AIM To study pathogenesis of Alzheimers disease and screen ?- secretase and ?- secretase inhibiting drug, PS-1(M 146L)and APP 751 gene double stably transfected CHO cell lines have been established. METHODS A? cDNA encoding human PS-1 was obtained by polymerase chain reaction from a human placental library. Mutant PS-1 (M 146L) cDNA was also generated by polymerase chain reaction from wild type PS-1 cDNA. Wild type and mutant PS1 were subcloned into CMV-based mammalian expression vectors PCI-neo,then recombined plasmid were co-transfected into APP expressing CHO cells at 1∶10 ratio using LipofectAmine. Stable expressing cell lines were screened and selected by using selection media. RESULTS Several CHO cell lines stably transfected with wide type or mutant PS-1 (M 146L) as well as APP 751 genes were established. Overexpression of PS-1 in CHO cell accumulated full length 45 kDa PS-1 protein. A? released to conditioned media were not changed in wild type PS-1 transfected APP expression CHO cells. A? 1～42 level in conditioned media of M 146L mutant PS-1 stably transfected of APP expression CHO cells were elevated about 1.6 fold. CONCLUSION Expression of M 146L mutant PS-1 in stably transfected APP expression CHO cells increased a secretion of A? 1～42. The PS-1 and APP double stably transfected CHO cell lines we generated can be used for either ?-or ?-secretase inhibitor study and related drug screening.

Objective To evaluate the role of mangled extremity severity score(MESS)in res-ervation and amputation of crush lower limbs in earthquake. Methods There were 122 patients with crush lower limb injuries,with MESS≥8 points in 34 patients who were primarily amputated,M ESS 5-7points in 19 who were principally preserved and MESS＜5 points in 69 who were preserved by means of debridement,external fixators,plast splints and vaeuum sealing drainage technique.Results All pa-tients were survived.with amputation rate of 29.5%. Conclusion MESS is an important reference for evaluation of reservation and amputation of crush limb injuries caused by earthquake.

Objective To explore operative indications,methods and effect of one stage total hip arthroplasty(THA)in treatment of acetabular fractures.Methods One stage total hip arthroplasty (THA)was carried out in 11 patients with acetabular fractures including 10 males and one female(at mean age of 42.4 years)8-37 days(mean24 days)after injury.There were anterior column fractures in three patients,posterior wall fracture in one,posterior column fracture in two,posterior column fracture combined with posterior wall fracture in two,transverse fracture in one,transverse fracture combined with posterior wall fracture in one and two-column fracture in one.Fresh acetabular fractures were first fixed with reconstruction plate or screws to restore shape of acestbular wall;then,granule or bulk of resected femoral head were implanted into acetabulum posterior to placement of acetabular cup prosthesis.While for old acetabular fractures,the resected femoral head was first implanted on acetabular superior wall and posterior wall and then acetabular cup prosthesis was placed.Results Follow-up for 6-45 months (mean 28 months)showed obdous improvement of hip joint function,with average Harris score of 78 points and average active degree of 95°.X-ray film presented loosening of acetabulum and osteolysis in one patient.All patients began weight bearing three months after operation,with no dislocation of joint prosthesis.Conclusions Under strict control of indications,one stage THA can be done for patients who miss operative reduction due to obvious acetabular fracture dislocation and severe articular cartilage injury.Stable aeetabular cup may beget satisfactory short-term clinical results.

BACKGROUND: Idiopathic scoliosis is a common spinal deformity in teenagers, which is managed mainly by orthomorphia. However, due to great trauma, long operative duration and large blood loss, a great amount of blood transfusion is needed during the surgery. Allogeneic blood transfusion should be reduced in order to release blood insufficient, decline blood transfusion expense, as well as avoid transfusion diseases. OBJECTIVE: To investigate the value of controlled hypotension combined with autotransfusion in idiopathic scoliosis orthomorphia.METHODS: Intraoperative controlled hypotension was performed during posterior orthomorphia surgery on all the 46 cases of idiopathic scoliosis, 17 cases in which were served as the control group, who underwent allogeneic blood transfusion without autotransfusion, while the other 29 cases were served as the experimental group, who underwent autotransfusion that including reinfusion of preoperative deposited autologous blood and intra-operative salvaged autologous blood. The blood loss volume and transfusion status in two groups were observed. RESULTS AND CONCLUSION: Blood loss volume in the control group was 400-1 000 (867±161) mL, and that in the experimental group was 350-1400 (842±376) mL, There was no marked difference between the two groups (P > 0.05). The volume of allogeneic blood transfusion in the control group was 500-1 800 (845±332) mL, which was greater than that in the experimental group [0-1 300(423±237) mL] (P < 0.01). The results suggested that controlled hypotension reduces intraoperative bleeding, and postoperative autotransfusion minimizes the need of allogeneic blood transfusion.

