Objective:To investigate the drug-resistant mutations of human immunodeficiency virus-1 (HIV-1) in patients who received highly active antiretroviral therapy (HAART) from 2014 to 2018.Methods:A total of 880 patients with HIV-1 infection who had been treated with HAART for more than six months in Chongqing Infectious Disease Medical Center from May 2014 to December 2018 were enrolled. Plasma samples were collected, and one-step reverse transcription-polymerase chain reaction (PCR) and nested PCR were taken to amplify protease and reverse transcriptase regions of HIV-1 pol gene region. The obtained amplified nucleotide sequences were compared with the drug resistance database for antiviral drug resistance analysis. Viral genotyping tool software was used to analyze HIV-1 subtype distribution. The categorical variables were compared using chi-square test. Results:Among 880 patients, the plasma HIV-1 viral load was (4.12±0.63) lg copies/mL, the CD4 + T lymphocyte count was (251±124)/μL, and the median duration of antiviral therapy was 26 months. In the subtypes analysis, the circulating recombinant form (CRF) 01-AE subtype was the largest proportion of HIV-1 subtypes, accounting for 38.9%(342/880), and the CRF07-BC subtype accounted for 28.5%(251/880), B+ C subtypes accounted for 16.2%(143/880). Drug-resistant mutations were detected in 534 patients, with a total drug resistance rate of 60.7%. The drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) were 51.0%(449/880), 58.6%(516/880) and 1.7%(15/880), respectively. The drug resistances to lamivudine, emtricitabine, efavirenz, and nevirapine were serious, and the medium/high resistance rates were 46.8%(412/880), 46.8%(412/880), 51.3%(451/880), and 53.6%(472/880), respectively, while those to zidomidudine (6.0%, 53/880), etravirin (9.0%, 451/880) and PI were not serious. M184IV (47.3%), K65R (22.2%) and K70RE (12.6%) were the most frequent mutations for NRTI. K103NS (25.1%), V106A (19.7%) and V179DE (14.4%) were the most frequent mutations for NNRTI. The most common drug-resistant mutations for PI were L10FIV (7.4%) and A71IVT (6.5%). The drug resistance rate of CRF01-AE subtype (69.3%, 237/342) was higher than those of CRF07-BC subtype (49.8%, 125/251) and B+ C subtype (51.0%, 73/143), the differences were statistically significant ( χ2=22.6 and 14.6, respectively, both P<0.05). Conclusions:The incidence of drug resistance is high among HIV-1 infected patients after six-month HAART treatment in Chongqing City. The drug resistance to NNRTI is the most common, followed by NRTI, while PI is less resistant. Drug resistance is the main reason for the virological breakthrough in HIV-1 infected patients.

