Background and aims:Advanced hepatocellular carcinoma(HCC)with pulmonary metastasis(PM)has a poor prognosis,and optimal treatment strategies remain controversial.This study aimed to compare the long-term outcomes of patients with advanced HCC with PM who were treated with resection of pul-monary metastases versus those treated with targeted therapies combined with immunotherapy.Methods:A retrospective analysis was conducted on the medical records of HCC patients with PM who underwent either pulmonary metastasectomy or immunotherapy combined with targeted therapies at the Eastern Hepatobiliary Surgery Hospital,Changhai Hospital of Shanghai,Fujian Provincial Hospital,and West China Hospital of Sichuan University from September 2013 to October 2022.One-to-one propensity score matching(PSM)was employed to control the influence of potential confounders,and the survival outcomes were compared.Results:A total of 119 HCC patients with PM were included in this study.The overall survival(OS)of patients who underwent pulmonary metastasectomy was significantly longer than that of patients who received immunotherapy targeted combinations(OS:1-year,80.0％vs.59.3％;2-year,31.7％vs.20.3％;3-year,20.0％vs.0;P＜0.001).After PSM,the long-term prognosis of the pulmonary metastasectomy group remained significantly better than that of the immunotherapy combination group(OS:1-year,87.0％vs.69.6％;2-year,34.8％vs.30.4％;3-year,21.7％vs.0;P=0.005).Multivariate analysis revealed that treat-ment allocation(hazard ratio(HR)=2.177,95％confidence interval(CI)=1.068-4.439)and hepatic tumor T stage(HR=2.342,95％CI=1.209-4.538)were independent risk factors for OS.Conclusions:Pulmonary metastasectomy was associated with improved survival compared to immu-notherapy combined with targeted therapies and may represent an optimal treatment option for highly selected HCC patients with resectable PM.

Trimethylamine N-oxide(TMAO)is a small-molecule organic compound.Clinical studies over the past decade have shown that elevated blood levels of TMAO are positively correlated with an increased risk of cardiovascular diseases(CVD).Vascular remodeling(VR)is a critical pathophysiological process in the progression of CVD and is widely involved in the onset and development of conditions such as hypertension and atherosclerosis.Current research in-dicates that TMAO participates in regulating the process of VR through various mechanisms,including promoting inflamma-tory responses,enhancing oxidative stress,and inducing vascular endothelial dysfunction.Present interventional strategies targeting TMAO primarily focus on microbial modulation.This review summarizes the sources and metabolic pathways of TMAO,outlines its potential pathogenic mechanisms in VR,and explores the role of TMAO in VR as well as its potential value as a therapeutic target,aiming to provide a theoretical reference for related medical research.

Cardiovascular diseases(CVD)are characterized by high morbidity,disability,and mortality rates,making them one of the leading causes of human death worldwide.Vascular remodeling refers to changes in the structure and function of blood vessels under pathological or physiological conditions,typically occurring during processes such as tissue damage repair and disease progression.Investigating the mechanisms of vascular remodeling helps in understanding the progression of CVD,thereby developing more effective early diagnosis and treatment plans,and providing new insights for the prevention and treatment of CVD.The modeling methods of vascular remodeling are the foundation for studying vascular remodeling.Significant progress has been made in vascular remodeling models for studying multiple disease mechanisms,and they are particularly important in the fields of atherosclerosis,hypertension,and vascular remodeling.Common animal models for vascular remodeling include rats,mice,pigs,and other species.Research methods cover mechanical injury,drug intervention,genetic modification,and so on.Different types of animal models have their own advantages.For example,mouse and rat models are suitable for gene studies and high-throughput screening,while rabbit and monkey models,due to their closer resemblance to human pathology,are helpful for simulating vascular remodeling under clinical conditions.Among them,rat models are widely used as frontline models in medical research due to their cost-effectiveness and ease of operation.Current vascular remodeling models mainly rely on classical methods(such as carotid artery balloon injury method,ligation method,and arterial clamping)and are combined with emerging dietary methods(such as high-fat diet,high-salt diet)for construction.Different rat modeling methods are selected according to different experimental needs.The combination of these methods can effectively simulate different mechanisms of vascular remodeling and provide reliable animal models for CVD research.In addition,these rat models can reflect vascular responses under different pathological conditions,offering an important experimental basis for drug development and the formulation of disease treatment strategies.Although these rat models provide valuable tools for vascular remodeling research,challenges such as large model variability,poor reproducibility,and differences from clinical manifestations remain.Future research should focus on improving the accuracy and reliability of existing models to develop new animal models.This article uses rats as examples to summarize the current research progress,model types,and applications of vascular remodeling models,particularly their value in CVD and vascular remodeling research,and provides a theoretical reference for future vascular remodeling-related research by reviewing the advantages and disadvantages of different rat vascular remodeling models.

