Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

Objective To evaluate the change of cardiac structure and function in patients with hypertrophic obstructive cardiomyopathy(HOCM)after ultrasound-guided percutaneous intramyocardial septal radiofrequency ablation(PIMSRA)via cardiac magnetic resonance(CMR).Methods Patients with HOCM who underwent PIMSRA,echocardiography and CMR preoperative scanning and one year after surgery were analyzed retrospectively.Myocardial structural and functional parameters were measured by Circle cardiovascular imaging post-processing software.The changes of myocardial parameters before and after surgery were compared by using paired sample t-test and Chi-square test.Results Compared with the preoperative assessment,patients'clinical symptoms and the cardiac function were significantly improved one year after surgery.The left ventricular outflow tract pressure gradient(LVOT-PG)was significantly decreased and length of mitral regurgitation was shortened one year after surgery compared with before surgery via ultrasound(P<0.05).Compared with the preoperative assessment,CMR showed that patients with end-systolic volume of left atrium,minimum volume of left atrium,transverse diameter of left atrium,thickness of ventricular septum and free wall of left ventricular at end-systolic section were significantly reduced,and left ventricular mass(LVM)was significantly decreased one year after surgery,with statistical significance between before and after surgery(P<0.001).One year after surgery,the left atrium ejection fraction(LAEF)was significantly increased(P<0.05),the maximum slope and the maximum signal intensity of the ventricular septum and the left ventricular free wall of the papillary muscle were significantly increased(P<0.001),and the peak time was significantly decreased(P<0.001)compared with before surgery.Conclusion After PIMSRA treatment,the systolic function of left atrium in HOCM patients is improved,and the microcirculation perfusion of left ventricular is significantly improved.

Objective To investigate the effect of resistant starch(RS)on the intestinal microbiota and metabolism in obese rats with type 2 diabetes mellitus(T2DM).Methods The Wistar rats were divided into normal control(NC)group,model group(Mod),acarbose intervention group(Aca)and RS intervention group(RS),with 8 rats in each group.TC,TG,HDL-C,and LDL-C were detected after 8 weeks of continuous administration.Lee's index,insulin sensitivity index(HOMA-IS),insulin resistance index(HOMA-IR),pancreatic β cell function index(HOMA-β),inflammatory factors,and area under the curve of glucose tolerance(AUC)were calculated.Serum TNF-α,IL-6 and lipopolysaccharide(LPS)were detected by ELISA.The steatosis of liver tissue was observed by HE staining,and the feces were collected for 16S rDNA sequencing in each group.Species difference analysis,Beta diversity analysis and other methods were used to analyze the structure and quantity of intestinal microbiota.Results The Lee's index was higher in the Mod,Aca and RS groups than in the NC group(P<0.05).Compared with the NC group,TC,TG,LDL-C,HDL-C,FIns,HOMA-IR,TNF-α,IL-6 and LPS were increased(P<0.05),HOMA-β and HOMA-IS decreased in the Mod,Aca,and RS groups(P<0.05).Compared with the Mod group,TC,TG,LDL-C,HDL-C,FIns,HOMA-IR,TNF-α,IL-6 and LPS decreased(P<0.05),and HOMA-IS and HOMA-β increased in the Aca and RS groups(P<0.05).Compared with the Aca group,IL-6 was increased(P<0.05),and LDL-C and HDL-C decreased in the RS group(P<0.05).The results of 16S rDNA sequencing showed that the total number of operational taxonomic units were increased and the diversity and uniformity of the intestinal microbiota were also increased in the Aca and RS groups.Conclusions RS can regulate glucose and lipid metabolism,improve IR,increase intestinal microbial diversity,regulate intestinal microbiota structure,and maintain intestinal health in obese rats with T2DM.

Objective:To explore whether disrupted colonization of the gut microbiota in early life accelerates the development of obesity later in life through programming adipose thermogenesis.Methods:Neonatal mice were treated with a mixture of antibiotics (ABX), and 16S rRNA sequencing confirmed that ABX treatment disrupted the establishment of gut microbiota. The mice were monitored for changes in body weight and fat content at weaning, adulthood, and under a high-fat diet (HFD) to assess obesity phenotypes. Additionally, glucose tolerance and insulin tolerance tests were conducted, along with measurements of blood glucose and lipid levels, to evaluate changes in glucose and lipid metabolism. The expression of uncoupling protein 1 (UCP1) in adipose tissue was assessed through immunohistochemistry and Western blotting to evaluate alterations in adipocyte thermogenic capacity.Results:The analysis of 16S rRNA sequencing technology revealed that ABX treatment significantly reduced both α- and β-diversity of the gut microbiota. Compared to untreated mice, the microbial composition in ABX treated mice showed significant differences, with a notable reduction in the abundance of beneficial bacteria, including Lachnospiraceae_NK4A136_group and Akkermansia muciniphila ( A. muciniphia). Subsequent monitoring indicated that ABX treatment did not affect body weight or fat content during the lactation period. However, a significant decrease in surface temperature was observed in the ABX group, specifically in the interscapular region. Immunohistochemistry and Western blot of UCP1 demonstrated impaired thermogenic capacity in adipose tissue. Interestingly, the impaired thermogenesis persisted in adult mice, leading to a decreased cold tolerance, although no changes of metabolic dysfunction, including body weight, body fat percentage, serum insulin and triglyceride levels, glucose tolerance, and insulin sensitivity. Upon switching to HFD, ABX-exposed mice exhibited significant increases in body weight, fat mass, and serum glucose, indicating a greater susceptibility to obesity. Further thermographic analysis and UCP1 detection suggested that this susceptibility to obesity was also linked to impaired thermogenic capacity in adipose tissue. Conclusion:Early-life gut microbiota is a critical determinant of long-term adipose thermogenesis. Disruption of the microbiota enhances the effect of diet-induced obesity.