Objective: To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products (sRAGE) levels in patients with chronic obstructive pulmonary disease(COPD). Methods: Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166, female 37, aged 52-92 years, average years(69.72±9.079)] and in 41 smoking elderly non-COPD patients[male 35,female 6, aged 55-89 years, average years(68.66±8.74)], and 167 non-smoking healthy subjects as the control group[male 132, female 35, aged 57-92 years, average years(69.13±7.21)] from April 2018 to January 2019. The relationship between the S100A8/A9, sRAGE and clinical biomarkers [the percentage of fored expiratory volume in one second(FEV₁) in the predicted value, FEV₁/fored vital capacity(FVC), neutrophile granulocyte(NEU)%, pack-year] were investigated. The diagnostic value of S100A8/A9, sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve. Results: The serum S100A8/A9 level [(2.70±1.11)μg/ml] in COPD patients was significantly higher than that in the smoking control group [(1.65±0.63) μg/ml] and the non-smoking control group[(0.99±0.48)μg/ml], t=5.807, P<0.000 1; t=18.45, P<0.000 1. The serum S100A8/A9 levels in patients with COPD[GOLD Ⅰ(2.08±1.08) μg/ml, GOLDⅡ (2.58±1.06) μg/ml, GOLD Ⅲ (2.69±1.12) μg/ml, GOLDⅣ (2.95±1.10)μg/ml] were significantly higher than the non-smoking control group(0.99±0.48)μg/ml, t=6.616, P<0.000 1; t=14.56, P<0.000 1; t=17.10, P<0.000 1; t=18.09, P<0.000 1.The serum sRAGE level [(0.29±0.25)ng/ml] in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml] and the non-smoking control group[(0.85±0.35)ng/ml], t=7.367, P<0.000 1; t=18.14, P<0.000 1. The serum sRAGE levels in patients with COPD[GOLD Ⅰ(0.46±0.40),GOLDⅡ (0.28±0.25),GOLD Ⅲ (0.29±0.25),GOLD Ⅳ (0.25±0.19)ng/ml] were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml], t=3.459, P=0.000 5; t=10.23, P<0.000 1; t=13.95, P<0.000 1; t=11.70, P<0.000 1. Serum S100A8/A9 levels were positively correlated with smoking amount and NEU% (r=0.458 5, P<0.000 1; r=0.228 3, P=0.001 1), negatively correlated with FEV₁/FVC, the percentage of FEV₁ in the predicted value, and sRAGE(r=-0.190 6, P=0.006 4; r=-0.186 3, P=0.007 8; r=-0.201 7, P=0.003 9). sRAGE levels were negatively correlated with NEU% (r=-0.155 9, P=0.026 4). In the ROC curve, the area under the curve of S100A8/A9, sRAGE and combined detection were 0.922[95%CI(0.897-0.947)], 0.926[95%CI(0.899-0.952)]and 0.966 [95%CI(0.950-0.983)], respectively. Conclusion S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators, which are expected to be as potential biomarkers of COPD.

Objective To look into the effect of ubiquitin (Ub) in muscles of gastric cancer patients on their nutritional status and prognosis.Methods Abdominal rectus muscles of 102 patients with gastric cancer and 53 patients with benign abdominal diseases were studied.The expressions of Ub mRNA and protein were assessed through real time-PCR and Western blot.Results The relative expression of Ub mRNA in rectus abdominis muscles of gastric cancer patients (4.10± 1.04) was significantly upregulated compared with the control group (3.17±0.32) (t =7.386,P=0.000).The expression of Ub protein in rectus abdominis muscles of patients with gastric cancer was upregulated compared with the controls (0.151 ±0.058 vs.0.084±0.046,t =7.275,P =0.000).The high expression of Ub mRNA in rectus abdominis muscles of gastric cancer patients was significantly associated with decreases in weight,body mass index,prognostic nutritional index,serum albumin and hemoglobin (x2 =11.780,6.557,11.849,15.742,8.360;P=0.001,0.010,0.001,0.000,0.004).The high expression of Ub mRNA in rectus abdominis muscles of gastric cancer patients was not correlated with the patients'sex,age,tumor size or Borrmann type (x2 =0.038,1.978,0.486,1.483;P=0.774,0.160,0.486,0.223),but it was related to the pathologic type,lymph node metastasis and TNM staging of gastric carcinoma (x2 =11.260,9.362,20.517;P=0.004,0.002,0.000).The survival rate of gastric cancer patients with high expression of Ub mRNA was lower than those with low expression (x2 =5.775,P =0.016).Conclusions Ub mRNA and protein were upregulated in rectus abdominis muscles of gastric cancer patients.The high expression of Ub mRNA in these patients was related to their nutritional status and prognosis,which might play an important role in the development of cachexia.

