Background and aims:Hepatocellular carcinoma(HCC)is a tumor of high heterogeneity and complexity,which poses significant challenges to effective treatment and patient prognosis because of its immune evasion characteristics.To address these issues,single-cell technology and machine learning methods have emerged as a promising approach to identify genes associated with immune escape in HCC.This study aimed to develop a prognostic risk score model for HCC by identifying intrinsic immune-evasion genes(IIEGs)through single-cell technology and machine learning,providing insights into immune infiltration,enhancing predictive accuracy,and facilitating the development of more effective treatment strategies.Materials and methods:The study utilized data from The Cancer Genome Atlas database to analyze gene expression profiles and clinical data related to intrinsic immune evasion in patients with HCC.Various tools,including the Human Protein Atlas,cBioPortal,single-cell analysis,machine learning,and Kaplan-Meier plot,were used to analyze IIEGs.Functional enrichment analysis was conducted to explore po-tential mechanisms.In addition,the abundance of infiltrating cells in the tumor microenvironment was investigated using single-sample gene set enrichment analysis,CIBERSORT,xCELL,and tumor immu-nophenotype algorithms.The expression of glycosylphosphatidylinositol anchor attachment 1(GPAA1)was examined in the clinical sample of HCC by quantitative real-time polymerase chain reaction,Western blotting,and immunohistochemical staining.Results:Univariate Cox analysis identified 63 IIEGs associated with the prognosis of HCC.Using random forest,least absolute shrinkage and selection operator regression analysis,and support vector machine,a risk score model consisting of six IIEGs(carbamoyl-phosphate synthetase 2,aspartate transcarbamylase,and dihydroorotase(CAD),phosphatidylinositol glycan anchor biosynthesis class U(PIGU),endoplasmic reticulum membrane protein complex subunit 3(EMC3),centrosomal protein 55(CEP55),autophagy-related 10(ATG10),and GPAA1)developed,which was validated using 10 pairs of HCC and adjacent non-cancerous samples.Based on the calculated median risk score,HCC samples were categorized into high-and low-risk groups.The Kaplan-Meier curve analysis showed that the high-risk group had a worse prognosis compared with the low-risk group.Time-dependent receiver operating characteristic analysis demonstrated the accurate predictive capability of the risk score model for HCC prognosis.Furthermore,immune infiltration analysis showed a positive correlation between the risk score model and 40 immune checkpoint genes as well as Th2 cells.Conclusions:A prognostic risk score model was formulated by six IIEG signatures and showed promise in predicting the prognosis of patients diagnosed with HCC.The utilization of the IIEG risk score as a novel prognostic index,together with its significance as a valuable biomarker for immunotherapy in HCC,provides benefit for patients with HCC in determining therapeutic strategies for clinical application.

Objective To retrieve,evaluate and summarise the relevant evidence in non-pharmacological management of venous thromboembolism in patients with haemorrhagic stroke during perioperative period so as to provide references for clinical practice. Methods According to the "6S" evidence pyramid mode,evidence was retrieved from top to bottom across databases such as BMJ Best Practice,UpToDate,JBI Evidence-Based Healthcare Centre,the National Guideline Clearinghouse (NGC),the National Institute for Health and Care Excellence (NICE),the Scottish Intercollegiate Guidelines Network (SIGN),the Registered Nurses' Association of Ontario (RNAO) guidelines network,the Canadian Heart and Stroke Foundation (HSF),the American Heart Association/American Stroke Association (AHA/ASA),the Neuro-Critical Care Society (NCS),the European Stroke Organization (ESO),Cochrane Library,PubMed,Medline,CNKI,Web of Science,Embase,the China Biomedical Literature Database,Wanfang Data,Medlive,VIP,and the Chinese Medical Journal Full-Text Database. The search focused on non-pharmacological management of perioperative venous thromboembolism in haemorrhagic stroke patients,including guidelines for clinical practice,expert consensus,systematic reviews and evidence summaries. The searched literatrue was from the inception of the databases to April 11th,2024. Two researchers independently evaluated the quality of the literature,extracted,integrated and summarised the best evidences. Results A total of 23 articles were included,comprising 12 guidelines,5 systematic reviews,4 expert consensuses and 2 evidence summaries. Thirty-one pieces of the best evidence were summarised and integrated into 5 topics,including multidisciplinary teamwork,risk assessment and screening,basic prevention,mechanical prophylaxis and health education. Conclusion This study has summarised the best evidence for non-pharmacological management of venous thromboembolism in patients with haemorrhagic stroke during the perioperative period. It provides evidence-based references for clinical medical staff to prevent and manage venous thromboembolism in patients with hemorrhagic stroke during perioperative period.

