Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL^O. 18 as the screening conditions, and.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To compare the therapeutic effects of different inhaled medications on patients with frequent cough in chronic obstructive pulmonary disease (COPD), including changes in symptoms and acute exacerbation.Methods:This study was based on the RealDTC study, and the study subjects were stable COPD patients from the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University from December 2016 to March 2023. The demographic characteristics, smoking status, history of biofuel exposure, history of acute exacerbation in the past year, lung function, COPD Assessment Test (CAT) score, modified British Medical Research Council Respiratory Difficulty Questionnaire (mMRC) score, and inhalation medication regimen of the patients were collected. Patients with frequent cough are defined as having a cough score of ≥2 in the first item of the CAT score. According to the type of inhaled medication, patients with frequent cough are divided into l long-acting muscarine anticholinergic (LAMA), long-acting β2 agonists (LABA)+ LAMA, inhaled corticosteroids (ICS)+ LABA, and ICS+ LABA+ LAMA groups. At the 6th month follow-up, CAT scores were collected and symptom control was evaluated, including minimum clinical improvement (MCID) (defined as a decrease of ≥2 points from baseline in CAT scores at the 6th month) and improvement in cough symptoms (defined as a decrease of ≥1 point from baseline in cough scores). During a one-year follow-up, the number of acute exacerbations was evaluated. The relationship between different inhaled medications and prognosis in patients with frequent cough in COPD was evaluated using multivariate logistic regression analysis.Results:A total of 653 patients with frequent cough in COPD were included, with a CAT score of (16.4±6.1) and a cough score of 3(2, 3). After 6 months of follow-up, 403 patients (61.7%) achieved MCID, and 394 patients (60.3%) had improved cough symptoms; During a one-year follow-up, 227 patients (34.8%) experienced acute exacerbation. After receiving inhalation medication treatment, the CAT scores and cough scores of four groups of patients with frequent cough, namely LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA, decreased compared to before treatment (all P<0.05). There was a statistically significant difference in the proportion of △CAT score, MCID, and acute exacerbation among the four groups of LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA (all P<0.05), while there was no statistically significant difference in the proportion of △cough score and cough score reduction ≥1 point (all P>0.05). The results of multivariate logistic regression analysis showed that compared with patients treated with LAMA or ICS+ LABA drugs, patients with frequent cough in COPD treated with LABA+ LAMA or ICS+ LABA+ LAMA drugs were more likely to achieve MCID and less likely to experience acute exacerbation (all P<0.05). Conclusions:Compared with LAMA or ICS+ LABA, patients with frequent cough in COPD who receive LABA+ LAMA or ICS+ LABA+ LAMA drug treatment are more likely to improve symptoms and have a lower risk of acute exacerbation.

Objective:To analyze the prognostic factors of children with septic shock in the pediatric intensive care unit.Methods:The clinical data of children diagnosed with septic shock in the pediatric intensive care unit of Guiyang Maternal and Child Health Hospital from April 2018 to April 2022 were retrospectively collected,and the children were divided into the death group and the survival group according to seven days regression.The basic data of the two groups were statistically compared，and the relationship between lactic acid，vasoactive-inotropic score one hour after admission，time of antibiotic initiation，serum potassium，serum sodium，serum calcium，serum troponin T，fluid resuscitation volume in the first hour，glutamyl aminotransferase，creatinine，total leukocyte count，C-reaction protein，brain natriuretic peptide were compared.The risk factors affecting the death of children were analyzed by Logistic regression.The relationship between fluid resuscitation volume in the first hour and prognosis was analyzed using the receiver operator characteristic (ROC) curve.Results:（1）A total of 67 children were included，19 died and 48 survived.（2）The first-hour liquid resuscitation dose in the survival group was lower than that in the death group，and the difference was statistically significant（ P<0.05）.（3）The ROC curve showed that the optimal cut-off of the first-hour liquid resuscitation dose was 25 mL/kg，with a sensitivity of 57.9% and a specificity of 72.9%.（4）In unifactorial analysis，lactic acid in the first hour of admission，early lactic acid after resuscitation，serum calcium，serum troponin T，alanine aminotransferase，combined septic encephalopathy，Glasgow coma score，and pediatric critical illness score were all risk factors for death in children within seven days（ P<0.05）.(5) Multivariate Logistic regression analysis showed that serum calcium（ OR=1.435， P=0.001）and lactic acid value after resuscitation（ OR=0.040， P=0.021）were independent risk factors for death in septic shock. Conclusion:The higher the total fluid resuscitation in the first hour，the higher the fatality rate.Serum calcium and early lactic acid after resuscitation are independent risk factors for death in children within seven days.

