Objective To observe the clinical findings about the endothelial cell injury related to the genesis of inflammatory cytokines and coagulation.Methods A total of 70 critically ill patients with SIRS (systemic inflammatory response syndrome) admitted to intensive care unit (ICU) between September 2009 and February 2010 were enrolled for a prospective and control study.According to diagnostic criteria of Sepsis/SIRS,the patients were divided into two groups:sepsis group (n =38) and SIRS group (n =32),and another 20 healthy volunteers served as control group.Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure,diabetes and its complications.The demographics of patients including age,sex,body mass index (BMI),smoking and alcohol addict were comparable among the different groups.The 6 ml peripheral blood samples were collected within 24 h after admission to ICU for enzyme-linked immunosorbent assay (ELISA) to detect the plasma levels of s-CD62P,TNF-α,and hsCRP.And variables of coagulation function such as platelet (PLT),prothrombin time (PT),activated partial thromboplastin time (APTT),D-dimer and antithrombin-Ⅲ (AT-Ⅲ) were analyzed during 24 h after admission to ICU.Meanwhile sequential organ failure assessment (SOFA) score of critically ill patients was evaluated.Data were expressed in mean ± standard deviation and were statistically analyzed by using SPSS 17.0 statistical software.The differences in plasma levels of s-CD62P of patients in each group were analyzed by ANOVA and Kruskal Wallis test.The relationship between s-CD62P and inflammatory cytokines as well as with coagulation were determined by Pearson correlation analysis.Changes were considered as statistically significant if P value was less than 0.05.Results ① Compared with control group and SIRS group,the levels of s-CD62P,TNF-α and high sensitive C-reactive protein (hs-CRP) were significantly higher in sepsis group (P ＜ 0.05).② The plasma levels of D-dimer,PT,APTT in sepsis group and SIRS group were significantly higher than those in control group,while the platelet count (PLT) and the activity of AT-Ⅲ were obviously lower (P ＜ 0.05).③ In sepsis group,the plasma levels of hs-CRP and TNF-α positively correlated with PT,APTT,D-dimer,and negatively correlated with AT-Ⅲ,PLT (P ＜ 0.05).④ Plasma levels of s-CD62P were significantly correlated with plasma levels of TNF-α,hs-CRP,D-dimer,PT,APTT,whereas correlated negatively well with PLT,AT-Ⅲ (P ＜ 0.05).Conclusions The plasma s-CD62P concentration is elevated as a early biomarker in patients with sepsis,and it acted as one of pathogenic factors responsible for endothelial cell damage.Coagulation and mediators of inflammation promotes each other,aggravating the severity of the sepsis.The plasma s-CD62P may be the important factor associated with initiation of coagulation development and inflammatory reaction.

Objective To investigate the influencing factors of successfully switching to sequential ventilation in patients with prolonged weaning due to acute respiratory failure (ARF) after thoracolaparotomy based on the initial rapid shallow breathing index (RSBI) at 60 min after spontaneous breathing trial (SBT), namely, the f/VT optimal value range of 80-120 times/ (min · L), thus providing the basis for determining the ideal timing of weaning in clinical practice.Methods A prospective observational study of sequential ventilation [RSBI during the initial SBT (60 min), 80-120 breaths/ (min · L)] was carried out in 42 patients on mechanical ventilation (≥ 48 h) due to post-thoracolaparotomy ARF in the ICUs.According to the duration of the mechanical ventilation, the patients were divided into 2 groups : successfully prolonged weaning group (≥ 7 days, n =24) and refractory weaning group (＜ 7 days, n =18).The patients with cardiac failure, aged less 18 or over 80, with hepatic dysfunction, or those needing gastrointestinal decompression after esophageal surgery or upper abdomen surgery were excluded.The demographics, APACHE Ⅱ scores and duration of mechanical ventilation of both groups were recorded, and the respiratory work and oxygen metabolism variables before the switch to sequential ventilation (within 24 hours after admission to ICU) and at the time of switching (24 hours in the ICU after admission) were recorded, respectively: clinical puhnonary infection score (CPIS), assessment of cough severity, pH, PaO2, PaCO2 and PaO2/FiO2;hemodynamic and microcirculation-related variables: HR, MAP, fluid balance, BNP and Lac;endocrine and metabolism variables : Hb, ALB and random serum cortisol (COR).The clinical features and the changes of the above-mentioned variables before and at the time of switching were compared between both groups.The independent sample t test was used for the single factor comparison and Mann-Whitney U test was applied to the non-normal distributions.The Fisher exact probability test was used for the single factor comparison of ranked data such as categorical variables.Results There were no significant differences in age, gender and severity of disease between two groups (P ＞ 0.05);the successfully prolonged weaning group had longer duration of invasive mechanical ventilation and ICU stay compared with the refractory weaning group (P ＜ 0.05).There were significant differences in cough severity, PaCO2, pH, HR and fluid balance between two groups before switching (P ＜ 0.05).Compared with those before switching, in the refractory weaning group there were marked decrease in Lac (P ＜ 0.05), obvious increase in cough severity, pH, Hb and ALB (P ＜ 0.05), but there was no significant difference in COR (P ＞ 0.05);while in the successfully delayed weaning group, there were significant decrease in CPIS, PaCO2, HR, MAP, BNP, fluid balance and Lac (P ＜ 0.05), and cough severity, pH, ALB and COR showed an upward trend (P ＜ 0.05).Conclusions The key of successful sequential ventilation is within the values of RSBI ranging from 80 to 120 times/ (min · L) during the initial SBT (60 min) selected as the switching point in patients with prolonged weaning after thoracolaparotomy.The major influencing factors for determining the ideal timing of switching include the matching status between respiratory endurance and respiratory work, the balance between myocardial strength and both cardiac preload and afterload, the severe disease associated with adrenal insufficiency, and malnutrition.

