ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

This study elucidated the structure-activity relationships (SAR) of three distinct opioid ligand series at the μ-opioid receptor (μ-OR) and investigated the ligand-dependent role of arrestin in downstream signaling. Radioligand binding assays across 13 compounds revealed that high-affinity μ-OR binding is not restricted to a single chemical scaffold. For fentanyl analogs, SAR analysis identified four key structural determinants: the N-phenethyl group (R1) is essential for μ-OR binding, the piperidine 4-position (R2) is sterically constrained and tolerates only small substituents such as carbomethoxy, the acyl side chain (R3) tolerates diverse chemical modifications including alkyl, alkoxy, and heteroaryl groups without substantial loss of affinity, and para-substitution on the phenethyl ring (R4) with electron-withdrawing groups like fluorine is well-tolerated. Analysis of non-fentanyl scaffolds (2-Methyl AP-237, W-15, and brorphine) demonstrated that specific side-chain functionalization, rather than core scaffold architecture, primarily determines binding potency. Comparison of classical opioids further revealed that structural flexibility, exemplified by methadone, can confer superior binding affinity compared to the rigid morphine scaffold. Consistent with this structural diversity, the contribution of arrestins to ERK activation varied substantially across compounds, suggesting that μ-OR-biased signaling is not dictated exclusively by intrinsic receptor properties but emerges from the interplay between receptor conformation and ligandspecific structural features. Collectively, our results provide a molecular framework for understanding opioid pharmacology with important implications for rational drug design aimed at minimizing adverse effects while maintaining analgesic efficacy.

Objective To synthesize qualitative studies on the experiences of postoperative lung cancer patients participating in pulmonary rehabilitation,aiming to comprehensively understand the barriers and facilitators influencing their engagement and to provide evidence-based insights for improving rehabilitation adherence.Methods Qualitative studies were retrieved from databases including Web of Science,PubMed,Cochrane Library,Embase,CNKI,Wanfang Data,VIPand Sinomed,with a search period spanning from database inception to January,2025.The methodological quality of eligible studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research.Extracted findings were mapped and synthesized using the Theoretical Domains Framework(TDF)and the Capability-Opportunity-Motivation-Behavior mode(COM-B).Results Ultimately,a total of 11 studies were included,yielding 48 findings.Using the Theoretical Domains Framework(TDF)and COM-B model,facilitators and barriers to pulmonary rehabilitation in postoperative lung cancer patients were mapped and consolidated into 14 categories,culminating in 2 synthesized findings.Conclusion Participation in pulmonary rehabilitation among postoperative lung cancer patients is influenced by multiple factors.Clinicians should develop patient-centered pulmonary rehabilitation plans by considering these factors and incorporating patients' attitudes and perspectives.

