 4 (TRPV4) protein in pemphigus vulgaris (PV), bullous pemphigoid (BP), dermatitis herpetiformis (DH), and epidermolysis bullosa acquisita (EBA), and explore the role of TRPV4 in the pathogenesis of these diseases.

METHODSTRPV4 protein in normal skin tissues and lesions of PV, BP, DH, and EBA were detected with immunohistochemistry.

RESULTSThe positivity rate of TRPV4 protein expression was 61.90% in PV, 81.81% in BP, 72.22% in DH, and 68.42% in EBA. TRPV4-positive rates in these lesions were significantly lower than the rate in normal skin tissues (93.33%) and also differed significantly among these lesions (PV

CONCLUSINLow TRPV4 expressions may affect the formation and reconstitution of skin connection. TRPV4 may play an role in the occurrence and development of autoimmune bullous skin disorders.

Dermatitis Herpetiformis ; metabolism ; Diagnosis, Differential ; Epidermolysis Bullosa Acquisita ; metabolism ; Humans ; Pemphigoid, Bullous ; metabolism ; Pemphigus ; metabolism ; Skin ; pathology ; TRPV Cation Channels ; metabolism

Objective To develop a human Tim-3 specific monoclonal antibody and evaluate its biological activity and possible use in clinical diseases associated with dysregulated Tim-3 expression .Methods The BALB/c mice were immu-nized by conventional method, and positive clones were used to develop anti-human Tim-3 antibody, the binding and neutralization activities of which in vitro and in vivo were investigated.Results ①A monoclonal antibody (clone L3D) which could specifically bind to human Tim-3 protein in ELISA assay was obtained and the subtype of the monoclonal antibody was IgG2a .②Flow cytometry indicated that the monoclonal antibody could bind to Tim-3 expressed in human U937 cells.This antibody also showed a cross activity to mice′Tim-3.③The monoclonal antibody inhibited the apoptosis of THP1 cells induced by Gal-9, the ligand of Tim-3.④Injection of Tim-3 antibody exacerbated sepsis in mice as marked by the decreased survival rate and increased expression of pro-inflammatory cytokines .Conclusion An anti-human Tim-3 monoclonal antibody is successfully obtained.The excellent binding and neutralization activities of this antibody enable it to be widely used in clinical diseases associated with deregulated Tim-3 expression .

Objective To investigate the expression of transient receptor potential lvanilloidreceptor 4 (TRPV4) protein in pemphigus vulgaris (PV), bullous pemphigoid (BP), dermatitis herpetiformis (DH), and epidermolysis bullosa acquisita (EBA), and explore the role of TRPV4 in the pathogenesis of these diseases. Methods TRPV4 protein in normal skin tissues and lesions of PV, BP, DH, and EBA were detected with immunohistochemistry. Results The positivity rate of TRPV4 protein expression was 61.90% in PV, 81.81% in BP, 72.22% in DH, and 68.42% in EBA. TRPV4-positive rates in these lesions were significantly lower than the rate in normal skin tissues (93.33%) and also differed significantly among these lesions (PV

Objective To investigate the expression of transient receptor potential lvanilloidreceptor 4 (TRPV4) protein in pemphigus vulgaris (PV), bullous pemphigoid (BP), dermatitis herpetiformis (DH), and epidermolysis bullosa acquisita (EBA), and explore the role of TRPV4 in the pathogenesis of these diseases. Methods TRPV4 protein in normal skin tissues and lesions of PV, BP, DH, and EBA were detected with immunohistochemistry. Results The positivity rate of TRPV4 protein expression was 61.90% in PV, 81.81% in BP, 72.22% in DH, and 68.42% in EBA. TRPV4-positive rates in these lesions were significantly lower than the rate in normal skin tissues (93.33%) and also differed significantly among these lesions (PV

Ischemic stroke,due to its high prevalence and mortality,has become one of the most important public health concerns globally.Nerve cell damage is the main biological event in its patho-logical process and there is still a lack of effective neuroprotective drugs for clinical use.Numerous studies have shown that inhibitions of histone deacetylases(HDACs)can exert neuroprotective effects in ischemic stroke.Due to the multiple types of HDACs and the relatively poor specificity of HDAC inhib-itors,it has been difficult to identify any HDAC that plays a key role in ischemic stroke.ClassⅠHDACs include four members:HDAC1,HDAC2,HDAC3,and HDAC8,and have been more in-depth in isch-emic stroke.The complex mechanisms of classⅠHDAC inhibitors that have been discovered so far involve neural cell function,neuroinflammation and blood-brain barriers.This article is intended to study the regulatory role of classⅠHDACs in ischemic stroke in the hopes of providing reference for the developments of effective drugs targeting HDACs.

Objective To investigate the pathological damage to and inflammation of different intestinal segments in a rat model of severe hemorrhage,and to explore the effect of polarization of intestinal macrophage on the pathophysiology of intestinal inflammation.Methods Male Wistar rats were randomly divided into two groups:the sham operation group and hemorrhage group.In the hemorrhage group,40％of the total blood volume was lost in 25-30 minutes,while in the sham operation group,only the femoral artery and vein were intubated without bleeding.The rats were killed at 0,3,6,12 and 24 hours.The entire intestine was isolated quickly,and sections of the intestine were cut at the duodenum,jejunum,ileocecal junction,colon and rectum for histopathological evaluation.ELISA was adopted to determine related inflammation factors while multi-color immunohistochemistry was used to calculate macrophage surface markers.The data was statistically analyzed.Results(1)Compared with the sham group,there was no significant difference in colon histology at 3 h and 6 h,but significant difference was detected in rectum scores only at 24 h.The scores of other intestinal segments were significantly different at each time point.The severity of ileocecal and colonic lesions after bleeding increased with time.The duodenum,jejunum and ileocecum were more critically injured at 3 h than the rectum at 6 h.The injury to the duodenum,jejunum,ileum and colon was much more pronounced than to the rectum at 12 h.(2)The expressions of TNF-α and IL-1β in the rectum were increased significantly at 12 h post operation.The expressions of IL-1β,TNF-α in the jejunum increased obviously at 3 h and 6 h,respectively.(3)Three hours after severe bleeding,the level of macrophages in the jejunum and ileocececal area increased significantly,and the percentage of M1 macrophages was higher.After 6 hours,the proportion of M2 macrophages in the jejunum and M1 macrophages decreased significantly.After 3 hours,the percentage of M1 macrophages in the colon decreased,but that of M2 macrophages increased.The proportion of M2 polarized macrophages in the duodenum and rectum increased at 3 h after severe bleeding but decreased at 6 h.Conclusion Pathological damage to intestinal sections after bleeding varies depending on the time,and is correlated with the inflammatory level of macrophages.