Objective To investigate the dynamic expression and clinical significance of toll-like receptor 4(TLR4)/CD80 in patients before and early after renal transplantation. Methods Thirty-two patients who received renal transplantation were enrolled in his study. All of them were primary recipients, and the level of panal reactive antibody less than 1%. The expression of TLR4 and CD80 in CD14, positive monocyte of peripheral blood from atients on the 1st, 4th, 7th, 14th, 21st, 28th and 35 th days after transplantation were measured by three-color fluorescent taining flow cytometry. The pa-tients were divided into rejection roup(7 cases) and non-rejection group(25 cases) according to rejec-tion episode record within 2 weeks. Normal control group(10 cases) enrolled healthy adult volunteers. Diagnosis of acute rejection depended on clinical symptoms, lab test, color doppler onography and re-nal biopsy. Results Before ransplanstation, the ressions of TLR4 and CD80 were (8.03± 0.84)% and (0.85±0.31)% in rejection group, (6.14±0.85)% and (0.84±0.39)% in non-rejec-tion group, (6.37±0.56)% and (0.85±0.35)% in normal control group. The expression of TLR4 of rejection group was higher than those of non-rejection group and normal control group(P<0.01). The expressions of CD80 of 3 groups had no significant difference(P=0.995). After ransplanstation, the expressions of TLR4 and CD80 increased to (16.50±1.02)% and (7.82±1.66)% in rejection group, (11.60±0.98)% and (2.26±0.96)% in non-rejection group at the 4th day, and reached the peak levels at the 7th day: (36.40±4.86)% and (9.53±1.97)% in rejection group, (22.70± 3.45)% and (1.87±0.72)% in non-rejection group, then displayed downtrend, rejection group de-creased to (7.10±0.82)% and (0.87±0.57)% at the 35th day, non-rejection group decreased to (7.20±0.76)% and (0.81±0.37)% at the 21st day. Compared with non-rejection group, rejection group showed higher peak expression value of TLR4/CD80 (P<0.01) and longer lasting time. Con-clusions The high expression of TLR4 may increase the risk of acute rejection. The up-regulated TLR4/CD80 levels early after renal transplantation may ontribute to the happeness of acute rejection.

0.05). In group B,the serum creatinine levels of cases treated with ulinastatin at 1,3,7,10 and 14 days after renal transplantation were (372.6? 128.1 ),(278.4?38.9),(145.9? 47.2 ),(133.2?39.8),(128.0?30.6)?mol/L,respectively;the values of controls were (496.3?125.6),(364.7?60.2),(196.2?36.8),(161.4?41.5),(149.8? 33.5 )?mol/L,respectively ( P

Recent clinical studies have found that there are still a large number of patients who do not respond to immune checkpoint inhibitors (ICIs). Improving immunotherapy response in ccRCC patients is an urgent clinical need. Targeting different components of the tumor immune microenvironment becomes a breakthrough point for overcoming the immunotherapy resistance and optimizing therapeutic strategies in advanced ccRCC. Several novel immunotherapeutic strategies are currently under clinical investigation, including targeting other co-inhibitory and co-stimulatory molecules, modified cytokine therapies, small-molecule immunomodulators, targeting immune metabolism, and cancer vaccines, each of which target different immunomodulatory pathways in the tumor immune microenvironment for the treatment of ccRCC. In this paper, we provide an overview of the current challenges faced by immunotherapy for advanced ccRCC and review novel immunotherapy strategies based on the tumor immune microenvironment.

Objective To determine the origin of cord serum leptin and its relationship with neonatal anthropometry. Methods Sixty five women and their babies took part in this prospective cohort study. Blood was taken from the women just before delivery and from the umbilical cord of their babies at delivery. Serum leptin was measured by radio immunoassay. Neonatal anthropometric measurements were recorded within 48 hours after delivery. Linear regression analysis was used to explore the relationship between serum leptin concentrations and anthropometric measures and multiple regression analysis then applied to determine which variables remained independently associated with leptin. Results The leptin concentration ( ?s )in maternal serum was (19.93?7.21) ng/mL and in cord blood was (10.50?3.45) ng/mL. Cord leptin levels correlated with placental weight, neonatal birthweight, skinfold thickness and ponderal index but not with maternal leptin levels. The correlation with Placental weight and neonatal birthweight remained significant after multiple regression analysis. Conclusions Relatively big serum leptin concentration gradient between mother and umbilical vessels indicates that placenta might play an important role in leptin production. We hypothesize that leptin might play an important role during pregnancy and fetal development.

Objective To study the role of placental leptin in intrauterine cord leptin production and its relationship with neonatal anthropometry. Methods Forty women and their babies were enrolled in this study. Placental tissue was obtained from mothers and assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR). Blood was taken from the umbilical cord of the babies at delivery. Serum leptin was measured by radio-immunoassay. Neonatal anthropometric measurements were recorded within 48 hours after delivery. Linear regression analysis was used to explore the relationship between placental leptin mRNA, serum leptin concentrations and anthropometric measures. Results Placental tissue expressed leptin mRNA at comparable or greater levels than adipose tissue. The placenta of the small for gestational age (SGA) neonates expressed leptin mRNA at significantly lower levels than that of the appropriate for gestational age (AGA) neonates (P=0.042), while the placenta of the large for gestational age (LGA) neonates expressed leptin mRNA at significantly higher levels than that of the AGA neonates (P=0.03). Placental leptin mRNA expression levels correlated with leptin concentrations in cord blood (r=0.61), newborn birth weight (r=0.60) and Ponderal Index (r=0.56). Conclusions Placenta provides a source of leptin for the growing fetus, and this placental leptin might be a growth factor in intrauterine fetal development.

