Objective To evaluate the clinical effects and adverse reaction of raltitrexed combined with radiation for esophageal carcinoma in elderly patients.Methods Sixty patients were randomly divided into two groups by the envelope method, 30 patients in experimental group received raltitrexed combined with radiotherapy and 30 patients in control group received radiotherapy only.Patients in both groups received conventional radiotherapy with a total dose of 56-60 Gy/28-30 F.In experimental group, raltitrexed 2.6 mg/m2 was administered concurrently with the radiotherapy on d1 and d22.Two cycles of concurrent chemotherapy were administered during radiotherapy.The short-term effects, survival times and adverse reactions of the two groups were compared.Results The total effective rates of experimental group and control group were 93.3% and 73.3%, respectively, and there was statistically significant difference between the two groups (χ2=4.320, P=0.038).The median survival times of experimental group and control group was 24.0 months and 12.0 months, respectively, and there was statistically significant difference by Log-rank test (χ2=6.048, P=0.014).The major adverse reactions of grade 3-4 in experimental group and control group were radiation-induced esophagitis (10.0% vs.3.3%;χ2=0.268, P=0.605), leukopenia (13.3% vs.10.0%;χ2=0.000, P=1.000), thrombocytopenia (3.3% vs.0;P=1.000), nausea and vomiting (6.7% vs.0;χ2=0.517, P=0.472), and the differences were not statistically significant.Conclusion Raltitrexed combined with radiotherapy can enhance the short-term effect and prolong the survival time for the elderly esophageal carcinoma patients, and the adverse reactions are mild.It is worthy of further clinical study.

Objective To detect the effect of deep hypothermia on the function of mitochondria in hippocampus after global ischemia in rats and to explore the protection mechanism. Methods The animal model of cardiopulmonary bypass (CPB) was established in rats that were then randomly divided into three groups,ie,control group,normothermia ischemia group and hypothermia ischemia group,eight rats per group.The mitochondria was extracted from the hippocampus of each rats for observing the mitochondrial respiratory function,the activities of succinate dehydrogenase (SDH),the cytochrome oxidese(CCO),the lnembrane fluidity and the content of intramitochondria free calcium and MDA. Resuits The content of intramitochondria free calcium and MDA in the normothermia ischemia group was increased significantly compared to the control group and that in the hypothermia ischemia group wag decreased significantly compared with the normothermia ischemia group(P<0.05).Respiratory state Ⅲ (R3),respiratory state IV(R4),P/O ratio and oxidative phosphorylation (OPR) in the normothermia ischemia group were decreased significantly compared to the control group (P<0.05).R3,R4,P/O ratio and OPR in the hypothermia ischemia group were increased significantly compared with the normothermia ischemia group (P<0.05).Membrane fluidity in the normothermia ischemia group wag decreased significantly compared to the control group (P<0.01),while that in the hypothermia ischemia group was increased significantly compared with the normothermia ischemia group(P<0.05).The activities of SDH and CCO in the normothermia ischemia group were decreased significantly compared to the control group (P<0.01),while those in the hypothermia ischemia group were increased significantly compared with the normothermia ischemia group (P<0.05). Conclusion Profound hypothermia exerts a protective effect on the function of mitochondria in the hippocampus after global ischemia in rats.

Objective To investigate the effects of TLR7 on imiquimod induced apoptosis of THP-1 derived macrophages.Methods Three cell lines ( THP-1 derived macrophages, MDCK cell line and HUVEC cell line) with different capabilities of expressing TLR7 were selected.The survival rates of cells af-ter the treatment with different concentrations of imiquimod were detected by MTT assay.The levels of IL-6 in the supernatants of TLR7 inhibitor chloroquine or TLR7-siRNA treated cells were detected by enzyme-linked immunosorbent assay.The apoptosis of cells was detected by flow cytometry after inhibiting the ex-pression of TLR7.Results Imiquimod induced the apoptosis of THP-1 derived macrophages, MDCK cell lines and HUVEC cell lines.The levels of IL-6 were significantly decreased as the expression of TLR7 was inhibited by treating THP-1 derived macrophages with chloroquine or TLR7-siRNA.Treating THP-1 derived macrophages with chloroquine or TLR7-siRNA did not affect the cell apoptosis induced by imiquimod.Con-clusion Imiquimod could induce the apoptosis of THP-1 derived macrophages through TLR7 independent pathway.