Objective To evaluate whether Vitamin B supplementation could prevent ischemic stroke recurrence.Methods Randomized controlled trials (RCTs) observing Vitamin B supplementation in patients with stroke was performed in databases including ScienceDirect, PubMed/Medline, China National Knowledge Infrastructure, Chinese Biomedical Data-Base, Wanfang Database, and VIP Chinese Science and Technology Journal Database to find related studies in English or Chinese published before August 2016. The patients in control group received a placebo or basic therapy without Vitamin B, and those in experimental group was treated with Vitamin B alone or Vitamin B on the basis of conventional treatment. The data were collected by two researchers independently and the quality of studies was assessed by the modified Jadad Scale. The Meta-analysis was performed using Stata 12.0, funnel plot was drawn, and Egger and Begg regressions were used to evaluate the publication bias, and sensitivity was also analyzed. Results Seven RCTs studies were enrolled to analyze with a total number of 9846 stroke patients, 4755 patients in control group, and 5091 in experimental group, respectively. ① Vitamin B supplementation for prevention of recurrent stroke: heterogeneity test results showed a heterogeneity in literatures enrolled (I2 = 62.9%,P = 0.009), and a random effect model was used for Meta-analysis. It was shown that the incidence of recurrent stroke in the experimental group was significantly lower than that in the control group [pooled relative risk(RR) = 0.64, 95% confidence interval (95%CI) = 0.47-0.87], which indicated that the supplementation of Vitamin B could prevent the recurrence of stroke. Cumulative Meta-analysis showed that Vitamin B supplementation exhibited positive effects in the prevention stroke recurrence from 2012. The 95%CI tended to be stable while demonstrating good change trend as sample growing. The publication bias evaluation results showed that the funnel plot was not symmetrical by visual inspection, further quantitative analysis showed thatP value from Egger regression was 0.008, while that from Begg regression was 0.035, bothP < 0.05, suggesting there were some publication bias. The sensitivity analysis showed that the overall results were stable and reliable. ② The effect of Vitamin B supplementation on plasma homocysteine (Hcy) levels in stroke patients: heterogeneity test results showed a heterogeneity in literatures enrolled (I2 = 96.2%,P = 0.000), and a random effect model was used for Meta-analysis. It was shown that compared with control group, the plasma Hcy levels of patients after Vitamin B supplementation in experimental group were significantly decreased [pooled weighted mean difference (WMD) = -6.92, 95%CI = -9.11 to -4.73), indicating that Vitamin B could significantly reduce plasma Hcy levels in stroke patients. Cumulative meta analysis showed that, as time went on, the relevant research samples were increased, 95%CI tended to be stable and the variation tendency was better. The publication bias evaluation results showed that the funnel plot was symmetry by visual inspection, and further quantitative analysis showed that theP value from Egger regression was 0.345, and that from Begg regression was 0.764, bothP > 0.05, which indicating that there was no evidence of publication bias in the study included.Conclusions Vitamin B supplementation was associated with a lower risk of recurrent stroke in stroke patients and could significantly improve the quality of secondary prevention of stroke. Furthermore, supplementation of Vitamin B could reduce plasma Hcy levels in stroke patients which might contribute to its effect in preventing stroke recurrence.

Objective To set up a three-dimensional finite element model (FEM) to investigate biomechanics of point contact locking plate (PC-LP) fixating femoral shaft fractures. Methods One intact fresh adult cadaveric femur was scanned by CT at 1 mm interval. Then, the data of CT were utilized to establish three-dimensional FEM by using software Mimics and PRO/E and simulate the different clini-cal loading conditions. The changes of theoretical stress of femur and PC-LP were analyzed under flexion, axial compression and torsion loads. Results (1) Under four-point bending load, the distribution of femur stress was in uniformity, with the largest stress of the PC-LP focused on the edge. (2) Under axial compression load of 250 N, the largest stress of the femur was focused on the screw holes on beth distal ends, with the largest stress of the PC-LP focused on the middle screw holes. (3) Under the torsion load cused on the middlepart and the middle screw holes. Conclusions Under the four-point bending, ax-ial compression and torsion loads, the distribution of femur stress is in uniformity, when the largest stress of the PC-LP focuses on edge or the middle screw holes, while that of the PC-LP on two screw holes of proximal or distal ends.

