Objective To discuss the maximum tolerated dose of oxaliplatin based on 5-fluorouracil derivative in patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy.Methods From Mar 2015 to Oct 2015,15 locally advanced rectal cancer patients (T3,T4/N +) who received intensity modulated radiotherapy and concurrent chemotherapy with capecitabine and oxaliplatin were enrolled in this study.The prescription dose was 50.6 Gy for gross tumor volume(GTV) and 41.8 Gy for clinical tumor volume(CTV) in 22 fractions within 30 d with concomitant boost.There were four dose-level groups of oxaliplatin as 100,110,120 and 130 mg/m2 tri-weekly and fixed capecitabine dose (825 mg/m2 bid d1-5 per week).The first 12 patients were randomly assigned into 4 groups.For the 130 mg/m3 group,another 3 patients were enrolled because of dose-limiting toxicity (DLT).Treatment related toxicities and response rates were evaluated.Results The most common adverse events(AE) were radiation enteritis,skin reactions,nausea,fatigue,urinary system AE and bone marrow suppression.There was a trend of increase by the dose level of oxaliplatin for toxicities.Groups 100,110 and 120 mg/m2 had none DLT,while group 130 mg/m2 had 1 patient for grade 3 thrombopenia and 1 patient for grade 3 nausea.Postoperative pathology showed that all patients achieved tumor downstaging,among which 0,1,2,3 cases achieved complete remission of the four groups,respectively.Conclusions The combination regimen of capecitabine and oxaliplatin is safe and effective according to the preliminary results.The maximum tolerated dose of oxaliplatin was 130 mg/m2 tri-weekly.

Objective To establish a universal stem loop primer (USLP) based real-time PCR method to scan mature miR profile and quantify it's expression.Methods The common universal stem-loop primer pairs were re-designed; 8 random nucleotides were introduced at 3 ' end for reverse transcription of the mature miR,establishing a miR scanning and quantifying system based on SYBR Green Ⅰ PCR (improved USLP method).10-fold gradient diluted standard miRNA-155 cDNA ( 1 ～ 109 copies/μ1) were utilized to evaluate the sensitivity of this method.The specificity was verified by melting curve assay; the precision was assessed by intra-assay coefficient of variation (ICV) of threshold cycle (Ct value) through 20 repeated detections of the standard miR-155 cDNA (2 × 105,2 × 106,2 × 107 copies/μl) ; cost of the primers and time were evaluated,compared with that of the conventional USLP method.Peripheral blood samples were cultured with phytohaemagglutinin (PHA) for0 h,16 h,24 h,48 h and 72 h,and 87 candidate miR that may be associated with human immunity from PubMed data were scanned and quantified from the cultured T cells.Results The sensitivity of the improved USLP method was 103 copies/μl of standard miR-155 cDNA.Melting curve assay showed a single melting peak at 80 ℃,suggesting the excellent PCR specificity of miR-155.Precision of our method quantifying miR-155 was acceptable (ICV ＜ 2.5％ ).Compared with the traditional stem loop primers,our method saved 75％ cost of primers ( 1 917 bp vs 7 851 bp) and 60％ test time of reverse transcription (85 min vs 205 min).By our method,85 of the 87 miR expression in T cells had no significant difference after the PHA stimulation; the expression of miR-150 (72 h) decreased by 10 times and that of miR-155 (48 h) increased 8 times after culture with PHA (Z =-2.032,P =0.042;Z =- 2.023,P =0.043,respectively ).Conclusions The improved USLP method is fast,precise,sensitive,and cost-effective.It could be used for miR profile scanning and quantifying in T cells.

