ObjectiveTo study the influence of anti-tuberculosis drugs on mitochondrial function in mice hepatocytes and to explore the mechanism of the anti-tuberculosis drugs induced liver injury.Methods A total of 150 mice were randomized into five groups:control group (C group),rifampin (RFP) group,isoniazid (INH) group,pyrazinamide (PZA) group and three antituberculosis drug combination group (MIX).The mice were administered intragastrically with 0.9 ％ NaC1 solution or RFP 135 mg · kg-1 · d-1 or INH 90 mg · kg-1 · d-1 or PZA 315 mg · kg-1 · d-1 or RFP+INH+ PZA (135±90+315) mg · kg-1 · d-1 once a day.Ten mice in each group were sacrificed at day 3,7 and 15 of administration,respectively.The following parameters in each group were monitored.the concentration of malondialdehyde (MDA),the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in mitochondrion of hepatocytes and the concentration of 8-hydroxydeoxyguanosine (8-OH-dG) in mitochondrial DNA (mtDNA).The data were analyzed by one-way ANOVA or rank sum test.Results Along with the prolonged medication duration,the concentrations of MDA all gradually increased in RFP group (Z=6.020,P=0.049),IN H group (Z=10.220,P=0.006) and MIX group (Z=7.460,P=0.024),whereas the activity of SOD significantly decreased in RFP group (F=6.751,P =0.011 ) and MIX groups (F=4.891,P =0.041 ) compared with control group and PZA group.Meanwhile,the activity of GSH-PX was significantly lower in RFP group compared to the other groups (F=32.445,P＜0.01).The changes of other parameters didn't show meaningful trend.The concentrations of 8-OH-dG in mtDNA also increased in all treated groups,and those were all significantly increased in RPF group (F=6.602,P＜0.01 ),PZA group (F=5.927,P＜0.01) and MIX groups (F=7.974,P＜0.01).Conclusions Antituberculosis drugs can induce higher MDA concentration in mitochondrion and higher 8-OH-dG concentration in mtDNA,while result in lower activities of SOD and GSH-PX.The liver damage tends to become more severe along with the prolonged medication duration.The combination of three antituberculosis drugs could aggravate the damage of mitochondrion in mice hepatocytes.

Objective To explore the relationship between the expression of LIGHT/HVEM in patients after allo-HSCT and the development of GVHD. Methods The expression of LIGHT and HVEM in T lymphocytes was detected by FACS Calibur. Results All patients achieved engraftment and hematopoiesis reconstitution, aGVHD occurred in 9 of 26 patients (34.6%) with grade Ⅲ-Ⅳ aGVHD in 3 cases. Seven cases developed cGVHD (26.9%). LIGHT was not expressed in T lymphocytes from healthy donors and patients without GVHD, while constitutive expression of HVEM was detected. When aGVHD occurred, the expression levels of LIGHT in T lymphocytes were significantly increased, while those of HVEM decreased. After GVHD was controlled, the expression levels of those co-stimulators went back to normal On the day 15 after transplantation, the expression of LIGHT in T lymphocytes of patients with aGVHD later was significantly higher, while that of HVEM lower than in those without aGVHD. The patients with aGVHD of grades Ⅲ-Ⅳ demonstrated higher LIGHT expression than in those with aGVHD of grades Ⅰ-Ⅱ. Conclusion The expression of LIGHT and HVEM might be involved in the development of GVHD after allo-HSCT and could be used as one of the useful indicators in predicting aGVHD.

BACKGROUND:The phenomenon of osteoinduction by biomaterials has been proven in animal experiments. OBJECTIVE:To investigate whether the ability of a biomaterial to initiate bone formation in ectopic implantation sites improves the performance of osteoinductive biomaterial as a scaffold for tissue-engineered bone. METHODS:We compared ectopic bone formation by combining autologous adipose-derived stromal cells with an osteoinductive and a nonosteoinductive biphasic calcium phosphate ceramic to create a tissue engineering construction in the muscle of dogs. Al implants were implanted in the back muscle of 10 adult dogs for 8 weeks and 12 weeks, including osteoinductive biphasic calcium phosphate ceramic+adipose-derived stromal cells (osteoinductive complex group), osteoinductive biphasic calcium phosphate ceramic (osteoinductive broup), nonosteoinductive biphasic calcium phosphate ceramic+adipose-derived stromal cells (nonosteoinductive complex group), and nonosteoinductive biphasic calcium phosphate ceramic (nonosteoinductive group). Micro-CT analysis and histomorphometry were performed to evaluate and quantify ectopic bone formation. RESULTS AND CONCLUSION:Ectopic bone formation was visible in the osteoinductive complex group and osteoinductive group, and the former group was superior to the latter one in quality of new bone (P<0.05). However, there was no ectopic bone formation in the other two groups. Micro-CT results were consistent with the histomorphological detection. These findings indicate that osteoinductive biphasic calcium phosphate ceramic, as a kind of bone tissue engineering scaffold material, has a better osteogenic capacity, while adipose-derived mesenchymal stem cells serve as seed cells to promote the ectopic bone formation.

