1.Enhancement of anti-tumor effect of immune checkpoint inhibitor anti-PD-L1 by shenqifuzheng injection and the mechanism study
Zhihua ZHOU ; Jingwen CHANG ; Yuanyuan YAN ; Yanan QI ; Jingjing HAN ; Xinyi ZHU ; Chen YU ; Hongyan WU ; Fangtian FAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(7):792-799
AIM:To investigate of the effect of Shenqifuzheng injection(SFI)combined with PD-L1 antibody on tumor immune microenvironment and its efficacy.METHODS:A subcutaneous transplanta-tion tumor model for B16F10-LUC melanoma was created.The expression of Ki67,CD31,CD8,CD16,CD163,FOXP3,LY6C,LY6G with labeling antibodies was used to detect CD8+T cells,Treg cells,NK cells,MDSCs cells,centrocytes,and granulocytes in the tumor tissues via immunohistochemistry.Flow cy-tometry was used to measure the ratios of CD11c+,IA/IE+,and CD80+cells in splenic tissue,as well as the ratios of CD8+T,CD4+T,and Treg cells in tumor tissue.Additionally,granulocyte count and NK cell expression were analyzed.RESULTS:The immuno-histochemistry results indicate that the drug admin-istration group effectively suppressed tumor angio-genesis and cell proliferation,while decreasing the expression level of immunosuppressive cytokines CD4+T cells,Treg cells,MDSCs and centroblasts.Ad-ditionally,CD8 and NK cell infiltration was promot-ed compared to the control group.The results of the flow analysis demonstrated a significant in-crease in the expression level of CD8+T cells within tumor tissues,as well as inhibition of CD4+T,Treg,and DC cell infiltration within the spleen in the drug administration group.Additionally,the tumor volume analysis indicated that the drug administra-tion group effectively inhibited tumor growth.The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen.Furthermore,the treatment effec-tively inhibited the infiltration of CD4+T and Treg cells.The results also indicate that the treatment significantly reduced tumor growth,with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group.Additionally,combin-ing drugs resulted in superior results compared to the PD-L1 antibody group alone.CONCLUSION:SFI combined with a PD-L1 antibody can have synergis-tic anti-tumor effects,potentially enhancing DC cell infiltration and promoting T cell activation.Immu-nohistochemistry results indicate a positive impact on the tumor immune microenvironment.
2.Prognostic value of albumin and aspartate aminotransferase/alanine aminotransferase ratio in patients with acute liver failure in hyperacute phase of sepsis: a multicenter retrospective cohort study
Xiaozhou LI ; Qianqian YIN ; Guangkuo ZHAO ; Yanan HAI ; Zhiping SUN ; Yunli CHANG
Chinese Critical Care Medicine 2024;36(11):1121-1126
Objective:To investigate the prognostic value of albumin (ALB), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT) in patients with acute liver failure (ALF) in hyperacute phase of sepsis which provided the basis for clinical evaluation and prognostic judgment and corresponding treatment options.Methods:A multicenter retrospective cohort study was conducted. Patients with ALF in hyperacute phase of sepsis admitted to Zhoupu Hospital Affiliated to Shanghai Health College, Shanghai Pudong New Area People's Hospital, and Shanghai Oriental Hospital from January 2019 to February 2024 were enrolled. General data such as gender and age of the patients were collected. Lactate dehydrogenase (LDH), liver function indexes [total bilirubin (TBIL), direct bilirubin (DBIL), AST, ALT, AST/ALT, ALB, total protein (TP), globulin (GLB), ALB/GLB ratio (A/G), blood amine, γ-glutamyl transpeptidase (γ-GT)], platelet count (PLT), creatinine, activated partial thromboplastin time (APTT), severity of illness scores [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), sequential organ failure assessment (SOFA)], serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), arterial blood lactic acid (Lac) within 24 hours after admission, and whether to use mechanical ventilation, whether to use vasoactive drugs, whether to use artificial liver treatment and prognosis during hospitalization also were collected. The differences of clinical data between patients with different prognosis were compared. The variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to determine the independent risk factors for death of patients with ALF in hyperacute phase of sepsis during hospitalization. