In the present study, a new compound named 17-(6-cinnamamido-hexylamino-)-17-demethoxygeldanamycin (CDG) was obtained by introducing the cinnamic acid (CA) group into the 17-site of geldanamycin (GDM). The anti-cancer effects of CDG in vitro and in vivo were evaluated. MTT assay was used to examine the inhibitory effect of CDG on the proliferation of MCF-7, HepG2, H460 and SW1990 cells. Immunofluorescent staining flow cytometry combined with Annexin V-FITC/PI staining were used to detect apoptotic cells. Transwell assay was used to analyze the effect of CDG on cell invasion and migration ability. Western blotting was used to detect the expression levels of RAF-1, EGFR, AKT, CDK4 and HER-2 of MCF-7, HepG2 and H460 cells. The toxicities of CDG and GDM were evaluated in mice. Using the subcutaneously transplanted MCF-7 xenograft in nude mice, inhibitory effect was evaluated in vivo. The results showed that CDG inhibited the proliferation of cancer cells (IC50: 13.6-67.4 microg.mL-1). After exposure to CDG for 48 h, most cells presented typical morphologic changes of apoptosis such as chromatin condensation or shrunken nucleus. The rates of apoptosis of MCF-7, HepG2, H460 and SW1990 cells incubated with 10 microg.mL-1 CDG were 23.16%, 27.55%, 22.21%, 20.47%, respectively. A dose-dependent reduction of migration of four cell lines was found after exposure to CDG. The decreased levels of RAF-1, EGFR, AKT, CDK4 and HER-2 showed that CDG possessed HSP90 inhibitory effect. The result of animal toxicity test on the mice suggested that CDG had lower toxicity than GDM. Meanwhile, CDG inhibited the growth of MCF-7 xenografts of athymic mice.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Benzoquinones ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase 4 ; metabolism ; Female ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; Humans ; Lactams, Macrocyclic ; chemical synthesis ; chemistry ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Proto-Oncogene Proteins A-raf ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

In recent years, the study of autophagy in spinal cord injury (SCI) gradually becomes the hot spot. However, the function of autophagy in the injured spinal cord is still controversial. In order to further understand the role of autophagy after SCI, we summarized the activation of autophagy, autophagic cell death, the relationship between autophagy and apoptosis, the function of autophagy in promoting the molecular metabolism and the role of autophagy after spinal cord injury. We concluded that the role of autophagy after SCI is a double-edged sword. Upregulating the level of autophagy appropriately can promote damaged proteins metabolism and inhibit apoptosis. However, excessive activation of antophagy may induce autophagic cell dealth. So we consider that the proper regulation of autophagy will be a new target in the treatment of SCI.
Animals ; Apoptosis ; Autophagy ; physiology ; Humans ; Spinal Cord Injuries ; etiology ; pathology

Recently, the D'Amico classification system is widely used for the risk stratification of prostate cancer (PCa) , although no consensus has been reached for the definition of high-risk PCa. This system defines high-risk PCa as a prostate-specific antigen (PSA) level > 20 ng/ml, a Gleason score of 8-10, or a clinical stage ≥ T2c. Because high-risk PCa is prone to recurrence and metastasis after treatment, a proper initial therapy plays a crucial role. Currently, radical prostatectomy and radiation therapy are considered to be two most important options for the initial treatment of high-risk PCa although it remains controversial which is better.
Humans ; Male ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Prostate-Specific Antigen ; blood ; Prostatectomy ; methods ; Prostatic Neoplasms ; blood ; pathology ; radiotherapy ; surgery ; Risk

Overlapping PCR technology was employed to splice IFN?and HSA genes in vitro. The spliced gene was inserted into Pichia pastoris secretory vector pPIC9K. The IFN?-HSA gene was designed for secretory expression under the control of promoter AOX1 and Mat a signal peptide in pPIC9K. The recombinant plasmid pPIC9K/IFN?-HSA was linearized by restriction enzyme SalI and transformed into Pichia pastoris KM71 by electroporation. The recombinant strains identified by G418 selection and confirmed by PCR analysis were induced by methanol to express fusion protein IFNp-HSA. SDS-PAGE and Western blot analysis of the fusion protein showed that the expressed fusion protein IFNp-HSA with an apparent 90kDa molecular weight had the antigenicity of HSA. The specific activity of culture supernatant was about 640IU/ml assayed by the standard amiviral activity test on WISH cells challenged with VSV virus.

OBJECTIVETo study the effects of ketamine combined with penehyclidine hydrochloride on the learning and memory abilities and the expression of synaptophysin in the hippocampus CA3 region in the brain of neonatal rats.

METHODSEighty seven-day-old Sprague-Dawly rats were randomly intraperitoneally injected with 50 mg/kg of ketamine (K group), 2 mg/kg of penehyclidine hydrochloride (P group), 50 mg/kg of ketamine plus 2 mg/kg penehyclidine hydrochloride (PK group) or normal saline (control group). The rats were trained and tested in a Morris water maze 14 days after administration. The immunhistochemical method was used to ascertain the expression of synaptophysin in the hippocampus CA3 region 24 hrs, 14 days and 28 days after administration.

