AIM:To investigate the histone modification changes of topoisomerase Ⅱα( TOPOⅡα) promoter regulatory factor Sp1 in the patients with chronic benzene poisoning .METHODS:The bone marrow samples were collect-ed from 25 chronic benzene poisoning cases and 25 controls.The chromatin immunoprecipitation assay was carried out to study the possible mechanism of TOPOⅡαpromoter regulatory factor Sp 1 expression changes .The mRNA expression of Sp1 was detected by RT-PCR.RESULTS:Compared with the controls , the histone H4 acetylation and histone H3 acetyla-tion of Sp1 in the chronic benzene poisoning patients significantly decreased (P<0.01), and histone H3K9 methylation level of Sp1 increased (P<0.01), but the histone H3K4 methylation level of SP1 was not obviously changed (P>0.05). The mRNA expression of Sp1 in the chronic benzene poisoning patients was significantly lower than that in the controls (P<0.05).CONCLUSION:In chronic benzene poisoning patients , the histone acetylation and methylation modification changes of TOPOⅡαpromoter regulatory factor Sp 1 accompanied with the changes of mRNA level are observed .Histone H4 and H3 acetylation and H3K9 methylation modification of Sp1 may play an important role in the benzene ’s hematopoiet-ic toxicities.

HSP90, which is the biomarker of cell stress and endogenous protective protein, functions as a molecular chaperone. Many client proteins of HSP90, including EGFR, Met, Raf-1, IKK and p53, play important roles in the occurrence and development of tumor. Binding of HSP90 inhibitors triggers the deactivation of HSP90, resulting in client protein degradation, and hence inhibits the tumor growth by blocking multiple targets involved in signaling of tumor proliferation. This review summarizes recent development of small molecule inhibitors bound to N-terminal of HSP90.
Antineoplastic Agents ; chemistry ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; Humans ; Neoplasms ; Signal Transduction

Objective To compare the kinematics of the knee joint of normal Chinese people and people after fixed-bearing posterior stabilized total knee arthroplasty while doing weight-bearing deep knee-bending using fluoroscopy analysis.Methods From June to December 2010,ten volunteers and ten patients with fixed-bearing posterior stabilized total knee arthroplasty (TKA) were required to perform weight-bearing deep knee-bending activity under surveillance of roentgenization,motion between femur and tibia was analyzed with interval of 15° according to two-to three-dimensional (2D-3D) registration technique.Results During weight-bearing deep knee-bending,the average weight-bearing maximal flexion was 136° in the normal group,which was significantly higher than the 125° in the TKA group.All 10 normal knees present posterior translation of femoral condyle during deep knee-bending,posterior translation of the lateral condyle was greater than medial condyle,thereby creating a medial pivot type of axial rotational pattern in which the tibia internally rotates relative to the femur as flexion increased.The average amount of posterior femoral translation of the medial condyle was 7.3±1.2 mm,whereas the lateral condyle translated posteriorly 19.3±3.1 mm.All knees experienced tibia rotated internally during progressive flexion,and the average amount of axial rotation for the ten subjects from 0° to 135° was 23.8±3.4°.From extension to maximal flexion,the average amount of posterior translation of medial condyle was 1.4±0.6 rmm,whereas the lateral condyle translated 6.4±1.7 mm in the posterior direction in the fixed-bearing posterior-stabilized TKA.The average amount of tibial internal rotation was 8.5°±3.4°.Conclusion In normal Chinese people,during knee flexion activities the lateral condyle experiences significantly more amount of posterior translation than the medial condyle,leading to the tibia present medial pivot internal rotation relative to the femur,and the PFC-Sigrna fixed-bearing posterior stabilized designs has the similar kinematics with normal knee,but the posterior condylar translation and tibial axial rotation are much less than the normal.

