The experimental study of cerebral ischemia plays an important role for understanding the pathogenesis of ischemic brain injury, but its correlation with the clinical therapeutic strategies has certain limitations. One of its main reasons is that the experimental models and methods can not or only partially repeat the pathophysiological processes of natural cerebral ischemia. In order to promote the understanding and interpretation of the experimental data, we review the commonly used experimental animal models and modeling methods and mainly elaborate the methods of current different in vivo and in vitro clinical evaluation. Based on these studies, we believe that the standardized clinical evaluations are hugely important for assessing the experimental results and clinical transformation.

Objective To investigate the effect of inhibition of endoplasmic reticulum stress (ERS) in ischemic preconditioning-induced cerebral ischemia tolerance.Methods A total of 120 adult male SpragueDawley rats were randomly allocated into three groups:sham operation,global cerebral ischemic and ischemic preconditioning groups (ischemic preconditioning for 3 minutes,and global cerebral ischemia for 15 minutes after 2 days).Three time points (day 1,day 3 and day 7) were set.Sugawara method was used to observe the changes of neurological behavior in rats.TUNEL staining was used to observe the conditions of cortical neuronal apoptosis.Immunofluorescence staining and Western blot analysis were used to detect the expression levels of ERS-related protein CHOP,GRP78,and caspase-12.Results The neurological behavior score showed that the sham operation group did not have neurological deficits.Both the global cerebral ischemic group and the ischemic preconditioning group had obvious neurological deficits,and they improved gradually with the passage of time,but after modeling,the neurological scores at each time point in the global cerebral ischemic were significantly lower than those in the ischemic preconditioning group:at day 1∶11.00 ±0.63 vs.14.33 ±0.33 (t =21.74,P＝0.001); at day 3∶ 12.17±0.31vs.15.17±0.48 (t=27.93,P =0.000); at day 7:14.67±0.49 vs.16.33 ±0.33 (t =7.81,P=0.020).TUNEL staining showed that at day 7 after ischemia,the positive cell count per mm2 in the sham operation,global cerebral ischemic and ischemic preconditioning groups were 4.83 ±1.85vs.395.67± 43.43 and 146.17± 27.38 respectively (F=23.62,P=0.001).The ischemic preconditioning group was significantly lower than that in the global cerebral ischemic group (P =0.001).Immunofluorescence staining showed that at day 7 after ischemia,the numbers of positive cells of CHOP (26.50±3.89vs.82.33±4.25; P=0.000),GRP78 (15.00±2.02vs.35.67±2.99; t=0.000),and caspase-12 (22.33 ± 2.76 vs.66.50± 7.25; P=0.000) in the ischemic preconditioning group were significantly less than those in the global cerebral ischemic group.Western blotting showed that at day 7 after ischemia,the expression levels of CHOP (1.22 ± 0.38 vs.3.22 ± 0.51; t =24.50,P =0.001),GRP78 (1.78 ± 0.45 vs.3.16 ± 0.76; t =14.29,P =0.005),and caspase-12 (2.89 ± 0.53 vs.5.96 ± 0.67; t =77.73; P =0.000) in the ischemic preconditioning group were significantly lower than those in the global cerebral ischemic group.Conclusions Ischemic preconditioning demonstrated a neuroprotective effect for the second lethal ischemia,its mechanism may be associated with the relief of ERS and downregulation of ERS-related protein.

BACKGROUND: With development of modern medical sciences, the out comes after meningioma surgery cannot be fully assessed using morbidity,livability and mortality merely. Quality of life (QOL) is a health-related multivariable index, which provides integrated inf ormation associated with physiological,sychological and social adaptation status of the patients to doctors. Assessment of the QOL in meningioma patients may be one of a relatively good method for guiding surgery and reducing reoccurrence of tuOBJECTIVE: To evaluate the QOL in meningioma patients and then to provide relevant data for assessing the outcomes of meningioma surgery comprehensively.DESIGN: It was a single-sample investigation. SETTING: Neurosurgery Department, Second People's Hospital of Wuxi City of Nanjing Medical University.PARTICIPANTS: Totally 147 patients underwent meningioma surgery in the Neurosurgery Department of the Second Affiliated Hospital of Wuxi City affiliated to Nanjing Medical University between January 1995 to January 2001 were selected, 61 males and 86 females, with a male/female ratio of 2:3 and an age ranging from 5-77 years old, in average of 43 years old, and the median was 43 years old.METHODS: Based on World Health Organization Quality of Life 100item questionnaire (WHOQOL-100) and Karnofsky Performance Scale (KPS), we designed a questionnaire on QOL in patients with meningioma.Outcomes of the transverse investigation on 147 meningioma patients were compared with healthy controls. Surgery-related QOL curve was used for identifying the threshold satisfactory point of QOL. In addition, with selfcontrol, influence of surgery on QOL was assessed.MAIN OUTCOME MEASURES: Relationship between QOL and clinical histories, radiological analysis, operation grading, histological properties and reoccurrence were investigated.RESULTS: All of the 147 patients entered the statistical analysis. ①In patient with meningioma, Cronbach's coefficient was 0.9521 and the correlated coefficient was 0.8685, which suggested that QOL questionnaire for patients with meningioma had a good reliability and validity. ②QOL ≥70 represented that the patient was satisfied with the QOL. ③In patients underwent surgical treatment, their physiological functions, self-help and self-care except for psychological functions were significantly improved (P ＜ 0.001 ).CONCLUSION: Surgical treatment enables patients to get a satisfied QOL. QOL questionnaire for patients with meningioma is helpful to provide relevant data for meningioma operation.

