JB25 and JB26 are new HIV-1 nonnucleoside reverse transcriptase inhibitors, and show potent anti-HIV activities. Sequential passage experiments with wild-type virus were performed to select and identify mutations induced by these two compounds in vitro. For the initial passage, compounds were present at approximately 2-fold IC50 in MT-2 cells. When cytopathic effect (CPE) was observed in more than 75% of the cells, the culture supernatants were collected. For the subsequent passages, fresh MT-2 cells were infected with 1 mL supernatants from the previous passage (regardless of the virus titer) and cultured in the presence of the compounds at concentrations that were increased 2-fold compared with that in the previous passage. This procedure was repeated with increasing concentrations for 12 passages. JB25 had amino acid substitution L100I (TTA-->ATA) at passage 6, and then changed into 100 M (ATA-->ATG) at passage 12, which was rare mutation form and had not been reported. At the same time, Y188C (TAT-->TGT) mutation appeared at passage 10. For JB26, there was a L100I (TTA-->ATA) mutation at passage 10. In a word, JB25 and JB26 showed a low genetic barrier to the development of resistance, and the resistance to JB26 developed slower than JB25. The mutations selected by JB25 and JB26 were mainly associated with codons 188 and 100 of HIV-1 reverse transcriptase.

Objective To compare the characteristics of ulcer wound healing in current commonly used C57BL/6J-db/db mouse models of spontaneous gene mutation-induced type 2 diabetes and in C57BL/6J mice with diabetes induced by streptozotocin (STZ), and to provide a basis for related experimental studies on diabetic ulcer in animal models.Methods To establish the mouse models of diabetic ulcer wound, observe the healing time and calculate the wound healing rate at 0, 3, 5, 7, 10, 14 days.Tissue samples were collected at days 7 and 14.HE and Masson staining, and immunohistochemistry (CD31 and PCNA) were used to observe the pathological changes of the wound tissues.Gene expressions of collagen-IIIα, fibronectin and α-SMA were detected by fluorescent quantitative analysis.Results The wound healing time of db/db mice was significantly delayed compared with the STZ mice, which was extended from 16.6±0.8 d to 20.2±1.3 d (P< 0.001).Compared with the STZ group, the growth of granulation tissue in the db/db group was slow, the length of newly formed epithelium was insufficient, the collagen deposition was disordered, and the wound healing was poor.At 7 days, the expression of CD31 and PCNA was significantly lower in the db/db group (P< 0.01), and at 7 and 14 days, the increase of collagen-IIIα and α-SMA genes up-regulation was significantly lower in the db/db group than in the STZ group.Conclusions Both the two types of diabetic mice show delayed wound healing.However, compared with the STZ-induced diabetic mice, the gene mutation db/db mice are more suitable for studies of diabetic ulcer wound healing as regarding the extent of the delay and the degree of difficulty of wound healing.

Objective To investigate the diagnostic value of combined detection of serum gastrin-releasing peptide precursor (ProGRP),neuron specific enolization enzyme(NSE)and carcinoembryonicantigen(CEA)in small cell lung cancer(SCLC). Methods 471 patients with lung tumor from department of respiratory medicine and thoracic surgery and 162 healthy people from medical examination center were studied.Serum levels of ProGRP,NSE and CEA were detected by using electrochemi-cal luminescence method.ROC curves were drawn and the area under the curve (AUC)was calculated.Results The levels of ProGRP and NSE were significantly higher in patients with SCLC than those in NSCLC,lung benign disease group and normal control group (P <0.01).The levels of CEA were significantly higher in SCLC than those in patients with lung be-nign disease group and normal control group (P <0.05).The AUC of ProGRP,NSE and CEA in the diagnosis of SCLC were 0.933,0.777 and 0.554,respectively.The sensitivity of ProGRP,NSE and CEA in the diagnosis of SCLC were 82.6%,60.4%,41.6% and the specificity were 95.2%,83.3% and 71.7% respectively.The sensitivity of combined detec-tion of ProGRP,NSE and CEA was 91.3% and the specificity was 65.3%.Conclusion The serum ProGRP detection has a higher diagnostic value for SCLC.The combined detection of ProGRP,NSE and CEA is useful in the early diagnosis of SCLC.

Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction. The purpose of this open-label, randomized, multi-center, angiographic trial was to assess the efficacy and safety of tenecteplase compared with alteplase in Chinese patients with acute myocardial infarction. Methods We recruited patients with acute ST-elevation myocardial infarction presenting within 6 hours of symptom onset from October, 2002 to March,2004, in 5 hospitals in Beijing. After giving informed consent, patients were randomly assigned a single-bolus injection of tenecteplase (30-50 mg according to body weight) or front loaded alteplase (100 mg), and underwent coronary angiography at 90 min after starting the study drug. All patients received aspirin and heparin (target activated partial thromboplastin time 50-70 s). The primary efficacy end point was the rate of TIMI grade 3 flow at 90 minutes. Other efficacy end points included TIMI grade 2/3 flow at 90 minutes. Safety end points included all stroke, intracranial hemorrhage (ICH), moderate/severe hemorrhage (except for ICH), all-cause mortality at 30-days, and major non-fatal cardiac events at 30 days. Results Overall 110 patients were eligible for statistical analysis, with 58 patients assigned to receive tenecteplase and 52 patients to alteplase. Tenecteplase produced a rate of TIMI grade 3 flow at 90 minutes after the start of thrombolysis(68.4%) similar to that of alteplase (66.7%, P=1.0); the rates of TIMI grade 2 or 3 were similar for patients treated with tenecteplase versus alteplase (89.5% versus 80.4%, respectively, P=0.278). At 30 days, rates for all strokes were similar for the two groups (5.17% for tenecteplase and 1.92% for alteplase, P=0.62); rates of ICH were 3.45% and 1.92% (tenecteplase and rt-PA,P=1.00) respectively. The rate of moderate/severe hemorrhage was 8.62% with tenecteplase and 5.77% with alteplase (P=0.72); total mortality was almost identical in the two groups (13.8% versus 9.6%, respectively, P=0.565) while the rates of non-fatal cardiac complications were 10.35% and 11.54% (tenecteplase and alteplase, P=1.0). Conclusions The efficacy of a single-bolus, weightadjusted tenecteplase fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, and TIMI 2 or 3 flow, but the 30-day mortality and ICH in both groups was so high that the use of tenecteplase is not permitted in China. These negative safety results might be due to the high rate of percutaneous coronary intervention (PCI) and high dose of bolus heparin and suboptimal concomitant medical therapy during hospitalization, so further studies are needed to confirm the safety for tenecteplase in Chinese patients.

Objective:To systematically review the effects of limited fluid intake on the prognosis of patients with heart failure.Methods:RCTs about the effects of limited fluid intake on the prognosis of patients with heart failure published up to March 31, 2021 were retrieved from PubMed, The Cochrane Library, CINAHL, Embase, Web of Science, CNKI, Wanfang, VIP, and SinoMed. Two independent researchers were employed to extract data and evaluate the quality of included literature. Rev Man 5.3 was used for Meta-analysis, sequential analysis to evaluate the reliability and authenticity of the research results, and the Egger's test for publication bias.Results:A total of 7 articles were included, with a sample size of 867 cases. Meta-analysis showed that the body weight [ MD=-3.04, 95% CI (-4.70, -1.38) , P<0.001], B-type natriuretic peptide [ MD=-249.32, 95% CI (-305.00, -193.63) , P<0.001], blood creatinine [ MD=-22.03, 95% CI (-24.98, -19.09) , P<0.001], readmission rate [ OR=0.30, 95% CI (0.20, 0.45) , P<0.001] of the limited fluid intake group in the chronic phase of heart failure were lower than those in the control group; the body weight [ MD=1.41, 95% CI (-3.73, 6.55) , P=0.59], B-type natriuretic peptide [ MD=64.52, 95% CI (-50.01, 179.06) , P=0.27], serum creatinine [ MD=3.83, 95% CI (-9.69, 17.36) , P=0.58], readmission rate [ OR=1.21, 95% CI (0.65, 2.27) , P=0.55] of the acute fluid intake group were not statistically different from those in the control group. Conclusions:Limiting fluid intake in the chronic phase of heart failure can effectively improve the patients' heart and kidney function and the prognosis of the disease. In the acute phase of heart failure, it may be necessary to combine multiple treatments to keep the patients at the best volume state.

Intestinal microbiota is the most complex and important microecosystem in the human body， and gut microbiota dysbiosis is closely associated with the development and progression of acute pancreatitis. Targeted regulation of intestinal microecology in assisting the treatment of acute pancreatitis has attracted more attention in recent years. This article describes the changes in intestinal microbiota and related mechanisms in patients with acute pancreatitis， summarizes the current research status of the use of probiotics， points out the research direction of probiotics as the adjuvant treatment regime， and proposes a new method for predicting the dominant flora in patients with acute pancreatitis， in order to bring new ideas for the treatment of acute pancreatitis.