Objective To study the intervention effect of narrative therapy on non-suicidal self-injury(NSSI),as well as anxiety and depression symptoms in adolescents with depressive disorder.Methods Sixty adolescents with depressive disorder and NSSI were randomly assigned to either the intervention group or the control group using coin flipping.The control group received conventional psychological support,while the intervention group received individual narrative therapy in addition to the conventional psychological support(twice a week,60 minutes per session,for a total of 3 weeks).Assessment of treatment efficacy was conducted using the Adolescent Self-Harm Questionnaire,Children's Depression Inventory,and Children's Anxiety and Mood Scale before the intervention,at the end of the intervention,and one month after the intervention for both groups.Results A total of 26 adolescents in the intervention group and 29 adolescents in the control group completed the entire study.At the end of the intervention and one month after the intervention,the intervention group showed a significant reduction in the NSSI frequency score,NSSI level,anxiety score,and depression score compared to before the intervention(P<0.017).Moreover,at the end of the intervention and one month after the intervention,the intervention group exhibited significantly lower NSSI frequency score,NSSI severity score,NSSI level,anxiety score and depression score compared to the control group(P<0.05).Conclusions Narrative therapy is effective in reducing NSSI frequency and alleviating NSSI severity,as well as anxiety and depression symptoms in adolescents with depressive disorder.[Chinese Journal of Contemporary Pediatrics,2024,26(2):124-130]

Objective To study the effects and mechanisms of tetramethylpyrazine(TMP)on tumor necrosis factor-α(TNF-α)-induced inflammatory injury in human coronary artery endothelial cells(HCAEC).Methods HCAEC were randomly divided into four groups:the control group(no treatment),the model group(treated with TNF-α,50 ng/mL for 24 hours),the TMP group(pre-treated with TMP,80 μg/mL for 12 hours followed by TNF-α treatment for 24 hours),and the SIRT1 inhibitor group(pre-treated with TMP and the specific SIRT1 inhibitor EX527 for 12 hours followed by TNF-α treatment for 24 hours).Cell viability was assessed using the CCK-8 method,lactate dehydrogenase(LDH)activity was measured using an LDH assay kit,reactive oxygen species(ROS)levels were observed using DCFH-DA staining,expression of pyroptosis-related proteins was detected by Western blot,and SIRT1 expression was analyzed using immunofluorescence staining.Results Compared to the control group,the model group showed decreased cell viability,increased LDH activity,ROS level and expression of pyroptosis-related proteins,and decreased SIRT1 expression(P<0.05).Compared to the model group,the TMP group exhibited increased cell viability,decreased LDH activity,ROS level and expression of pyroptosis-related proteins,and increased SIRT1 expression(P<0.05).In comparison to the TMP group,the SIRT1 inhibitor group showed decreased cell viability,increased LDH activity,ROS level and expression of pyroptosis-related proteins,and decreased SIRT1 expression(P<0.05).Conclusions TMP may attenuate TNF-α-induced inflammatory injury in HCAEC,which is associated with the inhibition of pyroptosis and activation of the SIRT1 signaling pathway.

Objective To understand the disease acceptance status and related factors in human immunodeficiency virus(HIV)-infected/acquired immunodeficiency syndrom(AIDS)patients,so as to guide the clinical development of intervention measures,and to provide empirical evidence for improving clinical outcomes.Methods Convenience sampling method was used to select 555 HIV-infected/AIDS patients who received treatment in the designated AIDS treatment clinic of a hospital.General data,disease acceptance,disease self-management efficacy and clinical out-comes(such as quality of life,CD4+T lymphocyte count and HIV viral load)of the studied subjects were collected.Results The average disease acceptance of HIV-infected/AIDS patients was(26.08±5.34)points.Multiple linear regression analysis showed that religious belief and self-management efficacy were related factors affecting the di-sease acceptance of patients(both P＜0.05),which could explain the 30.4％variation in disease acceptance of HIV-infected/AIDS patients,and the disease acceptance of patients was closely related to their quality of life(P＜0.001).Conclusion HIV-infected/AIDS patients have a moderate level of disease acceptance.Medical staff should fully consider patients'religious beliefs and self-management efficacy,so as to formulate targeted intervention mea-sures to improve patients'acceptance of disease,and further promote patients'quality of life.

