The rupture of carotid vulnerable plaques is the core pathological basis for major cardiovascular and cerebrovascular events. However， the insufficient alignment between existing animal models and the clinical disease and syndrome characteristics of traditional Chinese and western medicine has limited research progress. In this study， biomedical databases in China and abroad were systematically searched， and the modeling mechanisms and evaluation systems of carotid vulnerable plaque animal models were systematically assessed based on diagnostic criteria of both traditional Chinese and western medicine. Analysis of the clinical correspondence indicated that existing animal models can be categorized into four types： simple high-fat diet， surgical induction combined with high-fat feeding， genetic engineering combined with high-fat feeding， and drug induction combined with high-fat feeding. Among these， the compound strategy of surgical induction combined with high-fat feeding has become the current mainstream approach， showing good concordance with western medicine. The study found that the double balloon injury rabbit model and the ApoE^-/- mouse carotid artery tandem constriction combined with high-fat feeding model demonstrated a high degree of clinical correspondence with both traditional Chinese and western medicine in terms of vulnerable plaque imaging and pathological features. Nevertheless， existing models still face significant technical limitations in faithfully simulating plaque pathology and in translating findings to clinical applications. To address these challenges， integrating complex comorbidity mechanism construction， multimodal dynamic mechanism monitoring， and collaborative evaluation systems of traditional Chinese and western medicine could enable the development of highly concordant carotid vulnerable plaque disease-syndrome combination animal models. Such models would provide a reproducible experimental platform for targeted drug development to regulate plaque stability and for individualized precision treatment， as well as a theoretical basis for innovation in clinical diagnostic and therapeutic strategies.

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Recombinase polymerase amplification (RPA) is a newly developed isothermal amplification technology with high sensitivity and specificity. The combination of RPA and lateral flow strips (LFS) enables rapid identification of target genes. This technique has been widely used in medicine, food, botany, and other fields. This review generalizes the use of RPA-LFS technology for the diagnosing pathogenic microorganisms, providing a reference for point-of-care diagnosis of pathogenic microorganisms.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Background Recent studies have shown that mediator complex subunit 1 (Med1) can significantly affect hepatocyte proliferation and differentiation. Acting as a tumor suppressor, microRNA-637 (hsa-miR-637) can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis. However, the function of hsa-miR-637 and its target genes during liver regeneration remains to be elucidated. Methods This study used co-immunoprecipitation (Co-IP) assay, transfection, luciferase reporter assay, functional assay by cell counting kit-8 (CCK-8), Annexin V-FITC/propidium iodide apoptosis assay, and quantitative polymerase chain reaction analysis of chromatin immunoprecipitation (ChIP) for analysis. Results Hsa-miR-637 has been suggested to suppress the expression of two Med1-interacting nuclear receptors, identified as the peroxisome proliferator-activated receptor alpha (PPARA) and thyroid hormone receptor alpha (THRA) at the transcriptional and translational levels in the human liver HL-7702 cell line. The interaction between Med1 and PPARA/THRA in HL-7702 cells was then confirmed. The transcriptional repression of hsa-miR-637 on PPARA and THRA was also demonstrated. Moreover, hsa-miR-637 has been determined to suppress the proliferation of HL-7702 cells. Furthermore, cell cycle arrest of HL-7702 cells was induced by transfection of hsa-miR-637 at the S phase, but its apoptosis failed. Finally, PPARA was indicated to directly bind to the promoter of some transcription factors, like β-catenin, mouse double minute 2 (MDM2), and p53. Conclusions This study has confirmed that hsa-miR-637 plays an antiproliferative role during liver regeneration, which may contribute in understanding the regenerative process of the liver.