Objective To retrieve,evaluate and summarise the relevant evidence in non-pharmacological management of venous thromboembolism in patients with haemorrhagic stroke during perioperative period so as to provide references for clinical practice. Methods According to the "6S" evidence pyramid mode,evidence was retrieved from top to bottom across databases such as BMJ Best Practice,UpToDate,JBI Evidence-Based Healthcare Centre,the National Guideline Clearinghouse (NGC),the National Institute for Health and Care Excellence (NICE),the Scottish Intercollegiate Guidelines Network (SIGN),the Registered Nurses' Association of Ontario (RNAO) guidelines network,the Canadian Heart and Stroke Foundation (HSF),the American Heart Association/American Stroke Association (AHA/ASA),the Neuro-Critical Care Society (NCS),the European Stroke Organization (ESO),Cochrane Library,PubMed,Medline,CNKI,Web of Science,Embase,the China Biomedical Literature Database,Wanfang Data,Medlive,VIP,and the Chinese Medical Journal Full-Text Database. The search focused on non-pharmacological management of perioperative venous thromboembolism in haemorrhagic stroke patients,including guidelines for clinical practice,expert consensus,systematic reviews and evidence summaries. The searched literatrue was from the inception of the databases to April 11th,2024. Two researchers independently evaluated the quality of the literature,extracted,integrated and summarised the best evidences. Results A total of 23 articles were included,comprising 12 guidelines,5 systematic reviews,4 expert consensuses and 2 evidence summaries. Thirty-one pieces of the best evidence were summarised and integrated into 5 topics,including multidisciplinary teamwork,risk assessment and screening,basic prevention,mechanical prophylaxis and health education. Conclusion This study has summarised the best evidence for non-pharmacological management of venous thromboembolism in patients with haemorrhagic stroke during the perioperative period. It provides evidence-based references for clinical medical staff to prevent and manage venous thromboembolism in patients with hemorrhagic stroke during perioperative period.

Objective:To retrieve, evaluate, and sum up the evidence on target temperature management in stroke patients, and summarize the best evidence.Methods:Based on the "6S" pyramid model, clinical practice guidelines, expert consensus, evidence summary, and systematic review on target temperature management in stroke patients were searched from top to bottom in British Medical Journal Best Practice, UpToDate, Joanna Briggs Institute Evidence-Based Health Care Center, Guidelines International Network, Agency for Healthcare Research and Quality, National Institute for Health and Clinical Excellence, Scottish Intercollegiate Guidelines Network, Registered Nurses' Association of Ontario, American Heart Association, American Stroke Association, European Stroke Organization, Medlive, Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP and China Biology Medicine Disc. The search period was from database establishment to October 7, 2022. Two researchers received evidence-based nursing training independently evaluated the quality of the article, extracted, integrated, and summarized the best evidence.Results:A total of 12 articles were included, including three clinical practice guidelines, four systematic reviews, and five expert consensuses. 24 best pieces of evidence were summarized from five aspects, involving target temperature population, target temperature implementation, complication monitoring, nutritional support, and prognosis evaluation.Conclusions:This study adopts an evidence-based approach to systematically summarize the best evidence for target temperature management in stroke patients, which can provide the best decision-making basis for clinical medical and nursing staff to manage temperature in stroke patients, further standardize temperature monitoring and management, and offer scientific basis for future research and practice.