Cardiovascular diseases(CVD)are characterized by high morbidity,disability,and mortality rates,making them one of the leading causes of human death worldwide.Vascular remodeling refers to changes in the structure and function of blood vessels under pathological or physiological conditions,typically occurring during processes such as tissue damage repair and disease progression.Investigating the mechanisms of vascular remodeling helps in understanding the progression of CVD,thereby developing more effective early diagnosis and treatment plans,and providing new insights for the prevention and treatment of CVD.The modeling methods of vascular remodeling are the foundation for studying vascular remodeling.Significant progress has been made in vascular remodeling models for studying multiple disease mechanisms,and they are particularly important in the fields of atherosclerosis,hypertension,and vascular remodeling.Common animal models for vascular remodeling include rats,mice,pigs,and other species.Research methods cover mechanical injury,drug intervention,genetic modification,and so on.Different types of animal models have their own advantages.For example,mouse and rat models are suitable for gene studies and high-throughput screening,while rabbit and monkey models,due to their closer resemblance to human pathology,are helpful for simulating vascular remodeling under clinical conditions.Among them,rat models are widely used as frontline models in medical research due to their cost-effectiveness and ease of operation.Current vascular remodeling models mainly rely on classical methods(such as carotid artery balloon injury method,ligation method,and arterial clamping)and are combined with emerging dietary methods(such as high-fat diet,high-salt diet)for construction.Different rat modeling methods are selected according to different experimental needs.The combination of these methods can effectively simulate different mechanisms of vascular remodeling and provide reliable animal models for CVD research.In addition,these rat models can reflect vascular responses under different pathological conditions,offering an important experimental basis for drug development and the formulation of disease treatment strategies.Although these rat models provide valuable tools for vascular remodeling research,challenges such as large model variability,poor reproducibility,and differences from clinical manifestations remain.Future research should focus on improving the accuracy and reliability of existing models to develop new animal models.This article uses rats as examples to summarize the current research progress,model types,and applications of vascular remodeling models,particularly their value in CVD and vascular remodeling research,and provides a theoretical reference for future vascular remodeling-related research by reviewing the advantages and disadvantages of different rat vascular remodeling models.

Trimethylamine N-oxide(TMAO)is a small-molecule organic compound.Clinical studies over the past decade have shown that elevated blood levels of TMAO are positively correlated with an increased risk of cardiovascular diseases(CVD).Vascular remodeling(VR)is a critical pathophysiological process in the progression of CVD and is widely involved in the onset and development of conditions such as hypertension and atherosclerosis.Current research in-dicates that TMAO participates in regulating the process of VR through various mechanisms,including promoting inflamma-tory responses,enhancing oxidative stress,and inducing vascular endothelial dysfunction.Present interventional strategies targeting TMAO primarily focus on microbial modulation.This review summarizes the sources and metabolic pathways of TMAO,outlines its potential pathogenic mechanisms in VR,and explores the role of TMAO in VR as well as its potential value as a therapeutic target,aiming to provide a theoretical reference for related medical research.