Objective:To explore the feasibility of bedside ultrasound in monitoring gastric residual volume and predicting feeding intolerance during enteral nutrition in critically ill patients in intensive care unit.Methods:The data of critically ill patients admitted to emergency intensive care unit of the Second Affiliated Hospital of Zhejiang University School of Medicine from April 2018 to September 2018 were retrospectively analyzed. The following patients were finally included in this study: (1) abdominal computed tomography during the stay of emergency intensive care unit was performed due to the requirement of disease evaluation and management; (2) bedside ultrasound was performed to measure the gastric antrum cross-sectional area at 30 min prior to or after abdominal computed tomography. The outline of stomach wall in the imaging of abdominal computed tomography was traced with the help of VOLUME-Work Flow medical imaging software to calculate the value of gastric residual volume. The relationship between gastric antrum cross-sectional area under semi-sitting, horizontal and right-lateral positions and gastric residual volume was evaluated by Pearson correlation analysis. The difference of gastric antrum cross-sectional area between those critically ill patients with or without feeding intolerance was compared by independent-sample t test. The predictive value of gastric antrum cross-sectional area under different body positions on feeding intolerance during enteral nutrition was analyzed by ROC curve. Results:Totally, forty-two patients were enrolled and analyzed in this study, in which the mean age was (53±13) y, mean body mass index was (21.5±2.8) kg/m 2 and mean acute physiology and chronic health evaluation was 17.0±6.9. The value of gastric residual volume was (314.5±126.6) mL, and the values of gastric antrum cross-sectional area under semi-sitting, horizontal and right-lateral positions were (7.11±4.13) cm 2, (4.22±2.66) cm 2, (8.36±4.58) cm 2, respectively. The correlation analysis indicated that gastric residual volume was positively associated with gastric antrum cross-sectional area under semi-sitting, horizontal and right-lateral positions ( r=0.543, 0.604 and 0.618, respectively; all P<0.001). During enteral nutrition, 15 patients experienced feeding intolerance while 27 patients hadn’t feeding intolerance, in which the gastric antrum cross-sectional areas under semi-sitting, horizontal and right-lateral positions were significantly increased in those patients with feeding intolerance than those patients without feeding intolerance [semi-sitting: (8.53±4.07) cm 2vs (4.60±2.76) cm 2; horizontal position: (5.15±2.75) cm 2vs (2.61±1.32) cm 2; right-lateral position: (10.32±4.06) cm 2vs (4.95±3.20) cm 2, all P<0.005] . ROC curve analysis showed that the area under ROC curves of gastric antrum cross-sectional area under semi-sitting, horizontal and right-lateral positions for predicting feeding intolerance during enteral nutrition were 0.815, 0.833 and 0.849, respectively; when its values≥3.917 cm 2, 3.395 cm 2 and 4.402 cm 2 were used as the cut-off points, the sensitivities were 92.0%, 69.6% and 92.3%, and the corresponding specificities were 69.2%, 92.3% and 71.4%, respectively. Conclusions:Bedside gastric ultrasound could accurately evaluate the status of gastric residual volume in critically ill patients, and effectively predict their occurrence of feeding intolerance during enteral nutrition.

