Under the background of accelerating the development of new quality productivity,the current training of clin-ical compound talents in tertiary general hospitals is facing new challenges and is difficult to meet the growing health demands of the people.This study comprehensively employs multiple scientific methods such as the Delphi expert consultation method and lit-erature research to explore and construct a training system and path for clinical compound talents that meets the demands of new quality productivity development,consisting of 9 first-level indicators and 40 second-level indicators.While giving full play to the main,leading,and commanding role of high-level public hospitals,by cultivating clinical compound talents that meet the require-ments of new quality productivity,a path is sought in practice to improve the medical service level of tertiary general hospitals and promote the high-quality development of the medical and health care industry.

Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced athero-sclerosis in ApoE-/-mice.Methods Twenty-four ApoE-/-mice were randomly divided into the normal group,high-fat group,and high-fat+anti-PD-L1 mAb group.After 70 days,the blood samples were harves-ted.Blood vessels(aortic root to abdominal aorta)and liver from each groups were stained with Oil Red O.Hematoxylin-eosin staining(HE)was employed to vis-ualize structural changes in liver.Enzyme-linked im-munosorbent assay(ELISA)was applied to detect the serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)and inflammatory factors(IFN-γ,TNF-α,IL-1 β).Flow cytometry was used to detect the proportion of lymphocytes(CD4 and CD8).RT-PCR was utilized to assess the expressions of IFN-γ,TNF-α,IL-1 β,CD4 and CD8 in liver.Results Compared with the high-fat group,the treatment with anti-PD-L1 monoclonal antibody promoted vascular wall and liver lipid accumulation,and also up-regulated serum and liver content of cholesterol(CHO),triglyceride(TG)and high-density lipoprotein(HDL-c).Treatment with anti-PD-L1 monoclonal antibody up-regulated the con-tent of alanine aminotransferase(GPT)and aspartate aminotransferase(GOT)in serum and liver,but not al-kaline phosphatase(AKP).ELISA test indicated that treatment with anti-PD-L1 monoclonal antibody stimu-lated the serum level of IFN-γ,TNF-α and IL-1 β.Fur-thermore,the mRNA level of IFN-γ,TNF-α and IL-1 βin liver was also up-regulated after treatment with anti-PD-L1 monoclonal antibody.With flow cytometry,we observed that treatment with anti-PD-L1 monoclonal antibody promoted hepatic CD8+T and CD8+IFN-γ+T cell activation,but had no effect on CD4+IFN-γ+T cell activation under high-fat feeding conditions.Con-clusions Anti-PD-L1 monoclonal antibody adminis-tered under high-fat feeding conditions can damage liv-er function and aggravate atherosclerosis by activating liver CD8+IFN-γ+T cells.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Under the background of accelerating the development of new quality productivity,the current training of clin-ical compound talents in tertiary general hospitals is facing new challenges and is difficult to meet the growing health demands of the people.This study comprehensively employs multiple scientific methods such as the Delphi expert consultation method and lit-erature research to explore and construct a training system and path for clinical compound talents that meets the demands of new quality productivity development,consisting of 9 first-level indicators and 40 second-level indicators.While giving full play to the main,leading,and commanding role of high-level public hospitals,by cultivating clinical compound talents that meet the require-ments of new quality productivity,a path is sought in practice to improve the medical service level of tertiary general hospitals and promote the high-quality development of the medical and health care industry.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Purpose To evaluate the predictive value of multifunctional parameters of single photon emission computed tomography gated myocardial perfusion imaging(SPECT G-MPI)for major adverse cardiovascular events(MACE)in chronic kidney disease(CKD)with abnormal stress myocardial perfusion.Materials and Methods A total of 99 patients diagnosed with CKD from June 2017 to March 2024 who underwent stress and rest G-MPI indicating abnormal myocardial perfusion in Beijing Anzhen Hospital,Capital Medical University.The American Heart Association 17-segment 5-point method and PHASE software were used to obtain the left ventricular myocardial perfusion,functional and synchronization parameters.According to the occurrence of MACE,the patients were divided into MACE group and non-MACE group.Cox regression was used to analyze the predictors related to MACE.The receiver operator characteristic curve was used to analyze the performance of predictors,the survival curves were obtained by the Kaplan-Meier method,Log-rank test was used to compare the differences in different groups.Results Finally,we enrolled 99 CKD patients with abnormal stress myocardial perfusion.35 patients(35.35%)developed MACE during the follow-up period.Cox regression analysis showed that stress phase bandwidth(SPBW)(HR=1.015,95%CI 1.002-1.028)and sum difference score(SDS)(HR=1.105,95%CI 1.008-1.211)were independent risk factors for predicting MACE(both P<0.05).The optimal cut-off value of SPBW and SDS for predicting MACE were 69° and 6 points,the area under the curve was 0.801 and 0.778,respectively.The incidence of MACE in the SPBW≥69° group and SDS≥6 points group was higher than that in SPBW<69° group and SDS<6 points group(66.6%vs.13.2%,53.3%vs.20.4%,both P<0.05).Conclusion SPECT G-MPI multifunctional parameters can be used to predict the prognosis of CKD patients with abnormal stress myocardial perfusion.SPBW and SDS are independent risk factors for MACE in these patients.

