Background and objectives Proliferation of human vascular smooth muscle cells (VSMCs) induced by hyperinsulinemia is a very common clinical pathology. Extensive research has focused on PKC (Protein kinase C)-MAPK (mitogen-activated protein kinase)intracellular signal transduction and the phenotypic modulation accompanied by reorganization of intracellular F-actins in VSMCs.Methods DNA synthesis, signaling of ERK1/2 MAPKs, and changes in α-smooth muscle (SM) actin and F-actin were studied in hypertensive and normotensive human arterial VSMCs exposed to insulin and PMA with and without the PKC inhibitor, GF109203X.Results Differences among cell types in MAPK signaling, α-SM actin, and F-actin isoforms in VSMCs harvested from the arteries of patients with essential hypertension (EH) and normotension (NT) were identified in response to insulin treatment. Proliferation and activation of MAPK were more pronounced in EH VSMCs than in NEH VSMCs. Insulin exposure decreased expression of α-SM actin and was accompanied by rearrangement of intracellular F-actins in VSMCs, especially in the EH group. These effects were reversed by treatment with the PKC inhibitor. Conclusions Human mesenteric VSMCs of EH and NT patients differed in proliferation, MAPK signaling, and degree of changes in α-SM actin and F-actin isoforms immediately following insulin exposure in vitro.

ObjectiveTo compare the sedative effect and safety of dexmedetomidine and midazolam in the intensive care unit (ICU) patients undergoing ventilator bundle treatment.MethodsA prospective single-blind randomized controlled trial (RCT) was conducted. Ninety patients receiving ICU ventilator-assisted therapy and ventilator bundle treatments for more than 3 days in the First Department of Critical Care Medicine of the Second Hospital of Lanzhou University from January 2013 to December 2014 were enrolled. The patients were randomly divided into two groups for sedative treatment. The patients in dexmedetomidine group (n = 42) were given dexmedetomidine 0.2-0.7μg·kg-1·h-1 to achieve a goal of satisfactory sedation [Richmond agitation-sedation scale (RASS) score 0 to - 2 during the day, and -1 to -3 at night). The patients in midazolam group (n = 48) were given midazolam 2-3 mg intravenously first, and then 0.05 mg·kg-1·h-1 for maintenance. The drug dose was adjusted according to RASS every 4 hours to maintain the appropriate sedation depth. The patients in both groups received continuous intravenous infusion of fentanyl for analgesia. Ventilator bundle treatments included the head of a bed up 30°to 45°, awaken and extubation appraisal, daily use of proton pump inhibitors for peptic ulcer prevention, prevention of deep vein thrombosis (DVT), chlorhexidine mouth nursing, and removal of sputum by suction from subglottic area. When the patients in both groups obtained satisfactory target sedation, daily awakening was conducted, and spontaneous breathing test (SBT) was carried out to determine optional weaning time. When the condition was optimal, weaning was conducted, otherwise ventilator bundle treatments were continued. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), respiratory frequency (RR) were monitored before and 15, 30, 60, 120, 180 minutes after the treatment, and at the moment of extubation and 30 minutes after extubation. The duration of mechanical ventilation, extubation time, length of ICU stay, and the incidence of adverse events were also recorded. Results Both dexmedetomidine and midazolam could give rise to sedation with same score of analgesia in patients in both groups, and similar effect of sedation and analgesia could be achieved. Compared with midazolam, dexmedetomidine could significantly reduce the duration of mechanical ventilation (hours: 108.33±21.96 vs. 119.85±20.29,t = -2.586, P = 0.011), earlier extubation time (hours: 112.95±22.20 vs. 128.58±26.18,t = -3.031,P = 0.003), length of ICU stay (hours: 149.21±20.47 vs. 163.88±33.59,t = -2.457,P = 0.016), the incidence of delirium [9.5% (4/42) vs. 31.2% (15/48),χ2 = 6.349,P = 0.012], but it would elevate the incidence of severe hypotension [28.6% (12/42) vs. 8.3% (4/48),χ2 = 6.277,P = 0.012] and severe bradycardia [19.0% (8/42) vs. 8.3% (4/48),χ2 = 2.225,P = 0.136]. Both drugs could lower SBP, DBP, MAP, and HR, and the effect in dexmedetomidine group was more significant from 60 minutes after treatment [SBP (mmHg, 1 mmHg = 0.133 kPa): 113.12±14.42 vs. 124.40±15.79, DBP (mmHg): 69.02±9.62 vs. 76.94±10.41, MAP (mmHg): 83.76±10.50 vs. 92.77±11.87, HR (bpm): 79.19±12.28 vs. 87.42±17.77,P< 0.05 orP< 0.01]. Both sedatives could significantly lower the rate of spontaneous breathing, and the effect of midazolam group was more significant from 60 minutes after treatment compared with dexmedetomidine group (times/min: 18.27±4.29 vs. 20.07±4.11,P< 0.05).Conclusions The sedative effects of dexmedetomidine in the ICU patients treated with ventilator bundle treatment are satisfactory, and it can shorten the duration of mechanical ventilation, extubation time and length of ICU stay, reduce the incidence of delirium. However, monitoring should be strengthened in order to prevent and control the adverse effects such as severe hypotension and severe bradycardia.