Objective: To investigate the resuscitation effect of aortic balloon occlusion (ABO) on the traumatic cardiac arrest (TCA) in swine. Methods: Twenty-seven male domestic swine weighing (32.7±3.8)kg were utilized. After 40% of estimated blood volume was removed within 20 minutes, the animals were subjected to 5 minutes of untreated ventricular fibrillation and then 5 minutes of cardiopulmonary resuscitation. Additionally, fluid resuscitation was initiated coincident with the beginning of cardiopulmonary resuscitation. The animals were randomly divided into model group (n=12) and ABO group (n=15). Once cardiopulmonary resuscitation was implemented, aortic balloon was concurrently inflated to stop the blood flow of descending thoracic aorta at the level of the diaphragm in the ABO group. In the model group, aortic balloon was placed in the same position without inflation. During cardiopulmonary resuscitation, the changes of coronary perfusion pressure (CPP), forehead's regional cerebral oxygen saturation (rSO₂) and pressure of end-tidal CO₂ (PETCO₂) were continuously monitored, and the rate of return of spontaneous circulation (ROSC), duration of cardiopulmonary resuscitation, number of shocks and dose of epinephrine were recorded. At 5 minutes after successful resuscitation, the levels of arterial blood gas, lactate and jugular venous blood oxygen saturation (SjvO₂) were measured. Results: Compared with the model group, the values of CPP, rSO₂ and PETCO₂ during cardiopulmonary resuscitation were significantly increased in the ABO group [CPP: (33.5±5.6)mmHg vs. (23.1±5.2)mmHg at 1 minute, (35.3±6.0)mmHg vs. (26.8±7.4)mmHg at 2 minutes, (36.3±6.3)mmHg vs. (28.2±6.3)mmHg at 3 minutes, (40.1±7.1)mmHg vs. (30.5±6.2)mmHg at 4 minutes, (38.1±7.5)mmHg vs. (29.8±5.3)mmHg at 5 minutes; rSO₂: (45.4±5.2)% vs. (39.2±5.1)% at 1 minute, (47.2±3.6)% vs. (42.0±6.4)% at 2 minutes, (47.7±3.0)% vs. (41.5±5.4)% at 3 minutes, (47.0±2.5)% vs. (42.1±5.9)% at 4 minutes, (47.1±2.0)% vs. (41.5±7.4)% at 5 minutes; PETCO₂: (17.0±3.5)mmHg vs. (12.7±4.2)mmHg at 1 minute, (18.5±3.7)mmHg vs. (14.5±2.7)mmHg at 2 minutes, (20.7±5.3)mmHg vs. (15.5±3.2)mmHg at 3 minutes, (18.7±4.5)mmHg vs. (14.9±3.5)mmHg at 4 minutes, (18.2±3.2)mmHg vs. (14.5±4.2)mmHg at 5 minutes] (all P<0.05). The rate of ROSC was significantly higher in the ABO group than in the model group[100%(15/15) vs. 75%(9/12)] (P<0.05). Additionally, shorter duration of cardiopulmonary resuscitation, less number of shocks and lower doses of epinephrine were observed in the ABO group when compared with the model group[duration of cardiopulmonary resuscitation: 5(5, 5)minutes vs. 5(5, 12.5)minutes, number of shocks: 1(1, 1)times vs. 1(1, 4)times, dose of epinephrine: 0.62(0.62, 0.74)mg vs. 0.64(0.59, 2.59)mg] (all P<0.05). At 5 minutes after resuscitation, the level of arterial lactate was significantly decreased and the value of SjvO₂ was significantly increased in the ABO group compared with the model group[Lactate: (9.6±0.8)mmol/L vs. (10.8±1.4)mmol/L; SjvO₂: (50.0±8.6)% vs. (37.9±16.3)%] (both P<0.05). Conclusions In a swine model of TCA, ABO can increase cardiac and cerebral perfusion during cardiopulmonary resuscitation and improve the efficacy of cardiopulmonary resuscitation. It might provide a novel and effective method for the resuscitation of TCA in the clinical setting.

Objective? To understand the career maturity and professional identity among secondary and higher vocational run-through education nursing interns and to analyze the correlation between them. Methods In November 2018, we selected 84 nursing students from two "4+2" secondary and higher vocational run-through education classes in a higher vocational nursing college in Beijing as subjects by purposive sampling. All of the students were investigated with the Career Maturity Inventory(CMI)and Professional Identity Questionnaire for Nurse Students(PIQNS). A total of 84 questionnaire were sent out and 82 valid of them were collected. Results? Among 82 nursing interns, the total scores of CMI and PIQNS were (118.24±16.29) and (74.99±6.74). Career maturity had a positive correlation with professional identity (r=0.416,P＜ 0.01). The influencing factors of career maturity included independence of career choice and professional self-image among nursing interns (P＜0.01). Conclusions Nursing students have high levels of career maturity and professional identity. Educators should pay attention to the development of professional identity of them so as to improve their career maturity.