Objective:To investigate the protective effect of reduced glutathione (GSH) on diclo-fenac-induced acute kidney injury (AKI) in rats and its mechanism.Methods:Thirty-three male 8-week-old specified pathogen-free SD rats were randomly divided into control, model, and GSH groups (11 rats in each group) according to a random number table method. Diclofenac sodium solution (200 mg/kg) was intragastrically administered to rats in the model group and GSH group to establish the AKI model. Thirty minutes later, rats in the GSH group were treated with intragastric administration of GSH solution (500 mg/kg), while rats in the control and model groups were with 0.9% sodium chloride injection of equal volume. After 24 hours of administration, blood sample was collected and kidneys were isolated. Kidney function [blood urea nitrogen (BUN), serum creatinine (Scr)], kidney histopathology, and serum and kidney tissue oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and the inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin 6 (IL-6) were examined. The results of each examination results among rats of the 3 groups were compared.Results:The BUN and Scr in rats of the model group were significantly higher than those in the control and GSH groups[BUN: (14.34±8.47) mmol/L vs. (7.89±2.20) and (8.46±3.58) mmol/L; Scr: (34.44±6.56) μmol/L vs. (24.77±9.50) and (29.28±4.33) μmol/L, all P<0.05]. Glomerular and tubular morphological changes were observed in both model and GSH rats, but the change in rats of GSH group was less severe than that of the model group. The mean levels of MDA, TNF-α, and IL-6 in both serum and kidney tissue in rats of GSH group were significantly lower than those of the model group[MDA: (9.5±0.2) nmol/ml vs. (10.2±0.6) nmol/ml, (3.6±0.3) nmol/ml vs. (4.0±0.2) nmol/ml; TNF-α: (2.9±2.5) pg/ml vs. (5.4±3.0) pg/ml, (420.9±40.3) pg/ml vs. (470.4±31.3) pg/ml; IL-6: (92.1±34.4) pg/ml vs. (123.9±16.6) pg/ml, (7 547±604) pg/ml vs. (8 047±470) pg/ml, all P<0.05], while the activity of SOD was significantly higher than that in the model group[(102.8±2.8) U/ml vs. (99.7±4.1) U/ml, (387.0±12.7) U/ml vs. (375.9±11.7) U/ml, all P<0.05]. Conclusion:GSH has a protective effect on diclofenac-induced acute kidney injury in rats, and its possible mechanism is to inhibit oxidative stress and inflammatory reactions.

Objective:To investigate the protective effect of reduced glutathione (GSH) on diclo-fenac-induced acute kidney injury (AKI) in rats and its mechanism.Methods:Thirty-three male 8-week-old specified pathogen-free SD rats were randomly divided into control, model, and GSH groups (11 rats in each group) according to a random number table method. Diclofenac sodium solution (200 mg/kg) was intragastrically administered to rats in the model group and GSH group to establish the AKI model. Thirty minutes later, rats in the GSH group were treated with intragastric administration of GSH solution (500 mg/kg), while rats in the control and model groups were with 0.9% sodium chloride injection of equal volume. After 24 hours of administration, blood sample was collected and kidneys were isolated. Kidney function [blood urea nitrogen (BUN), serum creatinine (Scr)], kidney histopathology, and serum and kidney tissue oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and the inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin 6 (IL-6) were examined. The results of each examination results among rats of the 3 groups were compared.Results:The BUN and Scr in rats of the model group were significantly higher than those in the control and GSH groups[BUN: (14.34±8.47) mmol/L vs. (7.89±2.20) and (8.46±3.58) mmol/L; Scr: (34.44±6.56) μmol/L vs. (24.77±9.50) and (29.28±4.33) μmol/L, all P<0.05]. Glomerular and tubular morphological changes were observed in both model and GSH rats, but the change in rats of GSH group was less severe than that of the model group. The mean levels of MDA, TNF-α, and IL-6 in both serum and kidney tissue in rats of GSH group were significantly lower than those of the model group[MDA: (9.5±0.2) nmol/ml vs. (10.2±0.6) nmol/ml, (3.6±0.3) nmol/ml vs. (4.0±0.2) nmol/ml; TNF-α: (2.9±2.5) pg/ml vs. (5.4±3.0) pg/ml, (420.9±40.3) pg/ml vs. (470.4±31.3) pg/ml; IL-6: (92.1±34.4) pg/ml vs. (123.9±16.6) pg/ml, (7 547±604) pg/ml vs. (8 047±470) pg/ml, all P<0.05], while the activity of SOD was significantly higher than that in the model group[(102.8±2.8) U/ml vs. (99.7±4.1) U/ml, (387.0±12.7) U/ml vs. (375.9±11.7) U/ml, all P<0.05]. Conclusion:GSH has a protective effect on diclofenac-induced acute kidney injury in rats, and its possible mechanism is to inhibit oxidative stress and inflammatory reactions.