Objective To explore the relationship of the polymorphism of E-selectin gene A561C and essential hypertension (EH) among Chinese people. Methods Genotypes of E-selectin were analyzed in 95 EH patients with age ≤70 and 101 normal controls people matched in age and gender by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP). Serum levels of lipid, glucose, urea and creatinine were measured by biochemical techniques. Plasma soluble E-selectin were measured by enzyme-linked immunosorbent assay(ELISA). Results The frequency of E-selection genotypes AA, AC and CC in EH group were significantly higher than normal group (P

Objective To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). Methods A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. Results ① There were no significant differences in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score among groups. ② Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. ③ Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P < 0.05). ④ Compared with control group with the same sedative, the duration of mechanical ventilation, extubation time, length of ICU stay were significantly shortened, and the dosage of sedative drugs used was reduced in study group (all P < 0.05). In simulated circadian clock group, the duration of mechanical ventilation in dexmedetomidine group was significantly shorter than that of propofol group and combination group (hours: 75.75±26.78 vs. 102.00±26.31 and 100.31±25.38, both P < 0.05), and the length of ICU stay was significantly shorter than that of propofol group (days: 5.75±1.04 vs. 7.00±1.52, P < 0.05). ⑤ The occurrence of delirium was positively correlated with duration of mechanical ventilation (r = 0.705), extubation time (r = 0.704), length of ICU stay (r = 0.666, all P = 0.000), and no correlation was found between the occurrence of delirium and aMT6s level at 06:00, 12:00, 18:00, and 24:00 (r = -0.135, r = 0.163, r = 0.269, r = -0.077, all P > 0.05). Conclusions Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients. Trial registration Registration of clinical trials in China, ChiCTR-IPR-15006644.

Objective To analyze the status of Leishmania infantum asymptomatic infection in human population of a Kala-azar endemic area in Wenxian County,Gansu Province,and to evaluate the tests used.Methods Blood samples were tested by PCR using two pairs of primers,RV1-RV2 and K13A-K13B,for detecting Leishmania-specific DNA.ELISA and rK39-dipstick were used to detect Leishmania-specific antibodies.Results The positive rate of PCR,ELISA and rK39-dipstick was 30.9%(83/269),24.2%(65/269) and 0(0/269) respectively.Conclusion The prevalence of asymptomatic infection of L.infantum in humans is high in the area.PCR test based on RV1-RV2 and K13A-K13B primer pairs is a sensitive and specific method for detecting the asymptomatic infection.

Poly-hemoglobin is the active component of hemoglobin-based blood substitutes. The excess reactivity of glutaraldehyde with hemoglobin in solution leads to poly-hemoglobin of a wide molecular weight distribution and a high average molecular weight. A new polymerization method has been tested to decrease the molecular weight distribution and the average molecular weight. The poly-hemoglobin with lower degree of modification (polymerization) was found enriched on the cation exchange columns and further polymerized with glutaraldehyde. The poly-hemoglobin of narrower molecular weight distribution has been prepared in this way.
Blood Substitutes ; chemical synthesis ; chemistry ; Chromatography, Ion Exchange ; methods ; Hemoglobins ; chemical synthesis ; chemistry ; Humans ; Pyridoxal Phosphate ; analogs & derivatives ; chemical synthesis ; chemistry

Objective:To systematically review the efficacy of ultrasound-guided fluid resuscitation and early goal-directed therapy (EGDT) in patients with septic shock.Methods:Multiple databases including Wanfang, CNKI, SinoMed, VIP, PubMed, Embase, Cochrane Library and Web of Science were searched from initial to August 2019 for randomized controlled trial (RCT) studies about the comparison of ultrasound-guided fluid resuscitation and EGDT on resuscitation effect in patients with septic shock. Language, country and region were unlimited. Data extraction and quality evaluation were carried out by means of independent review and cross check results by two researchers.Results:Finally, only two English RCT studies were enrolled. In the two RCT studies, the ultrasound groups used inferior vena cava collapse index (VCCI) and ultrasound score to guide fluid resuscitation, which resulted in clinical heterogeneity. Because the results could not be pooled, only systematic review, not meta-analysis, could be done. There were measurement bias and selection bias in the two RCT studies, and the literature quality level was B and C respectively. System review results showed that using ultrasound would reduce 7-day mortality (15.0% vs. 35.0%, P = 0.039) and prescribe less of 24-hour intravenous fluids (mL: 900 vs. 1 850, P < 0.01) for patients with septic shock as compared with EGDT. Ultrasound was easy to assess the reactive capacity and cardiac function of patients with septic shock, so as to decrease the incidence of pulmonary edema, which was significantly lower than EGDT (15.0% vs. 37.5%, P = 0.022). However, there was no statistically significant difference in 28-day mortality, duration of mechanical ventilation or length of intensive care unit (ICU) stay between the two groups. Conclusion:The ultrasound-guided fluid resuscitation may be useful and practical for septic shock patients within 7 days after admission as compared with EGDT, but it cannot reduce the 28-day mortality, duration of mechanical ventilation or length of ICU stay.

