Objective To investigate the relationship between individual pharmacokinetics characteristics of cyclosporine (CsA) and the occurrence of acute rejection episodes or CsA-induced nephrotoxicities in kidney transplants. Methods The whole blood CsA concentrations were assayed 7 days after oral admi- nistration with a dosage of 6 mg/kg daily in 47 recipients. The blood samples drawn just prior to ingestion of the dose and subsequently at 1, 2, 3, 4, 5, 6, 8, 10, 12 h later were monitored with TDX. Recipients were grouped according to the varied situations of kidney transplant functions within one month after pharmacokinetics monitoring. Pharmacokinetics parameters of C_0, C_ max , T_ max , CL/F, T_ 1/2(a) , T_ 1/2(e) and AUC in each group were calculated and compared among the groups. Results Of 47 recipients, 12 cases had experienced AR episodes, 7 cases had suffered CsA-NT, and the remaining 26 cases survived with stable graft functions. Major pharmacokinetics parameters in AR group were T_ 1/2(a) , T_ 1/2(e) , CL/F, T_ max and AUC, which were significantly different from the corresponding parameters in the group with stable graft function. Pharmacokinetics curve of AR group was characterized with a earlier T_ max (usually less than 2 h), a sharp absorb peak and a abbreviated AUC, T_ 1/2(e) , CL/F, T_ max , and AUC in CsA-NT group, which was also significantly varied from that in the stable group. The curve of CsA-NT group, with a delayed T_ max (often more than 2 h), a broad absorb peak or double peaks, however, was predominantly distinguished from the previous AR curve. Levels of C_0 in the three groups were comparable when AR or CsA-NT occurred. Conclusion Pharmacokinetics monitoring accomplished by multiple point CsA level samples over the entire 12 h dosing interval is a more accurate assessment for drug exposure. It is suggested that patients who absorb and eliminate CsA quickly are likely to experience AR episodes. Meanwhile, those poor eliminators are at risk to suffer CsA-NT.

Objective To compare the effectiveness of medicated γintrauterine device (IUD) and medicated genefix IUD inserted immediately after abortion. Methods A multicenter clinical trail was performed for the study from Mar. 2012 to Jan. 2013. Totally 840 women who volunteered to participate were randomly allocated to γ-group (medicated γ IUD) or genefix-group (medicated genefix IUD) immediately after abortion. While 464 abortion women who had not used IUD or steroids contraceptive methods were chosen as control group. The effectiveness of the IUD were followed up for 1 year. All women were required to record the number of vaginal bleeding days and blood volume of vaginal bleeding within 3 months after abortion. Results At the 12th month, the expulsion was the most common reason for termination. The expulsion rates of genefix-group and γ-group were 2.48/100 women years and 3.12/100 women years, respectively (P>0.05). For the expulsion reasons, IUD moving down could account for more than seventy percent. The removal rate for IUD usage of two IUD groups were almost equal (3.91/100 women years verus 4.35/100 women years), the differences were not statistically significant (P>0.05). At the 90th day after abortion, comparing with control group, the bleeding and (or) spotting days of genefix-group and γ-group extended by 3.9 and 2.6 days respectively, the differences had statistical significance between the three groups (P<0.05). Among the bleeding and (or) spotting days, spotting days prolonged significantly. At the 12th month, spotting days of genefix-group andγ-group were (9.2±5.9) days and (8.5±4.6) days respectively, more than (5.2 ± 4.0) days of control group. The differences had statistical significance between IUD with control group (P<0.05), and had not between the two kinds of IUD (P>0.05). Conclusion The insertion of medicated genefix IUD and medicated γ IUD immediately after abortion is safe, feasible, has slight side effects and could be effective contraception.

OBJECTIVE To evaluate the value of central compartment neck dissection for cN0 papillary thyroid carcinoma.METHODS The clinical data of 46 cases with cN0 papillary thyroid carcinoma in our hospital from Jan.1999 to June 2004 were retrospectively studied.The level Ⅵ lymph nodes were removed during the operation.RESULTS In 46 cN0 cases,there were 11 cases(23.9 %) pathologically proved lymph nodes metastasis after operation.Four patients developed neck recurrence and underwent neck dissection.CONCLUSION It is necessary to probe the level Ⅵ lymph nodes during the operation for cN0 papillary thyroid carcinoma patients.

Objective To study the effect of metastasis-associated in colon cancer 1 ( MACC1 ) inhibition by small interference RNA( siRNA) on the formation of tumor cells that promote blood vessels, and to explore its possible molecular mechanism.Methods Synthesized MACC1 specific siRNA was transfected into human lung cancer cell lines XWLC-05. Then, the inhibitory effect of siRNA on the protein level of MET, MEK/p-MEK, ERK/p-ERK, and AKT/p-AKT was detected using Western blotting while the change in VEGF, bFGF and IL-8 protein level was detected using ELISA method. Results Western blotting results indicated that the expression level of MET, p-MEK and p-ERK was significantly decreased in the XWLC-05 cells transfected by MACC1 specific siRNA compared with control and nonsense siRNA groups, but the expression of total protein MEK and ERK did not change.Furthermore, the level of AKT and phosphorylated protein was not affected.ELISA results suggested that the secretion level of VEGF, bFGF and IL-8 was significantly suppressed at 48 h or 72 h compared with control and nonsense siRNA groups.Conclusion MACC1 may reduce the secretion levels of VEGF, bFGF and IL-8 via HGF/c-Met and MEK/ERK signal transduction pathways, and regulate angiogenesis of lung cancer.