Objective:To investigate the dynamic expression of histone methyltransferase (enhance of zeste homolog 2, EZH2) in peripheral blood B lymphocytes (CD19 +B) and memory B lymphocytes (CD19 +CD27 +B) of septic patients and its value in predicting prognosis in sepsis. Methods:From June 2018 to January 2020, 48 septic patients in the Intensive Care Unit of Shanghai East Hospital were enrolled, and 40 healthy adult volunteers were recruited as healthy controls. Septic patients were divided into the non-survivors (18 cases) and the survivors (30 cases) according to whether the patients survived at 28 days. Blood samples were collected at day 1, 3 and 7, blood routine, IL-6 and blood gas analysis were collected, and SOFA and APACHE Ⅱ scores were counted. Flow cytometry was used to detect the positive rate and the mean fluorescence intensity of EZH2 on CD19 +B lymphocytes, and the positive rate of EZH2 on CD19 +CD27 +B lymphocytes at different time points. In the healthy controls, fasting was taken only once in the morning. ROC curve was drawn and the area under the curve (AUC) was calculated to evaluate the value of expression of EZH2 on CD19 +B lymphocytes and CD19 +CD27 +B lymphocytes in predicting the prognosis of septic patients. Results:(1) Compared with the healthy controls, the positive rate and average fluorescence intensity of EZH2 on CD19 +B lymphocytes and the positive rate of EZH2 expression on CD19 +CD27 +B lymphocytes were significantly increased at day 1, 2 and 3 in septic patients ( P<0.05). Over time, the expression of EZH2 in CD19 +B lymphocytes and CD19 +CD27 +B lymphocytes increased gradually ( P<0.05). (2) Compared with the survivors, the positive rate of EZH2 on CD19 +B lymphocytes of the non-survivors was increased at day 1, but the positive rate of EZH2 on CD19 +CD27 +B lymphocytes of the non-survivors was decreased at day 3 and 7 ( P<0.05). (3) The positive rate of EZH2 on CD19 +B lymphocytes, APACHE Ⅱ score, SOFA score and IL-6 level in septic patients at day 1 were independently associated with 28-day mortality. (4) The AUC of APACHEⅡ score was 0.907 (95% CI: 0.825-0.990), and the sensitivity and the specificity were 88.89% and 76.67%. The AUC of SOFA score was 0.831 (95% CI: 0.706-0.955), and the sensitivity and the specificity was 66.67% and 86.67%; The AUC of EZH2 positive rate on CD19 +B lymphocytes were 0.799 (95% CI: 0.657-0.941), and the sensitivity and specificity were 88.89% and 80.77%, respectively, the sensitivity was better than SOFA score, and the specificity was higher than APACHEⅡ score. Conclusions:The high expression of EZH2 on B lymphocytes in septic patients is associated with poor prognosis. Dynamic monitoring of EZH2 expression on B lymphocytes has certain predictive value for sepsis.

Objective To compare the effect of different enteral nutritional support methods in elderly patients with severe pneumonia.Methods Elderly patients (average age over 65 years) with severe pneumonia admitted to our hospital from June 2015 to June 2018 were selected as the study subjects,and 86 patients finally completed the study.The patients were randomly divided into the control group and observation group with 43 patients in each group,and nasojejunal tubes were placed for patients in both groups.Patients in the observation group were fed with enteral nutrition emulsion through continuously-heated nutritional pump,while patients in the control group was meal served with enteral nutrition emulsion.Changes in blood biochemical parameters,immune indexes,inflammation indexes,oxygenation indexes,the GIDF and SOFA scores as well as curative effect (mechanical ventilation time and effective rate of treatment) were monitored and compared before and after 10 days of nutritional support treatment.SPSS 20.0 statistical software package was used for data analysis,and self paired t-test was used for comparison before and after intervention in the same group,x2 test was used in comparison between different groups,and the counting data was expressed as the rate (n,％).Results There was no significant difference in baseline data between patients in the two groups (P＞0.05).After ten days of intervention,compared with the control group,the levels of serum albumin and prealbumin in the observation group were higher [(31.22±2.36) g/L and (0.29±0.24) g/L,P=0.015 and P=0.023],the immune indexes were higher [IgG (13.24±0.70) g/L,P=0.020;IgM (1.43±0.19) g/L,P=0.011;CD4+/CD8+ 1.55±0.49,P=0.043],the inflammation indexes were lower [IL-6 (312.54±42.53) pg/mL,P=0.031;PCT (1.56±0.81) ng/mL,P=0.017],the oxygenation indexes were better [PaO2/FiO2 (315.58±20.37) mmHg,P=0.019],and the GIDF and SOFA scores were significantly lower[(10.6±l.2) and (8.5±1.7),P=0.041 and P=0.038].The clinical outcome showed that the mechanical ventilation time in the observation group was significantly shorter [(6.01±1.48) d vs (8.12 ± 1.17)d,P=0.039],and the total effective rate of treatment was better than the control group (67.44％ vs 41.86％,P=0.027).Conclusions Enteral nutrition support through continuously-heated nutritional pump can improve the nutritional status of elderly patients with severe pneumonia,reduce the incidence of gastrointestinal dysfunction,maintain stable organ fuction,thus resulting in better prognosis in elderly patients with severe pneumonia.