Objective To systematical evaluate the effect of Xuebijing injection in the treatment of multiple organ dysfunction syndrome (MODS).Methods With the keywords including Xuebijing, multiple organ dysfunction syndrome, multiple organ dysfunction and multiple organ failure, PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP and Wanfang Data from the database start until March 4th, 2018 were searched for relevant randomized controlled trials (RCTs) related to Xuebijing injection combined conventional treatment versus conventional treatment alone for MODS. The control group received conventional western medicine treatment, including etiological treatment, antibiotics, mechanical ventilation, nutritional support, and comprehensive treatment to maintain fluid, electrolyte, acid and alkali balance. The experimental group was given traditional western medicine combined with Xuebijing injection. The observation parameters included 7-day and 28-day mortality, acute physiology and chronic health evaluationⅡ (APACHEⅡ) and Marshall score, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the number of platelets, activated partial thromboplastin time (APTT) and prothrombin time (PT). According to the inclusion and exclusion criteria, two evaluators independently screened the literature, extracted data and evaluated the methodological quality of the included studies. RevMan 5.3 software was used for Meta analysis. Funnel plot was used to analyze publication bias.Results A total of 35 RCTs and 2131 patients were enrolled, including 1076 in the experimental group and 1055 in the control group. The results of Meta analysis showed that compared with control group, Xuebijing combined conventional treatment was in favor to decrease the mortality of patients with MODS [7-day mortality: odds ratio (OR) = 0.42, 99％ confidence interval (99％CI) = 0.26-0.69,P < 0.00001; 28-day mortality:OR= 0.31, 99％CI= 0.21-0.45,P < 0.00001], also could obviously reduce critical condition degree of APACHE Ⅱ score and the organ function of Marshall score [APACHEⅡ: mean difference (MD) =3.24, 99％CI = 2.00-4.49,P < 0.00001; Marshall score:MD = 1.95, 99％CI = 0.50-3.40,P = 0.0005]. Meanwhile, the results of conventional western medicine combined with Xuebijing in the removal of IL-6 and TNF-α, platelets increase and improvement of PT were better than those of conventional western medicine (IL-6:MD = 5.56, 99％CI = 1.44-9.68, P = 0.0005; TNF-α:MD = 4.97, 99％CI = 3.44-6.50,P < 0.00001; platelets:MD = -50.79, 99％CI = -74.84 to -26.74, P < 0.0001; PT:MD = 4.55, 99％CI = 3.96-5.14,P < 0.00001), however, there was no obvious advantage in improving APTT (MD = 0.96, 99％CI = -5.08-7.00,P = 0.68). The analysis of funnel map showed that the effect points of various studies were mainly centered on the amount of combined effect, and the "inverted funnel" type was generally symmetrical distribution. However, because the number of the included studies was less, the literature bias could not be completely eliminated.Conclusion Xuebijing injection may through its strong cytokines clearance, platelet increase and blood coagulation improvement to protect the organ function in patients with MODS, so as to reduce the mortality and improve the prognosis.

OBJECTIVETo investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system.

METHODSForty-five male Sprague-Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses.

RESULTSCompared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (P<0.01). The levels of serum resistin, and of resistin protein and mRNA in liver, were significantly higher in the MC group than in the NC group of rats (all P less than 0.01). The body weight of rats in the TP group was significantly lower than those in the MC group (P<0.05). The levels of serrn resistin, resistin protein and mRNA in the liver, and insulin resistance were significantly lower in the TP group than in the MC group of rats (all P<0.01). The PP group did not show significant differences in any of these measures, except for loss of body weight (P<0.05).

CONCLUSIONTelmisartan elicits preventive and protective effects in a NASH rat model.Telmisartan may improve insulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA.

Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Benzimidazoles ; Benzoates ; Cholesterol ; Diet, High-Fat ; Disease Models, Animal ; Insulin ; Insulin Resistance ; Male ; Non-alcoholic Fatty Liver Disease ; Rats ; Rats, Sprague-Dawley ; Resistin ; Triglycerides

Shengmai formula,composed of Ginseng Radix et Rhizoma,Ophiopogon Radix and Schisandrae Chinensis Fructus,is a classic and famous formula.It is a representative formula for"supplementing qi,nourishing yin,and generating fluid"in Traditional Chinese Medicine theory.To date,a wide range of Shengmai formulae have been developed according to different medical applications,but the quality evaluation standards are at a relatively low level,and most of them only specify the individual components of a single herb,making it difficult to ensure clinical efficacy and safety.At the same time,the physical and chemical identification methods of Shengmai formula have been constantly updated,allowing for greater progress in research on its main chemical components such as saponins,lignans and flavonoids.However,there is little systematic summarization of the chemical components and analytical methods.Based on the existing references,we systematically summarized ginsenosides,ophiopogonins,schisandra lignans,homoisoflavonoids and some other compounds in this paper,as well as the quality standards of Shengmai formulae and their analytical methods in order to aid clinical research and formulation manufacture.