ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

Objective: To explore the interaction between school bullying and insomnia in relation to depression-anxiety-stress emotions among primary and secondary school students,so as to provide a basis for preventing negative emotional states in adolescents. Methods: In October 2024, a stratified cluster sampling method was used to select 3 058 students in grade 5-6 of primary, junior and senior high school in Sheyang County of Jiangsu Province. The Delaware Bullying Victimization Scale, Insomnia Severity Index, Depression-Anxiety-Stress Scale-21, and Study Condition Questionnaire were employed to investigate school bullying, insomnia, depression-anxiety-stress emotions, and academic performance. The χ 2 test and Logistic regression were used to analyze the association between school bullying and insomnia interactions and depression-anxiety-stress emotions among primary and secondary school students, multiplicative interaction analysis was conducted, and additive interaction analysis was performed using R software. Results: The detection rates of depression-anxiety-stress emotions among primary and secondary school students were 21.6%, 28.4% and 10.8%, respectively. The detection rates of physical bullying, relationship bullying, verbal bullying and cyberbullying in school bullying were 10.6%, 14.0%, 22.3%, and 6.2%, respectively. The detection rate for insomnia was 23.1%. Results from Logistic regression analysis showed that, after adjusting for relevant factors, physical, relational, verbal, and cyberbullying and insomnia were positively correlated with the detection rates of depression ( OR = 5.72- 10.93), anxiety ( OR =6.35-12.17), and stress emotions ( OR =5.97-14.52) among primary and secondary school students (all P <0.01). The multiplicative interaction between physical, relational, verbal, and cyberbullying and insomnia was positively correlated with the detection rates of depression ( OR =8.00-18.01), anxiety ( OR =11.35-17.76), and stress emotions ( OR =7.64-9.12) in primary and secondary school students (all P <0.01). Additive interactions were observed between physical, relational, verbal, and cyberbullying and insomnia in relation to the detection rates of depression, anxiety, and stress emotions among primary and secondary school students (both RERI and AP >0 and the credible interval excluded 0, SI >1 and the credible interval excluded 1). Conclusion School bullying and insomnia are associated with depression, anxiety, and stress emotions among primary and secondary school students, and they exhibit both multiplicative and additive interactions.

ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

ObjectiveTo establish a tumor prognostic risk assessment model related to target genes of the miR-34 family. MethodsTarget genes of the miR-34 family were screened， and the scores of miR-34 target genes were assessed in 16 tumor types. Univariate Cox regression analysis was used to identify the tumor type with the strongest correlation between miR-34 target gene scores and overall survival （OS）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed to elucidate the functional roles and signaling pathways of miR-34 target genes. A prognostic risk model based on the miR-34 target genes was constructed using univariate Cox and LASSO regression analyses. Quantitative real-time PCR （qPCR） and dual-luciferase reporter assays were conducted to validate whether the target genes bind to miR-34 and measure their RNA expression levels in the relevant tumors. Additionally， the risk score was integrated with other clinical indicators to develop a nomogram prediction model for patient survival. ResultsA total of 65 target genes of the miR-34 family were screened. The cancer type exhibiting stronger correlation between the target gene scores and OS was lung adenocarcinoma （P = 0.003， HR= 5.150）. Furthermore， miR-34 target genes were predominantly enriched in oxidative stress pathways and various tumor-related processes. Three genes， LDHA， GALNT7， and SATB2， were identified as core components of the prognostic analysis model for lung adenocarcinoma. Additionally， the constructed nomogram model demonstrated robust predictive performance. ConclusionThe risk model and prognosis model of lung adenocarcinoma constructed based on the key target genes of miR-34 have good predictive performance.

OBJECTIVE To investigate the effects of osthole （OST） on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog （SHH） signaling pathway. METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group， OST low-dose， medium-dose and high-dose groups （OST-L group， OST-M group， OST-H group， 20， 30， 40 mg/kg OST）， high-dose OST+SHH inhibitor cyclopamide group （OST-H+cyclopamide group， 40 mg/kg OST+10 mg/kg cyclopamide）， with 12 rats in each group. Another 12 rats were selected as the control group. The wound healing of rats on 1， 7 and 14 days of administration was observed， and the wound healing rate of rats in each group was measured. The pathological changes and collagen deposition in rat wound tissue were observed； the levels of angiopoietin-1 （Ang-1） and basic fibroblast growth factor （bFGF） in wound tissue of rats were detected； the relative expressions of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor-2 （VEGFR-2） mRNA were also detected in wound tissue of rats； the protein expressions of VEGFA， VEGFR-2， SHH and glioma-associated oncogene homolog-1 （GLI1） were determined in wound tissue of rats. RESULTS Compared with Model group， the healing rate of skin wound， relative expression of collagen protein， the levels of Ang-1 and bFGF， the mRNA and protein expressions of VEGFA and VEGFR-2， and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups （P＜0.05）. The wound tissue underwent significant re- epithelialization， with reduced inflammatory cell infiltration and granulation tissue edema， and an increase in the number of new blood vessels. SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats. CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Objective: To evaluate the effect of bioactive peptides combined with probiotics on serum uric acid (SUA) in patients with hyperuricemia (HUA), so as to provide the evidence for prevention and treatment of HUA. Methods: The patients with HUA aged 18 to 65 years were selected and randomly divided into an intervention group and a control group. The patients in the intervention group received bioactive peptides combined with probiotics for 28 days at a dose of 3 g/d, while the patients in the control group received an equal dose of placebos. Demographic information, body mass index (BMI), blood pressure and blood lipid were collected through questionnaire surveys, physical examination and laboratory tests. SUA levels were detected before and after 14 days and 28 days of interventions. The differences of SUA levels between the two groups were compared using generalized estimation equation. Results: Totally 108 patients with HUA were recruited, including 54 patients in the intervention group and 53 patients in the control group (1 dropout). Before interventions, there were no statistically significant differences in gender, age, course of HUA, exercise duration, frequency of alcohol consumption, frequency of meat broth consumption, BMI, prevalence of hypertension and prevalence of dyslipidemia between the two groups (all P>0.05). After 14 days of interventions, the SUA levels of the patients in the intervention group decreased by 3.00 μmol/L, while those in the control group increased by 7.00 μmol/L. After 28 days of interventions, the SUA levels of the patients in the intervention group and the control group decreased by 26.00 μmol/L and 16.00 μmol/L, respectively. However, there was no statistically significant interaction between the intervention time and group (both P>0.05). Subgroup analysis showed that after 28 days of interventions, the decrease in SUA levels in the patients aged 55 years and older and without hypertension in the intervention group was greater than those in the control group (both P<0.05). Conclusions Bioactive peptides combined with probiotics showed no significant difference in reducing SUA levels in patients with HUA compared to the control group. The effect was more significant for patients aged 55 years and older and without hypertension.