BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

Objective To characterize the features of patent foramen ovale(PFO)-related cryptogenic stroke using diffusion-weighted imaging(DWI)and to investigate the correlation between infarct size and cardiac CT characteristics of PFO.Methods A retrospective,consecutive cohort study was conducted on acute ischemic stroke patients admitted to Neurology Department of Xuanwu Hospital,Capital Medical University from January 2022 to September 2024.Patients were categorized into PFO group,arterio-arterial embolism(AAE)group,and atrial fibrillation(AF)group based on etiological diagnosis.Baseline clinical data,including age,height,body mass index,admission National Institutes of Health stroke scale(NIHSS)score,history of old cerebral infarction,hypertension,diabetes mellitus,coronary heart disease,dyslipidemia,and smoking history were collected and compared.All patients underwent head MR within 24 h of admission.DWI was used to analyze and compare infarct characteristics across the three groups,including lesion number(single or multiple),location(cortical+subcortical,deep white matter,cortical+subcortical+deep white matter,cerebellum+thalamus+brainstem),size(≥15 mm or＜15 mm,based on maximum transverse diameter;for multiple lesions,if any lesion had a maximum diameter≥15 mm,it was categorized as≥15 mm),infarcted vascular territory(anterior,posterior,or both circulations),and specific arterial supply(anterior cerebral artery,middle cerebral artery,posterior cerebral artery,basilar artery,posterior inferior cerebellar artery,superior cerebellar artery,anterior choroidal artery,or multiple arteries).Patients in the PFO group additionally underwent cardiac CT to measure PFO-related parameters:tunnel length,width,height,septum secundum thickness,and fossa ovalis length.Spearman correlation analysis was performed to evaluate the relationship between infarct size and PFO cardiac CT features.Results A total of 232 acute ischemic stroke patients were included(mean age[57±17]years,ranged 19-86 years;141 males,91 females),comprising 116 in the PFO group,36 in the AAE group,and 80 in the AF group.(1)The proportion of males in the PFO group was higher than that in the AF group,it was lower than that in the AAE group.The age,body mass index and proportions of patients with hypertension,diabetes,hyperlipidemia,coronary heart disease were all lower than those in the other two groups(both P＜0.016 7),while other baseline characteristics showed no significant differences(all P＞0.05).(2)The PFO group exhibited a higher proportion of multiple infarcts compared to the AAE group(83.62％[97/116]vs.61.11％[22/36],P＜0.016 7),but a lower proportion than the AF group(83.62％[97/116]vs.98.75％[79/80],P＜0.016 7).The PFO group also showed a significantly higher proportion of cortical+subcortical infarcts(47.41％[55/116]vs.11.11％[4/36]and 6.25％[5/80],respectively,both P＜0.016 7)and infarcts with a maximum diameter＜15 mm compared to both AAE and AF groups(66.38％[77/116]vs.36.11％[13/36]and 11.25％[9/80],respectively,both P＜0.016 7).Furthermore,the PFO group had a lower proportion of anterior circulation infarcts(27.59％[32/116]vs.69.44％[25/36]in AAE group and 67.50％[54/80]in AF group,both P＜0.016 7),but a higher proportion of posterior circulation infarcts(62.07％[72/116]vs.16.67％[6/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).Specifically,middle cerebral artery infarcts were less common in the PFO group(18.97％[22/116]vs.66.67％[24/36]in AAE group and 52.50％[42/80]in AF group,both P＜0.016 7),while posterior cerebral artery infarcts were more common(48.28％[56/116]vs.8.33％[3/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).(3)Spearman correlation analysis revealed that infarct size was negatively correlated with PFO tunnel length(rs=-0.429,P=0.029),fossa ovalis length(rs=-0.408,P=0.038),and septum secundum thickness(rs=-0.525,P=0.006),but not correlated with PFO width or height(both P＞0.05).Conclusions PFO-related cryptogenic stroke is predominantly characterized by multiple small infarcts,primarily located in the cortical+subcortical regions and posterior circulation.Infarct size was found to be negatively correlated with PFO tunnel length,fossa ovalis length,and septum secundum thickness.Comprehensive assessment integrating DWI and cardiac CT features may facilitate the identification of PFO-related stroke.These findings warrant further validation through larger,prospective studies.

Objective:To conduct a Meta-synthesis on the characteristics of symptom help-seeking behavior in adult cancer patients, so as to provide evidence-based guidance for early intervention of symptom help-seeking behavior in cancer patients in China.Methods:Qualitative studies on symptom help-seeking behavioral characteristics of cancer patients were systematically searched in PubMed, Cochrane Library, Web of Science, ProQuest, Nature, ScienceDirect, China National Knowledge Infrastructure, WanFang Data, China Biology Medicine disc, and VIP. The search period was from database establishment to December 31, 2024. Included literature was independently evaluated using the Australian Joanna Briggs Institute Center for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. The results were integrated through the Meta-synthesis method.Results:A total of 15 papers were included, and 30 findings were distilled and grouped into nine categories, resulting in three integrated findings of low symptom perception and interpretation bias, coping styles of symptom disclosure, and factors influencing symptom help-seeking behaviors.Conclusions:Symptom help-seeking behaviors of cancer patients are influenced by a variety of factors, and understanding their behavioral characteristics is useful in informing the development of intervention strategies.

