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OBJECTIVE:To provide theoretic basis for the design and synthesis of novel high-activity biaryl aminothiazineβ-amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor,the research and development of new AD therapy drugs. METHODS:Totally 41 molecules of biaryl aminothiazine BACE1 inhibitors were selected. By SYBYL-X 2.0 software package, CoMFA and CoMSIA method were used to construct 3D-QSAR model of derivatized compounds. Surflex-dock molecular docking was applied to analyze binding mode of the compounds with BACE1. RESULTS:The q2 value of 3D-QSAR model established by CoMFA and CoMSIA method were all higher than 0.5,indicating good predictability. The established three dimensional contour plots could manifest the effect of substituents at different sites on activity of compounds. Surflex-dock analysis showed that biaryl aminothiazine and amino acid residues as ASP80, ASP276 and TYR246 in BACE1 had a key effect on hydrogen bonds. CONCLUSIONS:3D-QSAR model established on the basis of biaryl aminothiazine derivatized compounds show good predictability,which provides guidance for the structure optimization of the compound. TYR246 may be another potential active functional residue of biaryl aminothiazine inhibitor compound molecule combined with BACE1. Through 3D-QSAR analysis and molecular docking,new biaryl aminothiazine BACE1 inhibitor can be designed and synthesized so as to research and develop new drugs for AD.
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Human infection with avian influenza A (H7N9) is an acute contagious respiratory disease. Acute respiratory distress syndrome (ARDS) is a common complication in patients with severe avian influenza A (H7N9), for whom mechanical ventilation (MV) is an important supportive method. A patient, suffered from severe avian influenza A (H7N9) and complicated with ARDS, was admitted to the Second Affiliated Hospital of Guizhou Medical University in January 2017. With very intensive care for oxygenation, respiration and consciousness, and monitoring, she was successfully cured by comprehensive managements, among which noninvasive mechanical ventilation (NIV) was the major respiratory support method. The result demonstrate that, in patients with conscious state, satisfied expectoration ability and relatively good cooperation, and with close observation of oxygenation and respiratory rate, NIV may be accepted as an effective method for patient with ARDS caused by severe avian influenza A (H7N9).
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To investigate the sources of inconsistent findings between two randomized control trials ["initiation strategies for renal-replacement therapy in the intensive care unit" (AKIKI trial)vs "effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury" (ELAIN trial)],regarding "timing of renal replacement therapy (RRT) on mortality in patients with acute kidney injury (AKI).By reanalysis of the published data,it was found that demographics,severity of primary disease and stage of AKI before initiation of RRT were quite different between AKIKI and ELAIN trials.Interestingly,similar mortalities were demonstrated in late group of ELAIN trial,both of early and late groups of AKIKI trial [all patients were classified at Kidney Disease:Improving Global Outcomes (KDIGO) classification stage 3 of AKI,P＞0.05] although a significant reduction of mortality was determined in early group of ELAIN trial (KDIGO stage 2 of AKI).Therefore,it was concluded that inconsistent results were largely attributable to the heterogeneity of enrolled patients between ELAIN vs AKIKI trials,including demographics and severity of AKI(AKI stage) before initiation of RRT.
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Objective To investigate the clinical characteristics of DCD donor-derived CRKP infection and bleeding in kidney transplantation,and to summarize the experience of diagnosis,treatment and prevention.Methods A retrospective analysis was carried out from July 2016 to December 2017 in hospital,containing clinical data of 4 cases of CRKP-infected DCD donors and 7 cases of kidney transplantation recipients.Results In the CRKP culture of 4 cases of DCD donors,1 case was positive for blood culture,1 case was positive for urine culture,1 case was positive for sputum culture,and 1 case was negative for blood,urine and sputum culture.The corresponding 7 recipients were all positive for blood culture after renal transplantation,4 cases were positive for urine culture,3 cases were positive for sputum culture,and 5 cases were positive for perirenal drainage.Of the 7 patients,4 cases had renal artery hemorrhage,1 of them was died.The average bleeding time was 17.75 days after operation (14-19 days).In 7 patients with renal transplantation,CRP increasd.And in 3 cases of deaths,CRP was stably higher than normal.Meanwhile,CRP in 4 surviving patients gradually decreased to the normal range after effective anti-infection treatment.All 7 patients were treated with carbapenems;2 patients were dead without avibactam therapy;and 5 cases were treated with avibactam and carbapenems and survived,1 case died and 1 case had good renal function recovery.Conclusion Positive CRKP in blood,urine and sputum of DCD donors can lead to CRKP infection in kidney transplant recipients.Even if the body fluids of donors are all negative,the false negative results could not be excluded.Persistent or increased high-level CRP after operation is an early warning on CRKP infection.And CRP can be used as an indicator for evaluating the effectiveness of anti CRKP therapy.The combination of avibactam and carbapenem antibiotics is an effective regimen in the treatment of DCD donor-derived CRKP.
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Objective To analyze the maternal mortality in Sichuan province from 2015 to 2016 for the purpose of providing reference for the department of health and family planning,medical and health care institutions to take measures to reduce maternal mortality.Methods The death assessment panel reviewed 163 cases of maternal mortality data in Sichuan province from 2015 to 2016 in accordance with "twelve grid method" of the World Health Organization(WHO).The findings were descriptively analyzed.Results Provincial level had completed 163 cases of maternal death review,and it suggested that obstetric hemorrhage,pregnancy induced hypertension,venous thrombosis and pulmonary embolism,heart disease,amniotic fluid embolism were the five leading causes of maternal mortality in Sichuan province.Among the 163 evaluated death cases,death could be avoided in 124 cases(76.07％) and death was unavoidable in 39 cases(23.93 ％).According to the first influencing factors,among 124 cases of avoidable deaths in medical records,the death of 67 cases(54.03％) was caused by medical staff knowledge and skills,ranking first,including the county(37.90％) and township(5.65％);the death of 57 cases was caused by the personal family,accounting for 45.97％.Conclusion It's important for the reduction of maternal mortality in Sichuan province to strengthen standardized management of high-risk pregnant women,ensure the timely supply of blood resources in remote areas,and enhance the training of emergency medical knowledge for obstetric medical personnel.