Objective To study the effect of high-flow oxygen insuffiation (HFOI) via nasal cannula in reduction in re-intubation rate,length of ICU stay and improvement of respiratory function in patients at high risk of re-intubation after weaning from mechanical ventilation assessed by lung ultrasound score (LUS).Methods Single center randomized(random number) clinical trial was carried out in one intensive care units in China from May 2016 to May 2017 including critically ill patients ready for planned extubation with high-risk factors for re-intubation assessed by LUS when the LUS ≥ 14 was considered to be high risk.The comparisons of the length of ICU stay,re-intubation rate in case of respiratory failure,respiratory rate pulse rate SaO2 PaO2/FiO2 of patients at 6 h,24 h and 48 hours after extubation were made between HFOI and conventional oxygen therapy (COT) group.Results During the study period,32 patients were enrolled in the study.Of them,15 were assigned in HFOI group and 17 in COT group.The length of ICU stay (8.0±2.4)days vs.(10.9±3.5) days and re-intubation rate (6.7％ vs.23.5％) were significantly different between two groups (P＜0.05).The respiratory rate pulse rate SaO2 and PaO2/FiO2 of patients at 6 h after ex-tubation in HFOI group were improved than those in COT group (P＜0.05);and the SaO2 and PaO2/FiO2 of patients 24 h and 48 h after ex-tubation in HFOI group had much more improvement than those in COT group (P＜0.05).Conclusion Among high-risk adults who assessed by lung ultrasound score,high-flow oxygen therapy could reduce re-intubation rate length of ICU stay and improve the respiratory function.High-flow oxygen therapy may offer advantages for these patients.

OBJECTIVE To investigate the dynamic changes in urine metabolic profiles in rats induced by D-galactose (D-Gal),and to study the correlations between the differential metabolites and behavior indicators using the proton nuclear magnetic resonance (1H-NMR)-based metabonomics.METHODS Subcutaneous injection of D-Gal 100 mg· kg-1 for 10 weeks was adopted in the model group.The sample of urine was collected at day 0 (dO),d14,d28,d42,d56 and d70.NMR metabonomics technique was used for acquisition of data,which was analyzed by multivariate statistical analysis.The ability of learning and memory were measured by Morris water maze test from d70.After the behavioral test,the rats were sacrificed and the hippocampus was observed by hematoxylin-eosin staining.RESULTS Principal component analysis (PCA) results revealed that there was considerable difference between the model group and the normal control group at d70.According to the varible importance plot (VIP) calculation and S-plot scores,a total of 12 metabolites were screened and identified as potential biomarkers at d70.The differences of metabolites and Morris water maze test were subjected to correlation analysis,and the results showed that the levels of choline,lactate and dimethylglycine in the model group were significantly increased and negatively correlated with the times of crossing the platform (r =-0.90,-0.50 and-0.52;n=10).Formate was significantly negatively correlated with the time spent in the target area (r =-0.51,n=10),but choline and formate were significantly positively correlated with the escape latency (r =0.72 and 0.53;n=10).However,the levels of creatine and taurine decreased in the model group,which was significantly positively correlated to the times of acrossing platforms (r =0.89 and 0.71;n=10),while alanine was significantly positively correlated to the time spent in the target area(r =0.74,n=10).Taurine,alanine and creatine were significantly negatively correlated with the escape latency (r =-0.66,-0.50 and-0.85;n=10).The correlations between the differential metabolites and the behavioral indicators were further proved.CONCLUSION The metabolic profile changes in urine from D-Gal induced aging model rats are significantly correlated with impairement of ability in learning and memory.1H-NMR metabonomics in urinary metabolic profile changes may be used as an evaluation index in the D-Gal induced aging rats model.