Heat shock protein 70 (HSP70) family is one ofthe most conserved proteinin evolutionand plays critical,role in proteostasis.HSP70 is becoming an interesting target for multiple diseases such as cancer and Alzheimer's disease.There are many drugs targeted to HSP70 in preclinical study.In this review,the classification,the structure,the function of HSP70,and the drugs of the HSP70 family are reviewed.

Objective To investigate the effects of early physiotherapy in combination with atorvastatin on the levels of serum brain-derived neurotrophic factor (BDNF) and neurological function in patients with acute ischemic stroke.Methods Fifty patients with acute ischemic stroke were randomly divided into either an atorvastatin group (monotherapy group,n =25) or a early physiotherapy + atorvastatin group (combination treatment group,n =25).All patients received the prescribed drugs according to the diagnosis and treatment guidelines for ischemic stroke.The monotherapy group added atorvastatin calcium (20 mg,1 tablet every night orally).On the basis of the monotherapy group,the combination treatment group also conducted early physical therapy.At 2 and 6 weeks before and after treatment,a double-antboody sandwich enzyme-linked immunosorbent assay was used to detect the serum BDNF levels.The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the degree of neurological deficit.Barthel index (BI) was used to evaluate the activities of daily living.The modified Rankin scale (mRS) was used to assess the degree of disability.Results There was no significant difference in demographics and baseline data between the monotherapy group and the combination treatment group.The scores of NIHSS,BI,and mRS in both groups after treatment were significantly better than those before treatment (all P ＜ 0.001).There were no difference in the scores of NIHSS,BI and mRS at 2 weeks before and after treatment,but at 6 weeks after treatment,the scores of NIHSS (2.40 ± 1.38 vs.3.36 ± 1.73; P =0.035) and mRS (1.40 ± 0.87 vs.1.96 ±0.94; P =0.047) of the combination treatment group were significantly lower than those of the monotherapy group,and the BI scores (92.60 ±7.50 vs.85.20 ± 11.68; P=0.011) were significantly higher than those of the monotherapy group.After treatment,the serum BDNF levels were increased significantly in both groups.There were significant differences among all the time points (all P＜0.001).At 2 weeks after treatment,the serum BDNF levels (3.07 ±0.93 ng/ml vs.2.45 ±0.76 ng/ml; t =2.559,P =0.014) and at 6 weeks after treatment,those (2.90 ± 0.93 ng/ml vs.2.31 ± 0.77 ng/ml; t =2.433,P =0.019) in the combination treatment group were significantly higher than those in the monotherapy group.Spearman correlation analysis showed that the serum BDNF levels were significantly negatively correlated with the scores of NIHSS (r =-0.738,P ＜ 0.001) and mRS (r =-0.654,P ＜ 0.001),but they were significantly positively correlated with the BI scores (r =0.716,P ＜ 0.001).No serious adverse reaction occurred in both groups.Conclusions Early physiotherapy in combination with atorvastatin for the treatment of acute ischemic stroke can more effectively promote the recovery of neurological function,and its mechanism may be associated with the increased serum BDNF levels.

Objective:To investigate the protective effect of Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced immunological liver injuries, and explore the relevant mechanisms of action. Methods: A total of 40 female C57BL/6 mice were randomly divided into four groups:control group,EGCG group,TP group and TP+EGCG group. The ALT levels in serum was examined by Reitman Frankel method. The activity of hepatic MDA,SOD and GSH was examined by spectrophotometry. HE staining was used to observed the changes of the hepatic histopathology. The hepatic IL-17,IL-6 levels was examined by ELISA and the expression of hepatic TLR4 protein was examined by Western blot. Results:The results showed that serum alanine aminotransaminase ( ALT) levels of TP group were obviously elevated (P<0. 005,vs normal control group) and serum ALT levels were obviously reduced in EGCG treatment group(P<0. 005,vs normal TP group). There were no significantly differences between EGCG group and control group (P>0. 05). Meanwhile,EGCG could ameliorate hepatic pathological damage. Furthermore,in TP group,the activity of malondialdehyde ( MDA) ,the expression of Toll-like receptor 4 (TLR4) protein and the contentration of hepatic interleukin (IL)-17,IL-6 were higher than normal control group ( P<0. 005 ) . On the contrary, the activity of superoxide dismutase ( SOD ) and restored glutathione ( GSH ) were significantly lower than normal control group ( SOD, P<0. 05;GSH, P<0. 005 ) . In EGCG treatment group, the expression of TLR4 protein and the concentration of MDA,hepatic IL-17 and IL-6 were lower than TP group ( TLR4,P<0. 05;MDA,P<0. 005;IL-17,P<0. 005;IL-6,P<0. 005). On the contrary,SOD and GSH were significantly higher than TP group (SOD,P<0. 05;GSH,P<0. 005). Conclusion:This study suggests that EGCG possesses hepatoprotective effect against TP-induced immunological liver injury through its anti-inflammatory and anti-oxidant actions.