Objective To explore clinic value of nuclear myocardiac perfusion imaging (MPI) in perioperative coronary risk assessment in patients with heart diseases planning arthroplasty,and compare the conformity and effect on surgery planning between MPI and coronary computed tomography angiogram (CTA).Methods Prospectively collect clinical data of 228 patients with heart diseases planning joint arthroplasty,all patients had MPI and CTA test to assess perioperative coronary risk.The conformity and effect on surgery planning between the MPI and CTA was analyzed,and the occurrence of cardio-vascular complication was recorded.Results MPI showed that 215 patients had no myocardial ischemia except for 13.CTA showed that 113 cases had no coronary stenosis,51 cases had light coronary stenosis,39 cases had middle coronary stenosis and 12 cases had severe coronary stenosis in patients with no myocardial ischemia.CTA also found that 3 cases had no coronary stenosis,4 cases had light coronary stenosis,3 cases had middle coronary stenosis and 3 cases had severe coronary stenosis in patients with myocardial ischemia.The conformity between MPI and CTA was low.222 patients had completed operation except for 6 cases.MPI rather than CTA had conspicuous effect on surgery planning.There was no angina,myocardial infarction or cardiac death associated with myocardial ischemia.The postoperative cardio-vascular complications included 6 cases of heart failure,4 cases of atrial fibrillation and 1 case of cerebral infarction.Conclusion MPI is a direct index to judge blood supply of the myocardium,which can exactly predict the risk of perioperative myocardial ischemia and the prognosis.It's helpful for preoperative planning,reducing risk of perioperative complications through screening and excluding high-risk patients.

Humans ; Tranexamic Acid ; Atrial Fibrillation ; Antifibrinolytic Agents ; Arthroplasty ; Blood Loss, Surgical ; Arthroplasty, Replacement, Hip

This study is to observe the effect of N-(3-phenylallylidene)-6-fluoro-1, 8-(2, 1-propoxy)-7-(4-methylpiperazin-1-yl)-quinolin-4(1H)-one-3-carbonyl hyarazine (FQ16) on apoptosis of hepatocarcinoma SMMC-7721 cells in vitro. With different concentrations of FQ16 at different times used to treat SMMC-7721 cells in vitro, the proliferation of the cells and the inhibition effect of FQ16 on the cell proliferation were examined by MTT assay. Cell apoptosis was determined by Hoechst 33258/PI fluorescence staining, TUNEL and agarose gel electrophoresis method. The effect of FQ16 on topoisomerase II activity was measured by agarose gel electrophoresis using Plasmid pBR322 DNA as the substrate. Mitochondrial membrane potential (MMP, delta psi m) was measured by high content screening image system. The reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression changes of Bcl-2 mRNA and Bax mRNA. The caspase-9, caspase-8, caspase-3, p53, Bcl-2 and Bax protein expressions were detected by Western blotting analysis. The results showed that the cell proliferation was inhibited by FQ16 at 0.625 - 10 micromol L(-1) in a time-dose dependent manner. Treatment of SMMC-7721 cells with different concentrations of FQ16 for 24 h increased the percentage of the apoptosis cells obviously (P<0.05), the typical ladder DNA in apoptotic cells and a concomitant dissipation of the mitochondrial membrane potential. Compared with control group, FQ16 influenced obviously DNA topoisomerase II activity, stimulated DNA cleavage and inhibited DNA reunion mediated by topoisomerase II. In addition, FQ16 (3 - 7.39 micromol L(-1)) increased mRNA expression of Bax and protein expression of p53, Bax, caspase-9, caspase-3, separately, and induced cytosolic accumulation of activities caspase-9 and caspase-3, whereas the mRNA and protein expression of Bcl-2 decreased with no change of caspase-8. Therefore it can be concluded that the effects of inhibited topoisomerase II and mitochondrial-dependent pathways were involved in FQ16 induction of apoptosis of SMMC-7721 cells.
Antineoplastic Agents ; administration & dosage ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Topoisomerases, Type II ; metabolism ; Dose-Response Relationship, Drug ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Membrane Potential, Mitochondrial ; drug effects ; Molecular Structure ; Piperazines ; administration & dosage ; chemical synthesis ; chemistry ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; bcl-2-Associated X Protein ; metabolism