Objective Triple negative breast cancer(TNBC), a special breast cancer subtype, is lack of effective target therapy.The article aimed to investigate the role of lysophosphatidic acid (LPA) and Hippo Yes-associated protein (Hippo-YAP) signaling pathway in TNBC invasion and metastasis and the mechanisms.Methods The specific small interfering RNA (siRNA) of YAP was synthetized in vitro, and was transfected into MDA-MB-231 cells using liposome transfection.The experiment was divided into YAP-siRNA group, positive control group and blank control group.Each group is provided with 2 parallel holes.Evaluation was made on the effects of each group on Hippo-YAP, the mechanisms and regulation on upstream and downstream molecules of Hippo-YAP pathway.Results In experiment group, YAP content, the capacity of invasion and metastasis after transfection ([0.035±0.005], [2.200±1.000], [3.500±0.800]) significantly decreased compared with positive control group([0.343±0.012], [27.600±5.100], [22.300±5.000]) and blank control group([0.384±0.017], [26.500±4.800], [22.350±6.000]) (P<0.05).YAP expression levels at 60 min, 120 min, and 240 min in experiment group significantly decreased compared with positive control group and blank control group (P<0.05).YAP relative expression levels of 10, 20, 50 μmol/Lwere significantly lower than those of positive control group and blank control group (P<0.05).After respective interference of C3 transferase and Y27623, significant difference was found in the pYAP mRNA contents of experiment group([0.255±0.052], [0.326±0.017]), blank control group([0.048±0.032], [0.534±0.017]) and positive control group([0.052±0.021], [0.528±0.024])(P<0.05).The expression levels of YAP mNA and AREG mNA significantly increased in experiment group([0.176±0.032], [0.263±0.008]) compared with blank control group([0.043±0.013], [0.263±0.008]) and positive control group([0.049±0.025], [0.057±0.043])(P<0.05).Conclusion LPA induces breast cancer invasion and metastasis, which is YAP-dependent, time-dependent and concentration-dependent.LPA-Hippo-YAP singaling pathway may be one of the mechanisms promoting delayed metastasis of TNBC.

Objective:To translate the Cardiac Symptom Survey and analyze its reliability and validity in the post-valvular heart replacement survey and to provide the basis for the clinical application of this scale.Methods:The symptoms of 233 patients after heart valve replacement were investigated in Suining Central Hospital by Chinese version of the Cardiac Symptom Survey. The reliability of the scale was evaluated by Cronbach'α coefficient and the split half coefficient, the validity of the scale was evaluated by exploratory factor analysis and content validity index.Results:The internal consistency coefficient of the Chinese version of the Cardiac Symptom Survey ranged from 0.875 to 0.968, both above 0.870.The split half coefficient was 0.699,which demonstrated better internal consistency.The content validity index of the Chinese version of the Cardiac Symptom Survey ranged from 0.84 to 1.00.Factor analysis got five factors, which explained 68.133% of the total variance.Conclusions:The Chinese version of the Cardiac Symptom Survey has good reliability and validity in the investigation of the symptoms of patients after heart valve replacement, and can be used for the investigation and management of the symptoms of patients after heart valve replacement.

Objective To investigate the effect of the polymorphisms of multidrug resistance 1 (MDR1) C3435T and G2677T on Tacrolimus (Tac) individualized treatment and prognosis of grafts in the renal transplantation recipients (RTRs).Methods One hundred and twenty-seven RTRs who treated with Tac regimen and had a stable graft function were enrolled,and were divided into adjuvant treatment group and non-adjuvant treatment group according to whether given adjuvant drugs to raise Tac trough concentrations. MDR1 C3435T and G2677T SNPs were detected by using sequence specific primers PCR.Tac trough concentrations of whole blood were measured by using enzymelabeled immunosorbent assay.Tac concentration-to-dose ratio (C/D) standardized by body weight was compared according to the various genotypes and haplotypes of MDR1 C3435T and G2677TA SNPs.Results Adjuvant treatment group including 36 recipients had a higher frequency of C genotype of C3435T than un-adjuvant treatment group (68.05％ vs 48.35％,P ＜ 0.01 ). The frequency of G2677TA polymorphisms was of no significant difference between the two group recipients (P＞ 0.05).As to non-adjuvant treatment recipients,the mean Tac DD required and C/D were not significantly different among various polymorphisms of MDR1 G2677T/A and C3435T or various haplotypes (P＞0.05).During A follow-up period of 4 years,13 recipients suffered graft dysfunction in which 84.6％ (11/13) carried 3435C genotype (P＞0.05).Conclusion The frequency of MDR1 C3435T polymorphisms in RTRs is high in the recipients given adjuvant treatment to raise Tac concentrations.Recipients with 3435C genotype were prone to graft dysfunction.