Objective:To develop a new cocrystal form to improve bioavailability and druggability of curcumin. Methods:Solvent crystallization was used to prepare curcumin-lysine cocrystal, and two crystal forms ( a and b) were obtained. The two cocrystal forms were characterized by elemental analysis, differential scanning calorimetry and X-ray diffraction. The dissolution profiles of the two crystal forms were detected and compared with that of curcumin. Results:Curcumin combined with lysine at a stoichiometry of 1: 1 to form the cocrystal with much better solubility than curcumin. Conclusion: Curcumin-lysine cocrystal has ideal druggability, which means the cocrystal can be a new chemical entity used for subsequent development.

Purpose:To explore effects of dexamethasone and vincristine on apoptosis and activation of NF ?B of HL60 n cells induced by cytosine arabinoside (Ara C). Methods:Apoptosis induced by Ara C in HL60 n cells was analysed by Tunel and DNA electrophoresis. The DNA binding activation of NF ?B of HL60 n cells was determined by electrophoretic mobility shift assay(EMSA).Results:The apoptosis and activation of NF ?B of HL60 n cells could be induced by Ara C. Dexamethasone 1?mol/L and vincristine 0.1?mol/L increased significantly the apoptosis induced by Ara C (increased by 39.1% and 59.2%, P

Objective To evaluate the urodynamic and functional characteristics of 26 patients who had underwent orthotopic contient globular ileal neobladder. Methods The clinical date of 26patients who underwent radical cystectomy were reviewed. The neobladder pressure, capacity, urethral pressure and urinary flow rate were collected at 3-12 months after operation. Results The neobladders average pressure was less than 15 cm H2O when the volume was 400 ml. The pressure was 22.4 cm H2O at 100% capacity. The mean pressure of contractions was less than 40 cm H2O. The mean filling pressure after operation was relative stable while the difference between 3 months and 6 months was statistically significant. The difference between 6 and 9 and 12 month showed no statistical significance. The mean post-void residual was 42 ml. A mean voiding flow rate of 19. 6 ml/s could be obtained by Valsalva. Conclusion The neobladder not only could offer adequate capacity at low pressures but also could give a satisfied continent.

Objective To introduce the method of reconstructing posterolateral complex injury of the knee with the autogenous middle 1/3 of biceps femoris tendon and gracilis and evaluate its short-term outcome. Methods There were 21 cases of posterolateral complex injury of the knee reconstructed with the middle 1/3 of biceps femoris tendon and gracilis from January 2003 to December 2006. There were 13males and 1 female at age range of 18-49 years ( mean 34.3 years). The reconstructed ligaments included popliteal tendon, lateral collateral ligament and poplitrofibular ligament. An autogenous folded gracilis tendon was extracted and placed through trastibial bony tunnel from anterolateral to the posterior condylar of the tibia to reconstruct the popliteal tendon. An autogenous folded middle 1/3 of biceps femoris tendon was fixed in the isometric bony tunnel of the femoral lateral condyle. The anterior half was used to reconstruct the lateral collateral ligament, and the posterior half to reconstruct the poplitrofibular ligament. The posterolateral stability of the knee was evaluated mainly through examination varus instability of knee and external rotation range of leg. Results All cases were followed up for average 26 months (6-24months). Lysholm score of the knee was (43 ± 2) points preoperatively and (90 ± 3 ) points half year after operation, with significant improvement. Conclusions PCL injury may result in functional deficiency of the injured extremity. While the autogenous middle 1/3 of biceps femoris tendon and gracilis can yield a stable knee with good function, mini-trauma and satisfactory clinical results in reconstructing the posterolateral complex of the knee joint.

