Objective To explore the preventive effect of multidisciplinary collaborative evidence-based nursing on dysphagia in patients with orotracheal intubation in intensive care unit(ICU)after extubation.Methods A retrospective analysis was performed on 200 patients with orotracheal intubation in ICU who were admitted to Dongguan Traditional Chinese Medicine Hospital between January and December 2023.Of them,96 patients who were admitted to our hospital between January and May 2023 received routine nursing(routine group),104 patients who were admitted to our hospital between June and December 2023 received multidisciplinary collaborative evidence-based nursing(evidence-based group).The incidence of dysphagia after extubation,water swallowing test result,swallowing function measured with M.D.Anderson dysphagia inventory(MDADI),psychological state assessed by connor-davidson resilience scale(CD-RISC),quality of life assessed by swallowing quality-of-life questionnaire(SWAL-QOL),and the incidence of dysphagia complications(aspiration,aspiration pneumonia,and malnutrition)were compared between the two groups.Results The incidence of dysphagia after extubation and the water swallowing test class in the evidence-based group were lower than those in the routine group(both P<0.05).The total score of MDADI and CD-RISC scores in the evidence-based group were significantly higher than those in the routine group(P<0.05),while the SWAL-QOL scores were lower(P<0.05).The incidence of complications in the evidence-based group was significantly lower than that in the routine group(P<0.05).Conclusion Multidisciplinary collaborative evidence-based nursing can effectively reduce the incidence of dysphagia in patients with orotracheal intubation in ICU after extubation,improve swallowing function,psychological state and quality of life,and reduce the incidence of complications.

AIM:To appraise the bioequivalence and safety of the test preparation of ritonavir tab-lets and the reference preparation(trade name:Norvir?)in healthy adult subjects under fasting and postprandial conditions.METHODS:This study was a randomized,open-label,single-dose,four-period,fully repeated crossover design bioequivalence study protocol.Thirty-six healthy male and female volunteers were enrolled in the fasting and post-prandial conditions,and a single dose of the test preparation and reference preparation was orally administered.We used liquid chromatography-tan-dem mass spectrometry(LC-MS/MS)to finish the bioassay of the drug concentration of ritonavir in plasma.Pharmacokinetic parameters were statisti-cally analyzed using PhoenixWinNonlin8.1 software(Pharsight,USA)and a non-compartmental model.RESULTS:Under fasting conditions,the pharmacoki-netic parameters of the test and reference prepara-tions:Cmax(792.010±369.282)ng/mL and(856.939±394.427)ng/mL,AUC0-t(6 463.043±2 876.849)ng·mL-1·h and(6 907.690±3 046.132)ng·mL-1·h,AUC0-∞(6 603.617±2 916.352)ng·mL-1·h and(7 051.614±3 093.047)ng·mL-1·h.Here are the pharmacokinetic parameters for both the test prep-aration and the reference preparation in the post-prandial condition:Cmax(574.380±289.566)ng/mL and(615.796±297.382)ng/mL,AUC0-t(5 084.796±2 435.557)ng·mL-1·h and(5 414.167±2 416.952)ng·mL-1·h,AUC0-∞(5 219.144±2 487.793)ng·mL-1·h and(5 551.060±2 490.604)ng·mL-1·h.The 90%confidence interval of the geometric mean ratio of AUC0-t,AUC0-∞,and Cmax for the test preparation and reference preparation lied in the equivalent range of statistics.CONCLUSION:The tested preparation was bioequivalent to the reference preparation un-der fasting and postprandial conditions.

AIM:To appraise the bioequivalence and safety of the test preparation of ritonavir tab-lets and the reference preparation(trade name:Norvir?)in healthy adult subjects under fasting and postprandial conditions.METHODS:This study was a randomized,open-label,single-dose,four-period,fully repeated crossover design bioequivalence study protocol.Thirty-six healthy male and female volunteers were enrolled in the fasting and post-prandial conditions,and a single dose of the test preparation and reference preparation was orally administered.We used liquid chromatography-tan-dem mass spectrometry(LC-MS/MS)to finish the bioassay of the drug concentration of ritonavir in plasma.Pharmacokinetic parameters were statisti-cally analyzed using PhoenixWinNonlin8.1 software(Pharsight,USA)and a non-compartmental model.RESULTS:Under fasting conditions,the pharmacoki-netic parameters of the test and reference prepara-tions:Cmax(792.010±369.282)ng/mL and(856.939±394.427)ng/mL,AUC0-t(6 463.043±2 876.849)ng·mL-1·h and(6 907.690±3 046.132)ng·mL-1·h,AUC0-∞(6 603.617±2 916.352)ng·mL-1·h and(7 051.614±3 093.047)ng·mL-1·h.Here are the pharmacokinetic parameters for both the test prep-aration and the reference preparation in the post-prandial condition:Cmax(574.380±289.566)ng/mL and(615.796±297.382)ng/mL,AUC0-t(5 084.796±2 435.557)ng·mL-1·h and(5 414.167±2 416.952)ng·mL-1·h,AUC0-∞(5 219.144±2 487.793)ng·mL-1·h and(5 551.060±2 490.604)ng·mL-1·h.The 90%confidence interval of the geometric mean ratio of AUC0-t,AUC0-∞,and Cmax for the test preparation and reference preparation lied in the equivalent range of statistics.CONCLUSION:The tested preparation was bioequivalent to the reference preparation un-der fasting and postprandial conditions.