Objective To investigate the effects of traditional Chinese medicine colquhounia root tablet on the expression of tight junction protein claudin-2 and ZO-1 in bronchial epithelium tissues of rats with acute lung injury (ALI), and to study the mechanism of protective effect of colquhounia root tablet on ALI. Methods Twenty-four healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ALI group and colquhounia root tablet pretreatment group, with 8 rats in each group. The model of ALI was reproduced by intravenous injection of oleic acid 0.04 mL/kg, and the rats in cont rol group were given the same amount of normal saline (NS) instead. The rats in colquhounia root tablet pretreatment group were intragastric administrated with colquhounia root tablet of 600 mg·kg-1·d-1 (2 mL) for 10 days before model reproduction, and the rats in control group and ALI group were given the same amount of NS. At 4 hours after model reproduction, the blood was drawn from abdominal aorta, and bronchoalveolar lavage fluid (BALF) was collected for determination of protein content in plasma and BALF, and the lung permeability index (LPI) was calculated. The rats were sacrificed to collect lung tissues for determination of lung wet/dry weight ratio (W/D), the changes in pathology of lung tissue were observed after hematoxylin and eosin (HE) staining with light microscope, and lung injury score (LIS) was evaluated. The immunohistochemic al staining was used to detect the expression and localization of claudin-2 and ZO-1 in bronchial epithelium tissues. The protein expressions of claudin-2 and ZO-1 in bronchial epithelium tissues were determined by Western Blot. Results Compared with control group, the lung injury in ALI group was more obvious including cellular edema and structural disorder of intercellular connection by optical microscope, and LIS, W/D ratio, and LPI were significantly increased (LIS: 3.81±0.42 vs. 0.40±0.08, W/D: 7.68±0.64 vs. 4.44±0.39, LPI: 0.89±0.15 vs. 0.38±0.05, all P < 0.01). Claudin-2 and ZO-1 were mainly expressed in the bronchial epithelium cell, and the expression degrees were significantly weakened in ALI group as compared with control group. It was shown by Western Blot results that compared with control group, the protein expressions of claudin-2 and ZO-1 were significantly down-regulated in ALI group [claudin-2 protein (gray value): 0.43±0.31 vs. 2.16±1.33, ZO-1 protein (gray value): 1.25±0.41 vs. 2.82±0.76, both P < 0.01]. Compared with ALI group, colquhounia root pretreatment could effectively diminish the degree of ALI (LIS: 1.22±0.39 vs. 3.81±0.42, W/D: 4.62±0.84 vs. 7.68±0.64, LPI: 0.46±0.07 vs. 0.89±0.15, all P < 0.01), and the protein expressions of claudin-2 and ZO-1 were significantly up-regulated [claudin-2 protein (gray value): 2.98±0.91 vs. 0.43±0.31, ZO-1 protein (gray value): 2.35±0.51 vs. 1.25±0.41, both P < 0.01]. Conclusion Administration of colquhounia root table could attenuate lung injury induced by oleic acid with improving epithelial barrier function via up-regulate the expression claudin-2 and ZO-1, which play a protective effect on the lung of rats with ALI.