Objective To evaluate the value of indirect hemagglutination test(IHA)in schistosomiasis diagnosis. Meth?ods The literature concerned schistosomiasis diagnosis with IHA in the databases of Medline,CNKI,VIP and Wanfang Data from 1982 to 2014 was collected and evaluated. Results Totally 21 articles which were satisfied with the research criteria were analyzed with the Meta?analysis method. The IHA method had high value in schistosomiasis diagnosis,the AUCSROC of IHA in laboratory evaluation was 0.990 6,while in filed evaluation was 0.832 9,and the difference between them was significant(Z=4.50,P<0.05). Conclusion The diagnosis value of IHA in field evaluation is less than that in laboratory. In the process of the elimination of schistosomiasis,developing a new and higher sensitive reagent in schistosomiasis diagnosis is needed.

Objective:To analyze the learning effect of laparoscopic radical cystectomy(LRC)+ modified ileal conduit(MIC).Methods:From 2014 to 2019, 42 patients underwent MIC and their clinical data was retrospectively analyzed. 34 operations were performed by surgeon 1 and 8 operations by surgeon 2. We divided the 34 patients of surgeon 1 into three groups according to their surgical sequence (group A, 1st to 12th; group B, 13th to 23th; group C, 24 th to 34 th), the 8 cases of surgeon 2 was regarded as group D. The history of abdomen surgery in the 4 groups were 0, 1, 4, 3 cases, respectively ( P<0.05). There was no significant difference of the other baseline characteristics, such as age, BMI, American Society of Anesthesiologists. Then we compared several variables between the 4 groups like operation time, time of ileal conduit construction, blood loss, complication rate, lymph node yield, surgical margin, etc. The key steps of the MIC included isolating terminal ileum when the mesentery was transilluminated, performing end-to-end reflux ureterointestinal anastomosis after the efferent loop was fixed, closing the rent of the retroperitoneum. Results:All operations were performed intracorporeally with no transition to open surgery. The operative time for group A, B, C were 330.0(320.0, 360.0)min, 300.0(250.0, 308.0)min, 270.0(216.0, 324.0)min, respectively ( P =0.010). The time of ileal conduit construction of the 3 groups were 136.5(131.3, 147.5)min, 92.0(79.0, 119.0)min, 79.0(72.0, 115.0)min, respectively ( P <0.001). In addition, the difference of the two variables above between A and B, A and C groups separately reached statistical significance ( P<0.05), while the difference between B and C groups did not ( P>0.05). Other variables, such as blood loss, complication rate, lymph node yield, surgical margin, between the 3 groups reached no statistical significance ( P>0.05). The operative time of group D was 420.0(350.0, 450.0)min, and it reached statistical significance ( P<0.05) when compared with group A. There were no significant differences in other variables, such as blood loss, complication rate, lymph node yield, surgical margin, among the 2 groups ( P>0.05). Conclusions:The learning effect of LRC+ MIC was obvious. When surgeon volume increased, the operative time decreased significantly. Variables like estimated blood loss and complication rate of the 2 surgeons did not reached significant difference, which indicated reproductivity and safety of this procedure.

Objective Rheumatoid arthritis (RA) is a typical type Ⅲ hypersensitivity with a large number of immune complexes (IC) and complement deposits in the synovial tissue , but its specific pathogenesis is not yet clear.This article was to explore the expression of the antigenic profile of serum ICs in RA.Methods ICs were isolated from the serum of 55 patients with RA (41 cases of anti-CCP antibody [+] and 14 cases of anti-CCP antibody [-]), 41 with systemic lupus erythematosus (SLE), and another 41 healthy controls by polyethylene glycol (PEG) precipitation, separated by immunoprecipitation, digested with trypsin in gel, and then subjected to mass spectrometry for identification.The levels of total proteins were compared among different groups using Vennny 2.1.0.The protein expression was considered to be up-regulated when the total protein level of the RA group was >2 times and down-regulated when it was <0.5 times that of the control.Further functional analysis was performed on the differential proteins in RA using the STRING software.Results Totally, 277 proteins were identified in the serum ICs of the RA patients, including 162 in the anti-CCP (+) and 248 in the anti-CCP (-) RA group.Compared with the SLE and healthy control groups, only 129 proteins were found in the RA patients, including 38 in the anti-CCP (+), 109 in the anti-CCP (-) RA group, and 18 in both the two groups.Among the proteins identified in the RA patients and healthy controls, 2 and 11 were up-regulated while 17 and 21 down-regulated in the anti-CCP (+) and anti-CCP (-) RA group, respectively.Conclusion More differentially expressed proteins were identified in the anti-CCP (-) than in the anti-CCP (+) RA patients.The identification of differentially expressed proteins provides a new idea and direction for the investigation of the pathogenesis and new biomarkers of RA.