Objective To compare faster rehabilitation of different surgical approaches in total hip arthroplasty (THA)patients using a direct anterior approach or posterolateral approach.Methods Sixty-eight patients (35 in direct anterior THA and 33 in posterolateral THA) from September 2015 to March 2016 were recruited in the present study.The incision length,operation duration,intraoperative blood loss,serum creatinekinase (CK),C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),interleukin-6 (IL-6) and visual analogue scale (VAS) pain score were compared between two groups respectively.The Harris hip score,the University of California at Los Angeles (UCLA) pain,walking,and activity scores,postoperative hospital length of stays,gait analysis,component placement and complications were also compared.Results The mean incision length,operation duration,intraoperative blood loss were 11.23±0.97 cm,73.77±9.20 min and 157.15±35.83 ml in the DAA group respectively,while those in PLA group were 15.16±1.12 cm,64.12±13.31 min and 126.97±45.45 ml.The mean incision length of the DAA group were significantly less than that of the PLA group.The DAA group underwent longer operation time that associated with more intraoperative blood loss.The levels of CK and inflammation markers were increased in the PLA group compared with those in the DAA group.The VAS pain score was less in the DAA group than the PLA group within postoperative 72 hours.Functional recovery in the DAA group was faster than that in the PLA group based on the Harris hip score,UCLA scores,and gait analysis up to 3 months.There was no difference in these outcomes between the groups beyond 6 months.The average postoperative hospital length of stay was 2.95±0.24 days and 3.35±0.51 days for the DAA group and PLA group respectively.The patients in DAA group required less postoperative hospital length of stays.The angle of acetabular cup anteversion in the DAA group (16.4°±2.3°) was lesser than that in the PLA group (20.4°±2.8°).There was one intraoperative nondisplaced greater trochanter fracture in the DAA group,whereas no intraoperative complications were occurred in the PLA group.Conclusion The present study showed that using direct anterior approach in THA provided significant benefits for patients in terms of muscle damage,VAS score,hospital length of stays and functional recovery in the early stage postoperatively compared to using posterolateral approach.

Objective To observe the changes of potassium ion (K+), lactic acid (Lac) and glucose (Glu) in swine with traumatic hemorrhagic shock (THS) inside the dry-heat environment and to explore its possible mechanism. Methods A total of 40 local Landrace piglets were randomly(random number) divided equally into 4 groups: the normal temperature sham operation group (NS), the normal temperature traumatic hemorrhagic shock group (NTHS), the dry-heat sham operation group (DS group) and the dry-heat traumatic hemorrhagic shock group (DTHS). The experiment was carried out in the artifi cia climate cabin simulated the special environment of northwest of China. After exposed to their respective environment[dry-heat environment: (40.5±0.5), plus(10±2)% humidity; normal temperature environment: (25±0.5), plus(35±5)% humidity] for 3 h. Laparotomy were performed in swine of all groups, and then splenectomy and partial hepatectomy were performed only in NTHS and DTHS. The process of exsanguination from the external iliac artery was established to make the MAP reaching to 40-50 mmHg, and thus the traumatic hemorrhagic shock model of swine was successfully made. Blood samples were collected from external iliac artery at different intervals including the time just after exposure for 3 h and the successful establishment of traumatic hemorrhagic shock model (0 h) and then every 30 min after 0 h, serum levels of K+, Lac and Glu were detected. The features of varied serum K+, Lac and Glu were observed in each group. All data were statistically analyzed using One-way ANOVA and Pearson correlation analysis. Results After exposed , the level of serum K+inside the dry-heat environment was higher than that of swine inside the normal temperature group ( P<0.01), however the Glu level was lower in the swine inside dry-heat environment than that of swine inside the normal temperature ( P<0.01).The level of serum K+and Lac of DTHS group were rapidly increased from the establishment of the model to the death in about 3 h, while those of NTHS group were increased slowly. The level of K+and Lac were positively correlated in the two groups amd the correlation coeffi cient were rDTHS=0.927 (P<0.01) and rNTHS=0.539 (P<0.01),respectively. The level of Glu was progressively decrease in DTHS group, while in NTHS group, it was not noticeable. The level of K+and Glu were negatively correlated in the two group, the correlation coeffi cient were rDTHS=-0.804 (P<0.01) and rNTHS=0.420 (P<0.01),respectively. Conclusions The changes of serum K+, Lac and Glu occurred sooner and more obvious in traumatic hemorrhagic shock models inside dry heat environment (DTHS) group than those in NTHS group. The level of serum K+positively correlated with Lac, however, negatively correlated with Glu, which suggested that hyperkalemia and acidosis should be paid more attention to the treatment of traumatic hemorrhagic shock inside the dry heat environment, and the hypoglycemia should be treated at the same time.