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of ALB and AST/ALT for death of patients with ALF in hyperacute phase of sepsis during hospitalization.Results:A total of 73 patients with ALF in hyperacute phase of sepsis were included, with 22 survived and 51 died during hospitalization and the mortality of 69.86%. Compared with the survival group, the patients in the death group had lower ALB, γ-GT within 24 hours after admission and proportion of artificial liver treatment, and higher AST/ALT, SOFA score, LDH and proportion of use of vasoactive drugs. The differences were statistically significant. Multivariate Logistic regression analysis showed that ALB and AST/ALT were the independent risk factors for death in patients with ALF in hyperacute phase of sepsis during hospitalization [ALB: odds ratio ( OR) = 0.856, 95% confidence interval (95% CI) was 0.736-0.996, P = 0.044; AST/ALT: OR = 2.018, 95% CI was 1.137-3.580, P = 0.016]. ROC curve analysis showed that the area under the curve (AUC) of ALB for predicting in-hospital death in patients with ALF in hyperacute phase of sepsis was 0.760 (95% CI was 0.637-0.884, P < 0.001). When ALB ≤ 29.05 g/L, the sensitivity was 68.2%, and the specificity was 76.5%. The AUC of AST/ALT for predicting in-hospital death in patients with ALF in hyperacute phase of sepsis was 0.764 (95% CI was 0.639-0.888, P < 0.001). When AST/ALT ≥ 1.26, the sensitivity was 59.1%, and the specificity was 90.2%. Conclusions:The lower the ALB level, and the higher the AST/ALT within 24 hours after admission, the worse the prognosis of patients with ALF in hyperacute phase of sepsis. ALB and AST/ALT can be used as clinical indicators to evaluate the severity and prognosis of patients with ALF in hyperacute phase of sepsis.
3.Effect of exogenous IL-18 binding protein on sepsis-associated lung injury in rats and role of NLRP3 inflammasomes
Yan LI ; Yanan WANG ; Xuhua HUO ; Yulin CHANG ; Jingui GAO
Chinese Journal of Anesthesiology 2024;44(11):1391-1396
Objective:To evaluate the effect of exogenous interleukin-18 (IL-18) binding protein (IL-18BP) on sepsis-associated lung injury and the role of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in rats.Methods:This study was performed in two parts. Experiment Ⅰ Thirty-six SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200 g, were allocated into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), sepsis-associated lung injury group (SLI group), and sepsis-associated lung injury+ IL-18BP group (SI group). The rat model of sepsis-associated lung injury was developed using cecal ligation and puncture. The rats in group S underwent laparotomy without the subsequent ligation and puncture procedures. IL-18BP 1.5 mg/kg was intraperitoneally injected immediately after surgery in group SI. Experiment Ⅱ The aforementioned 36 rats were allocated into 3 groups ( n=12 each) using a random number table method: sepsis-associated lung injury + IL-18BP + vehicle group (SIV group), sepsis-associated lung injury + IL-18BP + MCC950 group (SIM group), and sepsis-associated lung injury + IL-18BP + nigericin group (SIN group). In SIV group, SIM group and SIN group, solvent, MCC950 (NLRP3 inhibitor, 5 mg/kg) and nigerin (NLRP3 agonist, 2 mg/kg) were intraperitoneally injected at 30 min before surgery respectively, and IL-18BP 1.5 mg/kg was intraperitoneally injected after operation. HE staining was used to observe the lung injury at 24 h after operation. The left lung tissues were obtained for calculation of the wet/dry weight (W/D) ratio. The concentrations of IL-18 and IL-18BP in broncho-alveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay. The percentage of NLRP3 positive cells in lung tissues was detected by immunofluorescence. The expression of IL-18, IL-18BP, cl-caspase-1 and gasdermin D (GSDMD) in lung tissues was detected by Western blot. Results:Experiment Ⅰ Compared with group S, the injury score of lung tissues, W/D ratio, concentrations of IL-18 and IL-18BP in BALF, and percentage of NLRP3 positive cells were significantly increased, and the expression of IL-18, IL-18BP, cl-caspase-1 and N-GSDMD was up-regulated in group SLI ( P<0.05). Compared with group SLI, the injury score of lung tissues, W/D ratio, concentrations of IL-18 and IL-18BP in BALF, and percentage of NLRP3 positive cells were