The use of genetic approaches to probe relative genes that control sensitivity to volatile anesthetics in intact model has recently emerged as the powerful tools and strategies in dissecting mechanisms of anesthesia. Multiple model organisms such as yeast, nematodes, fruitflies and mammals are currently being exploited, and a number of sensitive genes have been screened, with some of them being cloned, located, and function identified. The emerging technologies are likely to provide further great advances for elucidating the specific anesthetic molecular sites.

G1.(3)Among 5 groups,the highest incidences of nausea,vomiting and pruritis were observed in group G1 for about 24% 32%,but with no statistical difference compared with other groups.Conclusion: With equal doses of bupivacaine and fentanyl mixed,the concentration/volume ratios may affect the analgesic effects of postoperative epidural analgesia in patients with hepatectomy.

Objective To study the In vitro expansion of human CD8+ CD28- suppressor T cells and their immunological regulatory effect.Methods Human CD8 + CD28- suppressor T cells were expanded in vitro driven by the combination of cytokines and allogeneic antigen presenting cells (APCs).Flow cytometry was used to assess the development of CD28- subpopulation.Expanded CD8+ CD28- T cells were isolated by immunomagnetic microspheres and then added as third part modulators into mixed lymphocyte culture to assess their immunological regulatory characteristics.Results The combination of cytokines included IL-2,IL-7 and IL-15 and allogeneic APCs could increase the portion of CD8 + CD28- T cell subtype,and expansion fold of CD8+ CD28- T cell subtype was significantly increased as compared with others (P＜0.05).Expanded CD8+ CD28- T cells could suppress the proliferation of CD4+ T cells stimulated by allogeneic APCs.Moreover,this suppression had antigen specificity.Conclusion Human CD8 + CD28- suppressor T cells can be in vitro expanded in large amounts driven by the combination of cytokines and allogeneic APCs.Expanded CD8 + CD28- T cells in this study have antigen specific regulatory characteristics.

Objective To estimate the venous thromboembolism (VTE) risk and prevention in critically ill patients admitted to ICU and discuss the appropriate strategy for prevention.Methods A total of 276 critically ill patients staying longer than 48 hours in ICU were enrolled for a retrospective single-center study.VTE risk assessment,methods for mechanical and pharmacological prophylaxis and demographic data were recorded.Simplified Caprini scores for VTE risk were counted in the first day and 7th day after admission to ICU,and were compared among internal medicine,surgery and trauma subgroups.Relationship between VTE risk and the clinic index was analyzed by Pearson test and Spearman test with SPSS 17.0 software.The prophylaxis strategy applied to patients without low risk of VTE was explored.Results Simplified Caprini scores were (8.71 ± 4.90) and (9.24-± 5.30) on the first day and the 7th day after admission respectively.Simplified Caprini score was significantly related to APACHE Ⅱ score (r =0.397,P =0.027).Meanwhile,simplified Caprini score in surgical and traumatic patients was higher than that in medical ill patients (14.02 ±2.01),(14.5 ± 1.29) vs.(6.55 ±3.98),P ＜0.01.The total rate of early prophylaxis measures used with mechanical prevention (13.43％) and pharmacological prophylaxis (5.22％) was only 18.28％ within 48 hours after admissioin of patients with highest riskof VTE.Even on the 7th day after admission to ICU,the total rate of prophylaxis measure employed with mechanical prevention (11.92％) and pharmacological prophylaxis (11.56％) for VTE was 25.83％.Conclusions Critically ill patients in ICU were subjected to extremely high risk of VTE.The VTE risk related closely to the severity of critically illness existed throughout the whole period of the ICU stay.Constant assessment for VTE risk and bleeding risk should be made with frequent assessment for critically ill patients.

Objective To study a functional variable fragment of heavy chain(VH)antibody against the terminal protein(TP)region of hepatitis B virus(HBV)polymerase introduced by human immunodeficiency virus Tat protein transduction domain(TAT)and the inhibitive activity of TAT-VH on the replication of HBV in vitro.Methods The gene encoding TAT-VH was cloned into prokaryotic expression vector pET28a(+).Recombinant plasmid was transduced into E coli BL21(DE3)LysS,then the protein was expressed and purified.The purified TAT-VH fusion protein was added into HepG2.2.15 cell culture.The transduction efficiency was evaluated by indirect fluorescence assay(IFA).The cytotoxicity of TAT-VH was detected by Methabenzthiazuron(MTT)assay.HBV DNA level in HepG2.2.15 cell culture was measured using quantitative polymerase chain reaction(PCR).The data were analyzed by one-factor analysis of variance and t test.Results TAT-VH fusion protein was successfully expressed and purified.It was confirmed by IFA and MTT assay that TAT-VH was introduced into HepG2.2.15 cells and the cell growth was not affected.The level of HBV DNA in supernatant of HeDG2.2.15 cell culture with 5 000 nmol/L TAT-VH was(1.211±0.132)lg copy/mL,which was significantly lower than control group[(5.325±0.041)lg copy/mL,t=72.91,P＜0.05].Meanwhile,the level of intracellular HBV DNA was(3.521±0.411)lg copy/mL,which was significantly lower than control group[(8.532±0.132)lg copy/mL.t=28.41,P＜0.05].Conclusion The HBV replication is inhibited by anti-TP TAT-VH antibodies in vitro,which provides valuable experimemal basis for developing therapy of HBV infection with intracellular antibody.