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Objective To summarize the measures for nursing mechanical ventilated patients who suffered from respiratory failure caused by acute severe organophosphorus pesticide poisoning (ASOPP). Method Retrospectively, the nursing clinical data of 18 mechanically ventilated patients who suffered from ASOPP-induced respiratory failure in ICU from January 2013 to December 2014 were analyzed for summarizing the nursing measures concerning preventive extubation, airway humidification and sputum sucking, prevention of ventilator-associated pneumonia and final extubation. Result Sixteen ASOPP patients successfully recovered after hospital discharge and another two died from multiple organ function failure because of excessive pesticides. Conclusions Effective observation and nursing care of airways based on their characteristics in ASOPP patients including prevention of unexpected shedding , appropriate humidity of airways and prevention of infection of ventilator-associated pneumonia(VAP). All of these measures can reduce complications and contribute to the early recovery of patients.
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Objective To compare the incidences of agitation and circulatory fluctuation in mechanically ventilated patients receiving different sedatives for daily arousal,and develop a safe sedation strategy.Methods Ninety four patients in ICU,who received mechanical ventilation over 24 hours,were selected from five clinical centers.Based on the analgesia with continuous pumping of fentanyl,patients were randomly given midazolam(M group),propofol(P group)or sequential midazolam-propofol(M-P group)for sedation.The depth of sedation was maintained within SAS 2-4 by close monitoring.The administration of all sedatives and analgesics was terminated at 9:00 am till patients were fully waked up.The incidence of agitation,blood pressure,heart rate fluctuation,patients' arousal time,and their recollection to actual mechanical ventilation events after been transferred out of ICU were investigated.Results The mean SAS scores showed no difference in each group.The arousal time was significantly longer in group M than that in other two groups(P
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0.05).61 patients received no sedatives nor analgesics showed significantly higher incidence of SUE compared with those patients received either sedatives or analgesics(73.8% vs 37.3%,P
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Objective To investigate morbidity and analyze high risk factors of nosocomial infection in patients who underwent orthotopic liver transplantation (OLT) in our ICU, in order to draft possible preventive strategies. Methods The clinical data of 56 OLT patients from Apr 2002 to Dec 2004 were analyzed. Results Significantly high APACHE Ⅱ scores and total plasma bilirubin, low platelet count were found in patients with nosocomial infection. The number of patients who had received an additional operation and broad-spectrum antibiotics before OLT were greater in nosocomial infection (NI) group than in none-nosocomial infection (NNI) group. Notably, the longer the broad-spectrum antibiotics used before OLT, the higher the morbidity rate of nosocomial infection. No significant difference was found in age, Child-Pugh grade and plasma albumin level between the two groups. In addition, APACHE Ⅱ scores and total bilirubin level were significantly higher in patients acquired enterococcal infection than in those infected with other pathogenic microorganisms. Conclusions High APACHE Ⅱ score, high total bilirubin level, low platelet count and length of use of broad-spectrum antibiotics before OLT were closely associated with nosocomial infection. As an important indicator, change in total bilirubin level not only represented the liver function ,but also was one of the high risk factors to nosocomial infection in patients undergoing OLT.
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Objective Post-operative hypoxemia occurred frequently after extubation in patients who underwent orthotopic liver transplantation (OLT) in ICU. This study is to investigate the efficiency of hyperoxia solution in improving oxygenation. Methods Ten OLT cases, who post-operatively manifested hypoxemia after extubation, were enrolled in this study. Hyperoxia Ringer's solution (500ml) prepared by Jing-Shu-Yang (an apparatus of oxygen supply, Vanform Co., Shandong) was infused at a rate of 200ml/hr. Hemodynamic parameters, blood gas, and blood lactate were determined at the beginning, end of infusion, and 1 hour after the infusion, with recording of the following data: heart rate (HR), mean arterial pressure (MAP), pulmonary arterial pressure (PAP), and pulmonary capillaries wedged pressure (PCWP). Results Compared with the levels at the beginning of infusion, SpO2 and SvO2 increased significantly at the end of the infusion of 500 ml hyperoxia Ringer's solution, and they returned to the baselines 1 hour later, although regular Ringer′s solution was coutinuously given by the same infusion rate. HR, MAP and PCWP were kept stable with the solution infusion. Notably, PAP was decreased markedly at the end of infusion, and blood lactate level remained unchanged after the intervention. Conclusion Hyperoxia Ringer's solution infusion improved oxygenation in OLT patients who suffered from acute lung injury with hypoxemia postoperatively. PAP decreased markedly as hypoxemia was corrected.
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Objective To analyze causative factors and treatment of acute lung injury (ALI) after liver transplantation. Methods the correlative parameters, including electrocardiogram, blood oxygen saturation, blood pressure, hemodynamics, blood sugar, analysis of arterial blood gases, and other clinical examinations were monitored dynamically. The recipients were treated with oxygen inhalation, antibiotics, immunosuppressant, drugs for liver protection, nutritional support, diuretics, and vasodilators. Results Three of a total of 21 patients died within 48h post operation. Fourteen patients suffered from ALI (14/18, 77 8%), who recoverd after receiving appropriate treatment. Conclusion The occurrence of ALI is related to the primary disease, operative trauma, instability of the hemodynamics, and the quantity of blood loss. Systemic treatment is necessary for the patients with ALI besides the oxygen therapy.