Objective A phase Ⅱ trial of anti-programmed death-1 (PD-1) monoclonal antibody CT-011,an anti PD-1 humanized monoclonal antibody combined with rituximab therapy in patients with relapsed follicular lymphoma (FL) were conducted.Methods In order to evaluate the safety and efficacy of CT-011,the impacts of CT-011 on immune cells both from the peripheral blood (PB) samples and tumor microenvironment were examined.PB and core needle biopsies from involved lymph nodes were collected prior to and on day 14 after the first infusion of CT-011.PB mononuclear cells (PBMC) were analyzed by multiparametric flow cytometry to determine various immune cell subsets.Whole genome gene expression profiling (GEP) was performed on core needle biopsies.Results A significant increase in the absolute number of PB immune cells were observed in day 14 samples compared with baseline including total lymphocyte count (P ＜ 0.01),CD+3 T cells (P =0.01),CD+4 T cells (P ＜ 0.01).Comparison of GEP from core needle biopsies obtained pretreatment and day 14 (n =8 pairs) showed up regulation of several genes associated with T cell activation.Conclusion Administration of CT-011 was associated with increase in the numbers of CD+4 T cells and resulted in activation of T cells in the PB and the tumor microenvironment in FL.These results provide insight into the mechanism of action of CT-011 and offer a predictive biomarker for selection of patients for future clinical trials with this class of agents in FL.

Objective To investigate the effects of down-regulation of Beclin 1, which is an autophagy regulatory molecule, expression induced by RNA interference on the proliferation and apoptosis in skin fibroblasts of naked mole rat. Methods The expression levels of Beclin 1 were detected after starvation or H2 O2 treatment.The fibroblasts were transi-ently transfected with specific siRNA targeting Beclin 1 and then screened by real-time PCR and Western blot.Cell prolifer-ation and apoptosis were determined using CCK-8 detection kit and flow cytometry ( FCM ) .The expressions of related genes were detected by Western blot.Results The expression of Beclin 1 gene at mRNA and protein levels was signifi-cantly lower in fibroblasts of the naked mole rat.Starvation and H2 O2 treatment induced changes of the Beclin 1 expression. Inhibition of Beclin 1 gene expression can inhibit cell proliferation and induce early and late apoptosis.The protein levels of p53, BAX, Bcl2, LC3B, p-AKT and mTOR were reduced after transient transfection with Beclin 1-siRNA.Conclusions The expression of Beclin 1 in fibroblasts of naked mole rat are changed in response to starvation or H2 O2 stimulation.Inhi-bition of Beclin 1 gene expression can inhibit cell proliferation and induce apoptosis.Therefore, Beclin1 gene may play a regulatory role in autophagy, proliferation and apoptosis in the skin fibroblasts of naked mole rat.

Objective The Nuss procedure is a minimally invasive pectus repair.The aim of this study was to explore the changes in quality of life in patients who underwent a Nuss procedure.Methods 96 patients,who underwent a Nuss procedure in our institution,were interviewed at preoperation,1 year after operation with the bar in place,and before the planned bar removal.The Nuss Questionnaire modified by George Krasopoulos et al,which evaluates psychosocial and physical well-being,was independently used by patients.Results Most of the scoring of the individual questions and the total score of individual patients revealed a significant improvement,both in preoperation vs.1 year after operation and 1 year after operation vs.before the planned bar removal.Conclusion The Nuss procedure has been shown to improve the quality of life in patients with pectus excavatum deformity in the short term.

Objective To explore the mechanism of dendrobine in the treatment of diabetic kidney disease(DKD)by intervening immunity using network pharmacology,bioinformatics and Western blot.Methods The targets of dendrobine were screened by Pharmmaper,Superpred and other databases.The disease targets of DKD were screened from GeneCards,OMIM and other databases.The immune-related targets were searched in Immport,In-nateDB and other databases.The intersection of the above three was obtained via Venn diagram.The PPI map of intersection targets was constructed by STRING software combined with Cytoscape software,and the core targets in the interaction network were mined by CytoHubba plug-in.The data set GSE142025 was obtained from GEO,and immune infiltration and WGCNA analysis were performed using the R language CIBERSORT package.GSE1009,GSE30122 and GSE142025 were used for gene differential expression analysis and ROC verification.The correla-tion between core targets and immune cell phenotype was analyzed.Molecular docking and molecular dynamics sim-ulation analysis were used to test the binding force of dendrobine to key targets.Western blot was used to detect the expression of HSP90AA1 in HK-2 cells.Results A total of 128 intersecting genes,including HSP90AA1,LCK and EGFR,were obtained,and the core targets involved HSP90AA1,LCK and STAT3;molecular docking and molecular dynamics simulation analyses showed that the protein of HSP90AA1 could bind well with dendrobine.Western blot experiments showed that compared with the control group,HSP90AA1 was significantly down-regula-ted in the high glucose group.Compared with the high glucose group,HSP90AA1 was significantly up-regulated in the dendrobine group.Conclusion Dendrobine can intervene in diabetic kidney disease by regulating the expres-sion of HSP90AA1.

This study summarizes the skills training work of the National College Students' Clinical Skills Competition for 9 consecutive years, and explores a set of teaching methods suitable for the standardized training of residents of anesthesiology. This method is applied to the clinical operation, professional theory, clinical thinking, humanistic care, doctor-patient communication and other aspects of the standardized training of residents. The results show that the teaching effect of all aspects of standardized training of residents is more practical and efficient, and residents can quickly master the basic operation skills of anesthesia in a short time, indicating that the training method of clinical skills competition of college students can be applied in the standardized training of anesthesia residents, which can effectively improve the training effect.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.