significantly decreased, the expression of IL-18, cl-caspase-1 and N-GSDMD was down-regulated, and the expression of IL-18BP was up-regulated in group SI ( P<0.05). Experiment Ⅱ Compared with group SIV, the injury score of lung tissues, W/D ratio, concentrations of IL-18 in BALF, and percentage of NLRP3 positive cells were significantly decreased, and the expression of IL-18, cl-caspase-1 and N-GSDMD was down-regulated in group SIM, and the injury score of lung tissues, W/D ratio, concentrations of IL-18 in BALF, and percentage of NLRP3 positive cells were significantly increased, and the expression of IL-18, cl-caspase-1 and N-GSDMD was up-regulated in group SIN ( P<0.05). Conclusions:Exogenous IL-18BP can reduce sepsis-associated lung injury, and the mechanism is related to inhibition of activation of NLRP3 inflammasomes in rats.
4.Construction and validation of a predictive model for ventilator-associated pneumonia in premature infants undergoing mechanical ventilation in the neonatal intensive care unit
Yongqin GUO ; Yingying DOU ; Jianli LI ; Ruimin CHANG ; Yanan HAO
Chinese Journal of Practical Nursing 2024;40(33):2578-2587
Objective:To construct a prediction model for ventilator-associated pneumonia (VAP) in mechanically ventilated preterm infants in the neonatal intensive care unit (NICU) and to test its clinical effect.Methods:This was a cross-sectional study. A total of 740 preterm infants admitted to the NICU for mechanical ventilation from July 2018 to June 2023 were retrospectively selected as the study subjects, and were divided into the modeling set (518 cases) and the validation set (222 cases) according to the ratio of 7∶3 using the computer-generated random number method. The modeling set was divided into the VAP group (181 cases) and the non-VAP group (337 cases) according to whether VAP occured, and 21 clinical characteristics were analyzed, using single factor difference analysis to screen predictive factors, the independent risk factors of VAP in mechanically ventilated preterm infants were determined by multivariate Logistic regression analysis, and the nomogram model was made by R software. Then, the nomogram model was tested by validating the data of the validation set. The receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test, calibration curve and clinical decision curve were used to evaluate the efficacy and practical value of the model.Results:There were 88 males and 93 females in the VAP group, with 156 cases of gestational age<34 weeks and 25 cases of gestational age≥34 weeks. There were 155 males and 182 females in the non-VAP group, with 196 cases of gestational age<34 weeks and 141 cases of gestational age≥34 weeks. Birth weight ( OR=0.114, 95% CI 0.044-0.268, P<0.05) and oral care of breast milk ( OR=0.124, 95% CI 0.0.057-0.249, P<0.05) were protective factors for VAP in mechanically ventilated preterm infants, and Apgar score at 5 min after birth ( OR=2.895, 95% CI 1.318-6.419, P<0.05), serum prealbumin at 72 h of mechanical ventilation ( OR=4.837, 95% CI 2.643-9.063, P<0.05), gastric contents reflux ( OR=6.754, 95% CI 3.156-15.240, P<0.05), and time of mechanical ventilation ( OR=7.784, 95% CI 3.491-18.160, P<0.05) were independent risk factors for VAP in mechanically ventilated preterm infants. The area under the curve (AUC) of the ROC curve of the modeling set was 0.929 (95% CI 0.907-0.950, P<0.01), and the validation set (AUC) was 0.917 (95% CI 0.882-0.952, P<0.01), the model has good discrimination. The C indices of the modeling set and the validation set were 0.93 and 0.92 respectively by sampling 500 times by the Bootstrap method, indicating that the model had good consistency, and the decision curve suggested that the prediction model was far from the extreme curve and the net return value was high, indicating that the nomogram prediction model constructed this time had high prediction value. Conclusions:Birth weight, Apgar score at 5 min after birth, time of mechanical ventilation, oral care of breast milk, serum prealbumin at 72 h of mechanical ventilation, and gastric contents reflux are independent influencing factors for VAP in mechanically ventilated preterm infants. The nomogram prediction model constructed can provide a visual and simple evaluation tool for early identification of high-risk children and reducing the occurrence of VAP.
