The study was aimed to assess the impact of Brucea javanica oil emulsion(BJOE)on the responsiveness of programmed death receptor-1(PD-1)monoclonal antibody to lung adenocarcinoma in mice.The experimental approach involved subcutaneously inoculating Lewis's lung adenocarcinoma(LLC)cells into C57BL/6 mice,which were then divided into four groups:model group,25 ml·kg-1 BJOE group,10 mg·kg-1 PD-1 group,and combination group(25 ml·kg-1 BJOE and 10 mg·kg-1 PD-1).Tumor volume,mass,and inhibition rate were evaluated;the apoptosis within tumor tissue was detected by TUNEL staining;CD4+and CD8+T cell proportions within tumor tissues were analyzed by flow cytometry;the levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and granzyme B in tumor tissue were measured by enzyme-linked immunosorbent assay(ELISA).Additionally,LLC cells were categorized into a control group and three BJOE treatment groups(10,30,50 μl·ml-1),and programmed death ligand 1(PD-L1)expression in tumor tissues and LLC cells were assessed by Western blotting.Data showed that as compared with the model group,PD-1 monoclonal antibody alone did not significantly alter tumor volume,tumor mass,CD4+and CD8+T cell proportions,cytokine levels(IFN-γ,TNF-α,Granzyme B),or apoptosis in lung cancer-bearing mice.However,BJOE treatment reduced tumor volume and mass,enhanced CD4+and CD8+T cell proportions,increased cytokine levels,and augmented apoptosis(all P<0.05).Furthermore,the combination therapy of BJOE and PD-1 monoclonal antibody yielded significantly greater reductions in tumor volume and mass,with heightened CD4+and CD8+T cell proportions,cytokine levels,and apoptosis compared to either treatment alone(all P<0.05).Both BJOE treatment and the combination therapy significantly upregulated PD-L1 protein expression in tumor tissues compared to the model or PD-1 monoclonal antibody groups(P<0.05).Similarly,BJOE treatment at all tested concentrations significantly increased PD-L1 protein expression in LLC cells as compared to the control group(P<0.05).In conclusion,BJOE could upregulate PD-L1 expression in LLC cells and enhance the sensitivity of lung adenocarcinoma-bearing mice to PD-1 monoclonal antibodies.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

To investigate whether there is mutation in DC-SIGN promoter region in patients with chronic hepatitis B (CHB) and healthy persons previously infected with hepatitis B virus (HBV) and to explore the relationship between the mutation in dendritic cell-specific intercellular adhension molecule-3-grabbing nonintegrin (DC-SIGN) promoter region and HBV.Methods The studied population was composed of two cohorts:47 CHB patients and 20 healthy persons previously infected with HBV.The mutation in DC-SIGN promoter region was detected with PCR,single-stranded conformational polymorphism and heteroduplex analysis,cloning,sequencing and aligning the published DC-SIGN promoter sequence.Results The characteristic mutation within DCSIGN promoter region in HBV infected individuals was observed.In the DC-SIGN promoter region,4 hot spot mutations located in positions - 139,- 142,- 222,and - 336 were observed in the CHB patients,but only 1 spot mutation located in position - 139 was observed in the healthy persons previously infected with HBV.The -336C which was absent in the healthy persons previously infected with HBV was shown in 11 CHB patients (23.40％).The - 139T was far more frequent in the healthy persons previously infected with HBV ( 100％ ) than in the CHB patients (34.04％).Conclusion In the DC-SIGN promoter region,-336C may be a genetic risk factor for developing CHB,but -139T may be associated with protection against HBV.