Objective To introduce the clinical types of perforator branches of anterosuperior malleolus flap and explore its application.Methods Anterosuperior malleolus flap coupling with dorsal pedal flap was used for repairing the soft tissue defect of hands in 18 patients,in which anterosuperior malleolus flap-dorsal pedal single flap in 12 cases,anterosuperior malleolus flap-dorsal pedal bilobate flap in 4 cases,anterosuperior malleolus flap-dorsal pedal trilobate flap in 2 cases;Anterosuperior malleolus retrograde island (bone) flap was used in recovering pedal soft tissue in 22 patients,the flap pedicled from stem of anterior tibial artery in 16 cases,dorsal pedal flap-anterosuperior malleolus flap in 2 cases,the flap from perforate vessels without injuring the anterior main tibial artery in 2 cases,the bone flap combined with the distal of tibia in 2 cases.Results In the 18 cases of hands,17 cases survived,and 1 case of flap mild necrosis at the distal site took a second-phase skin-grafting to repair.Twenty cases of anterosuperior malleolus retrograde island (bone) flap survived,and the other 2 cases needed secondary skin-grafting to repair the necrosis edge of flaps because of venous limited.After a follow-up from 3 to 6 months,30 cases showed the satisfied postoperative outlook,with the good healing of the donor sites.Typing the 40 cases according to the location of perforator branches of the anterosuperior malleolus flap,20 cases locate in the medial of anterior tibial muscle,16 cases locate between the anterior tibial muscle and extensor hallucis longus,4 cases locate between extensor hallucis longus and extensor digitorum longus.Conclusion Knowing the clinical types of the perforator branches of anterosuperior malleolus flap is not only helpful for the accurate processes of operations、preventing cutaneous branches,but also improving the success rate of surgery.

Objective To investigate a detective methods of choledocholithiasis.Methods Using retrospective study methods, a logistic regression descriminant analysis of 16 factors related to choledocholithiasis was made and a relative discriminant model was constructed.Results Logistic regression analyses that had sex, history of jaundice or jaundice, the widest inner diameter of choledochus, AST,ALT and the history of cholecystectomy, cholecystolithiasis and pancreatitis included into discriminant model, gave the best predictive result. A test sample showed the discriminant model had a sensitivity of 89.4%, and a specificity of 80.0%.Conclusions Discriminant analysis of logistic regression with clinical data is helpful for diagnosis and treatment of choledocholithiasis.It can also increase the accuracy of the predicion of cholecystolithiasis and serve as a clinical guide.

