Objective To investigate the value of drug intervention for difficult weaning from mechanical ventilation. Methods A prospective single-blind randomized controlled trial was conducted. 120 patients with difficult weaning from mechanical ventilation encountered in Department of Critical Care Medicine of Peking University Third Hospital from January 2008 to December 2013 were included,and the patients were divided into treatment group and control group according to random number table,with 60 cases in each group. Patients received furosemide therapy in the treatment group 3 days before weaning up to 48 hours after weaning in order to control negative liquid balance. Enema was given the day before weaning to reduce abdominal pressure. On the weaning day,all of the patients received nitroglycerin and beta blocker or cedilanid to prevent or control elevation of blood pressure and heart rate in the process of weaning. All patients in treatment group received anisodamine in small dosage 2 hours before extubation.The patients in control group received conventional treatment without drug intervention. Baseline indexes of two groups were compared,including the heart rate,respiration rate(RR),mean arterial pressure(MAP),pulse blood oxygen saturation(SpO2),blood gas,hemoglobin(HG),albumin(ALB)and creatinine(Cr). The main reasons of difficulty in weaning,sedative and analgesic drug selection,presence of abdominal discomfort before weaning,interval between sputum suction before extubation,liquid balance at the beginning of the investigation and at time of weaning,24 hours and 48 hours after weaning,failures of spontaneous breathing test(SBT),length of mechanical ventilation,length of ICU stay,and total length of mechanical ventilation and total length of ICU stay during hospitalization. Results There was no statistically significant difference in the heart rate,RR,MAP,SpO2,blood gas,HG,ALB,Cr at the beginning of the investigation between the two groups. The main reasons for difficult weaning in both groups of patients were respiratory dysfunction,cardiac insufficiency,and central nervous system dysfunction. The use of propofol combined dexmedetomidine in the treatment group was more frequent than the control group〔16.7%(10/60)vs. 1.7%(1/60),χ2=8.107,P=0.004〕,and there was no statistically significant difference in the use of other combinations of sedative drugs between the two groups. Abdominal discomfort before weaning was milder in treatment group as compared with control group〔10.0%(6/60)vs. 25.0%(15/60),χ2=4.675,P=0.031〕. The interval between sputum suction before extubation in the treatment group was significantly longer than that of the control group〔hours:1(1,2)vs. 1(1,1),Z=-2.209,P= 0.027〕. SBT failure was less frequent in treatment group compared with control group〔times:0(0,1)vs. 1(1,2),Z=-6.561,P=0.000〕. Liquid balance was better in the treatment group than the control group at time of weaning,24 hours and 48 hours after weaning〔at time of weaning:-567.71 (-755.95,-226.41)vs. 1 256.76(472.48,1 796.63),Z=-9.038,P=0.000;24 hours after weaning:-5.03 (-530.28,245.09)vs. 342.28(125.36,613.25),Z=-4.711,P=0.000;48 hours after weaning:115.50(-450.26, 485.00)vs. 330.00(16.25,575.25),Z=-1.932,P=0.053〕. Compared with control group,length of mechanical ventilation〔days:1.0(1.0,2.0)vs. 2.0(2.0,3.0),Z=-6.545,P=0.000〕,ICU stay time〔days:3.0(3.0,4.0) vs. 4.0(4.0,5.0),Z=-6.545,P=0.000〕,and total length of mechanical ventilation〔days:8.0(6.0,12.0)vs. 11.0(8.0,15.0),Z=-4.091,P=0.000〕and total length of ICU stay during hospitalization〔days:12.5(9.2,19.0) vs. 17.0(12.0,29.5),Z=-2.722,P=0.000〕were all significantly shorter in the treatment group. Conclusions Adjuvant drugs therapy is helpful in patients weaning from the mechanical ventilation,and can shorten length of mechanical ventilation and ICU stay time. Propofol,combined dexmedetomidine,is helpful for weaning.

Recent years, chemical constituents from spice volatile oils have gained worldwide concern owing to its multiple pharmacological effects and safety for using as the natural antibacterial agents. However, their poor dissolution, strong volatility, serious irritation, weak stability, easy oxidation and low bioavailability characteristics are the major obstacle in the preparation of effective oral formulation and practical application. Therefore, there is an urgent need to select a novel carrier system that can delivery the chemical constituents from spice volatile oils more efficiently with improving their stability as well as alleviating the irritation, and develop the functional food, health products and even medicine for exerting their pharmacological effects, which also is the focus and nodus of the research on their application. This review presents recent systematic studies on their novel carrier systems, including cyclodextrin inclusion complex, liposomes, nanoemulsions, nanoparticles, solid dispersion and so on, and summarizes the characteristics, application range and problems of each novel carrier systems, in order to provide some beneficial thoughts in further developing new products of chemical constituents from spice volatile oils.
Chemistry, Pharmaceutical ; instrumentation ; methods ; Drug Carriers ; chemistry ; Nanoparticles ; chemistry ; Oils, Volatile ; chemistry ; Plant Extracts ; chemistry ; Spices ; analysis