Objective To investigate the clinical characteristics, operation time and methods for patients with central brain herniation caused by bifrontal contusions. Methods A retrospective study was performed on the medical records of patients with central brain herniation caused by bifrontal contusions admitted from January 2000 to December 2006. There were 45 males and 18 females, at age range of 20-72 years (average 43 years). The majority of the patients were victims of falls and traffic accidents. There were 29 patients treated with immediate operation and 34 with emergency operation. All the operations involved simultaneous bilateral craniectomy for decompression, including 17 patients treated with bilateral decompressive craniectomy and 46 with unilateral decompressive craniectomy. Results The prognosis was favorable in 19 patients with GOS score of 5 or 4 points, severely disabled in seven with GOS score of 3 points, vegetative in four with GOS score of 4 points and the worst in seven with GOS score of 1 point. Of all, 19 patients suffered severe mental disorders especially personality change and disturbance of intelligence. Seven patients were complicated by epilepsy and three by hydrocephalus. Conclusions Based on early clinical manifestations of central brain herniation combined with imaging manifestations, bilateral balance decompression craniectomy can reduce the mortality and morbidity and improve the cure rate of patients with central herniation caused by bifrontal brain contusions.

Objective To investigate the neuroprotective effect of sophocarpine against transient focal cerebral ischemia via down-regulation of the acid-sensing ion channel 1(ASICl) in rats.Methods Twenty-five SD rats were randomly allocated into sham operation,cerebral ischemia/reperfusion,and 5,10,and 20 mg/kg sophocarpine pretreatment groups (n=5 in each group).A rat focal ischemia model was induced by the intraluminal suture method.Five,10 and 20 mg/kg sophocarpine were injected intraperitoneally for pretreatrnent.2,3,5-triphenyltetrazolium chloride staining was used to detect cerebral infarct volume.TUNEL staining was used to detect apoptosis.Immunohistochemistry and Western blot were used to detect the expression of ASIC1 and ASIC2.Results The infarct volume after ischemia-reperfusion was(181.21±9.21)mm3,while the 5,10,and 20 mg/kg sophocarpine pretreatment groups were(150.12±6.19),(52.31±4.20),and(32.18±3.82)mm3,respectively;the neurological function scores in the cerebral ischemia/reperfusion group was(3.62±0.36),while the 5,10,and 20 mg/kg sophocarpine pretreatment grows were(3.15±0.36),(1.92±0.18),and(1.85±0.21),respectively;The surviving neurons only accounted for(31.2±2.8)% of the total cell number in the cerebral ischemia-reperfusion group,while they accounted for(51.2±3.7)%,(76.5±2.1)%,and(77.1±4.1)% in the 5,10,and 20 mg/kg sophocarpine pretreatnmat groups.Compared with the cerebral ischemia/reperfusion group,the cerebral infarct volume was decreased significantly in the sophocarpine pretreatrnent groups(all P<0.01),the neurological function scores were decreased significantly(all P<0.01),and the number of apoptotic cells was decreased significantly (all P<0.01).Immunohistochemistry showed that the number of ASIC-1 positive cells in the sham operation,cerebral ischemia-reperfusion,and 5,10,and 20 mg/kg sophocarpine pretreatment groups were(162.5±8.3),(165.1±5.3),(138.3±7.2),(82.1±6.3),and(69.2±5.5)/mm respectively;Western blot showed that the ASIC1 protein expression was decreased sigaificantly in the 10 and 20 mg/ky sophocarpine pretreatment groups (P<0.01),while there WaS no significant difference in the ASIC2 protein expression.Condusions Sophocarpine may play a neuroprotective role for cerebral ischemia-reperfusion injury in rats via down-regulating the expression of ASIC1 protein.

Objective:To investigate the effect of CpG ODN on the immune responses and immune-contraception induced by ZP~(121-140) synthetic peptide.Methods: BALB/e mice were given an injection into the left tibialis anterior muscle of ZP~(121-140) synthetic peptide with 20 μg CpG ODN or CFA,then the mice were given other injections at 2,4,6 weeks using the same formulation.The mice' s blood was collected before each vaccination and after the last vaccination every 2 weeks.The specific IgG and IgA in sere and non-specific cytokines IFN-γ,TNF-α,IL-10 in vaginal mucosa were measured by ELISA.The ovarial pathological changes were undertaken using hemattxylin and eosin-stained paraffin sections.Results:The specific IgG in sera and IgA in vaginal mucosa induced by ZP~(121-140) synthetic peptide combined with CpG ODN were no more than those of ZP~(121-140) synthetic peptide combined with CFA.There were significant increases in IFN-γ,and TNF-α when CpG ODN was mixed with ZP121-140 synthetic peptide and the increase of CpG ODN was more significant than that of CFA.Otherwise there was a significant decrease in IL-10 when CpG ODN was mixed with ZP~(121-140) synthetic peptide and the decrease of CpG ODN was more significant than thai of CFA.There was no significant difference in the rate of pregnancy between CpG ODN group and CFA group,but the average number of birth mice in CpG ODN group was less than that in CFA group.No pathological changes were found in the ovaries of experimental mice.Conclusion: The adjuvant effect of CpG ODN is more advantageous than that of CFA in contraception vaccine research.