OBJECTIVE To optimize the extraction and separation process of chebulagic acid and chebulinic acid from Terminalia chebula. METHODS Based on single factor experiment， with particle size， liquid-solid ratio， extraction time and extraction times as factors， using the contents of chebulagic acid and chebulinic acid as indexes， orthogonal experiment was designed to optimize the extraction process of chebulagic acid and chebulinic acid. Taking sample concentration， elution solvent and the ratio of eighteen-group bonded silicone reverse phase （ODS） to the amount of raw medicine as factors， the separation processes of chebulagic acid and chebulinic acid were optimized. RESULTS The optimal extraction process of chebulagic acid and chebulinic acid included ethanol volume fraction of 70%， ultrasonic extraction， particle size of 120 mesh， liquid-solid ratio of 25∶1 （mL/g）， extraction time of 20 min， and extracting for 2 times. After 3 experiments， the average comprehensive score was 99.33 （RSD＝ 0.68%， n＝3）， and the average contents of chebulagic acid and chebulinic acid were 107.05 and 58.32 mg/g， respectively. The optimal separation process of the two components included the concentration of sample loading solution was 0.5 g/mL （1 mL was equivalent to 0.5 g of medicinal materials）， the ratio of ODS to the amount of raw medicine was 10∶1.5 （g/g）， methanol-water （1∶4， V/V） eluted chebulagic acid， methanol-water （3∶7， V/V） eluted chebulinic acid. After 3 experiments， the average total yields of the two components were 53.33%， 39.23%. After recrystallization， the purity of both components was 100%. CONCLUSIONS Established extraction and separation process of chebulagic acid and chebulinic acid is simple and feasible.

OBJECTIVE To study the content changes of ch emical constituents of processed products of Terminalia chebula at different temperatures ，and to compare its anti-ulcerative colitis effect. METHODS Processed products of T. chebula at different temperatures（160，180，200，220，240，260，280，300 ℃）were prepared by sand scalding technology. HPLC method was adopted to determine the contents of gallic acid ，chebulagic acid ，chebulinic acid and ellagic acid in crude drug and processed products of T. chebula at different temperatures. The mice were divided into blank group ，model group ，Mesalazin enteric-coated tablets group （positive control ，0.4 g/kg），crude drug and processed products groups of T. chebula at different temperatures （1.3 g/kg），with 10 mice in each group. Except for blank group ，other groups were given 6％ acetic acid 0.1 mL via anus to induce ulcerative colitis model. After modeling ，blank group and model group were given water intragastrically ，and other groups were given relevant drug intragastrically ，20 mL/kg，once a day ，for consecutive 7 days. The general physical signs of mice in each group were observed and the body weight was recorded. The colorectal length and index ，serum levels of related inflammation indexes [superoxide dismutase （SOD），malondialdehyde （MDA），interleukin-10 （IL-10），IL-1 β ，tumor necrosis factor α （TNF-α）] were detected. The pathomorphological changes of colon and rectum were observed ，and the comprehensive score of pharmacodynamics was performed. RESULTS With the increase of processing temperature ，the contents of chebulagic acid and chebulinic acid decreased gradually ，the content of gallic acid increased first and then decreased ，and the content of ellagic acid increased. Compared with model group ，the general physical signs ，body weight ，colorectal length ，colorectal index and related inflammation indexes were all improved significantly in crude drug and processed products groups of T. chebula at different temperatures（P＜0.05 or P＜0.01）. The glandular recess structure of colorectal tissue was repaired ，the infiltration of inflammatory cells was reduced ，and the comprehensive score of efficacy of processed products prepared at 260 ℃ was the highest. CONCLUSIONS The contents of chemical components in T. chebula processed at different temperatures change significantly and their anti-ulcerative colitis effects are different. The processed products of T. chebula prepared at 260 ℃ show the best anti-ulcerative colitis effect.