Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.

Objective:To investigate the mechanism of improving liver injury by enhancing the abundance of Akkermansia mu-ciniphila(AKK bacteria)with hepatocyte-specific Yap1 knockout during PD-1 monoclonal antibody treatment.Methods:Hepatocyte-specific Yap1 knockout mice(genotype Yap1Flox/Flox;albumin-Cre,labeled as Yap1LKO)and control mice(genotype Yap1Flox/Flox,labeled Yap1Flox),aristolocholic acidⅠ(AAⅠ)and CCl4 were used to induce liver injury,Yap1LKO mice and Yap1Flox mice were randomly di-vided into control group and PD-1 monoclonal antibody group.After the intervention,real-time PCR detected changes in the abun-dance of AKK bacteria in the fecal microbial DNA of mice,16S rRNA gene sequencing further analyzes intestinal flora changes,the livers of mice were made into wax blocks for HE staining to observe the histopathological changes of the liver.Results:Yap1Flox mice exhibited balloon-like edema degeneration of hepatocytes and infiltration of inflammatory factors in the manifold area,compared with Yap1Flox mice,Yap1LKO mice had reduced the abundance of AKK bacteria in the intestine,fibrosis of the liver,and the degree of dam-age was more serious;PD-1 monoclonal antibody treatment alone did not increase the abundance of AKK bacteria in the intestines of mice,and fibrosis appeared in the liver;however,the abundance of intestinal AKK bacteria in Yap1LKO mice treated with PD-1 mono-clonal antibody increased,the ratio(F/B value)of Firmicutes to Bacteroides at the phylum level decreased,and the morphology of he-patocytes returned to normal and the degree of liver damage decreased.Conclusion:In AAⅠ and CCl4 induced liver injury mice,he-patocyte-specific Yap1 knockout reduced the abundance of AKK bacteria in the intestine,and the degree of liver injury was more se-vere than that in Yap1Flox mice.When treated with PD-1 monoclonal antibody,hepatocyte-specific Yap1 knockout could increase the abundance of AKK bacteria in the intestine,change the composition of intestinal flora,maintain intestinal homeostasis and ameliorate liver injury.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective To investigate and analyze the current situation regarding the implementation of hydration and renal function monitoring during perioperative period of peripheral vascular interventions,so as to provide references for effectively preventing contrast-induced nephropathy(CIN).Methods Through literature review,expert interview,and research group discussion,a survey questionnaire was designed.Using the"Wenjuanxing"platform,an investigation of the current situation about the implementation of hydration and renal function monitoring during perioperative period of peripheral vascular interventions was conducted among the medical staff of 141 hospitals in 27 provinces(autonomous regions/municipalities)from May to June of 2023.Results A total of 325 professionals participated in the survey,84.92％of whom(276/325)implemented hydration.A total of 265 medical workers gave feedback on intravenous hydration status:90.57％of them(240/265)adopted 0.9％sodium chloride solution,and the median volumes of infusion before,during and after surgery were all 1 000 mL.A total of 239 medical workers gave feedback on oral hydration status:56.07％of them(134/239)adopted quantitative drinking water mode,the amount of drinking water varied from a minimum of 500 mL to a maximum of 2 000 mL,which was given before surgery as well as within 6 hours after surgery.In addition,10.15％(33/325)of the respondents did not monitor creatinine levels,and 26.77％(87/325)of the respondents did not monitor urine volume.Conclusion At present,there is no unified hydration scheme during perioperative period of peripheral vascular interventions,and the monitoring of renal function is inadequate.It is necessary for medical staff to learn the knowledge of CIN prevention.At the same time,hydration strategies that are safe,effective,comfortable for patients and that can reduce the clinical workload of medical workers need to be further explored.

Objectives:To summarize the relevant evidence of non-invasive cardiac output monitoring management in critically ill patients and provide evidence-based basis for strengthening the standardization and accuracy of non-invasive cardiac output monitoring by clinical medical staff.Methods:We searched UpToDate,British Medical Journal Best Practice Database,The UK National Institute of Clinical Medicine guideline library,PubMed,Embase,American Society of Critical Care Medicine,American Association of Critical Care Nurses,Wanfang database,China Knowledge Network,SinoMed and other databases to collect relevant clinical decisions,guidelines,best practices,evidence summaries,systematic reviews,expert consensuses and randomized controlled trials related to non-invasive cardiac output monitoring management.The search period is from the inception to August 2023.After screening and quality evaluation by the evidence-based team,relevant evidence that meets the standards was extracted.Results:A total of 11 articles were obtained,including 7 systematic reviews,4 expert consensus.Finally,20 best evidences were obtained about the non-invasive cardiac output monitoring management in critically ill patients,including the patients suitable for non-invasive cardiac output monitoring,correlation with the invasive cardiac output monitoring,and the source of error in the monitoring process,involving 5 aspects such as monitoring population,clinical application,interference factors,precautions and personnel training.Conclusions:Clinical medical staffshould strengthen the training of non-invasive cardiac output monitoring technology in critically ill patients,and appropriate practical evidence should be selected in combination with the specific clinical situation to improve the application standardization and measurement accuracy of non-invasive cardiac output monitoring in critically ill patients.