OBJECTIVE: To provide reference for China to comprehensively promote and perfect the "two-vote system" for drug purchase. METHODS: The effects of "two-vote system" on interested parties, the existing problems of drug purchase and its financial reasons were analyzed; the finance strategies were put forward to deal with the existing problems of drug purchase. RESULTS & CONCLUSIONS: "Two-vote system" has certain impact on drug production enterprises, drug circulation enterprises, public medical institutions and government drug supervision departments. At present, the existing problems of drug purchase mainly include that the mechanism of "drug to support hospital" has promoted the virtual-high price of drugs; drug enterprises pull drug sales by the way of rebate; hidden rules disrupt the circulation of drugs as "be subordinate to" "amateur performance". Financial reasons mainly include that the mode of "drug to support hospital" pursuit the maximization of its own interests unilaterally and ignore the drug cost burden of patients; some enterprises have poor investment, lack of R&D investment, have weak internal financial control measures, lack of social responsibility consciousness, rely on "be subordinate to" "amateur performance" profit, underestimate financial risk, etc. The drug production enterprises should adjust marketing model and reduce cost; drug circulation enterprises should predict positioning scientifically and expand profit space; public medical institutions should reform financial supply and reduce drug cost; government drug supervision departments should reduce the supervision cost and improve the comprehensive efficiency. Only by deepening the reform of the medical and health care system, improving the supporting measures for the "two-vote system" in drug purchase can the problems existing in the circulation of drugs be solved gradually.

In order to construct a novel multifunctional targeting nano-carrier based on pH-redox characteristics of tumor microenvironment,ketone bonds and disulfide bonds were bonded to the oligomeric hyaluronic acid (oHA) being sensitive to pH and the reduction environment.The chemical structure of oligomeric hyaluronic acid-8-mercaptomenthone 1,2-glycerolketal (oHMST) was characterized by 1H NMR,IR and ESI-MS.Curcuminloaded micelles were prepared by dialysis.The single factor investigation was carried out on the dosage form.Some properties,including particle size zeta potential,the morphology of micelles,and pH-sensitivity were studied.The materials were synthesized successfully.The micelles were spheric with a diameter of about 100 nm.The Zeta potential of the micelles was-(21.97 ± 1.08) mV.The in vitro test showed that oHMST carriers have good pH-sensitivity and redox-sensitivity.

Objective To screen the risk factors for blood coagulation abnormality in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods A total of 140 patients undergoing elective OPCABG were included in this study,and combined intravenous-inhalational anesthesia was performed during operation.The patients were divided into normal group and abnormal group according to whether or not blood coagulation abnormality developed during operation and within 48 h after operation.The data such as gender,age,body mass index,American Society of Anesthesiologists physical status,the number of operation per year for surgeons,comorbidities (hypertension and diabetes mellitus),preoperative hematocrit (Hct),left ventricular ejection fraction,arterial oxygen pressure,liver function,operation time and requirement for intraoperative continuous cardiac output monitoring,positive end expiratory pressure,tranexamic acid,ulinastatin and hydroxyethyl starch,postoperative acidosis and hypothermia were recorded.Results Blood coagulation abnormality was found in 43 patients,and the incidence was 31％.The results of logistic regression analysis showed that the number of operation per year for surgeons＜ 50,preoperative abnormal liver function,preoperative Hct＜35％,surgery time≥240 min,no use of continuous cardiac output monitoring during operation and postoperative hypothermia were risk factors for blood coagulation abnormality in patients undergoing OPCABG.Conclusion The number of operation per year for surgeons＜50,preoperative abnormal liver function,preoperative Hct ＜ 35％,operation time ≥ 240 min,no use of continuous cardiac output monitoring during operation and postoperative hypothermia are risk factors for blood coagulation abnormality in patients undergoing OPCABG.

Objective To This article mainly takes the Shenzhen Baoan people's Hospital pre-hospital department as the observation object,analyses the spacial site data distribution of pre-hospital,to realize optimum allocation for pre-hospital resource.Methods By means of the intelligentized ambulance,the site data of the pre-hospital is obtainecd,so is the pre-hospital hot map.With the hot map,the special pre-hospital characteristics is researched.Results The three spatial data characteristics of pre-hospital medical are proposed,i.e.,non-uniform,relative stability,individual difference.Conclusions These three characteristics provide us with a new method and a new basis for decision making.In this paper,based on the pre-hospital characteristic,a modeling method of non-uniform relative stability model is proposed,and the optimized distribution of hospital site is discussed by applying planning mathematics.