5.Effect of siRNA-mediated α-TAT1 gene silencing on migration behavior of endothelial cells in rats with hepatopulmonary syndrome
Chang LIU ; Jiaxi ZHU ; Yanan LIU ; Mu XU ; Jingli CHEN
Journal of Army Medical University 2024;46(3):215-224
Objective To investigate the effect of silencing alpha tubulin acetyltransferase 1(α-TAT1)on migration behavior of endothelial cells induced by hepatopulmonary syndrome(HPS).Methods Online database Tabula Muris was used to analyze the expression of α-TAT1 in various cell subsets in the lungs.Twenty-four male SD rats were randomly divided into control group(Sham group,n=6)and common bile duct ligation group(HPS group,n=18).The rats in HPS group were euthanasized at 2 and 4 weeks after modelling,and then the expression of α-TAT1 in pulmonary vascular endothelial cells was detected by immunofluorescence colocalization.The sera from the Sham and HPS rats were used to stimulate human umbilical vein endothelial cells(HUVECs)for 12 and 24 h,respectively.Then the obtained HUVECs were divided into 4 groups:Sham serum+siRNA NC group,Sham serum+siRNA α-TAT1 group,HPS serum+siRNA NC group,HPS serum+siRNA α-TAT1 group.The expression levels of α-TAT1 and Ace-α-tubulin in HUVECs were detected by Western blotting.Immunofluorescence assay was applied to observe the levels of polymerized microtubules of α-Tubulin in HUVECs after nocodazole(10 μmol/L)pretreatment to evaluate the stability of microtubule structure.Cell scratch assay combined with cell immunofluorescence assay was employed to observe the nuclear localization of Golgi apparatus and cell migration ability of HUVECs.The angiogenesis ability of HUVECs was tested by in vitro angiogenesis test.Results In vivo and in vitro experiments showed that the expression of α-TAT1 in endothelial cells was significantly increased after HPS inducement.The expression levels of α-TAT1 and Ace-α-tubulin were significantly down-regulated,and the stability of microtubules was weakened in the siRNA α-TAT1 interference group(P<0.01).In addition,the distribution of GM 130 labeled Golgi apparatus in the protrusion of HUVECs was down-regulated in the siRNAα-TAT1 interference group,as well as the migration ability(P<0.01).And the length of angiogenesis and network level were also significantly declined(P<0.01).Conclusion Silencing α-TAT1 reduces the migrαtion and angiogenesis of endothelial cells in HPS,which was associated with weakened stabilization of microtubule.