Objective To investigate the radiosensitiation effect of berberine on human nasopharyngeal carcinoma ( NPC) in hypoxia condition and explore the underlying mechanisms. Methods MTT assay, clonogenic assay and flow cytometry were performed to analyze cell proliferation, colony formation and apoptosis, respectively. Male nude mice inoculated subcutaneously with CNE-2 cells were used to examine the radiosensitization effect of berberine in vivo. The expressions of HIF-1α and VEGF were assessed by Western blot. Results Berberine efficiently inhibited the proliferation of CNE-2 cells in time-dependent and dose-dependent fashions with an IC50 of ( 14?9 ± 2?2 ) μmol/L. Clonogenic survival assay showed that berberine ( 5 μmol/L ) sensitized CNE-2 cells to ionizing radiation in hypoxia and its SERD0 was 1?27. Under hypoxic condition, berberine alone (5, 15 μmol/L) could induce apoptosis (t=5?01, 9?02,P<0?05) and it further promoted 8 Gy radiation-induced apoptosis (t =5?31, 9?91,P <0?05). Moreover, berberine significantly delayed the tumor growth in the combination group (berberine +irradiation) compared with the mice received irradiation alone or PBS (t =2?96, 14?52, P <0?05). Immunobloting assay showed that berberine inhibited the upregulation of HIF-1α and VEGF induced by hypoxia in CNE-2 cells. Conclusion Berberine confers radiosensitivity on hypoxic NPC in vitro and in vivo, which is probably associated with the downregulation of HIF-1α and VEGF expressions.

Objective The construction of suicide plasmid vector could be used to make mutation of pgm gene which attenuates the virulent of Brucella melitensis strain 16, the research may lay a foundation for the development of novel live attenuated vaccines. Methods Sucrose sensitive gene as forward screening sign and fusion sequences of kanamycin resistance gene were constructed based on plasmid pucl9; pucS1.6K suicide plasmid vector was established by modifying pgm gene with fusion sequences of kanamycin resistance gene (insertion mutation); pgm gene mutation of Brucella melitensis strain 16 was obtained by electro transformation and mutation was confirmed by PCR amplification. Results The results showed that the identified Brucella melitensis strain 16 pgm gene was inactivated after insertion of kanamycin resistance gene, and the mutant pgm gene DNA fragment length was approximately 3525 bp, in line with expectations, Brucella pgm gene mutant melitensis strain 16 was successfully constructed. Conclusions The construction of suicide plasmid vector and precise mutation of Brucella melitensis strain 16 is successful, the study is not only provided an effective technology platform for constructing mutants of Brucella but also lays a foundation for the development of novel live attenuated vaccines.

In this study, OVA-induced asthma mice was taken as the model, and orally administered with different concentration of ethanol extracts of crude and processed Stemona tuberosa, in order to determine the cytokine level released from Th1 and Th2 in splenocytes. RT-PCR was carried out to determine the genetic expression of T-bet/GATA-3 in lung, and compare the differentiation between ethanol extracts of crude and processed S. tuberosa in therapeutic effect on asthma in mice. According to the results, compared with the crude samples, processed samples significantly increased the levels of inflammatory factor INF-gamma (P < 0.05) and decreased IL-5 (P < 0.05) in splenocytes. According to the RT-PCR results, the administration of processed samples could increase the ratio of T-bet/GATA-3 (P < 0.05). The experiment showed that ethanol extracts of both crude and processed S. tuberosa could treat asthma by regulating Th1/Th2 ratio, but processed samples showed more notable effect. This indicated that crude and processed S. tuberosa had significant pharmacological difference. Therefore, it was more rational to apply processed S. tuberosa in clinical treatment of asthma and chronic cough, which layed a foundation for further revealing the processing mechanism of S. tuberosa.
Administration, Oral ; Animals ; Asthma ; drug therapy ; immunology ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; GATA3 Transcription Factor ; metabolism ; Gene Expression Regulation ; drug effects ; Mice ; Mice, Inbred BALB C ; Stemonaceae ; chemistry ; T-Box Domain Proteins ; metabolism ; Th1 Cells ; drug effects ; secretion ; Th2 Cells ; drug effects ; secretion

Objective:To explore the effect of ulinastatin on prevention of acute respiratory distress syn-drome (ARDS).Methods:A prospective multicentral cohort study was conducted.The patients from three intensive care units (ICUs)of grade A tertiary hospitals in Beijing and a ICU of grade A tertiary hospitals in Cangzhou from January 2012 to December 2014,included 77 ARDS at-risk patients with uli-nastatin treatment and 108 ARDS at-risk patients without ulinastatin treatment (control)were eligible. Both groups received normal treatment;additionally,the intervention group received 600 000 units of uli-nastatin via intravenous infusion for 5 days.The control group received the same amount of saline via in-travenous infusion for 5 days.Venous blood human neutrophil elastase (HNE)and peptidase inhibitor 3 (PI3)levels were measured on days 1,3,and 7,respectively.Other outcomes included acute physiolo-gy and chronic health evaluation scoring Ⅱ (APACHE Ⅱ),body temperature,respiratory rate,heart rate,mean arterial pressure,white blood cell counts,PaO2 /FiO2 ,ARDS incident,mechanical ventila-tion time,ICU treatment and hospitalization duration,28 days mortality.Results:The PI3 levels showed no statistical difference on day 1,but significant differences on day 3 and day 7 between the two groups (P <0.01).HNE /PI3 ratio showed no statistical difference on day 1,but significant differences on day 3 and day 7 (P <0.05).PaO2 /FiO2 was significantly higher in ulinastatin group on day 3 and day 7 (P <0.05).The incident rate for ulinastatin group was 15.58%,lower than that for the control group (33.33%),and the difference was statistically significant (P <0.05).The mechanical ventilation time and ICU treatment time in ulinastatin group was shorter than that in the control group,and the difference was statistically significant (P <0.05).There were no significant effects in other factors.Conclusion:Increased dose of ulinastatin can recover the balance of HNE and its antagonist,lower the HNE’s damage to lungs,and further reduce the ARDS incident rate.