Objective:To investigate the effects of short-peptide-based enteral nutrition on nutritional status, immune function, and chemotherapy-related adverse reactions in children with acute lymphoblastic leukemia (ALL).Methods:A total of 106 children with ALL receiving chemotherapy at the Affiliated Hospital of Jining Medical University between January 2021 and April 2022 were enrolled. According to the principle of between-group baseline data matching, the patients were divided into observation group and control group by random number table method, with 53 cases in each group. All patients received chemotherapy according to the CCCG-ALL-2020 protocol established by the Multi-center Cooperative Group of the Chinese Society of Pediatric Oncology (2020). The control group received a regular diet, while the observation group received a regular diet supplemented with short-peptide-based enteral nutrition. The incidence rates of malnutrition, hypoproteinemia, hypoalbuminemia, abnormal immunoglobulin levels (IgG, IgM, IgA), and adverse reactions (liver injury, infection) were compared between both groups before chemotherapy and at the end of each of the following seven chemotherapy phases: Induction remission therapy (PVDL), Induction remission therapy (CAT), Early intensification therapy (CAT+), Consolidation therapy (HDMTX), Interim maintenance therapy, Reinduction therapy, and prior to the end of Maintenance therapy. Normally or approximately normally distributed measurement data were expressed as xˉ± s and compared by independent samples t-test. Counting data were expressed as n (%) and compared by χ2 test. Results:During the CAT phase, the incidence of malnutrition was significantly lower in the observation group than in the control group [20.8% (11/53) vs. 39.6% (21/53), χ2=4.48, P=0.034]. The incidence of hypoproteinemia was significantly lower in the observation group during HDMTX, Reinduction, Interim maintenance, and prior to the end of Maintenance therapy [47.2% (25/53) vs. 69.8% (37/53), χ2=5.60, P=0.018; 45.3% (24/53) vs. 67.9% (36/53), χ2=5.53, P=0.019; 41.5% (24/53) vs. 64.2% (34/53), χ2=5.45, P=0.020; 28.3% (15/53) vs. 54.7% (29/53), χ2=7.62, P=0.006, respectively]. The incidence of hypoalbuminemia was significantly lower in the observation group during CAT+, HDMTX, Reinduction, Interim maintenance, and prior to the end of Maintenance therapy [5.7% (3/53) vs. 22.6% (12/53), χ2=6.29, P=0.012; 9.4% (5/53) vs. 26.4% (14/53), χ2=5.19, P=0.023; 9.4% (5/53) vs. 28.3% (15/53), χ2=6.16, P=0.013; 7.6% (4/53) vs. 24.5% (13/53), χ2=5.68, P=0.017; 3.8% (2/53) vs. 18.9% (10/53), χ2=6.01, P=0.014, respectively]. For IgG, incidence was significantly lower in the observation group during Interim maintenance, Reinduction, and prior to the end of Maintenance therapy [7.6% (4/53) vs. 22.6% (12/53), χ2=4.71, P=0.030; 20.8% (11/53) vs. 39.6% (21/53), χ2=4.48, P=0.034; 11.3% (6/53) vs. 26.4% (14/53), χ2=3.94, P=0.047, respectively]. For IgM, incidence was significantly lower in the observation group during the CAT and CAT+ phases [45.3% (24/53) vs. 66.0% (35/53), χ2=4.63, P=0.032; 58.5% (31/53) vs. 77.4% (41/53), χ2=4.33, P=0.037, respectively]. For IgA, incidence was significantly lower in the observation group during Reinduction therapy and Interim maintenance [22.6% (12/53) vs. 45.3% (24/53), χ2=6.06, P=0.014; 9.4% (5/53) vs. 24.5% (13/53), χ2=4.28, P=0.038, respectively]. For liver injury, incidence was significantly lower in the observation group during the CAT, CAT+, and prior to the end of Maintenance phases [22.6% (12/53) vs. 43.4% (23/53), χ2=5.16, P=0.023; 26.4% (14/53) vs. 50.9% (27/53), χ2=6.72, P=0.010, 11.3% (6/53) vs. 26.4%(14/53), χ2=3.94、 P=0.047,respectively]. For infection, incidence was significantly lower in the observation group during the CAT+ and HDMTX phases [35.9% (19/53) vs. 56.6% (30/53), χ2=4.59, P=0.032; 24.5% (13/53) vs. 43.4% (23/53), χ2=4.21, P=0.040, respectively]. Conclusions:Short-peptide-based enteral nutrition demonstrates significant advantages in the treatment of pediatric ALL. It provides substantial support for patient treatment and recovery by improving nutritional status, modulating immune function, and reducing chemotherapy-related adverse reactions.

AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.