ObjectiveTo investigate the clinical effect of endoscopic sphincterotomy with balloon dilation (ESBD) versus sphincterotomy (EST) alone in the treatment of large common bile duct stones. Methods Foreign databases (including PubMed, CochraneCentral, and Embase) and Chinese databases (including CNKI and Wanfang Data) were searched for randomized controlled trials (RCTs) on the clinical effect of ESBD versus EST in the treatment of large common bile duct stones published up to July 8, 2019. Related data were extracted and RevMan5.3 was used for analysis. Results A total of 13 RCTs with 1926 patients were included, with 973 patients in the ESBD group and 953 patients in the EST group. The meta-analysis showed that there were significant differences between the ESBD group and the EST group in stone clearance rate (odds ratio ［OR］=1.53, 95% confidence interval ［CI］: 1.03-2.29, P=0.04), one-time clearance rate (OR=1.77, 95%CI: 1.06-2.93, P=0.03), rate of use of mechanical lithotripsy (OR=0.40, 95%CI: 0.25-0.63, P＜0.000 1), bleeding rate (OR=0.23, 95%CI: 0.11-0.50, P＜0.001), incidence rate of cholangitis (OR=0.31, 95%CI: 0.12-0.78, P=0.01), incidence rate of early complications (OR=0.59, 95%CI: 0.42-0.84, P=0.003), and time of operation (mean difference=-8.89, 95%CI: -17.56 to -0.22, P=0.04), while there were no significant differences between the two groups in perforation (OR=0.27, 95%CI: 0.05-1.30, P=0.10) and pancreatitis after endoscopy (OR=1.03, 95% CI: 0.66-1.61, P=0.91). ConclusionIn endoscopic treatment of large common bile duct stones, ESBD has several advantages over EST in stone clearance rate, rate of use of mechanical lithotripsy, bleeding rate, incidence rate of cholangitis, and time of operation.

Objective To evaluate the effect of propofol on the expression of programmed death-ligand-1 (PD-L1) in pancreatic cancer cells and the relationship with NMDA/Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ)/hypoxia-inducible factor-1α (HIF-1α) pathway.Methods Human pancreatic cancer cells were divided into 5 groups (n=16 each) by a simple random sampling method:control group (group C),propofol group (group P),KN93 (CaMK Ⅱ inhibitor) group,MK801 (NMDA receptor antagonist) group and propofol plus rapastinel (NMDA receptor agonist) group (group PR).Cells were cultured in DMEM supplemented with 10％ fetal bovine serum in group C.Cells were incubated for 8 h with 50 μmol/L propofol in group P.Cells were incubated for 8 h with 10 μmol/L KN93 in group KN93.Cells were incubated for 8 h with 500 μmol/L MK801 in group MK801.Cells were incubated for 8 h with 50 μmol/L propofol and 20 μmol/L rapastinel in group PR.After the end of treatment in each group,the cell viability was measured using CCK8 assay,the expression of PD-L1,HIF-1α,CaMK Ⅱ and phosphorylated CaMK Ⅱ (p-CaMK Ⅱ) was detected by Western blot,and intracellular calcium concentrations were determined by Fluo3/AM probe.Results Compared with group C,the cell viability was significantly decreased,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was down-regulated,and intracellular calcium concentrations were decreased in P,KN93 and MK801 groups (P＜0.05),and no significant change was found in group PR (P＞0.05).Compared with group P,the cell viability was significantly enhanced,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was up-regulated,and intracellular calcium concentrations were increased in group PR (P＜0.05).Conclusion The mechanism by which propofol inhibits the malignant potential of pancreatic cancer cells may be related to inhibiting NMDA/CaMK Ⅱ/HIF-1α pathway and down-regulating PD-L1 expression.

Objective:To establish the quality evaluation method of Prunellae spica dispensing granules based on three quality indexes of standard decoction. Methods:Fourteen batches of Prunellae spica were collected from different habitats. According to technical requirements, fourteen batches of Prunellae spica standard decoction and three batches of formula granules were prepared and the paste-forming rates were calculated. The fingerprints of Prunellae spica standard decoction and formula granules were established by Ultra High Performance Liquid Chromatography (UPLC). The similarity values of fingerprints between dispensing granules and standard decoction were calculated. The content and transferring rate of Rosmarinic acid were determined and calculated. Results:The average paste-forming rate of Prunellae spica was (12.59±2.32)%. The paste-forming rates of the three batches were 11.14%, 10.78% and 10.39% respectively. The average content of Rosmarinic acid in standard decoction was (18.99±9.74)mg/g. The average transferring rate was (60.58±7.87)%. The contents of three batches were 7.40 mg/g, 7.49 mg/g and 7.09 mg/g. The transferring rates were 52.06%, 50.10% and 50.40% respectively. Nine common fingerprint peaks were identified in the fingerprints of standard decoction and formula granules, two of which were identified as Rosmarinic acid and Caffeic acid by comparison of reference substance. The fingerprints similarity of Prunellae spica dispensing granules and standard decoction were 0.954, 0.973 and 0.952, respectively. Conclusions:The quality indexes of three batches of formulation granules are consistent with standard decoction. This method could provide reference for the establishment of quality standard of Prunellae spica dispensing granules.

Genotoxic or potentially genotoxic impurities seriously threaten people′s health, therefore, it is necessary to identify and quantify these impurities in pharmaceutical materials even at trace levels. Due to the special requirements on the sensitivity, selectivity, analyte stability and matrix effect, development of analytical methods is a challenge for the determination of genotoxic impurities. This paper reviews the recent advances in analytical methods for trace levels of commonly encountered genotoxic or potentially genotoxic impurities, including alkyl halides, alkyl sulfonates, hydrazines, epoxides and acyl halides, which would be helpful to control these impurities.