Objective:To explore the application effects of a teaching for understanding (TfU) model based on outcome-based education (OBE) in clinical nursing internship in dermatology.Methods:We assigned 34 nursing interns at the department of dermatology of a grade A tertiary hospital in Chengdu in 2021 to observation group to receive instruction using an OBE-based TfU model and another 34 nursing interns in 2022 to control group to be taught using a traditional teaching model. The two groups were compared for theoretical and practical assessment scores, core competencies, clinical communication, and satisfaction with teaching. SPSS 26.0 was used to perform the t-test and chi-square test. Results:The observation group had significantly higher scores than the control group for theoretical assessment [(90.63±2.84) vs. (85.84±4.50)] and practical assessment [(93.15±1.67) vs. (91.12±2.71)]; core competencies overall [(154.38±8.05) vs. (150.18±6.96)] and lifelong learning [(20.18±1.90) vs. (18.85±1.85)], general clinical skills [(23.06±3.30) vs. (18.85±1.85)], and critical thinking and reasoning ability [(11.68±1.47) vs. (10.62±1.41)]; and communication abilities overall [(90.94±5.36) vs. (84.50±5.79)] and harmonious relationship establishment [(20.21±1.86) vs. (18.76±1.92)], patient problem confirmation [(16.91±1.69) vs. (15.26±2.09)], keen listening [(17.35±1.32) vs. (15.44±2.06)], and effective information transmission [(8.91±1.60) vs. (7.85±1.73)] compared with the control group (all P<0.05). The score of satisfaction with teaching of the observation group was significantly higher than that of the control group [(94.12±4.99) vs. (90.53±7.38), P<0.05). Conclusions:The TfU model based on OBE can effectively improve nursing students' theoretical and practical assessment scores, core competencies, communication skills, and satisfaction with internship teaching, which is conducive to their all-round development and professional practice. In addition, this study provides innovative ideas and reform directions for clinical nursing practice teaching.

Objective To construct and validate a risk prediction model for poor inhalation in chronic obstructive pulmonary disease(COPD)patients receiving inhaler therapy,providing a decision support tool for personalized prevention of poor inhalation.Methods A cross-sectional study was conducted to collect data related to COPD patients receiving inhaler therapy,forming a dataset.The dataset was randomly divided into a training set and a test set in a ratio of 4∶1.Four different methods for missing value imputation,3 methods for variable feature selection,and 18 machine learning algorithms were employed to successfully construct 216 models on the training set.The monte carlo simulation method was used for resampling in the test set to validate the models,with the area under curve(AUC),accuracy,precision,recall,and F1 score used to evaluate model performance.The optimal model was selected to build the poor inhalation prediction platform.Results A study involving 308 patients with COPD found that 135(43.8%)were at risk of adverse inhalation.Using 33 predictor variables,216 risk prediction models were developed.Of these models,the ensemble learning algorithm yielded the highest average AUC of 0.844,with a standard deviation of 0.058[95%CI=(0.843,0.845)].The differences in predictive performance among the 216 models were statistically significant(P＜0.01).Under the ensemble learning algorithm,adherence to inhaler use(38.087 4%),inhaler satisfaction(25.680 1%),literacy(24.031 3%),number of inhalers(5.482 3%),age(4.204 5%)and number of acute exacerbations in the past year(2.184 7%)contributed most to the predictive model.The model exhibited superior performance,with an AUC of 0.869 3,an accuracy of 83.87%,a precision of 86.96%,a recall of 74.07%,and an F1 score of 0.8.Conclusion This study has developed a predictive model for poor inhalation risk in COPD inhaler therapy patients using machine learning algorithms,which exhibits strong predictive capabilities and holds potential clinical application value.