Objective To compare the efficacy and safety between thermal ablation combined with synchronous transcatheter arterial chemoembolization(TACE)and TACE in patients with liver metastasis of neuroendocrine tumors of different pathologic grades.Methods A retrospective analysis was performed on patients with liver metastases of neuroendocrine tumors admitted to Department of Interventional Radiology,Zhongshan Hospital,Fudan University from Nov 1,2006 to Jul 31,2022.The patients were divided into synchronous ablation group and TACE group according to treatment mode and subgroups according to pathological grade.The lesions were evaluated by postoperative imaging examination.The patients were followed up until Jul 31,2023,and surgery-related complications were recorded.The endpoint of prognosis were progression-free survival(PFS)and overall survival(OS).Results A total of 86 patients with neuroendocrine tumor were collected,including 34 patients in simultaneous ablation group and 52 patients in TACE group.According to WHO classification,21 patients at G1 stage,45 patients at G2 stage and 20 patients at G3 stage were included.No serious postoperative complications occurred in all patients.The median OS was 47.0(95%CI:31.2-62.8)months in the TACE group and 56.0(95%CI:8.3-73.4)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.50).The median PFS was 18.0(95%CI:6.0-30.0)months in the TACE group and 29.0(95%CI:10.0-48.0)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.22).Of the 45 patients at G2 stage,27 received TACE with a median OS of 47.0 months,and 18 received synchronous ablation with a median OS of 59.0 months,and there was no statistical difference between the two groups(P=0.45).The median PFS was 12.0 months in the TACE group and 32.0 months in the synchronous ablation group,and the difference between the two groups was statistically significant(P=0.03).Conclusion Comparing with TACE,simultaneous ablation can delay disease progression in patients with liver metastasis of neuroendocrine tumors to a certain extent and has good safety,especially for patients with liver metastases of neuroendocrine tumors with intermediate or low grade.

AIM To observe the effects of Yiqi Fumai Lyophilized Injection on a mouse model of chronic heart failure after acute myocardial infarction and H9C2 cells with injury induced by oxygen and glucose deprivation.METHODS Thirty C57BL/6J mice were randomly divided into the sham-operation group,the model group,and the Yiqi Fumai group,among which the chronic heart failure model was made by ligation of anterior descending coronary artery and given 4 weeks corresponding drug administration.The H9C2 cells were divided into the normal group,the OGD model group,the low-dose,medium-dose and high-dose Yiqi Fumai groups,and the JQ1(BRD4 inhibitor)group.The following detections were conducted:heart ultrasound among the mice;the HE staining of the myocardial tissue for the observation of the morphological changes,spectrophotometry of cellular ATP level,JC-1 method for the determination of the mitochondrial membrane potential,RT-qPCR for the assessment of the mRNA expressions of ANP、BNP and BRD4,TUNEL method for the determination of level of cardiomyocytes apoptosis,and Western blot for the determination of the protein expressions of BRD4,AMPK and p-AMPK in both the mice and H9C2 cells.RESULTS Compared with the sham-operation group,the model group displayed decreased heart function(P＜0.01);obviously more hypertrophic or morphologically irregular cardiomyocytes;up-regulated mRNA expressions of ANP,BNP and BRD4(P＜0.01);increased cardiomyocyte apoptosis rate(P＜0.01);decreased p-AMPK/AMPK protein expression(P＜0.01);and increased BRD4 protein expression(P＜0.01).Compared with the model group,the Yiqi Fumai groups shared improvement in terms of all the aforementioned indices levels(P＜0.05,P＜0.01).Compared with the H9C2 cells of the normal group,those of the OGD model group displayed up-regulated mRNA expressions of ANP,BNP and BRD4(P＜0.01);increased apoptosis rate(P＜0.01);decreased p-AMPK/AMPK protein expression(P＜0.01);increased BRD4 protein expression(P＜0.01),and decreased mitochondrial membrane potential and ATP levels(P＜0.01).Compared with the OGD model group,the groups treated with either Yiqi Fumai or JQ1 demonstrated improvement in terms of the aforementioned indices levels(P＜0.05,P＜0.01).CONCLUSION Yiqi Fumai Lyophilized Injection exhibits its efficacy in improving cardiac function,myocardial energy metabolism,intracellular mitochondria dysfunction and biogenesis in a mouse model of chronic heart failure after myocardial infarction.The effects may be mediated by regulation of BRD4/AMPK signaling pathway.