AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.

Background/Aims: The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. Methods: The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. Conclusions Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

Objective To investigate the effects and mechanisms of TAR DNA-binding protein 43(TDP-43)on oxygen-glucose deprivation(OGD)-induced apoptosis in mouse atrial myocytes(HL-1 cells).Methods The in vitro cultured mouse atrial myocytes(HL-1 cells)were divided into:(1)control group and groups with different OGD treatment times(2,4,8,16 h),and cell viability was detected by CCK-8 assay,and TDP-43 protein expression level was detected by Western blotting,which was used to determine the time point of OGD induction for the subsequent study;(2)control and OGD groups,flow cytometry was used to detect apoptosis,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect adenosine triphosphate(ATP)relative content,microplate method to detect malondialdehyde(MDA)content,and WST-1 method to detect superoxide dismutase(SOD)content.Mouse atrial myocytes(HL-1 cells)transfected with lentivirus were divided into:(1)negative control lentiviral intervention group(NC-shRNA),TDP-43 knockdown lentiviral intervention group(TDP-43-shRNA1,TDP-43-shRNA2,TDP-43-shRNA3),and Western blotting was used to detect the TDP-43 protein expression level,and the group with the highest lentiviral knockdown efficiency was selected as the TDP-43-shRNA for subsequent experiments;(2)NC-shRNA group,TDP-43-shRNA group,OGD+NC-shRNA group,OGD+TDP-43-shRNA group,under normoxic and OGD conditions,flow cytometry was used to detect the apoptosis rate,MitoTracker staining to detect mitochondrial morphology,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect the relative content of ATP,flow cytometry to detect the fluorescence intensity of reactive oxygen species(ROS),microplate to detect the content of MDA,and WST-1 to detect the content of SOD.Results CCK-8 method showed that,with the prolongation of OGD time,the viability of mouse atrial myocytes(HL-1 cells)gradually decreased;Western blotting assay showed that the expression level of TDP-43 protein gradually increased,and both of them showed a strong time-dependence.Compared with control group,mouse atrial myocytes(HL-1 cells)viability was the lowest(P<0.05)and TDP-43 protein expression was the highest(P<0.05)at 16 h of OGD,accordingly,OGD 16 h was chosen as the induction time point for subsequent experiments.Compared with control group,the apoptosis rate,the fluorescence intensity ratio of mitochondrial membrane potential and the content of MDA increased,the relative content of ATP and SOD decreased in OGD group,and the differences were all statistically significant(P<0.05).Western blotting detection showed that compared with NC-shRNA group,the TDP-43-shRNA2 group had the most obvious reduction in TDP-43 protein expression level(P<0.05)and the highest knockdown efficiency,so the TDP-43-shRNA2 group was selected for subsequent experiments.The results of flow cytometry showed that under normoxic conditions,there was no significant change in the apoptosis rate in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);and under OGD conditions,the apoptosis rate in OGD+TDP-43-shRNA group reduced when compared with OGD+NC-shRNA group(P<0.05).MitoTracker staining results showed that the mitochondrial morphology of TDP-43-shRNA group was intact without significant changes compared with NC-shRNA group;the mitochondria of OGD+NC-shRNA group increased in number,most of which were fragmented and scattered in distribution;compared with OGD+NC-shRNA group,the mitochondrial morphology of OGD+TDP-43-shRNA group was restored.Under normoxic conditions,there were no significant changes in mitochondrial membrane potential,relative ATP content,ROS fluorescence intensity,MDA content,and SOD content in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);however,under OGD conditions,the ratio of fluorescence intensity of mitochondrial membrane potential of cells the fluorescence intensity of ROS,and the content of MDA decreased,and the relative content of ATP and the content of SOD increased in OGD+TDP-43-shRNA group compared with that of OGD+NC-shRNA group,and all of these differences was statistically significant(P<0.05).Conclusion TDP-43 exacerbates OGD-induced mitochondrial dysfunction by regulating cardiomyocyte apoptosis;therefore,knockdown of TDP-43 expression is expected to be a potential therapeutic strategy for ischemic cardiomyopathy.

Endoscopy ; Humans ; Retrospective Studies ; Trachea ; Tracheal Stenosis/surgery* ; Tracheostomy/adverse effects*

Objective: To evaluate the recognition of acute respiratory infection (ARI) by a pretrained model based on electronic medical records (EMRs). Methods: 38 581 EMRs were obtained from Chongqing University Three Gorges Hospital in December 2021. Bidirectional encoder representation from transformers (BERT) pretrained model was used to identify ARI in EMRs. The results of medical professionals were considered as the gold standard to calculate the sensitivity, specificity, Kappa value, and area under the curve of the receiver operating characteristic (AUC). Results: There were 3 817 EMRs in the test set, with 1 200 ARIs. A total of 1 205 cases were determined as ARI by the model, with a sensitivity of 92.67% (1 112/1 200) and a specificity of 96.45% (2 524/2 617). The model identified ARI with similar accuracy in males and females (AUCs 0.95 and 0.94, respectively), and was more accurate in identifying ARI cases in those aged less than 18 than in adults 18-59 and adults 60 and older (AUCs 0.94, 0.89 and 0.94, respectively). The current model had a better identification of ARIs in outpatient patients than that in hospitalized patients, with AUCs of 0.74 and 0.95, respectively. Conclusion: The use of the BERT pretrained model based on EMRs has a good performance in the recognition of ARI cases, especially for the outpatients and juveniles. It shows a great potential to be applied to the monitoring of ARI cases in medical institutions.
Adult ; Male ; Female ; Humans ; Electronic Health Records ; Respiratory Tract Infections/diagnosis* ; Outpatients