RESULTSIn the Morris water maze training, the rats in the PK group performed worst, followed by the K group. The rats from the P and NS groups performed well. Compared with the NS group, the expression of synaptophysin in the K and the PK groups decreased significantly 24 hrs and 14 days after administration (p<0.05). The PK group had lower synaptophysin expression than the K group 24 hrs and 14 days after administration (p<0.05). Up to 28 days after administration, the synaptophysin expression increased in all of the four groups and there were no significant differences between groups.

CONCLUSIONSKetamine combined with penehyclidine hydrochloride may inhibit more significantly learning and memory abilities and the synaptophysin expression in the hippocampus CA3 region than ketamine alone in neonatal rats. Penehyclidine hydrochloride alone has no effect on learning and memory abilities and the synaptophysin expression. The synaptophysin expression may increase to a normal level by training and with increasing age.

Animals ; Animals, Newborn ; Cholinergic Antagonists ; pharmacology ; Drug Therapy, Combination ; Excitatory Amino Acid Antagonists ; pharmacology ; Hippocampus ; chemistry ; drug effects ; Ketamine ; pharmacology ; Maze Learning ; drug effects ; Memory ; drug effects ; Quinuclidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; physiology ; Synaptophysin ; analysis

Objective To compare the clinical efficacy of kidney transplantations from donors with acute kidney injury (AKI) and without AKI,and summarize the experience of evaluation and application.Methods The clinical data of 240 kidney transplantations from donation after citizen's death (DCD) performed in our hospital between November 2011 and March 2015 were retrospectively analyzed.The recipients were classified into AKI group (n =37) and non-AKI group (n =203) according to donors' renal function and urine output.Basic characteristics and evolution of the donors and recipients were compared between the two groups.Results The donor serum creatinine was significantly higher in the AKI group than that in the non-AKI group (P＜0.01).Most transplant recipients accepted ATG for immune induction therapy in the AKI group,while Basiliximab was given in the non-AKI group,which was significantly different (P＜0.01).Delayed graft function developed more frequently and longer in the AKI group than in the non-AKI group (P＜0.01).However,patient and graft survival rates did no differ between the AKI and non-AKI groups (P＞0.05).There was no significant difference in other indexes between the two groups (P＞0.05).Conclusion The transplants from donors with AKI showed higher incidence of delayed graft function but no effect on 1-year allograft and patient survival.This type of kidney transplantation is safe and effective.

PURPOSEThis study aims to explore the biomechanical mechanism of lower limb injuries to the driver by establishing a finite element (FE) simulation model of collisions.

METHODSFirst a minibus FE model was integrated with a seat belt system. Then it was used to rebuild two collisions together with the total human model for safety (THUMS) provided by Toyota Motor Corporation: a rear-end collision between a minibus and a truck and a head-on collision of a minibus to a rigid wall. The impact velocities of both collisions were set at 56 km/h. The vehicle dynamic response, vehicle deceleration, and dashboard intrusion in the two collisions were compared.

RESULTSIn the minibus rear-end truck collision, the peak values of the von Mises equivalent stress at the tibia and the femur were 133 MPa and 126 MPa respectively; while in the minibus head-on rigid wall collision, the data were 139 MPa and 99 MPa. Compared with the minibus head-on rigid wall collision, the vehicle deceleration was smaller and the dashboard intrusion was larger in the minibus rear-end truck collision.

CONCLUSIONThe results illustrate that a longer dashboard incursion distance corresponds to a higher von Mises equivalent stress at the femur. The simulation results are consistent with the driver's autopsy report on lower limbs injuries. These findings verify that FE simulation method is reliable and useful to analyze the mechanisms of lower limb injuries to the driver in minibus frontal collisions.

Accidents, Traffic ; Automobile Driving ; Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Lower Extremity ; injuries

OBJECTIVETo determine the main genotype of hepatitis B virus (HBV) in Xinjiang.

METHODS200 HBsAg positive serum specimens were detected from more than 2000 serum of Xinjiang inhabitants, and HBV S gene was detected by using nPCR amplifying, and compared with the standard S region HBV nucleotide sequences of genotypes A-H retrieved from GenBank, then analyzed and drawn the polygenetic tree by MEGA3 software.

RESULTGene in 127 (63.5%) serum specimens was detected from 200 samples. Among 127 serum specimens, 10 (7.8%) was genotype B, 58 (45.7%) was genotype C, and 59 (46.5%) was genotype D.

CONCLUSIONGenotype B, C and D have been found in Xinjiang.