Aim To explore the potential mechanisms underlying therapeutic effects of cordycepin in asthma by utilizing network pharmacology,molecular docking,and in vitro cellular validation.Methods The thera-peutic targets associated with asthma and the drug tar-gets of cordycepin were systematically identified through comprehensive database searches.An overlap analysis of the two gene sets was performed,followed by the construction of a protein-protein interaction(PPI)network and topological analysis to identify the core targets.The core targets were subjected to Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway a-nalysis and Gene Ontology(GO)enrichment analysis,and a drug-target-pathway network was constructed.To validate the interaction between cordycepin and core targets,molecular docking and molecular dynamics sim-ulations were conducted.Subsequently,the pharmaco-logical effects and underlying mechanisms of cordyce-pin were validated in vitro using Beas-2B cells,emplo-ying Cell Counting Kit-8(CCK-8)assay and quantita-tive real-time reverse transcription PCR(RT-qPCR).Results A total of 438 potential targets of cordycepin were identified,113 of which overlapped with asthma-related therapeutic targets.Topological analysis based on the PPI network revealed 22 core targets.Using KEGG enrichment analysis,165 significantly enriched pathways were identified,including the TNF and HIF-1 signaling pathways.Molecular docking analysis re-vealed high binding affinities between cordycepin and select core targets,which further corroborated by mo-lecular dynamics simulations.In vitro experiments showed that after cordycepin pretreatment,the upregu-lation of MAPK1,HIF1A,MTOR,MYC,IL10,and JUN mRNA was significantly rescued in HDM-stimulated Beas-2B cells.Conclusions Cordycepin exerts anti-asthmatic effects by targeting MAPK1 and other key molecules,thereby providing a scientific foundation for its further development and clinical application.

Objective:By combining image memory with educational games, electrocardiogram (ECG) images were integrated with card games to simplify complex ECG knowledge and visualize abstract concepts. This approach stimulated students' motivation to learn within the game, thereby enhancing their cognitive abilities and aiding them in mastering ECG-related knowledge.Methods:Through literature search and brainstorming, ECG learning flash cards and game process were designed. Using the convenience sampling method, 55 medical students from a university were selected to conduct the self-designed questionnaire before and after using ECG flash cards to evaluate the efficacy of flash cards in enhancing ECG learning outcomes. A descriptive qualitative study was conducted on the satisfaction with the flash cards.Results:Before the intervention, there was no significant difference in the score of students from different majors. For students who had studied ECG within 1 month and 6 months, the difference in correct recognition rate between them was relatively small, which were 57.50% and 54.51%, respectively. For students who had not studied ECG, the correct recognition rate after training was only 18.06%. After the intervention, 42 valid questionnaires were collected. The overall correct rate of ECG recognition increased by 17.86%. The correct recognition rate of ventricular fibrillation increased significantly from 30.91% to 64.29%; the correct recognition rate of supraventricular tachycardia was improved only by 5.50%. The correct ECG recognition rate was significantly higher after the intervention than before the intervention ( P<0.01). The results of qualitative interviews indicated that the ECG game cards were interesting, practical, and generalizable. However, there was room for improvement in the distinctiveness of key graphics, the richness of information on cards, and the diversity of rule design. Conclusions:ECG recognition is hard to master for beginners. The use of ECG flash cards simplifies the process of ECG recognition and stimulates students' initiative in learning, thus improving the overall correct ECG recognition rate.

Objective: Hundreds of countries have implemented lockdown policies to slow the spread of coronavirus disease-2019 (COVID-19), but the impact of these measures on maternal mental health is not well understood. Methods: This study integrated a stress-process model to examine the pathways from lockdown-related stressors to prenatal psychological outcomes, with COVID-19 coping strategies (COP) and self-efficacy in managing negative affect (NEG) as mediators and lockdown duration, hours on pandemic-related information, and number of pregnancies as moderators. Pregnant women in Shanghai completed the Regulatory Emotional Self-Efficacy Scale, COVID-19 Coping Scale, Depression, Anxiety, and Stress Scale-21. Structural equation modeling (SEM) was used to test and modify the hypothetical model, and moderated mediation and slope analyses were undertaken. Results: In the final SEM demonstrating satisfactory fit, three stressors—decreased household income, insufficient daily supplies, and acquired infections—showed positive direct relationships with NEG and COP. Acquired infections, NEG, and COP were identified as direct predictors of mental health outcomes. The relationship between these three stressors and mental health was mediated by NEG and COP. Additionally, the number of pregnancies moderated the mediating effect of COP; this effect was more pronounced among first-time pregnant women than those with multiple pregnancies. Conclusion This study provides insights into how lockdown measures impact psychological outcomes in pregnant women quarantined at home. Interventions aimed at increasing coping strategies may be more effective for primiparous women during future public health emergencies.