Objective To develop a simple high-resolution melting ( HRM) analysis method for differentiation of Pc and P2 variants in class 1 integron.Methods DNA fragments containing Pc and P2 variants were amplified from plasmids pACW ( PcW ) and pACWP2 ( PcW-P2 ) respectively , then these purified PCR products and P 2 promoters were analyed full-length amplicon by HRM .Eight DNA fragments containing different Pc promoters were amplified and site-specific mutated from plasmids pACS ( PcS ) , pACH2 ( PcH2 ) , pACH1 ( PcH1 ) , pACW ( PcW ) , genomic DNA of Klebsiellar pneumonia HS07-68 (PcWTGN-10)and HS05-1792(PcH2TGN-10)respectively.The purified PCR products and eight Pc variants were characterized by HRM analyses of an unlabeled probe and full-length amplicon.This assay was applied to the differentiate Pc and P2 variants in 109 class 1 integrons from 95 urine clinical Escherichia coli isolates in Huashan Hospital during 2004 -2007.The differentiation results were compared with that determined by direct sequencing .Results P2 promoter with a significant higher melting temperature ( Tm ) can be identified by HRM analysis clearly .P2 promoters were identified in 2 class 1 integrons and consistent with direct sequencing results .Eight Pc variants were classified into three groups: PcS, PcSTGN-10 , PcW, PcWTGN-10, PcH1, PcH1TGN-10.Using direct HRM analysis.PcH2, PcH2TGN-10 were classified into four groups:PcS, PcH1, PcH2, PcW, PcSTGN-10 , PcH1TGN-10 , PcH2TGN-10 , PcWTGN-10 according to the melting curves of the unlabeled probe .Combined the HRM analyses of the whole amplicon and unlabeled probe , the eight Pc variants can be differentiated from each other .Five different Pc variants, PcS, PcW, PcH1, PcH2TGN-10 and PcWTGN-10 , were identified and consistent with direct sequencing results .Conclusions This developed a simple Pc and P 2 variants differentiation method via simultaneous HRM analyses of an unlabeled probe and full-length amplicon .This method is cost-effective and accurate , could be used in differentiation of Pc and P2 variants of class 1 integrons in clinical isolates .

Pharmacometrics,developed from the conventional pharmacokinetics,is the science of applying mathe-matical and statistical methods to characterize,understand,and predict a drug's pharmacokinetic,phannacodyna-mic,and biomarker-outcome behaviors.Pharmacometrics has been widely valued for its utility of modeling and simulation in drug research and development,therapeutic drug monitoring and individualized therapy.This paper reviewed the advances of pharmacometrics employed in new drug research and development and therapeutic drug monitoring both at home and abroad.

In this study, we evaluated the influence of different variance from each of the parameters on the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST). Besides, we estimated the index of sensitivity within whole course of blood sampling, designed different sampling times, and evaluated the quality of parameters' and the efficiency of prediction. It was observed that besides CL1/F, the index of sensitivity for all of the other four parameters (V1/F, V2/F, CL2/F and k(a)) in tacrolimus PopPK model showed relatively high level and changed fast with the time passing. With the increase of the variance of k(a), its indices of sensitivity increased obviously, associated with significant decrease in sensitivity index for the other parameters, and obvious change in peak time as well. According to the simulation of NONMEM and the comparison among different fitting results, we found that the sampling time points designed according to FAST surpassed the other time points. It suggests that FAST can access the sensitivities of model parameters effectively, and assist the design of clinical sampling times and the construction of PopPK model.

The effects of GPA, anti-GPA IgG, ?1acid glycoprotcin (?1-AGP), ovomucoid (OM) and wheat germ agglutinin (WGA) on the invasion of erythrocytes by P. falciparum were obseryed in vitro. GPA, anti-GPA IgG and WGA at low concentrations had obviously inhibitory effects on thc invasion. There were hyperbolic relationships between the concentrations of these inhibitors and their inhibition rates. OM, ?1-AGP and non-spccific anti-serum had no obvious effect on the invasion. It is confirmed for the first time from the biological characteristics of receptor-ligand interaction that thc combination of GPA with P. falciparum merozoites has high spccificity, high affinity with a tendency to sa-turation and can produce specific biological effects.