ObjectiveTo investigate the diagnostic value of EUS-FNA for pancreatic masses and correlated influential factors. MethodsWe retrospectively analyzed the clinical data of 101 patients with pancreatic lesions who underwent EUS-FNA from January 2008 to January 2010. The clinical data enrolled 10 factors including patient gender, patient age, lesion location, lesion size, lesion characteristics, negative suction pressure, times of access, real-time cytological diagnosis, type of EUS and operators' experiences.ResultsThe overall diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EUS-FNA were 85. 1％, 81.1％, 96. 3％, 98. 4％ and 65.0％, respectively. Univariable logistic regression analysis indicated that lesion size, lesion characteristics, negative suction pressure, operators' experience were correlated factors of EUS-FNA positive rate, while lesion size was the only correlated factor of EUS-FNA diagnostic accuracy ( OR =1. 984,95 ％ CI: 1. 141 ～ 3. 451, P =0. 015 ). Every 1 cm the lesion increased, by 1.67 times of opportunity the positive rate became, by 1.83 times of opportunity the accuracy was. The lesion size and lesion characteristics were independent correlated factors of EUS-FNA positive rate (OR=2.012, P=0.000; OR =10.218, P=0. 002). The positive rate of EUS-FNA in solid lesions was 10. 2 times of that in cystic lesions. Lesion size was the independent correlated factors of EUS-FNA diagnostic accuracy (OR =1. 984, P =0. 015 ). ConclusionEUS-FNA can effectively make a pathological diagnosis of pancreatic masses with high diagnostic accuracy and specificity. EUS-FNA diagnostic positive rate and accuracy were both positively correlated with pancreatic lesion size. EUS-FNA positive rate of solid pancreatic lesions is significantly higher than that of cystic lesions.

Dry powder inhalers (DPIs) have received considerable attention because of their propellant-free composition and stability. DPIs include the DPI devices and inhalation powders. The purpose of this review is to address the development of the DPIs, including the mechanisms of absorption, the products, the devices, the preparation technology, and the characteristics.
Administration, Topical ; Drug Delivery Systems ; Dry Powder Inhalers ; Lung ; Technology, Pharmaceutical ; methods

Objective To investigate the neuroimaging features in mitochondrial encephalomyopatbies with lactic acidosis and stroke-like episodes(MELAS).Methods Twenty-two clinically diagnosed patients who came from department of neurology,Huashan hospital in October 2003 to July 2006 were analyzed for CT,MRI,MRI contrast,MRA and MRS.Results In all 22 patients,the neuroimaging results of 21 were positive.There were 9 patients lying in hemisphere,12 in both cerebral hemispheres,including occipital,parietal,temporal and frontal lobe.The abnormal areas showed low signal intensity on T_1-weighted MRI,high signal intensity on T_2-weighted MRI and fluid attenuated inversion recovery(FLAIR)images.The lesions of 12/16 patients on MR contrasted images were enhanced.The lesions of one patient showed malacoma-like changes,one showed Fahr syndrome' s change and another showed high signal intensity on MR contrasted images.Conclusion Although the neuroimaging features of MELAS are complicated,the specific ones could help to make the diagnosis.

Asymmetric reduction of bulky diaryl ketones is still one of the challenging tasks in biocatalysis. By genomic data mining, a putative carbonyl reductase gene pascr was found in Pichia pastoris GS115. pascr was cloned and over-expressed in Escherichia coli Rosseta2 (DE3). The recombinant enzyme was purified to homogeneity by Ni-NTA column and its catalytic properties were studied. PasCR strictly used NADPH as cofactor, gel filtration and SDS-PAGE analysis suggested that the native form of PasCR was a dimmer. PasCR exhibited the highest activity at 35 degrees C in phosphate buffer at pH 6.5. The enzyme catalyzed the reduction of some bulky diaryl ketones, such as 4-methylbenzophenone, 2-methylbenzophenone and 4-chlorobenzophenone, especially for 4-methylbenzophenone, the product S--alcohol was obtained with 85% ee.
Alcohol Oxidoreductases ; genetics ; Amino Acid Sequence ; Catalysis ; Cloning, Molecular ; Ketones ; chemistry ; Molecular Sequence Data ; Pichia ; enzymology ; genetics ; Stereoisomerism