Objective: To investigate the effects of silk fibroin on the immobilization of thrombin. Methods: The immobilized thrombin was prepared using silk fibroin as the carrier and glutaraldehyde as the crosslinking agent. With activity yield as the index, the process conditions of silk fibroin immobilized thrombin were determined by an orthogonal test. Results:The optimum process con-ditions of immobilized thrombin treated with silk fibroin were as follows:the immobilization time was 6 h, the enzyme dosage was 2 400 NIH·g-1 casein, the temperature was 25℃ and pH was 7. 6. The activity recovery of immobilized thrombin was 67. 22%. Conclu-sion:Silk fibroin has the positive immobilization effect on thrombin.

Mesenchymal stem cells (MSCs) can be obtained from a variety of human tissues. Placenta has become an attractive stem cell source for potential applications in regenerative medicine and tissue engineering. The aim of this study was to localize and characterize MSCs within human chorionic membranes (hCMSCs). For this purpose, immunofluorescence labeling with CD105 and CD90 were used to determine the distribution of MSCs in chorionic membranes tissue. A medium supplemented with a synthetic serum and various concentrations of neurotrophic factors and cytokines was used to induce hCMSCs to neural cells. The results showed that the CD90 positive cells were scattered in the chorionic membranes tissue, and the CD105 positive cells were mostly located around the small blood vessels. hCMSCs expressed typical mesenchymal markers (CD73, CD90, CD105, CD44 and CD166) but not hematopoietic markers (CD45, CD34) and HLA-DR. hCMSCs differentiated into adipocytes, osteocytes, chondrocytes, and neuronal cells, as revealed by morphological changes, cell staining, immunofluorescence analyses, and RT-PCR showing the tissue-specific gene presence for differentiated cell lineages after the treatment with induce medium. Human chorionic membranes may be the source of MSCs for treatment of nervous system injury.
Adipocytes ; Blood Vessels ; Cell Lineage ; Chondrocytes ; Chorion* ; Cytokines ; Fluorescent Antibody Technique ; HLA-DR Antigens ; Humans* ; Membranes* ; Mesenchymal Stromal Cells* ; Nerve Growth Factors ; Neurons ; Osteocytes ; Placenta ; Regenerative Medicine ; Stem Cells ; Tissue Engineering ; Trauma, Nervous System

ObjectiveTo systematically review the efficacy and safety of laparoscopic choledochoscopy combined with holmium laser lithotripsy through a meta－analysis. MethodsThis study was conducted based on PRISMA guidelines， with a PROSPERO registration number of CRD42023406221. Chinese databases including CNKI， Wanfang Data， and VIP and foreign language databases such as PubMed， Embase， the Cochrane Library， and Web of Science were searched for original articles on traditional laparotomy versus laparoscopic choledochoscopy combined with holmium laser lithotripsy in the treatment of bile duct stones. Dichotomous variables were assessed by odds ratio （OR） and 95% confidence interval （CI）， while continuous variables were assessed by weighted mean difference （WMD） and 95%CI， and a sensitivity analysis was performed for outcome measures with relatively high heterogeneity. The Begg test and Egger test were used to evaluate publication bias. Stata 15.0 and Review Manager 5.3 were used to perform the statistical analysis. ResultsA total of 26 retrospective studies from China were included in this study， with 2 238 patients in total. The meta－analysis showed that compared with traditional laparotomy for the treatment of bile duct stones， laparoscopic choledochoscopy combined with holmium laser lithotripsy had significantly shorter time of operation （WMD＝－1.26， 95%CI： －1.36 to －1.16， P<0.001）， length of hospital stay （WMD＝－1.93， 95%CI： －2.64 to －1.12， P <0.001）， and time to bowel function recovery （WMD＝－1.52， 95%CI： －1.68 to －1.35， P<0.001）， significantly less intraoperative blood loss （WMD＝－1.79， 95%CI： －1.93 to －1.66， P<0.001）， a significantly lower rate of intraoperative residual stone （OR＝0.15， 95%CI： 0.11－0.20， P<0.001）， and significantly fewer complications （OR＝0.17， 95%CI： 0.13－0.23， P<0.001）. ConclusionCompared with traditional laparotomy， laparoscopic choledochoscopy combined with holmium laser lithotripsy shows better efficacy in the treatment of bile duct stones.