Objective To evaluate Zeus robot-assisted laparoscopic cholecystectomy. Methods Forty patients were divided into two groups receiving respectively Zeus robot-assisted laparoscopic cholecystectomy (group A, 20 cases), and laparoscopic cholecystectomy (group B, 20 cases). A variety of clinical parameters were evaluated. Compared between these two groups. Results Camera clearing (1.1?1.0) times and time used for operation field adjustment in group A (2.2?0.7) min were significantly less than those in group B (4.5?1.5,7.5?1.2) min. Dissection actions(337?86)times and operative errors(10%) in group A were less than those in group B(389?94) times,25%. The operation time(104.9?20.5) min and setup time (29.5?9.8) min in group A were longer than those in group B (78.6?17.1) min,(12.6?2.5) min. The blood loss,and postoperative hospital stay were similar. There were no postoperative complications in either groups, and conversion to open surgery was done in one each patients. Conclusions Compared with laparoscopic technique, Zeus robotic surgical system offers greater ability of controlling operation field, precise and stable operative manipulations though it requires longer operation time.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Objective To explore the influence of mononuclear cells (MNC), CD34+ cells, CD3+ , CD3+ CD4+ , CD3+ CD8+ , CD4+ CD25+ T cells, CD3- CD16+ CD56+ natural killer cells (NKs), and dendritic cells (DCs) doses in graft on acute graft-versus-host disease (aGVHD) following HLA-identical sibling allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT).Methods Sixty-five patients receiving HLA-identical sibling allo-PBSCT were studied.The number of CD34+, CD3+, CD3+ CD4+, and CD3+ CD8+ T cells in the graft was counted by fluorescence-activated cell sorting (FACS).The number of CD4+ CD25+ T cells, CD3 CD16+ CD56+ NKs, and DCs in the graft was also measured by FACS in 31 patients among above-mentioned 65 patients.The doses of each kind of cells in the graft were calculated according to per kilogram of recipients body weight.The patients were divided into high or low dose groups according to whether or not more than or equal to median of MNC, CD34+, CD3+, CD3+ CD4+, CD3+CD8+, CD4+ CD25+, CD3 CD16+ CD56+ or DC cell doses, respectively.Acute GVHD was analyzed between two groups.Results The frequency of the cumulative incidence of grade Ⅱ～Ⅳ aGVHD was increased in CD3+ CD4+ and CD3+ CD8+ T cells high dose groups as compared with correspondingly low dose groups, but the difference had no statistically significant difference (P = 0.089 and 0.098, respectively).Recipients in CD4 + CD25 + T cells high dose group had significantly reduced cumulative incidence of grade Ⅲ～Ⅳ aGVHD as compared with those in correspondingly low dose group (P< 0.05).The cumulative incidence of total aGVHD was significantly higher in DC1 high dose group than in correspondingly low dose group (P<0.05) and the cumulative incidence of grade Ⅱ～Ⅳ aGVHD was also higher in high dose group, but the difference had no statistically significant difference (P = 0.069).There was no significant difference in cumulative incidence of total and grade Ⅱ～Ⅳ aGVHD between MNC, CD34+ , CD3+, NK or DC2 high dose groups and correspondingly low dose groups (P>0.05, respectively).Conclusion Recipients in DC1 high dose group have significantly increased cumulative incidence of total aGVHD, but those in CD4+ CD25+ T cells high dose group have significantly reduced cumulative incidence of grade Ⅲ～Ⅳ aGVHD.

OBJECTIVETo assess clinical therapeutic effect and safety of acupuncture combined with fuxiting on depression.

METHODSFifty-three cases of depression were divided into an observation group (n = 30) treated by acupuncture combined with fuxiting and a control group treated by fuxiting. Their clinical therapeutic effects were assessed by HAMD, HAMA and CGI, and adverse effects by TESS.

RESULTSAfter treatment of 6 weeks, the total effective rate was 80.0% in the observation group and 69.6% in the control group with no significant difference between the two groups (P > 0.05). There were significant differences in scores of HAMD and HAMA before and after treatment in the two groups (P < 0.01), with no significant difference between the two groups (P > 0.05). The adverse effect in the observation group was less and milder than that in the control group.

CONCLUSIONAcupuncture combined fuxiting has good therapeutic effect on depression with less and mild adverse effects.

OBJECTIVETo evaluate the value of a back propogation (BP) network on prediction of birth defect and to give clues on its prevention.

METHODSData of birth defect in Shenyang from 1995 to 2005 were used as a training set to predict the prevalence rate of birth defect. Neural network tools box of Software MATLAB 6.5 was used to train and simulate BP Artificial Neural Network.

RESULTSWhen using data of the year 1995-2003 to predict the prevalence rate of birth defect in 2004-2005, the results showed that: the fitting average error of prevalence rate was 1.34%, RNL was 0.9874, and the prediction of average error was 1.78%. Using data of the year 1995-2005 to predict the prevalence rate of birth defect in 2006-2007, the results showed that: the fitting average error was 0.33%, RNL was 0.9954, the prevalence rates of birth defect in 2006-2007 were 11.00% and 11.29%.

CONCLUSIONCompared to the conventional statistics method, BP not only showed better prediction precision, but had no limit to the type or distribution of relevant data, thus providing a powerful method in epidemiological prediction.