ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

Objective To systematically explore influencing factors of internet addiction behaviors among junior school students across different grades from multiple dimensions.Methods This study enrolled all students from a junior high school in Wuhan.Annual questionnaire surveys were conducted from October 2021 to September 2024 to collect data on demographic characteristics,study and living situation,mental health,and internet addiction behaviors.Students were combined according to grade level during the survey period.An exposure-wide association analysis(ExWAS)strategy was employed to identify grade-specific influencing factors in each dimension of internet addiction.Results Common influencing factors across all three grades included academic interest(OR=0.45～0.50,95％CI:0.29～0.76)in the study dimension and living situation dimension and stress(OR=1.06,95％CI:1.03～1.10)in mental health dimension.Grade-specific influences of internet addiction existed in these two dimensions:In grade 7,the affinity with father(OR=0.97,95％CI:0.94～1.00),alcohol experimentation(OR=2.33,95％CI:1.54～3.53),and perpetrating bullying(OR=2.16,95％CI:1.04～4.49)were the main factors;In grade 8,mod-erate-to-high intensity physical activity(OR=0.50,95％CI:0.31～0.81),the affinity with father(OR=0.97,95％CI:0.94～1.00),bullying victimization(OR=2.32,95％CI:1.50～3.60),and anxiety symptoms(OR=2.01,95％CI:1.26～3.20)were the main factors;In grade 9,perpetrating bullying(OR=3.19,95％CI:1.31～7.78)and anxiety symptoms(OR=1.91,95％CI:1.18～3.10)were the main factors.Conclusion Influencing factors of internet addiction behaviors vary across grades in junior high school.Prevention and control strategies should incorporate grade-specific characteristics to implement targeted measures,thereby enhancing early identification capabilities and intervention effectiveness.

Objective To systematically explore influencing factors of internet addiction behaviors among junior school students across different grades from multiple dimensions.Methods This study enrolled all students from a junior high school in Wuhan.Annual questionnaire surveys were conducted from October 2021 to September 2024 to collect data on demographic characteristics,study and living situation,mental health,and internet addiction behaviors.Students were combined according to grade level during the survey period.An exposure-wide association analysis(ExWAS)strategy was employed to identify grade-specific influencing factors in each dimension of internet addiction.Results Common influencing factors across all three grades included academic interest(OR=0.45～0.50,95％CI:0.29～0.76)in the study dimension and living situation dimension and stress(OR=1.06,95％CI:1.03～1.10)in mental health dimension.Grade-specific influences of internet addiction existed in these two dimensions:In grade 7,the affinity with father(OR=0.97,95％CI:0.94～1.00),alcohol experimentation(OR=2.33,95％CI:1.54～3.53),and perpetrating bullying(OR=2.16,95％CI:1.04～4.49)were the main factors;In grade 8,mod-erate-to-high intensity physical activity(OR=0.50,95％CI:0.31～0.81),the affinity with father(OR=0.97,95％CI:0.94～1.00),bullying victimization(OR=2.32,95％CI:1.50～3.60),and anxiety symptoms(OR=2.01,95％CI:1.26～3.20)were the main factors;In grade 9,perpetrating bullying(OR=3.19,95％CI:1.31～7.78)and anxiety symptoms(OR=1.91,95％CI:1.18～3.10)were the main factors.Conclusion Influencing factors of internet addiction behaviors vary across grades in junior high school.Prevention and control strategies should incorporate grade-specific characteristics to implement targeted measures,thereby enhancing early identification capabilities and intervention effectiveness.