Adolescent ; Adult ; Aged ; Child ; China ; Female ; Genotype ; Hepatitis B ; ethnology ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Rural Health ; Young Adult

OBJECTIVE: To measure the anatomic data of the proximal femur and to design an internal fixation instrument aiming at subtrochanteric fracture. METHODS: We measured the anatomic data of 56 pairs of the matching proximal femur specimens: the diameter of femoral head (HD), the axis length of femoral head (HAL), 135 degree femoral head-neck axis length (HNAL), 135 degree femoral head-neck axis upper length (HNAUL), 135 degree femoral head-neck axis underside length (HNADL), the anterior-posterior axis diameter of femoral neck (NAPD), the upper-underside diameter of femoral neck (NUUD), femoral neck-shaft angle (NFA), femoral shaft lateral cortex-greater trochanter angle (SLGA), the medial-lateral diameter of lesser trochanter level's femoral shaft (LSMLD), the anterior-posterior diameter of lesser trochanter level's femoral shaft (LSAPD), the medial-lateral diameter of 5 cm below lesser trochanter femoral shaft (5 cm MLD), and the anterior-posterior diameter of 5 cm below lesser trochanter femoral shaft (5 cm APD). Part of the data was analyzed and compared. RESULTS: HD was (46.69+/-3.73) mm, HAL was (39.22+/-4.17) mm, HNAL was (95.45+/-8.16) mm, HNAUL was (84.02+/-7.11) mm, HNADL was (99.95+/-9.34) mm, NAPD was (26.27+/-3.15) mm, NUUD was (32.24+/-3.31) mm, NFA was 126.21 degree+/-7.13 degree, SLGA was 16.38 degree+/-4.04 degree, LSMLD was (31.05+/-3.57) mm, LSAPD was (27.63+/-2.96) mm, 5 cm MLD was (26.36+/-3.22) mm, and 5 cm APD was (25.59+/-2.75) mm. NFA was positively correlated with SLGA (r=0.396, P=0.003). CONCLUSION It is necessary to design internal fixator to fit the anatomical feature of Chinese femur for the treatment of subtrochanteric fracture, and we should thoroughly consider the angle of the SLGA.
Anthropometry ; Cadaver ; Equipment Design ; Femur Head ; anatomy & histology ; Femur Neck ; anatomy & histology ; Fracture Fixation, Internal ; instrumentation ; Hip Fractures ; surgery ; Humans

BACKGROUND: Epithelial to mesenchymal transition (EMT) is a key process in determining distant metastasis and intra-hepatic dissemination of hepatocellular carcinoma (HCC). Follistatin (FST) family members are considered to be an attractive therapeutic targets and prognostic indicators in cancers. As a derivative of FST, Follistatin Like 5 (FSTL5) may play a similar role in HCC cells. This study aimed to investigate the expression and function of FSTL5 in HCC and its role in EMT. METHODS: FSTL5, E-cadherin and vimentin in HCC, and paracancerous tissues were detected by immunohistochemistry. Correlation of FSTL5 expression with overall survival was assessed. The proliferation and invasion of HCC cell lines SK-Hep1 and MHCC-LM3 were analyzed by cell counting kit-8 and Transwell assays. The expression of FSTL5, E-cadherin, and vimentin in HCC cells was examined by polymerase chain reaction and Western blot analysis. T-test was used to analyze the difference in proliferation and invasion ability between groups. The Spearman rank correlation test was used to detect the correlation between the expression of FSTL5 and E-cadherin or vimentin. RESULTS: The expression of FSTL5 in HCC was lower than that in paracancerous tissues (9.97% vs. 82.55%, χ = 340.15, P < 0.001). Patients with high FSTL5 expression had a better prognosis (χ = 8.22, P = 0.004) and smaller tumor diameter (χ = 45.52, P < 0.001), less lymph node metastasis (χ = 5.58, P = 0.02), earlier tumor node metastasis stage (χ = 11.29, P = 0.001), a reduced number of tumors (χ = 5.05, P = 0.02), lower alpha-fetoprotein value (χ = 24.36, P < 0.001), more probability of hepatitis carrying (χ = 40.9, P < 0.001), and better liver function grade (χ = 5.21, P = 0.02). Immunohistochemistry showed that FSTL5 expression in HCC tissues was positively correlated with E-cadherin expression (r = 0.38, P < 0.001) and negatively correlated with vimentin expression (r = -0.385, P < 0.001). Furthermore, over-expression of FSTL5 up-regulated the expression of E-cadherin and down-regulated the expression of vimentin in SK-Hep1 (negative control [NC] vs. FSTL5-interfering group [Lv-FSTL5]: E-cadherin [t = 45.03, P < 0.001], vimentin [t = 67, P < 0.001]) and MHCC-LM3 (NC vs. Lv-FSTL5: E-cadherin [t = 50, P < 0.001], vimentin [t = 72.75, P < 0.001]) cells at mRNA level. The same as protein level. In addition, the over-expression of FSTL5 inhibited the proliferation (NC vs. Lv-FSTL5: SK-Hep1, 3 d [t = 7.324, P = 0.018], 4 d [t = 6.23, P = 0.021], 5 d [t = 10.21, P = 0.003]; MHCC-LM3, 3 d [t = 4.32, P = 0.037], 4 d [t = 7.49, P = 0.012], 5 d [t = 9.3661, P = 0.009]) and invasion (NC vs. Lv-FSTL5: SK-Hep1, t = 21.57, P < 0.001; MHCC-LM3, t = 18.04, P < 0.001) of HCC cells. CONCLUSIONS Down-regulation of FSTL5 may contribute to EMT of HCC, and FSTL5 is a potential target in the treatment of HCC.