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To investigate the effect of NOD-like receptor family pyrin domain containing 3(NLRP3)knockdown on a mouse model of nonalcoholic steatohepatitis(NASH)induced by high-fat high-carbohydrate(HFHC)diet.Methods A total of 44 mice were randomly divided into normal diet group(CON group)with 20 mice and HFHC group with 24 mice.At the end of week 14 of modeling,4 mice were randomly selected from the HFHC group for the pre-experiment of adeno-associated virus(AAV)by tail vein injection,and NLRP3 knockdown was verified after 4 weeks.After NLRP3 knockdown was verified at the end of week 18,the remaining 40 mice were given a single tail vein injection of AAV,and then they were divided into CON+NLRP3 knockdown negative control group(CON+NLRP3-NC group),CON+NLRP3 knockdown group(CON+NLRP3-KD group),HFHC+NLRP3-NC group,and HFHC+NLRP3-KD group,with 10 mice in each group.At the end of week 24,the activation of NLRP3 inflammasome was observed;related indicators were measured,including body weight,liver weight,liver index,and glucose metabolism(fasting blood glucose,fasting insulin,and Homeostasis Model Assessment of Insulin Resistance[HOMA-IR]index);the indicators of liver lipid content(liver triglyceride[TG]and oil red O staining),liver inflammation(serum alanine aminotransferase[ALT]activity,HE staining,and inflammation-related genes),and liver fibrosis(Sirius Red staining and fibrosis-related genes)were measured.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the CON+NLRP3-NC group based on the results of Western Blot,the HFHC+NLRP3-NC group had significant increases in the protein expression levels of NLRP3,pro-Caspase1,Caspase1,ASC,and IL-1β,while the HFHC+NLRP3-KD group had significant reductions in these levels(all P<0.05).The HFHC+NLRP3-NC group showed varying degrees of increase in body weight,liver weight,liver index,and glucose metabolism indicators,while the HFHC+NLRP3-KD group showed significant improvements in these indicators(all P<0.05).As for hepatic fat deposition,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had a significant increase in liver TG,with a large number of red lipid droplets shown by oil red O staining,and the HFHC+NLRP3-KD group had significant reductions in liver TG and the number of lipid droplets in the liver(all P<0.01).In terms of liver inflammation,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had significant increases in serum ALT,NAFLD activity score,and inflammation-related genes,while the HFHC+NLRP3-KD group had significant reductions in these indicators(all P<0.01).As for liver fibrosis,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had significant increases in collagen fiber area and fibrosis-related genes,and the HFHC+NLRP3-KD group had significant reductions in fibrosis-related genes(all P<0.05)and a tendency of reduction in collagen fiber area(P>0.05).Conclusion NLRP3 knockdown can significantly improve hepatic fat deposition and inflammation in a mouse model of HFHC-induced NASH.

AIM To identify the in vivo metabolites of Cynanchum auriculatum Royle ex Wight extract in functional dyspepsia rats by UHPLC Q-Exactive Plus Orbitrap HRMS.METHODS The rat models for functional dyspepsia were established.The analysis was performed on a 40℃ thermostatic Hypersil GOLD C18 column(2.1 mm×100 mm,1.9 μm),with the mobile phase comprising of water(containing 0.1％formic acid)-acetonitrile(containing 0.1％formic acid)flowing at 0.3 mL/min in a gradient elution manner,and electrospray ionization source was adopted in positive and negative ion scanning.RESULTS Total 4 prototypes(baishouwubenzophenone,deacylmetaplexigenin,qingyangshengenin,syringic)and 110 metabolites were identified,12 of which were common metabolites in feces and urine,56 of which were unique metabolites in urine,42 of which were unique metabolites in feces.The metabolic pathway of prototypes contained phase Ⅰ metabolism(reduction,oxidization,etc.),phase Ⅱ metabolism(sulfonation,glucuronidation,etc.)and phase Ⅰ,Ⅱ composite reactions.CONCLUSION This effective and comprehensive method can lay the theoretical foundation for further discovery of potential active metabolites in C.auriculatum.