OBJECTIVE：To evaluate the efficacy ，safety and econom y of donepezil in the treatment of Alzheimer ’s disease （AD），so as to provide evidence-based evidence for clinical rational drug use. METHODS ：Retrieved from PubMed ，Embase，the Cochrane Library ，CNKI，Wanfang database ，CBM and health technology assessment （HTA）organization websites ，systematic review/Meta-analysis，economic evaluation and HTA reports about donepezil in the treatment of AD were collected during the inception to Feb. 2021. Data extraction and quality evaluation were carried out for the literature that met the inclusion and exclusion criteria，and the research results were summarized and analyzed qualitatively. RESULTS ：A total of 26 studies were included ， including 15 systematic reviews/Meta-analysis ，and 11 economic studies ；HTA reports were not included. The results showed that in terms of effectiveness ，compared with placebo ，donepezil could significantly improve the cognitive function ，activity of daily life，mental behavior and overall function of AD patients （P＜0.05）；compared with rivastigmine ，donepezil could significantly improve cognitive function of AD patients （P＜0.05）；compared with galantamine ，donepezil could significantly improve cognitive function and overall function （P＜0.05），but there was no statistical significance in terms of improving mental behavioral symptoms（P＞0.05）；there was no statistical significance between donepezil and memantine in improving cognitive function ， psychobehavioral symptoms and activities of daily living in AD patients （P＞0.05），but donepezil was weaker than memantine in overall functional （P＜0.05）. In terms of safety ，there was no significant difference in the tolerance and mortality in patients using donepezil and placebo （P＞0.05）；donepezil was better tolerated than rivastigmine and galantamine （P＜0.05）；there was no significant difference in the incidence of ADR for donepezil compared with placebo ， metamine and other non-placebo mail：15201008872@163.com controlled drugs （P＞0.05）. Economic studies showed that # compared with rivastigmine ，placebo and no AD-related drug treatment，donepezil could prolong quality adjusted life years （QALY）and saved medical costs ，which was more cost-effective. Compared with conventional treatment for basic disease and memantine，although donepezil could prolong QALY ，whether it had economic advantages still needed to confirmed in combination with national or regional health resource conditions. CONCLUSIONS ：Donepezil is ralatively effective ，safe and economical in the treatment of AD.

INTRODUCTION: Large-volume paracentesis (LVP) is the first-line treatment for decompensated cirrhosis with refractory ascites. While ascitic drain removal (ADR) within 72 hours of the procedure was once considered safe, it was uncertain whether ADR within 24 hours could further reduce the risk of ascitic drain-related bacterial peritonitis (AdBP). This study aimed to investigate the association between the timing of ADR and the presence of AdBP. METHODS: All patients with cirrhosis with refractory ascites who underwent LVP in our institution from 2014 to 2017 were studied. AdBP was diagnosed based on an ascitic fluid neutrophil count ≥ 250 cells/mm RESULTS: A total of 131 patients who underwent LVP were followed up for 1,806 patient-months. Their mean age was 68.3 ± 11.6 years, and 65.6% were male. Their mean Model for End-Stage Liver Disease score was 15.2. The overall incidence of AdBP was 5.3%. ADR beyond 24 hours was significantly associated with a longer median length of stay (five days vs. three days, p < 0.001), higher risk of AdBP (0% vs. 8.9%, p = 0.042) and acute kidney injury (AKI) following LVP (odds ratio 20.0, 95% confidence interval 2.4-164.2, p = 0.021). The overall survival was similar in patients who underwent ADR within and beyond 24 hours of LVP. CONCLUSION ADR within 24 hours of LVP is associated with a reduced risk of AdBP and AKI. As AdBP is associated with resistant organisms and AKI, we recommend prompt ADR within 24 hours, especially in patients who have Child-Pugh class C alcoholic cirrhosis.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

OBJECTIVE：To rapidly evaluate the effectiveness，safety and economics of rosuvastatin （RSV）in the treatment of dyslipidemia，so as to provide evidence-based support for clinical drug use. METHODS ：Retrieved from PubMed ，Embase， Cochrane Library ，CNKI，Wanfang database and CBM ，etc.，health technology assessment （HTA）related website and database were searched systematically to select HTA report ，Meta-analysis/systemic evaluation and pharmacoeconomics study about RSV versus placebo or other positive drugs in the treatment of dyslipidemia. According to the inclusion and exclusion criteria ，two researchers independently screened the literatures ，extracted and summarized the data ，then performed qualitative description of results. RESULTS ：Totally 11 Meta-analysis and 11 pharmacoeconomic studies were included ，and no relevant HTA report was retrieved. Results of the study showed that compared with the control group ，RSV could regulate dyslipidemia ，and reduce the levels of LDL-C ，TG，TC，C-reactive protein and sdLDL ；RSV could also reverse atherosclerotic plaque ，reduce all-cause mortality with good safety. In terms of economy ，compared with other statins or placebo ，RSV could prolong quality-adjusted life year，its incremental cost-effectiveness ratio is lower than the desired payment threshold ，which had more economic advantages. CONCLUSIONS：RSV is effective ，safe and economical in the treatment of hyperlipidemia.