BACKGROUND:Different methods and biomaterials have been applied in animal experiments and clinical practice to prevent the formation of epidural scars,Biodegradable and sticky semi-fluid gels are the most often used material.Salvia miltforrhiza radix (SMR) and carbomer have been clinically confirmed to be the safe and effective drugs and gel agents. OBJECTIVE:To observe the effect of SMR-gel on preventing epidural adhesion after laminectomy.DESIGN:A complete randomized grouping design, a controlled experiment. SETTING:Department of Orthopaedics,Shenzhen People's Hospital (Second Clinical College of Jinan University). MATERIALS:Thirty-six healthy pure New Zealand rabbits were used,either male of female,clean degree,2-3 years of age. They were randomly divided into four groups with 9 rabbits in each group:blank control group,gel contro group, HA group and SMR-gel group. Carbomer934 powder (Shanghai People's Pharmaceutical Factory, batch number: 20000510) , hyaluronic acid (HA) [Shandong Bausch & Lomb Freda Pharaceutical, Co., Ltd.,No.H10960136,2 mL (20 mg)].METHODS:The experiments were carried out in the animal laboratory of Shenzhen People's Hospital from April 2002 to August 2003.①Preparing SMR-gel:SMR was prepared into extract powder.Carbomer934 powder was added by water for dissolving and swelling and stayed overnight,then SMR-gel was prepared by dipping with triethanolamine,adding with SMR extract powder (2 g),then adding with purified water till 100.0 g and stirring uniformly.②The rabbits were anesthetized. and the lamina of vertebra was totally resected at L3 and L6 (reserving superior and Inferior articular processes).then defects of 10 mm×5 mm were made to expose the dura mater.The vertebral defects were added with 1 mL carbomer gel, 1 mL HA (20 g/L) and 1 mL SMR-gel in the gel control group,HA group and SMR-gel group respectively.whereas nothing was added in the blank control group.③Gross samples:Three rabbits were killed 4,6 and 8 weeks postoperatively in each group.vertebraI ventral fascia were stripped to remove the spinal segments (L3,L6) for operation completely,and totally 24 samples for each time.One sample was selected in each group 4 weeks postoperatively. and the samples were observed under H-600 transmission electron microscope (Hitachi). ④The adhesion compactness of scar tissue with dura mater was evaluated in the 24 samples of the 4 groups at 8 weeks postoperatively:There were 4 grades:No obvious adhesion between dural sac and scar tissue for grade O:Extensive and compact adhesion between dural sac and scar tissue. impossible blunt dissection between dural sac and scar tissue.incomplete dural sac after sharp dissection for grade Ⅲ.Each spinal segment was cut into 4 parts equally,and all were prepared into sections and stained,then the thickness of epidural scar was determined with Tiger2000 image analyzer. ⑤The rank sum test was used in the scar adhesion compactness grading evaluated with naked eyes,whereas analysis of variance.and two-two comparison were used in analyzing the thickness of epidural scar.P＜0.05 was considered as significant difference.MAIN OUTCOME MEASURES:①Results of gross scar adhesion compactness grading at 8 weeks and comparison of the thickness of epidural scar at 4.6 and 8 weeks;②Results of gross observation,histological examination and ultrastructure.RESULTS: All the 36 rabbits were involved in the analysis of results. ①Results of gross observation and pathohistological examination:There was compact adhesion at each time point in the blank control group,part adhesion in the gel control group and HA group, and no obvious adhesion in the SMR-gel group.②Results of quantitative analysis:The rabbits with lower scores of scar adhesion compactness grading In the blank control group,gel control group and HA group were obviously fewer than those in the SMR-gel group (W=45-52,P＜0.05-0.01).The scar thickness at 4 and 8 weeks in the SMR-gel group was obviously less than that in the other 3 groups(F=128.657,152.246,80.891,P＜0.01).③Results of observation under transmission electron microscope:The proliferation of fibroblasts at 4 week was active in the blank control group,gel control group and HA group,but inactive in the SMR-gel group.CONCLUSION:①SMR can inhibit the fibroblasts to proliferate,differentiate and synthetize into secretory collagens,and then inhibit the formation of epidural scar adhesion.②HA can be absorbed by organs very early,which reduces its role in preventing adhesion.Whereas carbomer gel can stay longer, and it plays a role in inhibiting and blocking adhesion in the whole process of wound repairing.

BACKGROUND: During recent years, mononucleotide polymorphism of some genes is possibly related to affectability of osteoarthritis (OA). However, previous researches mainly compare the gene expression of synoviocytes between OA and rheumatoid arthritis (RhA); therefore, the correlation of gene expression between synovioblast and fibroblast in other tissues should be further studied as compared with OA.OBJ ECTIVE: To observe the differences of gene expression between OA synovioblast and skin fibroblast.DESIGN: Observational contrast analysis.SETTING: People's Hospital of Shenzhen City.PARTICIPANTS: Synovium tissue was derived from OA patients who received replacement of knee joint in the Department of Orthopaedics, People's Hospital of Shenzhen City. All OA patients met the diagnostic criteria of osteoarthritis established by American College of Rheumatology in 1995. Three patients including 1 male and 2 females aged more than 65 years old and they did not have cardiac and pulmonary disease and diabetes mellitus. Three male normal volunteers who aged 25 to 35 years did not have rheumatic disease, osteoarthritis and dermatosis. All subjects provided a confirmed consent. The main reagents were detailed as follows: RPMI1640 culture medium, fetal bovine serum and TRIZOL agent (Invitrogen Life Technologies Company, USA); pGEM-T pUC (Progema Company, USA);Display PROFILE-BASIC and Display PROFILE Probe kits (Qbiogen Company, USA).METHODS: The experiment was carried out in People's Hospital of Shenzhen City from January to June 2005. Synovium of OA patients were treated with primary culture to obtain synovioblast; meanwhile, skin fibroblast treated with primary culture from normal subjects was regarded as the control group. Restricted enzyme section differential display was used to separate the different-expressed genes of synovioblast and skin fibroblast in OA patients. In addition, blast technique was used to compare the resulted ranks with Genbank ranks.MAIN OUTCOME MEASURES: Differences of gene expression between synovioblast and skin fibroblast in OA patients.RESULTS: Gene expressions of superoxide dismutase (SOD), TFPI2, CXCL2, CXCL6 and transforming growth factor (TGF) were high in synovioblast of OA patients as compared with those in skin fibroblast of normal subjects.CONCLUSION: Gene expressions of SOD, TFPI2, CXCL2, CXCL6 and TGF are high in synovioblast of OA patients as compared with those in skin fibroblast of normal subjects. This suggests that gene may play a certain role in onset of OA.