6.Professor YAN Huimin's Experience in Pattern Identification and Treatment of Chest Tightness Variant Asthma in Children Based on the Method of Regulating Qi Movement
Yujing FU ; Chang LIU ; Jing HAO ; Yanan LI ;
Journal of Traditional Chinese Medicine 2024;65(10):1001-1004
To summarize the clinical experience of Professor YAN Huimin in pattern identification and treatment for chest tightness variant asthma in children with the method of regulating qi movement. It is believed that children's chest tightness variant asthma is mainly located in lungs and involves liver and spleen, and the core mechanism of the disease is disturbance of qi movement. On the basis of regulating qi, syndrome differentiation and treatment is conducted: for pattern of lung qi deficiency and cold, phlegm-fluid retention, the treatment is appropriate to tonify the lung and benefit qi, and warm phlegm-fluid, which commonly used in modified Yupingfeng Powder (玉屏风散) and Xiaoqinglong Decoction (小青龙汤); for pattern of phlegm and qi binding constraint, the treatment is appropriate to soothe the liver and resolve constraint, and dissolve phlegm and dissipate masses, which commonly used in modified Banxia Houpo Decoction (半夏厚朴汤) and Jinlingzi Powder (金铃子散); for pattern of qi deficiency and blood stasis, the treatment is appropriate to tonify the deficiency to reinforce healthy qi, and move qi to invigorate blood, which commonly used in modified Xuefu Zhuyu Decoction (血府逐瘀汤). It is emphasised that during the treatment process, the developmental dynamics of the disease should be grasped, patterns and treat should be identified, and special attention to the changes of qi movement should be paid.
7.Regulatory Effect of Naoxintong Capsules on Short-chain Fatty Acids in Mice with Cerebral Ischemia-reperfusion Injury Based on LC-MS/MS
Jing ZHANG ; Yu LI ; Yuxin LEI ; Mengli CHANG ; Yanan WANG ; Jing XU ; Shihuan TANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):141-148
ObjectiveTo explore the mechanism of Naoxintong capsules' intervention in cerebral ischemia-reperfusion by building a mouse cerebral ischemia-reperfusion model based on short-chain fatty acids. MethodC57BL/6J male mice were randomly divided into the sham group, model group, Naoxintong group (158.9 mg∙kg-1), and Ginaton group (12.1 mg∙kg-1) according to the random number table method. The model of cerebral ischemia-reperfusion (MCAO/R) was prepared via the filament occlusion method. The effect of Naoxintong capsules on brain injury in MCAO/R mice was evaluated by the neuroethological score, cerebral infarction area determination, Nissl staining, and immunofluorescence staining. Hematoxylin-eosin (HE) staining and Western blot were employed to evaluate the effect of Naoxintong capsules on the intestinal barrier in MCAO/R mice. The content of short-chain fatty acids in mouse feces was detected by LC-MS/MS. ResultCompared to the sham group, the model group exhibited significant increases in the cerebral infarction area, neuroethological score, and cell apoptosis rate (P<0.01), with a notable decrease in the number of Nissl bodies (P<0.01). The protein expression levels of Claudin-1 and Occludin were significantly reduced (P<0.05). Compared with the model group, the intervention of Naoxintong capsules significantly decreased the cerebral infarction area (P<0.05) and improved the neuroethological score (P<0.01) and cell apoptosis rate (P<0.01), with the number of Nissl bodies (P<0.01) and expression levels of Claudin-1 and Occludin proteins (P<0.01) increased. LC-MS/MS results showed that compared to the sham group, the model group featured a significantly reduced content of acetic acid, propionic acid, and butyric acid in feces (P<0.01), while valeric acid, isovaleric acid, and isobutyric acid levels were increased (P<0.01). The intervention of Naoxintong capsules notably lowered the content of valeric acid, isovaleric acid, and isobutyric acid (P<0.01). ConclusionNaoxintong capsules can improve brain and intestinal barrier damage and play a protective role in cerebral ischemia-reperfusion by regulating the content of short-chain fatty acids.