Objective To investigates the role of duodenum and bile duct preserving pancreatic head resection (DBPPHR) in treatment of benign or low-grade malignant diseases located in the head of pancreas.Methods The clinical data of 31 patients who underwent DBPPHR between April 2012 to May 2016 in Zhejiang Provincial People's Hospital and Zhangzhou Municipal Hospital of Fujian Province were analyzed retrospectively.Results Of the 31 patients,4 patients underwent laparoscopic DBPPHR.One patient in the open group was converted to pancreaticoduodenectomy.For the open group,the mean operation time was (165.3 ±63.6) min;the mean estimated blood loss was (258.1 ± 156.9) ml;and the mean postoperative stay was (11.7 ± 6.3) days.The postoperative complications included 1 reoperation due to postoperative bleeding,1 bile leakage and 13 patients developed grade A pancreatic fistula (48.2％).For the laparoscopic group,the mean operation time was 350.0 (280.0 ～ 450.0) min;the mean estimated blood loss was 425.0 (250.0 ～600.0) ml;and the mean postoperative stay was 14 days.Three patients developed postoperative pancreatic fistula (grade A).The pathological diagnosis were:12 patients with pancreatolithiasis,8 patients with serous cystadenoma,4 patients with branched intraductal papillary mucinous neoplasm,5 patients with neuroendocrine tumor and 2 patients with mucinous cystadenoma.The follow-up period was 1 ～ 48 month,and there was no patient with diabetes or diarrhea.Conclusions DBPPHR was safe and efficacious.It is less invasive to treat benign or low-grade malignant diseases located in the head of pancreas.

Objective To approach the effect of protective mechanical ventilation on acute lung injury after orthotopic liver transplantation, by observing changes of plasma markers of lung injury and inflammatory mediators.Methods Sixty patients scheduled for liver transplantation under general anesthesia, 42 males and 18 females, aged 21-62 years, weighing 43-80 kg, ASA physical status Ⅱ-Ⅳ, were randomly divided into 2 groups: protective mechanical ventilation group (group P) and unprotective mechanical ventilation group (group U).Pulmonary artery blood for plasma markers of lung injury and inflammatory mediators were collected at the following time points: before operation (T1), 3 hours after mechanical ventilation (T2), 2 hours (T3) and 4 hours in neohepatic stage (T4).These mediators included clara cell secretory protein (CC16), surfactant proteins (SP-D), soluble receptor for advanced glycation end-products (sRAGE), TNF-α, IL-6 and IL-8.Moreover, blood gas results were recorded at these 7 time points: T1-T4, 2 hours after operation (T5), before tracheal extubation (T6) and 2 days after operation (T7).The postoperative awakening time, tracheal extubation time, ICU stay time and the incidence of ALI were recorded.Results Compared with T1, plasma level of CC16 in the two groups increased at T2 and T3 (P<0.05 or P<0.01), however, plasma level of SP-D, sRAGE, TNF-α, IL-6 and IL-8 did not increase until T3 (P<0.01).Moreover, plasma level of sRAGE, TNF-α, IL-6 and IL-8 at T4 were higher than those at T1 (P<0.05 or P<0.01).Compared with T1, OIs in the two groups increased at T2, T5 and T6 (P<0.05 or P<0.01), while decreased at T4 in group P (P<0.01) and at T3 and T4 in group U (P<0.01).In group P, patients showed a lower plasma level of CC16 at T2 and T3 (P<0.05 or P<0.01), a higher OI at T3 (P<0.05) and an earlier tracheal extubation after operation [(8.9±3.2) h vs (9.3±2.8) h, P<0.05] compared with group U.There was no significant difference of acute lung injury incidence between the two groups after operation, which was 5(16.6%) and 7 (23.3%), respectively.Conclusion Protective mechanical ventilation may promote oxygenation index, and shorten tracheal extubation time, thus protect lung function of patients in liver transplantation to some extend.