Objective:To analyze the clinical efficacy of internal fixation and prosthesis revision in the treatment of periprosthesis fracture after total knee arthroplasty.Methods:A total of 35 patients (35 knees) with periprosthetic fractures after total knee arthroplasty were retrospectively analyzed from January 2008 to January 2022 in the Department of Orthopaedics, West China Hospital, Sichuan University, including 13 males and 22 females, aged 71.4±4.1 years (range, 62-81 years). Left knee 19 cases, right knee 16 cases. There were 20 cases of Rorabeck type II and 15 cases of Rorabeck type III. The initial replacement was performed using a fixed platform post-stabilized knee prosthesis, which was fixed with bone cement. Patients with Rorabeck type II were treated with internal fixation alone (internal fixation group) and patients with Rorabeck type III underwent revision with replacement prosthesis (revision group). The Hospital for Special Surgery (HSS) score, range of motion (ROM) of knee joint, alignment of lower extremity and incidence of postoperative complications were compared between the two groups.Results:All patients successfully completed the operation and were followed up for 5.2±3.6 years (range, 1-12 years). Intraoperative blood loss was 680±102 ml (range, 420-1100 ml). The operative time in the internal fixation group was 105±17 min, which was less than 140±21 min in the revision group, and the difference was statistically significant ( t=-5.450, P<0.001). There was no complication of nerve or blood vessel injury during the operation. Five cases in the internal fixation group had unsatisfactory lower extremity force lines (>3° deviation from normal) after surgery, and all lower extremity force lines in the revision group were satisfied, and the difference in the satisfaction rate of lower extremity force lines between the two groups was not statistically significant ( P=0.057). The fracture healing time, knee ROM and HSS scores at the last follow-up were 5.1±1.3 months, 86°±5° and 84±5 in the internal fixation group and 4.8±1.5 months, 83°±6° and 82±4 in the revision group. One case in the revision group was diagnosed postoperatively with periprosthetic infection with pathogen culture suggestive of Candida albicans, recurrent anterior knee sinus tracts and patellar ectasia, which progressed to osteomyelitis, and mid-thigh amputation was performed 1 year after revision. Conclusion:The stability of prosthesis is an important reference for the treatment of periprosthetic fractures after total knee arthroplasty. Strong internal fixation in patients with unloosened prosthesis and revision with replacement of prosthesis in patients with loose prosthesis can achieve good knee joint function.

As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development. Fragments in a small library, with lower molecular mass and high "ligand efficiency", are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods. Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good "drug-like" lead and candidate compounds. In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.
Computer-Aided Design ; Crystallography, X-Ray ; Drug Discovery ; methods ; Ligands ; Magnetic Resonance Spectroscopy ; Peptide Fragments ; chemical synthesis ; chemistry ; Protein Conformation ; Small Molecule Libraries ; Surface Plasmon Resonance