On the basis of the origin comparison of known endothelial genesis inhibitors, a 417-bp cDNA fragment was amplified from umbilical cord by RT-PCR and cloned into the expression vector pPIC9, followed by transformation into Pichia pastoris GS115. The resulted yeast was induced with methanol to express recombinant protein. The resulted protein was purified from culture broth and designated as EDI-8t. The in vitro study showed that EDI-8t, originated from collagen VIII, could specifically inhibit the growth and migration of bovine aortic endothelial cells (BAEC) stimulated by basic fibroblast growth factor (bFGF). The protein also exhibited the activity to cause cell apoptosis. In vivo EDI-8t showed the identical activity comparing with endostatin to inhibit the growth of liver tumor transplanted into nude mice. Interestingly, EDI-8t showed higher activity than endostatin to inhibit tumor growth in metastatic model of melanoma mice.
Amino Acid Sequence ; Angiogenesis Inhibitors ; biosynthesis ; genetics ; isolation & purification ; Animals ; Antineoplastic Agents ; pharmacology ; Base Sequence ; Cattle ; Cells, Cultured ; Collagen Type VIII ; chemistry ; genetics ; Endothelium, Vascular ; metabolism ; Genetic Vectors ; genetics ; Human Umbilical Vein Endothelial Cells ; chemistry ; Humans ; Mice ; Mice, Nude ; Molecular Sequence Data ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacology

Objective:To explore the efficacy and safety of camrelizumab combined with apatinib as the second-line treatment for patients with advanced gastric cancer.Methods:The clinical data of 19 patients with advanced gastric cancer in Hebei General Hospital from August 2019 to March 2022 were retrospectively analyzed. All patients received camrelizumab combined with apatinib as the second-line treatment. The treatment efficacy and adverse reactions were evaluated; the survival analysis was performed using Kaplan-Meier method; Cox proportional hazards model was used to analyze the influencing factors for overall survival (OS) of patients.Results:Among 19 patients, no one achieved complete remission, 4 patients (21.1%) achieved partial remission, 9 patients (47.4%) had stable disease. The objective response rate (ORR) and disease control rate (DCR) were 21.1% (4/19) and 68.4% (13/19), respectively. The ORR of patients with deficient mismatch repair (dMMR) was higher than that of patients with proficient mismatch repair (pMMR) [100.0% (2/2) vs. 11.8% (2/17), P < 0.05], and patients with programmed death receptor ligand 1 (PD-L1) combined positive score (CPS) ≥1 had a higher DCR than patients with PD-L1 CPS < 1 [100.0% (5/5) vs. 25.0% (1/4), P < 0.05]. The median follow-up time of 19 patients was 14.7 months (12.0-17.4 months), the median progression-free survival time and OS time were 2.8 months and 5.7 months (95% CI 2.4-8.9 months). Increased lactate dehydrogenase (LDH) was negatively correlated with OS ( χ2 = 10.262, P = 0.001). Multivariate Cox regression analysis showed that LDH was an independent influencing factor for the OS of patients (<250 U/L vs. ≥250 U/L: HR = 0.149, 95% CI 0.039-0.657, P = 0.005). The most common treatment-related adverse reactions were fatigue (52.6%, 10 cases), anemia (47.4%, 9 cases), thrombocytopenia (36.8%, 7 cases), rash (36.8%, 7 cases), and reactive capillary hemangioma (36.8%, 7 cases). Conclusions:Camrelizumab combined with apatinib as the second-line treatment for advanced gastric cancer have good efficacy and safety.

OBJECTIVETo explore an early stage repair method for soft tissue defect of limbs of modern firearm wound, and to improve treating result.

METHODSDefects of the hind limbs of dogs were repaired with skin, muscle and myocutaneous flaps.

RESULTSWounds healed within 2 weeks in the experimental group except one that healed in 3 weeks because of infection. Limb function was close to normal. The treatment result was better in the experimental group than the control.

CONCLUSIONSSkin, muscle and myocutaneous flaps can cover soft tissue defect at an early stage, prevent and reduce infection, promote the healing and recovery of combined injury, reduce the time of treatment and disability rate.

Animals ; Debridement ; Dogs ; Hindlimb ; injuries ; Microsurgery ; Soft Tissue Injuries ; surgery ; Wound Healing ; Wounds, Gunshot ; surgery