Objective To evaluate the clinical application of female orthotopic ileal neobladder.Methods Modified radical cysteetomy plus orthotopic ileal neobladder was performed on 19 female pa-tients with bladder cancer from June 1999 to January 2008.The mean age of the patients was 52(45-66) years,mean course of disease was 4.4 months (16 days-1.9 years).Of all the patients,there were 10 cases with grade 1,7 cases with grade 2 and 2 cases grade 3.According to the UICC stage system,5 patients were T1 stage,12 T2 and 2 T3a.All the patients received modified radical cystecto-my without resection of uterus and anterior vagina,meanwhile the nerves around urethra were protec-ted.0.8-1.2 cm proximal end of the urethra was excised and 30 cm distal ileum was used for the re-construction of the neobladder.Results Sixteen cases were followed up for 6-102 months,mean 71 months.Fifteen patients survived without disease recurrence,1 patient died of myocardial infarc-tion 17 months postoperation.The daytime and night continent rate was 100$,93% at 9 months postoperative.The average voiding volume of the 15 patients was 519.0 ml.The average residual vol-ume was 29.2 ml,and Qmax was 18.6 ml/s.The average filling and voiding pressure was 16.7 cm H2O and 53.0 cm H2O.Intravenous urography showed slight hydronephrosis in 1 case.Conclusion Female orthotopic ileal neobladder could be a good choice because of the continence,fewer complica-tions,lower pressure and enough bladder capacity.

Objective To study the effect of positive lymph node number on the survival of patients with esophageal carcinoma. Methods From July 1995 to July 2005, a total of 11,447 resected lymph nodes were obtained from 1140 patients who underwent curative resection of the primary tumor with systematic lymphadenectomy at Shanxi cancer hospital. The survivals were analysed by life tables and Kaplan-Meier methods, the related factors of lymph node metastasis were assessed by Chi-square test. Results The number of positive lymph nodes was negatively related to survival rates of esophageal carcinoma. According to the number of lymph nodes resected (≥8 nodes versus <8 nodes), there was significant difference in metastatic lymph node ratio. Conclusion The number of positive lymph node can reflect the prognosis of patients better. The authors suggest that the modification of the tumor-lymphnode-metastasis (TNM) staging classification (TNM) to include the number of positive lymph nodes in the N1 category.

Objective To explore the expression, correlation with clinicopathologic parameters, and clinical significance of MIS18 binding protein 1 (MIS18BP1) in bladder cancer. Methods TCGA and GEO databases were used to analyze the mRNA expression of MIS18BP1 in tumors and controls, and the results were verified via qRT-PCR. UALCAN online database was utilized in the analysis of the expression of MIS18BP1 and its correlation with clinicopathological parameters and the degree of immune cell infiltration. Immunohistochemistry was employed to analyze the expression of MIS18BP1 in bladder cancer and its relationship with clinicopathological features. The ROC curve was applied to evaluate the diagnostic value of MIS18BP1 mRNA in bladder cancer. Results Bioinformatics analysis and qRT-PCR results revealed the increased expression of MIS18BP1 mRNA in bladder cancer compared with that in the control group (P<0.05). Immunohistochemistry unveiled the significantly high positive rate of MIS18BP1 protein in bladder cancer (P<0.05) and its correlation with the clinical stage of tumors, depth of invasion, and lymph node metastasis (P<0.05). The immune infiltration analysis showed the association of MIS18BP1 with immune cell infiltration in bladder cancer. Conclusion The increased expression level of MIS18BP1 gene and protein in bladder cancer may regulate the development of bladder cancer by influencing immune cell infiltration.