Background: Mechanical ventilation, particularly one-lung ventilation (OLV), can cause pulmonary dysfunction. This meta-analysis assessed the effects of dexmedetomidine on the pulmonary function of patients receiving OLV. Methods: The Embase, PubMed, MEDLINE, Cochrane Library, ClinicalTrials.gov, and Chinese Clinical Trial Registry databases were systematically searched. The primary outcome was oxygenation index (OI). Other outcomes including the incidence of postoperative complications were assessed. Results: Fourteen randomized controlled trials involving 845 patients were included in this meta-analysis. Dexmedetomidine improved the OI at 30 (mean difference [MD]: 40.49, 95% CI [10.21, 70.78]), 60 (MD: 60.86, 95% CI [35.81, 85.92]), and 90 min (MD: 55, 95% CI [34.89, 75.11]) after OLV and after surgery (MD: 28.98, 95% CI [17.94, 40.0]) and improved lung compliance 90 min after OLV (MD: 3.62, 95% CI [1.7, 5.53]). Additionally, dexmedetomidine reduced the incidence of postoperative pulmonary complications (odds ratio: 0.44, 95% CI [0.24, 0.82]) and length of hospital stay (MD: −0.99, 95% CI [−1.25, −0.73]); decreased tumor necrosis factor-α, interleukin (IL)-6, IL-8, and malondialdehyde levels; and increased superoxide dismutase levels. However, only the results for the OI and IL-6 levels were confirmed by the sensitivity and trial sequential analyses. Conclusions Dexmedetomidine improves oxygenation in patients receiving OLV and may additionally decrease the incidence of postoperative pulmonary complications and shorten the length of hospital stay, which may be related to associated improvements in lung compliance, anti-inflammatory effects, and regulation of oxidative stress reactions. However, robust evidence is required to confirm these conclusions.

Objective To evaluate the efficacy and safety of recombinant adenovirus-p53(rAdp53) injection combined with radiotherapy and hyperthermia in the treatment of unresectable advanced soft tissue sarcoma.Methods In this retrospective study, we evaluated 76 patients with unresectable advanced primary or recurrent soft tissue sarcoma treated in our hospital from November 2005 to November 2012.These patients received radiotherapy and hyperthermia with rAdp53(p53 group, n=41) or without rAdp53(control group, n=35).rAdp53((1-2)×1012viral particles each time, once a week, 8 times on average) was injected into the tumor or infused into the pelvic cavity.Radiotherapy (2 Gy each time, 5 times a week) was performed for the planning target volume at 56.3±5.3 Gy in the p53 group and 58.1±4.2 Gy in the control group, with no significant difference between the two groups (P>0.05).Superficial or deep thermotherapy was employed 8 times on average (twice a week).Clinical features, response rate, time to progression (TTP), overall survival (OS), and adverse events were compared between the two groups (P>0.05).The Kaplan-Meier method was used to calculate OS;the log-rank test was used for survival difference analysis and univariate prognostic analysis;the chi-square test was used for comparison of categorical data.Results At 2 months after treatment, the p53 group had significantly increased response rate (partial response+ complete response+ stable disease)(85% vs.54%, P=0.003) and local control rate (49% vs.23%, P=0.020) as well as prolonged TTP (12 months vs.5 months, P=0.010) and OS (48 months vs.31 months, P=0.049), as compared with the control group.No adverse events caused by radiotherapy and hyperthermia except transient fever were seen in the two groups.Conclusions Concurrent radiotherapy and hyperthermia combined with rAdp53 injection is effective and safe for patients with advanced soft tissue sarcoma.

Objective To investigate the efficacy of concurrent chemoradiotherapy for anal squamous cell carcinoma (ASCC) in the era of intensity-modulated radiotherapy.Methods A total of 19 patients with ASCC who underwent definitive radiotherapy in our hospital since 2011 were collected.The survival curves were depicted with K-M method.Risk factors of disease progression were analyzed using case-control study.Results The median follow-up time was 31 months.The 3 year-LFS and 3 year-OS were 88.1％ and 91.7％,respectively.Grade 3 acute toxicities during the chemoradiotherapy were mainly white blood cell reduction (15.8％),platelet reduction (10.5％),diarrhea (15.8％),and skin reaction (31.6％).Compared with historical data,volumetric intensity modulated arc therapy was superior to conventional radiotherapy in the treatment outcome and normal tissue protection in ASCC.Univariate analysis showed that concurrent chemotherapy with capecitabine was a favorable factor in disease progression (P＜ 0.05).Conclusions Volumetric intensity modulated arc therapy for ASCC may have advantages in terms of efficacy and normal tissue protection.Concurrent chemotherapy with a double-drug regimen containing capecitabine may be a beneficial factor in disease progression.