Objective:To establish a predictive model of acute physiological and chronic health status score (APACHEⅡ) and the British Thoracic Society modified pneumonia score (CURB-65) score on the prognosis of patients with emergency severe pneumonia complicated with acute respiratory distress syndrome (ARDS) and to evaluate the predictive effect.Methods:The relevant clinical data of patients with severe pneumonia combined with ARDS admitted to the Emergency Intensive Care Unit (EICU) of General Hospital of Ningxia Medical University from January 2017 to December 2021 were retrospectively collected, and different logistic regression models were established. On this basis, three prediction models (model 1: APACHE Ⅱ score, model 2: CURB-65 score, Model 3: APACHE Ⅱ score combined with CURB-65 score) were established and the accuracy of the prediction model was evaluated by repeating 50 times of 10-fold cross-validations. The efficacy of the prediction model was evaluated by C statistics, Kendall's tau-a rank correlation coefficient, R2, Brier score, calibration curve, net reclassification index (NRI), composite discriminant improvement index (IDI) and decision curve (DCA).Results:The study eventually included 108 patients, including 81 males and 27 females, with mean age (57.92 ± 16.56) years. Forty-eight patients survived and 60 patients died. The age of the death group was older, and APACHEⅡ score and CURB-65 score of the death group were all greater than those in the survival group, and the differences were statistically significant ( P<0.05). Different logistic regression models showed that the OR value of model 1 was 1.12 (95% CI: 1.06 -1.20), that of model 2 was 2.21 (95% CI: 1.43 - 3.40), and that of model 3 was 1.10 (95% CI: 1.03 - 1.18) and 1.95 (95% CI: 1.24 - 3.07). The average accuracy of model 1, model 2, and model 3 were 0.68±0.14, 0.66±0.11, and 0.72±0.13, respectively. The C statistic, Kendall's Tau-a rank correlation coefficient, R2 and Bril score of model 3 were better than those of model 1 and model 2, and the different models fit well ( P<0.05). The calibration curve results of 500 resampling showed that the calibration degree of model 2 was better than that of model 1 and model 3, and the predictive ability of model 3 was improved compared with model 1, and the IDI was increased by 0.08 ( P<0.01). Compared with model 2, the reclassification ability of cases and the comprehensive discrimination ability of model 3 were improved ( P<0.01). The decision curves of different models showed that the net benefit of model 3 was higher than that of single model 1 and model 2 when the prediction probability was about 25% to 55%, while the benefits of model 1, model 2 and model 3 in other probability prediction intervals were basically equal. Conclusions:Both APACHE Ⅱ score and CURB-65 score have certain predictive power for prognosis of patients with emergency severe pneumonia and ARDS, and their combination has the best prediction effect. CURB-65 score has fewer parameters, and its prognostic benefit in emergency patients with severe pneumonia complicated with ARDS is basically equivalent to APACHE Ⅱ score, which may be more suitable for the prognosis evaluation of emergency patients with severe pneumonia complicated with ARDS.

Objective:To explore the responsibilities of respiratory nurses in the management of chronic obstructive pulmonary disease (COPD) patient and the difficulties in disease management, so as to provide reference basis for formulating COPD management training strategies for respiratory nurses.Methods:Using phenomenological methodology, 14 nurses from the Department of Respiratory and Critical Care Medicine in the General Hospital of Ningxia Medical University and the First People′s Hospital of Yinchuan were interviewed in a personal semi-structured way from May to August 2021, and the data were sorted and analyzed according to Colaizzi 7-step analysis method.Results:Nurses′understanding of the responsibilities of COPD patient management could be summarized into five themes: dynamic monitoring and management of patients′ health, nursing decision-making of sudden changes in patients′ condition, implementation of patients′ out of hospital follow-up, promotion of improvement of patients′ self-management behavior, and cooperation among multidisciplinary team members. The difficult experience of nurses in the management of COPD patients abstracted five themes: lack of professional knowledge of COPD management, lack of clinical nursing decision-making authority, lack of human and financial support for follow-up, lack of communication skills with patients, and lack of multidisciplinary team formation in the hospital.Conclusions:Respiratory nurses have a clear understanding of the responsibilities of COPD patient management, but there are multiple difficulties in performing their responsibilities. We should pay attention to the responsibility positioning and difficulty support of nurses′ COPD management, and formulate targeted training strategies to promote the improvement of COPD nursing quality.