OBJECTIVE: To analyze the differentially phosphorylated proteins in DENV-2-infected human umbilical venous endothelial cells (HUVECs) and explore the possible pathogenic mechanism of DENV-2 infection. METHODS: The total proteins were extracted from DENV-2-infected HUVECs and blank control HUVEC using SDT lysis method. The phosphorylated proteins were qualitatively and quantitatively analyzed using tandem mass spectrometry (TMT). The identified differentially phosphorylated proteins were analyzed by bioinformatics analyses such as subcellular localization analysis, GO enrichment analysis, KEGG pathway analysis and protein-protein interaction (PPI) analysis. Western blotting was used to detect the expressions of phosphorylated Jun, map2k2 and AKT1 proteins in DENV-2-infected HUVECs. RESULTS: A total of 2918 modified peptides on 1385 different proteins were detected, and among them 1346 were significantly upregulated (FC > 1.2, P < 0.05) and 1572 were significantly downregulated (FC < 0.83, P < 0.05). A total of 49 phosphorylated conserved motifs were obtained by amino acid conservative motif analysis. The most abundant differentially phosphorylated peptides in protein domain analysis included RNA recognition motif, protein kinase domain and PH domain. Subcellular localization analysis showed that the differentially modified peptides were mainly localized in the nucleus and cytoplasm. GO enrichment and KEGG pathway analysis showed that the differential peptides were mainly enriched in the regulation of stimulation response, biosynthesis of small molecules containing nuclear bases, and migration of phagosomes and leukocytes across the endothelium. PPI and KEGG joint analysis showed that the up-regulated and down-regulated differentially phosphorylated proteins were enriched in 15 pathways. In DENV-2-infected HUVECs, Western blotting detected differential expressions of phosphorylated proteins related with the autophagy pathway, namely JUN, MAP2K2 and AKT1, and among them p-JUN was significantly down-regulated and p-AKT1 and p-MAP2K2 were significantly upregulated (P < 0.01). CONCLUSION DENV-2 infected HUVECs show numerous differentially expressed proteins. The downregulation of p-JUN and upregulation of p-MAP2K2 and p-AKT1 suggest their potential roles in regulating autophagy, which is probably involved in the mechanism of DENV-2 infection.
Humans ; Autophagy ; Cell Death ; Cell Nucleus ; Human Umbilical Vein Endothelial Cells/virology* ; Dengue ; Proteome

Puerarin (Pue), known as a phytoestrogen, has salient bioactivities and is promising against cardiovascular diseases. This article summarizes the underlying molecular mechanisms of Pue in treating cardiovascular diseases, especially regulating the intracellular signal transduction, influencing ion channels, modulating the expression of microRNA, and impacting on the autophagy, which are mainly involved in the inflammatory signaling pathways, fatty acid/lipid metabolism, oxidative stress, apoptosis, and the like. The protective effect of Pue against cardiovascular diseases mainly involves attenuating the myocardial injury and decreasing the myocardial fibrosis, improving the myocardial ischemia/reperfusion injury, as well as inhibiting the myocardial hypertrophy and atherosclerosis. The molecular mechanisms of Pue's cardiovascular protective effects for the first time and comment on the state-of-the-art research methods and principles of Pue's regulation of small molecules were reviewed, so as to provide the rationale for its basic research and clinical applications.

OBJE CTIVE To investigate the clinical characteristics of a dverse drug reactions of asparaginase-associated pancreatitis（AAP），so as to provide reference for clinical safe medication. METHODS Analysis and identification were performed on a severe adverse reaction case of acute pancreatitis complicated with diabetic ketoacidosis and liver injury in a patient with acute lymphoblastic leukemia in our hospital after using pegaspargase. Retrieved from Wanfang database ，CNKI，PubMed and Embase database，case reports of AAP were collected and summarized in terms of patient demographics ，drug use ，incubation period and adverse reaction outcome. Combined with this case ，the disease characteristics and potential risk factors of AAP were analyzed and discussed. RESULTS After analysis and identification ，it was determined that AAP occurred in this patient. A total of 47 case reports were retrieved from the database ，and a total of 52 patients（including this patient ）were included in the analysis ，including 29 males and 23 females，mainly minors （65.4％）. L-asparaginase was the main asparaginase preparation that causes AAP （80.8％）. Gastrointestinal symptoms were the main prodromal symptoms （92.3％），which could be accompanied by other asparaginase related adverse reactions. AAP could occur after 1-33 times of administration ，and the median latency was 14 days after administration；compared with children ，median latency of AAP in adult patients was shortened significantly （11 d vs. 16 d，P＝ 0.049）；the median latency of AAP had longer tendency in patients treated with pegaspargase than that of L-asparaginase （17 d vs. 12.5 d，P＝0.490）. Of the cases included in the analysis ，8 patients died due to AAP ，1 of which was related to re-exposure to asparaginase preparations. CONCLUSIONS Acute pancreatitis is a serious and potentially fatal adverse drug reaction of ； asparaginase preparations. Clinical medical staff should pay attention to the characteristics of AAP ，consider the possibility ： of AAP when the patients have gastrointestinal symptoms and do a good job in patient education and pharmaceutical care to minimize the damage caused by AAP to patients.