Objective:To evaluate the early diagnostic value of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) in acute kidney injury induced by sepsis.Methods:A total of 85 sepsis patients admitted to the EICU and GICU in Shanghai East Hospital from September 2017 to June 2019 were divided into theAKI group ( n=37) and the non-AKI group ( n=48) according to KIDGO diagnostic criteria, and 20 healthy volunteers were served as the control group. The clinical data were recorded and samples of urine were collected at 0 h, 6 h, 12 h, 1 d, 3 d and 7 d post sepsis. The levels of TIMP-2 and IGFBP-7 in the urine were analyzed with ELISA at different time points. Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC), the early diagnostic value of urinary TIMP-2 and IGFBP-7 in sepsis-induced AKI patients was determined. Results:Compared with the control group, the levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher at the above time points ( P<0.05), while those of the non-AKI group showed no significant differences. The levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher than the those of the non-AKI group ( P<0.05). ROC analysis showed that when the AUC of urine TIMP-2 peaked at 1 d, the sensitivity and specificity reached 97.5% and 81.2%, separately with the cutoff value of 151.23 ng/mL. Furthermore, when the AUC of urine IGFBP-7 peaked at 12 h, the sensitivity and specificity reached 100% and 72.8%, separately with the cutoff value of 14.91 ng/mL. Interestingly, when the AUC of combined TIMP-2×IGFBP-7 peaked at 12 h, the sensitivity reached 98.0% and specificity reached 91.5% with the cutoff value of 2.09 [(ng/mL) 2/1 000]. There was no significant correlation between the levels of TIMP-2 and IGFBP-7 with SOFA and APACHEⅡ score at 1 d, 3 d and 7 d post sepsis in the AKI group ( P>0.05). Conclusions:Urine TIMP-2 and IGFBP-7 have early diagnostic value in sepsis-induced AKI. Besides, the combination of the two biomarkers have superior predictive value than each single of them.

Objective:To find out the key factors that affect the clinical outcome of euploid single blastocyst transfer.Methods:This retrospective study included 956 patients' clinical data of frozen euploid single blastocyst transfer cycles for preimplantation genetic testing (PGT) in Shanghai Ji Ai Genetics and IVF Institute from January 2014 to January 2018. According to the outcome of transplantation, the patients were divided into pregnancy group ( n=509) and non-pregnancy group ( n=447), and the clinical data between the two groups were compared to screen out the key factors affecting the pregnancy rate of transplantation; at the same time, the pregnancy group was further divided into live birth subgroup and miscarriage subgroup, and the clinical data between the two subgroups were compared and the significant factors affecting the abortion were screened by logistic regression. Results:The endometrial thickness of pregnancy group was significantly thicker than that of non-pregnancy group [9(8,10) mm vs. 8(8,10) mm] ( P=0.006); the clinical pregnancy rate and the live birth rate of blastocyst with good quality were significantly higher than those with poor quality (59.2% vs. 46.3%, 50.2% vs. 37.7%) ( P=0.001). In addition, compared with miscarriage subgroup, blastocyst development time was a risk factor of abortion, and the OR value was 0.536 (95% CI=0.309-0.929). Conclusion:In the frozen embryo transfer cycles of single euploid blastocyst, the thicker endometrium, the faster development and the higher score of blastocyst are the key factors for the success of the implantation. In the process of maintaining the late pregnancy, the faster development of blastocyst (D5) has a higher live birth rate and a lower miscarriage rate.

Objective:To find out the key factors that affect the clinical outcome of euploid single blastocyst transfer.Methods:This retrospective study included 956 patients' clinical data of frozen euploid single blastocyst transfer cycles for preimplantation genetic testing (PGT) in Shanghai Ji Ai Genetics and IVF Institute from January 2014 to January 2018. According to the outcome of transplantation, the patients were divided into pregnancy group ( n=509) and non-pregnancy group ( n=447), and the clinical data between the two groups were compared to screen out the key factors affecting the pregnancy rate of transplantation; at the same time, the pregnancy group was further divided into live birth subgroup and miscarriage subgroup, and the clinical data between the two subgroups were compared and the significant factors affecting the abortion were screened by logistic regression. Results:The endometrial thickness of pregnancy group was significantly thicker than that of non-pregnancy group [9(8,10) mm vs. 8(8,10) mm] ( P=0.006); the clinical pregnancy rate and the live birth rate of blastocyst with good quality were significantly higher than those with poor quality (59.2% vs. 46.3%, 50.2% vs. 37.7%) ( P=0.001). In addition, compared with miscarriage subgroup, blastocyst development time was a risk factor of abortion, and the OR value was 0.536 (95% CI=0.309-0.929). Conclusion:In the frozen embryo transfer cycles of single euploid blastocyst, the thicker endometrium, the faster development and the higher score of blastocyst are the key factors for the success of the implantation. In the process of maintaining the late pregnancy, the faster development of blastocyst (D5) has a higher live birth rate and a lower miscarriage rate.