Objective:To investigate the mechanism of improving liver injury by enhancing the abundance of Akkermansia mu-ciniphila(AKK bacteria)with hepatocyte-specific Yap1 knockout during PD-1 monoclonal antibody treatment.Methods:Hepatocyte-specific Yap1 knockout mice(genotype Yap1Flox/Flox;albumin-Cre,labeled as Yap1LKO)and control mice(genotype Yap1Flox/Flox,labeled Yap1Flox),aristolocholic acidⅠ(AAⅠ)and CCl4 were used to induce liver injury,Yap1LKO mice and Yap1Flox mice were randomly di-vided into control group and PD-1 monoclonal antibody group.After the intervention,real-time PCR detected changes in the abun-dance of AKK bacteria in the fecal microbial DNA of mice,16S rRNA gene sequencing further analyzes intestinal flora changes,the livers of mice were made into wax blocks for HE staining to observe the histopathological changes of the liver.Results:Yap1Flox mice exhibited balloon-like edema degeneration of hepatocytes and infiltration of inflammatory factors in the manifold area,compared with Yap1Flox mice,Yap1LKO mice had reduced the abundance of AKK bacteria in the intestine,fibrosis of the liver,and the degree of dam-age was more serious;PD-1 monoclonal antibody treatment alone did not increase the abundance of AKK bacteria in the intestines of mice,and fibrosis appeared in the liver;however,the abundance of intestinal AKK bacteria in Yap1LKO mice treated with PD-1 mono-clonal antibody increased,the ratio(F/B value)of Firmicutes to Bacteroides at the phylum level decreased,and the morphology of he-patocytes returned to normal and the degree of liver damage decreased.Conclusion:In AAⅠ and CCl4 induced liver injury mice,he-patocyte-specific Yap1 knockout reduced the abundance of AKK bacteria in the intestine,and the degree of liver injury was more se-vere than that in Yap1Flox mice.When treated with PD-1 monoclonal antibody,hepatocyte-specific Yap1 knockout could increase the abundance of AKK bacteria in the intestine,change the composition of intestinal flora,maintain intestinal homeostasis and ameliorate liver injury.

Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.

Objectives:To summarize the relevant evidence of non-invasive cardiac output monitoring management in critically ill patients and provide evidence-based basis for strengthening the standardization and accuracy of non-invasive cardiac output monitoring by clinical medical staff.Methods:We searched UpToDate,British Medical Journal Best Practice Database,The UK National Institute of Clinical Medicine guideline library,PubMed,Embase,American Society of Critical Care Medicine,American Association of Critical Care Nurses,Wanfang database,China Knowledge Network,SinoMed and other databases to collect relevant clinical decisions,guidelines,best practices,evidence summaries,systematic reviews,expert consensuses and randomized controlled trials related to non-invasive cardiac output monitoring management.The search period is from the inception to August 2023.After screening and quality evaluation by the evidence-based team,relevant evidence that meets the standards was extracted.Results:A total of 11 articles were obtained,including 7 systematic reviews,4 expert consensus.Finally,20 best evidences were obtained about the non-invasive cardiac output monitoring management in critically ill patients,including the patients suitable for non-invasive cardiac output monitoring,correlation with the invasive cardiac output monitoring,and the source of error in the monitoring process,involving 5 aspects such as monitoring population,clinical application,interference factors,precautions and personnel training.Conclusions:Clinical medical staffshould strengthen the training of non-invasive cardiac output monitoring technology in critically ill patients,and appropriate practical evidence should be selected in combination with the specific clinical situation to improve the application standardization and measurement accuracy of non-invasive cardiac output monitoring in critically ill patients.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To compare the therapeutic efficacy, safety and drug cost between generic enteric-coated mycophenolate sodium (EC-MPS) and branded EC-MPS in immunosuppressive treatment for adult recipients of renal transplantation (RT) .Methods:From January, 2022 to October, 2023, 60 adult RT patients were continuously enrolled and randomized into two groups. Patients receiving generic EC-MPS were selected as cohort 1 (n=30) while those taking branded EC-MPS designated as cohort 2 (n=30). Hepatic/renal function, blood routine parameters, drug concentrations, adverse events (AEs) and drug costs were recorded and compared between two cohorts at baseline (<3 days before/after day of RT, W0), week 1 (W1), week 4 (W4), week 8 (W8), week 12 (W12) and week 24 (W24) post-RT.Results:Only urine protein was elevated at W24[0.4 (0-0.6) vs 0 (0-0.2) g/24 h, P=0.049]in cohort 1 as compared with cohort 2. Aspartate aminotransferase at W12 (15.6±3.3 vs 20.3±9.7 U/L, P=0.010), leucocyte count at W1 (8.4±2.3 vs 10.1±3.8 ×10 9/L, P=0.045) and platelet count at W1 (158.5±51.5 vs 185.8±46.8 ×10 9/L, P=0.036) all declined in cohort 1 as compared with cohort 2. However, these parameters at other timepoints did not vary between two cohorts (all P>0.050). In addition, blood concentration of MPS after dosing, area under the concentration-time curve and trough concentration of tacrolimus at different timepoints were not different between two cohorts (all P>0.050). Similarly, helper T cells (Th), suppressor T cells (Ts), Th/Ts and B cells at W4/12 did not vary between two cohorts (all P>0.050). Concerning drug cost, no difference existed in the number of tablets or length of stay between two cohorts (both P>0.050). However, cost of EC-MPS (￥1 333.5±419.6 vs ￥2 368.6±596.0, P<0.001) and total cost during hospitalization (￥96 403.3±29 159.8 vs ￥117 062.8±28 782.1, P=0.001) were lower in cohort 1 than cohort 2. The most common AEs in cohort 1 included acid regurgitation (n=19, 63.3%), hypoalbuminemia (n=16, 53.3%), anemia (n=12, 40.0%) and hypokalemia (n=11, 36.7%). And the most common AEs in cohort 2 included acid regurgitation (n=20, 66.7%), anemia (n=14, 46.7%) and hypoalbuminemia (n=9, 30.0%). Notably, the incidence of all AEs was not different between two cohorts (all P>0.050) . Conclusion:Generic EC-MPS has comparable therapeutic efficacy and safety profile with lower drug cost in adult RT patients. It provides more options for maintenance treatment in RT patients.