Objective To explore the value of MRI simulation in the pre-operative radiotherapy for locally advanced low rectal carcinoma.Methods A total of 40 patients diagnosed with locally advanced low rectal carcinoma by endoscopic biopsy and radiological staging examinations were included in this study.There were 22 male and 18 female with nedian age 58 years (range 31-80).Patients underwent CT and MRI simulation scanning in the same position and fixing device.GTV under CT images and MRI inages were delineated respectively by two experienced radiologists.Primary tumor length,tumor volume and distance of distal tumor from the anal verge were calculated by treatment planning system(TPS).The two groups of data were compared.Results The distance of distal tumor to the anal verge were all no more than 5 cm on digital examination.The mean length of GTVcT was remarkably longer than that of GTVMRI [(5.21 ±1.65) cm vs.(4.46 ± 1.51) cm,t =5.059,P ＜0.05].The mean volume of GTVcTWaS significantly larger than that of GTVMRI[(55.71 ±31.57) cm3vs.(44.02 ±25.11) cm3,t=6.977,P＜ 0.05)].The mean distance of distal tumor to the anal verge was (3.72 ± 0.93) cm,significantly longer than that of lower bounds of GTVCT to the anal verge,which had a high consistency with GTVMRI.The IMRT plan was based on CT-MRI fusion images.There were no 3-4 grade adverse effects of radiotherapy.The overall pCR rate was 32.5％.Conclusions MRI simulation could define smaller GTV and more precise lower bounds than CT.With improved accuracy of target volumes contours,the application of MRI simulation may promote the efficacy of radiotherapy and result in a reduction in the incidence of toxicities.

Objective To introduce the development strategy of“Internet Plus”AIDS prevention services and its implementation results from 2010 to 2015 in Guangzhou, China. Methods A gay men's health column was created for an active website aimed at men who have sex with men (MSM), in collaboration with local community organizations and the Guangzhou CDC. We designed intervention tools (including scenario-based applications and HIV risk self-assessment systems) and an online HIV testing service platform, integrated with applied psychology and behavioral theory as well as the“Internet Plus”concept, to intervene in HIV infection risk factors among MSM. Data of clients who accessed the“Internet Plus”AIDS services from 2010 to 2015 were used to evaluate service operation. Six-year consecutive surveys, conducted between April and July of each service year, were collected using a national AIDS sentinel surveillance questionnaire. For each year of surveillance, information on HIV prevalence, HIV interventions received during the past year, unprotected anal intercourse in the past 6 months, and HIV testing in the past year were compared using the chi-squared (χ2) test, to roughly reflect the effect of“Internet Plus”AIDS prevention services. Results As of 31 December 2015, a total of 34 395 MSM had received“Internet Plus”services and HIV testing. The number of MSM tested increased from 2 338 in 2010 to 8 054 in 2015. From 2010 to 2015, newly identified HIV cases in each year were 59, 166, 312, 283, 291, and 270, which accounted for 25.0%, 32.8%, 38.8%, 35.1%, 30.5%, and 23.2% of MSM HIV cases of Guangzhou, respectively. Sentinel surveillance data showed that during the study period, 3 047 MSM were investigated, with 405, 400, 401, 633, 608, and 600 each year, respectively. The proportion of participants who had received any HIV intervention during the past year was 74.3% (301), 70.8% (283), 83.3% (334), 85.0%(538), 69.1%(420), and 83.8%(503) each year, respectively (trend χ2=6.53, P=0.011). HIV testing done during the past year accounted for 44.0%(178), 44.3%(177), 49.4%(198), 53.4%(338), 56.1%(341), and 60.2%(361) each year, respectively (trendχ2=40.83, P<0.001). Unprotected anal intercourse in the past 6 months accounted for 59.3% (240), 62.0% (248), 56.6% (227), 57.0% (361), 48.4% (294), and 43.7%(262) each year, respectively (trend χ2=42.21, P<0.001). Conclusion The“Internet Plus”AIDS prevention services in this study represent a manner to enhance traditional HIV prevention strategies. We found these services to be effective in implementation of the national AIDS control and prevention strategy, especially for the expansion of intervention, testing, and case identification among high-risk populations.