8.Construction of Performance Evaluation Index System for Public Hospitals Based on Performance Prism Model
Aide XU ; Jia LIU ; Yanan CHANG ; Liqi TIAN
Chinese Hospital Management 2024;44(10):38-42
Objective To construct the performance evaluation index system of public hospitals,and provide reference for promoting the high-quality development of public hospitals.Methods Delphi method and analytic hierarchy process were used to determine the performance evaluation index system of public hospitals based on performance prism model.Results It established a public hospital performance evaluation system including 5 first-level indicators,16 second-level indicators and 40 third-level indicators of government,staff,patients,suppliers and regulatory agencies.The weights of the five first-level indicators are 0.254 8,0.476 8,0.154 4,0.073 4 and 0.040 6,respectively.Among the 16 second-level indicators,salary,quality and safety,practice environment,medical quality and operation efficiency rank the top 5.The combined weights were 0.268 5,0.174 3,0.165 4,0.080 9 and 0.060 6,respectively.Among the 40 tertiary indicators,the satisfaction of medical staff,the quality control index of single disease,organizational support,the intensity of antibacterial drug use and the case mortality of the low-risk group were investigated.The combined weights were 0.212 0,0.110 0,0.107 0,0.064 3 and 0.0624,respectively.Conclusion The performance evaluation index system of public hospitals based on the performance prism model established is helpful to guide hospitals to think about hospital strategic reform,process optimization and capacity improvement from the multi-dimensional perspective of internal and external stakeholders,so as to improve development performance and promote social harmonious development,and to improve performance,promote high-quality development.
9.Construction of Performance Evaluation Index System for Public Hospitals Based on Performance Prism Model
Aide XU ; Jia LIU ; Yanan CHANG ; Liqi TIAN
Chinese Hospital Management 2024;44(10):38-42
Objective To construct the performance evaluation index system of public hospitals,and provide reference for promoting the high-quality development of public hospitals.Methods Delphi method and analytic hierarchy process were used to determine the performance evaluation index system of public hospitals based on performance prism model.Results It established a public hospital performance evaluation system including 5 first-level indicators,16 second-level indicators and 40 third-level indicators of government,staff,patients,suppliers and regulatory agencies.The weights of the five first-level indicators are 0.254 8,0.476 8,0.154 4,0.073 4 and 0.040 6,respectively.Among the 16 second-level indicators,salary,quality and safety,practice environment,medical quality and operation efficiency rank the top 5.The combined weights were 0.268 5,0.174 3,0.165 4,0.080 9 and 0.060 6,respectively.Among the 40 tertiary indicators,the satisfaction of medical staff,the quality control index of single disease,organizational support,the intensity of antibacterial drug use and the case mortality of the low-risk group were investigated.The combined weights were 0.212 0,0.110 0,0.107 0,0.064 3 and 0.0624,respectively.Conclusion The performance evaluation index system of public hospitals based on the performance prism model established is helpful to guide hospitals to think about hospital strategic reform,process optimization and capacity improvement from the multi-dimensional perspective of internal and external stakeholders,so as to improve development performance and promote social harmonious development,and to improve performance,promote high-quality development.
10.Construction of Performance Evaluation Index System for Public Hospitals Based on Performance Prism Model
Aide XU ; Jia LIU ; Yanan CHANG ; Liqi TIAN
Chinese Hospital Management 2024;44(10):38-42
Objective To construct the performance evaluation index system of public hospitals,and provide reference for promoting the high-quality development of public hospitals.Methods Delphi method and analytic hierarchy process were used to determine the performance evaluation index system of public hospitals based on performance prism model.Results It established a public hospital performance evaluation system including 5 first-level indicators,16 second-level indicators and 40 third-level indicators of government,staff,patients,suppliers and regulatory agencies.The weights of the five first-level indicators are 0.254 8,0.476 8,0.154 4,0.073 4 and 0.040 6,respectively.Among the 16 second-level indicators,salary,quality and safety,practice environment,medical quality and operation efficiency rank the top 5.The combined weights were 0.268 5,0.174 3,0.165 4,0.080 9 and 0.060 6,respectively.Among the 40 tertiary indicators,the satisfaction of medical staff,the quality control index of single disease,organizational support,the intensity of antibacterial drug use and the case mortality of the low-risk group were investigated.The combined weights were 0.212 0,0.110 0,0.107 0,0.064 3 and 0.0624,respectively.Conclusion The performance evaluation index system of public hospitals based on the performance prism model established is helpful to guide hospitals to think about hospital strategic reform,process optimization and capacity improvement from the multi-dimensional perspective of internal and external stakeholders,so as to improve development performance and promote social harmonious development,and to improve performance,promote high-quality development.

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