Chronic obstructive pulmonary disease (COPD) is characterized by high prevalence, high disability and high mortality, which seriously threatens the health of the elderly. Medications are an important form of COPD treatment, and poor compliance will seriously affect the treatment effectiveness. Starting from the elderly COPD patients, this paper reviews the current status, influencing factors and intervention measures of medication compliance, so as to provide a reference for the research on medication compliance in elderly COPD patients.

Objective:To explore the evaluation value of sequential organ failure assessment (SOFA) score at different time points in the prognosis of patients with severe pneumonia combined with acute respiratory distress syndrome (ARDS).Methods:A retrospective cohort study method was conducted, including patients with severe pneumonia and ARDS admitted to the emergency intensive care unit (ICU) of General Hospital of Ningxia Medical University from January 2015 to December 2019. General clinical data such as gender, age, and the SOFA scores at 1, 2, 3, and 7 days after admission were recorded. According to the diagnostic test, the prognostic evaluation value of SOFA score in patients with severe pneumonia combined with ARDS at different time points and different ages was analyzed.Results:A total of 88 cases were included in this study, eventually, 42 cases were survived and 46 cases died, the mortality was 52.27%. The age of the death group was significantly older than the survival group (years old: 60.67±14.66 vs. 51.91±15.97), the SOFA score at each time point were significantly higher than those in the survival group (9.83±3.50 vs. 7.54±2.67, 9.98±3.75 vs. 7.48±2.92, 10.84±4.14 vs. 7.23±2.94, 11.71±4.03 vs. 6.51±3.22, respectively at 1, 2, 3, 7 days after admission, all P < 0.01). The receiver operator characteristic curve (ROC curve) showed that the SOFA score at 1, 2, 3, and 7 days after admission had a certain predictive value for the prognosis of patients with severe pneumonia combined with ARDS (all P < 0.01), and with the prolong of ICU stay, the area under ROC curve (AUC) of SOFA score had gradually increased. On the 7th day after admission, the SOFA score had the highest sensitivity in predicting severe pneumonia combined with ARDS patients, which was 92.86%, and the specificity was the highest on the 3rd day after admission, which was 88.10%. The AUC in day 7 was significantly higher than day 2 (0.85 vs. 0.72) , there was no statistically significant difference of AUC at other time points. After stratifying by age, the diagnostic of sensitivity, specificity, accuracy, and AUC of SOFA score for the prognosis had gradually increased, and the predictive value was better. However, only on day 3 after admission, the AUC of SOFA score was significantly higher than day 1 (0.80 vs. 0.77, P < 0.05), and there was no significant difference in AUC at other time points. In patients older than 60 years old, the AUC of the SOFA score predicting the prognosis of patients was relatively small on day 1 and day 2 (0.67, 0.68, respectively), the ability was poor. There was no statistically significant difference in the AUC of SOFA scores at each time point in evaluating the prognosis of patients. The trends over time of patients at different ages and time points showed that regardless of age, the SOFA scores of the patients in the death group showed an upward trend, while showed a downward trend in the survival group, the difference reached the largest on the 7th day after admission, and the death group was significantly higher than the survival group (age < 60 years old: 12.50 vs. 6.69; age≥60 years old: 11.58 vs. 6.21). Conclusion:The initial SOFA score has a certain value in the evaluation of prognosis of severe pneumonia patients combined with ARDS, but the effect is poor for elderly patients.

Vibrio splendidus is an opportunistic pathogen in aquaculture. It can infect a variety of aquaculture animals and has caused huge losses to the aquaculture industry. In this study, a novel and efficient method for detecting V. splendidus was developed by combining the exonuclease Ⅲ amplification strategy with a nucleic acid test strip developed based on gold nanoparticles-labeled DNA probe. The results could be directly visualized by naked eyes, and this system overcame the difficulty in preparation of the monoclonal antibody used in conventional immunostrip. Upon optimization of experimental conditions, the detection limit of the strip was 5 ng/mL for the synthetic oligonucleotide DNA fragment and 10 ng/mL for the actual genomic DNA sample of V. splendidus. This test strip was more sensitive compared with the PCR method and was specific for the detection of V. splendidus. The rapid preparation of nucleic acid strip and the efficient detection of V. splendidus open a new way for the prevention and control of aquatic diseases.
Animals ; DNA Probes ; Gold ; Metal Nanoparticles ; Vibrio/genetics*

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.