Objective:To screen the independent influencing factors of restoration of spontaneous circulation (ROSC) in patients after cardiopulmonary resuscitation (CPR) and establish a predictive model, and explore its clinical value.Methods:A retrospective case control study was conducted. The clinical data of cardiac arrest patients admitted to the emergency department of Tangdu Hospital of Air Force Military Medical University and received CPR from January to July 2023 were analyzed, including general information, blood biochemical indicators, main cause of cardiac arrest, whether it was defibrillation rhythm, duration from admission to CPR, and whether ROSC was achieved. The clinical data between the patients whether achieved ROSC or not were compared. The binary multivariate Logistic regression analysis was used to screen the independent influencing factors of ROSC in in-hospital CPR patients. According to the above influencing factors, the ROSC prediction model was established, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the model for ROSC.Results:A total of 235 patients who received CPR in the emergency department were enrolled, including 153 cases (65.11%) of in-hospital CPR and 82 cases (34.89%) of out-of-hospital CPR. The ROSC ratio was 30.21% (71/235). Among all patients, the majority were aged 61-80 years [40.43% (95/235)], and cardiogenic disease was the main cause of cardiac arrest [32.77% (77/235)]. Among 153 patients with in-hospital CPR, 89 were non-ROSC and 64 were ROSC with ROSC rate of 41.83%. Compared with the non-ROSC group, the patients in the ROSC group had lower blood lactic acid (Lac), N-terminal pro-brain natriuretic peptide (NT-proBNP), Lac/albumin (Alb) ratio (LAR), and ratio of non-defibrillation rhythm [Lac (mmol/L): 5.50 (2.33, 9.65) vs. 7.10 (3.50, 13.35), NT-proBNP (μg/L): 0.87 (0.20, 8.68) vs. 3.00 (0.58, 20.17), LAR: 0.14 (0.07, 0.29) vs. 0.19 (0.10, 0.43), non-defibrillation rhythm ratio: 68.75% (44/64) vs. 93.26% (83/89)], higher actual base excess (ABE) and Alb [ABE (mmol/L): -3.95 (-12.75, 0.23) vs. -7.50 (-13.50, -3.35), Alb (g/L): 38.13±7.03 vs. 34.09±7.81], and shorter duration from admission to CPR [hours: 3.25 (1.00, 14.00) vs. 8.00 (2.00, 27.50)], the differences were statistically significant (all P < 0.05). Binary multivariate Logistic regression analysis showed that LAR [odds ratio ( OR) = 0.037, 95% confidence interval (95% CI) was 0.005-0.287], non-defibrillation rhythm ( OR = 0.145, 95% CI was 0.049-0.426), and duration from admission to CPR ( OR = 0.984, 95% CI was 0.972-0.997) were independent influencing factors for ROSC in hospitalized CPR patients (all P < 0.05). Based on the above influencing factors, a ROSC prediction model was constructed through regression analysis results. The ROC curve analysis showed that the area under the ROC curve (AUC) for predicting ROSC in in-hospital CPR patients was 0.757 (95% CI was 0.680-0.834), Yoden index was 0.429, sensitivity was 76.6%, and specificity was 66.3%. Conclusions:LAR, non-defibrillation rhythm and duration from admission to CPR were independent influencing factors for ROSC in patients with in-hospital CPR. The ROSC prediction model established based on the above influencing factors has a good predictive value for ROSC of CPR patients in hospital, and can guide clinicians to evaluate the prognosis of patients through relevant indicators as early as possible.

Objective:To analyze the early warning value of laboratory examination on admission of patients with hemorrhagic fever with renal syndrome to critically ill patients.Meetods:In this study, a retrospective case-control study was used to analyze the clinical data and laboratory examination results of patients with hemorrhagic fever with renal syndrome admitted to the emergency department of Tangdu Hospital of Air Force Medical University from January 2021 to January 2022. According to the patient's laboratory indexes and clinical symptoms, the patients were divided into mild, moderate, severe and critical groups. The general data of the two groups were compared, and the independent risk factors of critically ill patients were screened by multi-factor logistic regression analysis, the predictive model of severe HFRS patients was constructed, and the ROC curve was drawn. .Results:Of the 164 patients with HFRS, 50 were in the severe group and 114 in the mild group. The serum levels of WBC, AST, ALT, Cr, BUN, DD and PCT in the severe group were higher than those in the mild group, while the levels of PLT, ALB and PTA in the severe group were lower than those in the mild group. Multiple logistic regression analysis showed that WBC, PLT and PCT were independent influencing factors for the progression of critically ill patients. The predictive model of severe HFRS was established as follows: logit (P) = -0.321 + 0.040 WBC (×10 9/L) -0.045 PLT (×10 9/L) + 0.086 PCT(ng/mL). The early warning ef?cacy of WBC, PLT, And PCT for severe HFRS was further analyzed. The area under the ROC curve (area under curve, AUC) was 0.779, 0.842, 0.862, and the optimal threshold was 10.435×109/L, 41.5 ×109/Land 2.97 ng/mL, respectively. The AUC of joint detection is 0.900, the sensitivity is 88.0%, and the speci?city is 82.5%, which is better than that of a single laboratory. . Conclusions:HFRS laboratory indexes have certain clinical signi?cance for the identi?cation of critically ill patients, in which serum WBC, PLT and PCT indexes are the risk factors of severe HFRS, which provides a theoretical basis for clinical diagnosis, treatment and prognosis of severe HFRS patients.

Background::Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods::Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results::A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 ( RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process. Conclusions::RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.