Purpose To evaluate the predictive value of multifunctional parameters of single photon emission computed tomography gated myocardial perfusion imaging(SPECT G-MPI)for major adverse cardiovascular events(MACE)in chronic kidney disease(CKD)with abnormal stress myocardial perfusion.Materials and Methods A total of 99 patients diagnosed with CKD from June 2017 to March 2024 who underwent stress and rest G-MPI indicating abnormal myocardial perfusion in Beijing Anzhen Hospital,Capital Medical University.The American Heart Association 17-segment 5-point method and PHASE software were used to obtain the left ventricular myocardial perfusion,functional and synchronization parameters.According to the occurrence of MACE,the patients were divided into MACE group and non-MACE group.Cox regression was used to analyze the predictors related to MACE.The receiver operator characteristic curve was used to analyze the performance of predictors,the survival curves were obtained by the Kaplan-Meier method,Log-rank test was used to compare the differences in different groups.Results Finally,we enrolled 99 CKD patients with abnormal stress myocardial perfusion.35 patients(35.35%)developed MACE during the follow-up period.Cox regression analysis showed that stress phase bandwidth(SPBW)(HR=1.015,95%CI 1.002-1.028)and sum difference score(SDS)(HR=1.105,95%CI 1.008-1.211)were independent risk factors for predicting MACE(both P<0.05).The optimal cut-off value of SPBW and SDS for predicting MACE were 69° and 6 points,the area under the curve was 0.801 and 0.778,respectively.The incidence of MACE in the SPBW≥69° group and SDS≥6 points group was higher than that in SPBW<69° group and SDS<6 points group(66.6%vs.13.2%,53.3%vs.20.4%,both P<0.05).Conclusion SPECT G-MPI multifunctional parameters can be used to predict the prognosis of CKD patients with abnormal stress myocardial perfusion.SPBW and SDS are independent risk factors for MACE in these patients.

Objective:To evaluate the clinical predictive value of SPECT myocardial perfusion imaging (MPI) in the occurrence of cardiac death in patients with chronic kidney disease (CKD).Methods:A retrospective follow-up was performed for 160 patients (109 males, 51 females; age: 68.5(61.0, 74.0) years) who underwent MPI in Beijing Anzhen Hospital, Capital Medical University between June 2017 and March 2024. The 17-segment 5-point method was used for image analysis to obtain the left ventricular myocardial perfusion and functional parameters. The patients were followed up for cardiac death, and divided into death group and survival group. Clinical data of those 2 groups were compare by χ2 test, the independent-sample t test or Mann-Whitney U test. Cox proportional hazards regression analysis was used to analyze the predictors related to cardiac death. The ROC curve was used to analyze the performance of predictors. Survival curves were obtained by the Kaplan-Meier method, and log-rank test was performed to compare the difference between 2 groups. Results:The follow-up time of 160 patients with CKD was 26.0(10.0, 46.5) months. Of 160 patients, 17 died and 143 survived. There were statistically significant differences in body mass index (BMI), previous myocardial infarction, previous revascularization, hypersensitive C-reactive protein (hs-CRP), positive MPI, left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS) between the death group and the survival group ( χ2 values: 4.58-16.13, t values: -2.34, -3.97, Z values: from -2.81 to 5.02, all P<0.05). Multivariate Cox regression analysis showed that SSS (hazard ratio ( HR)=1.153, 95% CI: 1.062-1.252, P=0.001) and hs-CRP ( HR=1.031, 95% CI: 1.004-1.058, P=0.023) were independent risk factors for cardiac death in patients with CKD. The optimal cut-off value of SSS for predicting cardiac death in those patients was determined to be 8 with the AUC of 0.815, and the incidence of cardiac death in the SSS ≥8 group was significantly higher than that in the SSS<8 group (33.3%(12/36) vs 4.0%(5/124); χ2 = 25.44, P<0.001). Conclusion:MPI is an important imaging method for the evaluation of cardiac death in patients with CKD, SSS and hs-CRP are important risk factors in predicting cardiac death in those patients.

Tumor immunotherapy has emerged as a highly esteemed and rapidly evolving field in recent years,marked by the development of numerous significant therapeutic approaches. Among these,immune checkpoint inhibitors stand out as a pivotal strategy,attracting considerable attention due to their substantial research progress. This article provides a comprehensive review of the current research advancements in ten key immune checkpoints related to anti-tumor therapy,including PD-1/PD-L1,CTLA-4,LAG-3,TIM-3,TIGIT,and VISTA. By conducting an in-depth analysis of their mechanisms of action,clinical applications,and future research directions,this review aims to offer valuable insights and guidance for optimizing strategies in tumor immunotherapy.