AIM:This study aimed to confirm the glycolytic inhibitory activity of 3-bromopyruvic acid(3BP)and to assess whether this inhibition could ameliorate hypoxia-induced pulmonary hypertension in rats.METHODS:PAH model rats were generated from normal SD rats via exposure to normal pressure and hypoxia.Intervention groups I and II(6 rats per group)were then intraperitoneally injected with 3BP(15 mg/kg),and the normal and hypoxia groups(6 rats per group)were given the same amount of normal saline for a total of 21 d.The average pulmonary artery pressure of the rats in each group was measured via right heart catheterisation,and hilar tissue measurements.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the ratio of RV/(LV+S)was calculated as an index of right ventricular hypertrophy.Right lower lung tissues were fixed in 4%paraformaldehyde-PBS buffer,sec-tioned in conventional paraffin(5 μm thick),stained with HE and Masson,photographed under a microscope.Then the thickness ratio of the tunica media and the area ratio of collagen fibres were calculated.The expression of pyruvate kinase isozyme type M2(PKM2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and pyruvate de-hydrogenase(PDH)proteins in the hilar tissues of each group were detected by western blot,whereas interleukin-1β(IL-1β)and IL-18 contents were detected using ELISA,and lactic acid content was detected using a lactic acid kit.RE-SULTS:The results showed that 3-brpa effectively inhibited glycolysis and significantly improved hypoxia-induced pulmo-nary hypertension in rats.Compared with the hypoxia group,in intervention group II,PKM2 expression was decreased(P<0.05),PDH expression increased significantly(P<0.01),and NLRP3 expression was decreased(P<0.05).The IL-18 and IL-1β contents decreased(P<0.05 or P<0.01,respectively).Pulmonary hemodynamic indexes showed that the pro-portion of the right ventricle and the mean pressure of the pulmonary artery decreased(P<0.05 or P<0.01,respectively).The HE and Masson staining results showed that the thickness ratio of the tunica media and the area ratio of collagen fibres decreased significantly(P<0.01).Lactic acid content was significantly decreased(P<0.01).CONCLUSION:This study showed that 3BP can inhibit glycolysis and alleviate hypoxia-induced pulmonary hypertension in rats.

Aim To explore the potential mechanisms underlying therapeutic effects of cordycepin in asthma by utilizing network pharmacology,molecular docking,and in vitro cellular validation.Methods The thera-peutic targets associated with asthma and the drug tar-gets of cordycepin were systematically identified through comprehensive database searches.An overlap analysis of the two gene sets was performed,followed by the construction of a protein-protein interaction(PPI)network and topological analysis to identify the core targets.The core targets were subjected to Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway a-nalysis and Gene Ontology(GO)enrichment analysis,and a drug-target-pathway network was constructed.To validate the interaction between cordycepin and core targets,molecular docking and molecular dynamics sim-ulations were conducted.Subsequently,the pharmaco-logical effects and underlying mechanisms of cordyce-pin were validated in vitro using Beas-2B cells,emplo-ying Cell Counting Kit-8(CCK-8)assay and quantita-tive real-time reverse transcription PCR(RT-qPCR).Results A total of 438 potential targets of cordycepin were identified,113 of which overlapped with asthma-related therapeutic targets.Topological analysis based on the PPI network revealed 22 core targets.Using KEGG enrichment analysis,165 significantly enriched pathways were identified,including the TNF and HIF-1 signaling pathways.Molecular docking analysis re-vealed high binding affinities between cordycepin and select core targets,which further corroborated by mo-lecular dynamics simulations.In vitro experiments showed that after cordycepin pretreatment,the upregu-lation of MAPK1,HIF1A,MTOR,MYC,IL10,and JUN mRNA was significantly rescued in HDM-stimulated Beas-2B cells.Conclusions Cordycepin exerts anti-asthmatic effects by targeting MAPK1 and other key molecules,thereby providing a scientific foundation for its further development and clinical application.