OBJECTIVE To establis h the fingerprint of Cynanchum auriculatum，to conduct its chemical pattern recognition analysis，and to determine the contents of four components at the same time. METHODS High performance liquid chromatography （HPLC）method was adopted. The determination was performed on ACE UExcel C 18 column with mobile phase consisted of acetonitrile-0.1％ phosphoric acid solution （gradient elution ）at the flow rate of 1.2 mL/min. The determination wavelength was set at 210 nm，and the column temperature was 40 ℃. The sample size wa s 10 μL. Taking qingyang shengenin as the reference ，HPLC fingerprints of 16 batches of C. auriculatum medicinal materials were drawn and similarity was evaluated by using the Similarity Evaluation of Chromatographic Fingerprints of Traditional Chinese Medicine （2012 edition）， and the common peaks were determined. SPSS 26.0 software andSIMCA 14.0 software were used for cluster analysis ，principal component analysis and orthogonal partial least squares- discriminant analysis. The differential components affecting the quality of C. auriculatum were screened by taking the value of variable importance in projection （VIP）greater than 1 as the standard ；same HPLC method was used to determine the contents of syringic acid ，acyl asclepiadelenin ，baishouwubenzophenone and qingyang shengenin. RESULTS There were 29 common peaks in 16 batches of C. auriculatum ，with a similarity of 0.723-0.998. Four common peaks were identified ，namely syringic acid （peak 7），acyl asclepiadoidin （peak 9），baishouwubenzophenone（peak 13）and qingyang shengenin（peak 15）. The results of cluster analysis showed that 16 batches of C. auriculatum could be clustered into three categories ，among which S 1 were grouped into one category，S3 were grouped into one c ategory，S2，and S 4-S16 were grouped into one category. The results of principal component analysis showed that the cumulative variance contribution rate of the five principal components was 88.706％，and the classification results were consistent with the results of cluster analysis. The results of orthogonal partial least squares-discriminant analysis showed that the common peaks （from large to small ）with VIP value greater than 1 were peak 20，peak 10，peak 25，peak 12， peak 15（qingyangshengenin），peak 21，peak 14，peak 16，peak 26，peak 22 and peak 17. The linear ranges of syringic acid，acyl asclepterin，baishouwubenzophenone and qingyangshengenin were 0.715 3-45.778 0，2.379 4-152.281 0，0.642 0- 41.085 0，14.541 6- 930.662 0 µg/mL respectively （all R 2＞0.999）. The quantitative limits were 0.357 7，0.475 9，0.642 0 and 2.423 6 μg/mL；the detective limits were 0.146 0，0.164 1，0.248 8 and 0.833 3 μg/mL，respectively. RSDs of precision ，repeatability and stability （24 h）tests were less than 3％；the average recoveries were 99.11％（RSD＝2.00％，n＝9），98.54％（RSD＝2.21％，n＝9）， 96.33％（RSD＝2.54％，n＝9）and 95.96％（RSD＝2.93％，n＝9）；the contents were 17.12-147.80，95.23-583.10（S8 below the quantitative limit ），16.91-210.88 and 211.68-3 587.15（S1 below the quantitative limit ）μg/g，respectively. CONCLUSIONS Established HPLC fingerprint and the method of content determination are stable ，reliable，accurate and reproducible. Combined with analysis of chemical pattern recognition ，it can be used for the quality control of C. auriculatum .