Objective To explore the effect of 2-aminoethoxy-diphenyl borate(2-APB)on H2O2-induced chondro-cyte apoptosis and its mechanism.Methods The experiment was divided into control group,H2O2 group,2-APB group and H2O2+2-APB group.CCK-8 method was used to detect the cell viability of each group;The effect of 2-APB on the morphological changes of chondrocytes induced by H2O2 was observed under microscopy;TUNEL meth-od and flow cytometry were used to detect chondrocyte apoptosis;Flow cytometry was used to detect Lipid reactive oxygen species(ROS);Western blot was used to detect the protein expressions of Cleaved-PARP,p-PKCα and HIF-1α in H2O2-induced cells by 2-APB;Immunofluorescence was used to detect the fluorescent expression of HIF-1α in cells induced by H2O2 by PKCα inhibitor BIM-1.Results 2-APB inhibited H2O2-induced apoptosis in chon-drocytes,and the inhibitory effect was the most significant when the concentration of 2-APB was 100 pmol/L(F=235.80,P＜0.01);22-APB could inhibit the positive rate of H2O2-induced apoptosis of chondrocytes(F=114.80,P＜0.01)and the level of ROS(F=52.99,P＜0.01).and inhibited the expression of Cleaved-PARP(F=10.10,P＜0.05),p-PKCα(F=24.56,P＜0.05)and HIF-1α proteins(F=6.85,P＜0.05).The PKCα in-hibitor BIM-Ⅰ could inhibit the increase in HIF-1α fluorescence intensity caused by H2O2.Conclusion 2-APB can inhibit chondrocytes apoptosis induced by H2O2 through the PKCα/HIF-1α pathway and thus protect chondro-cytes.

Objective:To evaluate the global and segmental myocardial work in patients with cardiac amyloidosis (CA) by left ventricular pressure-strain loop (PSL) noninvasively.Methods:Eighteen patients with CA in Beijing Chao-Yang Hospital from March 2018 to December 2020 were included as CA group, 20 healthy subjects were selected as control group. The global longitudinal strain (GLS) and mechanical dispersion (MD) of left ventricle were analyzed by two-dimensional speckle tracking imaging. The left ventricular PSL was used to assess global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE). The mean value of left ventricular basal, mid and apical myocardial work index (MWI), constructive work (CW), waste work (WW) and work efficiency (WE) were calculated and compared between the two groups.Results:①Compared with the control group, GLS was decreased and MD was increased in CA group (all P<0.05). ②GWI, GCW, GWW and GWE were decreased in CA group compared with the control group (all P<0.05). ③In CA group, the MWI, CW and WE of the basal, mid and apical segments were lower than those of control group (all P<0.05), WW of the basal and mid segments were lower than those of apical segment(all P<0.05). The impairment of MWI, WW and WE in basal and mid segment were more significant than those of apical segment (all P<0.05). ④GWI, GCW and GWE were positively correlated with GLS ( r=0.854, 0.816, 0.748; all P<0.001) and LVEF ( r=0.674, 0.634, 0.650; all P<0.01), and negatively correlated with MD ( r=-0.657, -0.672, -0.710, all P<0.01). GWI and GCW were negatively correlated with E/e′ ( r=-0.493, -0.539; all P<0.05). Conclusions:The global, basal, mid and apical left ventricular myocardial work indices are decreased in CA patients. MWI, CW and WE show an apical sparing pattern. Quantitative assessment of myocardial work by PSL may provide more valuable information for CA patients.

Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile -cyclodextrin (-CD) metal-organic framework (CD-MOF) large molecular cages in which azilsartan (AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague-Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering (SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the -CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six -CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.

Objective To study and compare the efficacy of surgery and conservative treatments for patients with critical(30 to 50 ml) spontaneous deep supratentorial intracerebral hemorrhage. Methods The clinical data of 420 patients diagnosed as spontaneous deep supratentorial intracerebral hemorrhage in Affiliated Hospital of Yan'an and Central Hospital of Baoji from August 2011 to September 2016 in this study were retrospectively analyzed. All patients were divided into surgery group(210 cases) and conservative group(210 cases) according to the difference of treatment methods. Large trauma craniotomy was used by the operation group, external ventricular drainage as the standby in necessary. The treatment of conservative group mainly included reduction of intracranial pressure, blood pressure management, prevention of complications and other individualized treatment. The primary outcome was neurological functional status of patients at 6 months of discharging, and the secondary outcomes included the mortality at 1 month and 6 months of discharging, and complications. Continuous data were presented as (x)± s and were compared using the t test, while categorical data were presented as number and percentage and were compared using the χ2 test. Results No obvious difference on mRS score and NIHSS score occurred between two groups(All P>0.05). Stratified analysis, patients with midline shift >5 mm and with intraventricular hemorrhage were more likely to have a favorable outcome from surgery compared with conservative group(18.2％ vs.8.1％, X =4.099, P=0.043; 17.3％ vs.5.0％, χ2 =4.836, P=0.028). The mortality at 1 month days and 6 months in surgery group were significantly lower than that in conservative group(19.0％ vs.31.0％, X2 =7.937, P=0.005; 23.8％ vs.36.7％, X2=8.228, P=0.004). Meanwhile, the incidence of pulmonary infection and with long-term pipe in surgery group were significantly higher than those in conservative group(31.9％ vs.15.7％, X2 =15. 173, P=0.000; 28.6％ rs.19.5％ =4.706, P=0.030). Conclusion Surgery can reduce the 1 month and 6 months mortality in patients with spontaneous deep supratentorial hemorrhage and improve the functional outcomes in patients with large midline shift or with intraventricular hemorrhage compared with conservative treatment.

Objective To evaluate the reliability and validity of the Chinese version of the Diabetes,Hypertension and Hyperlipidemia(DHL) Knowledge Instrument in community diabetic patients.Methods A face-to-face interview was conducted among 513 patients with diabetes in the community from January to March 2016 by using the Chinese version of DHL Knowledge Instrument.Forty of them were randomly sampled and reinvestigated 4 weeks later.The analyses on Cronbach's α coefficient,test-retest reliability,content validity,discriminant validity and construct validity were performed to evaluate reliability and validity of the DHL Knowledge Instrument.Results The qualified questionnaires were collected from 488 participants,including 232 males and 256 females with a mean age of (66 ± 6)years.The overall scores of the Chinese version of DHL Knowledge Instrument was 67.7 ± 18.0 and the scores of diabetes,hypertension,hyperlipidemia,medications and general issues sub-scales were 82.0 ± 22.5,65.9 ± 25.2,38.2 ± 34.3,75.5 ± 20.8 and 72.1 ± 22.9,respectively.The standardized Cronbach's α coefficient of the total scale was 0.849 and the test-retest reliability of the total scale was 0.706 (P ＜ 0.01).In term of content validity,the correlation coefficient was from 0.580 to 0.827 among total scale and sub-scales (P ＜ 0.01).In term of discriminant validity,the difference between the high and the low score group on total scale and sub-scales were significant (t value =-13.486 to-35.528,all P ＜ 0.01).In term of construct validity,based on exploratory factor analysis,the scale was revised.According to confirmatory factor analysis of revised scale,four factor model containing 20 items was well fitted (X2 =159.689,df =134,P =0.064);the GFI (goodness of fit index) =0.966,AGFI (adjusted goodness of fit index) =0.952,RMSEA (root mean square error of approximation) =0.020.Conclusion The Chinese version of DHL Knowledge Instrument possesses good reliability and validity and is suitable to evaluate the knowledge of community diabetic patients,and the modified version may work better than the original one.

Objective To explore the impact of TIMP 3 regulated by miR-181b as a target gene on invasion and migration of hepatocellular carcinoma (HCC) in vitro.Methods The expressions of miR-181b were detected using SYBR Green real-time fluorescence quantitative polymerase chain reaction on liver cancer specimens and on HCC cell lines.The protein expression of TIMP 3 in HCC was detected using westen blot,and SKHep-1 as a cell line expressing high miR-181b was chosen through reporter gene experiment.TIMP-3 as a target gene regulated by miR-181b and its effect on invasion and migration treated by anti-miR-181 b were studied using transwell and cell scarification test,respectively.Results The expression of miR-181b in HCC was higher than cancer-adjacent tissues and normal liver tissues.The differences among them were significant.There was a correlation between the high expression of miR-181b and invasiveness and metastasis in HCC.The protein expression of TIMP-3 in HCC was significantly lower than normal liver tissues and cancer-adjacent tissues.Expression of miR-181b mRNA was detected in various HCC cell lines such as Hep3B,HepG2,Huh 7,SKHep-1,SNU182,SNU449 and hepatocyte,with the expression of miR-181b in SKHep-1 being the highest (P＜0.01).TIMP3-3UTR was low when the expression of miR-181b was high (P＜0.05).The invasion and migration abilities of SKHep-1 were significantly inhibited by anti-miR-181b (P＜0.05).Conclusion The data suggested that miR-181b promoted invasion and migration of SKHep-1 by down-regulating TIMP-3 in HCC.