Objective:Varicocele(VC)induces male infertility by mediating changes in the testicular microenvironment,in which testicular hypoxia and high-pressure are important pathological conditions.This study aims to compare the mouse spermatogenesis(GC-2spd)cells and Sertoli(TM4)cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling,and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model.Methods:On the basis of cell hypoxia induced by CoCl2,the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution.After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model,the cells were divided into normal group,hypoxia model group and composite model group.And the levels of OS,programmed cell death,inflammatory factors,and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods.Results:The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L,respectively,and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg(P＜0.05).Compared with the normal group,the SOD levels of GC-2 and TM4 cells decreased(all P＜0.05),CAT level decreased(all P＜0.05),and MDA level increased(all P＜0.01),and the OS level of GC-2 and TM4 cells was more obvious than that of the hy-poxia model group(all P＜0.05).Compared with the normal group,apoptosis occurred in GC-2 and TM4 cells after composite model-ing(all P＜0.05).Compared with the normal group,the mRNA expressions of IL-1β,IL-18,TNF-α and COX-2 in GC-2 and TM4 cells significantly increased(P＜0.01)and higher than those in hypoxia model group(P＜0.05)and induced pyroptosis(P＜0.01).The expression level of GSDMD increased(P＜0.05).Conclusion:The cell model with hypoxia and high pressure com-bined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone,but also further cause in-flammatory response damage and pyroptosis,which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC.This cell model can be used for studying the pathogenesis of VC-associated male infertility,evalu-ating drug efficacy,and exploring pharmacological mechanisms.

Background and Aims:Laparoscopic cholecystectomy(LC)is a common surgical method for the treatment of gallbladder diseases.However,some patients experience symptoms such as dyspepsia after surgery,which can affect their quality of life.Compound azinomide enteric-coated tablets,a novel drug,may improve dyspeptic symptoms after LC.This study was conducted to explore the clinical efficacy of compound azinomide enteric-coated tablets in treating post-LC dyspepsia symptoms through a multicenter clinical trial.Methods:A multicenter,superior efficacy,open-label,parallel-controlled design was used.Patients with postoperative dyspepsia were enrolled in 7 centers between January 2023 and May 2024.Patients were randomly assigned to either the observation or control groups using a random number table.The observation group received compound azinomide enteric-coated tablets,while the control group was treated with a combination of oryzae pancreatin tablets and ursodeoxycholic acid tablets.Both groups were treated for 4 weeks.The primary endpoints included gastrointestinal symptom scores and quality of life scores assessed before and at 14 and 28 d after treatment.Additionally,the incidence of adverse reactions and cost-effectiveness ratio(CER)were compared between the groups.Results:A total of 303 patients were included,with 150 in the observation group and 153 in the control group.Baseline characteristics were balanced between the groups before treatment(all P>0.05).After treatment,the observation group showed significantly higher effective rates at 14 d and 28 d than the control group(44.7%vs.29.4%;98.0%vs.73.9%,both P<0.05).The observation group also had significantly lower symptom scores and quality of life scores at both 14 and 28 d,with a significantly higher improvement rate in symptom scores compared to the control group(all P<0.05).Further analysis of the improvement rate and treatment efficacy for individual symptoms revealed that,except for the 14-d improvement in abdominal pain/discomfort,the observation group showed better improvement in all other symptoms at 14 d and in all symptoms at 28 d compared to the control group(all P<0.05).No adverse reactions were observed in either group.The CER for the observation group was 283.78 yuan/efficacy rate at 14 d and 128.57 yuan/efficacy rate at 28 d,while the control group's CER was 729.93 yuan/efficacy rate at 14 d and 290.22 yuan/efficacy rate at 28 d.Conclusion:Compound azinomide enteric-coated tablets demonstrated good clinical efficacy in treating dyspepsia symptoms after LC with excellent safety and high cost-effectiveness.Despite some limitations,the results provide a new treatment option for dyspepsia after LC.Larger-scale randomized controlled trials are needed to validate this study's conclusions further.

Background and Aims:Laparoscopic cholecystectomy(LC)is a common surgical method for the treatment of gallbladder diseases.However,some patients experience symptoms such as dyspepsia after surgery,which can affect their quality of life.Compound azinomide enteric-coated tablets,a novel drug,may improve dyspeptic symptoms after LC.This study was conducted to explore the clinical efficacy of compound azinomide enteric-coated tablets in treating post-LC dyspepsia symptoms through a multicenter clinical trial.Methods:A multicenter,superior efficacy,open-label,parallel-controlled design was used.Patients with postoperative dyspepsia were enrolled in 7 centers between January 2023 and May 2024.Patients were randomly assigned to either the observation or control groups using a random number table.The observation group received compound azinomide enteric-coated tablets,while the control group was treated with a combination of oryzae pancreatin tablets and ursodeoxycholic acid tablets.Both groups were treated for 4 weeks.The primary endpoints included gastrointestinal symptom scores and quality of life scores assessed before and at 14 and 28 d after treatment.Additionally,the incidence of adverse reactions and cost-effectiveness ratio(CER)were compared between the groups.Results:A total of 303 patients were included,with 150 in the observation group and 153 in the control group.Baseline characteristics were balanced between the groups before treatment(all P>0.05).After treatment,the observation group showed significantly higher effective rates at 14 d and 28 d than the control group(44.7%vs.29.4%;98.0%vs.73.9%,both P<0.05).The observation group also had significantly lower symptom scores and quality of life scores at both 14 and 28 d,with a significantly higher improvement rate in symptom scores compared to the control group(all P<0.05).Further analysis of the improvement rate and treatment efficacy for individual symptoms revealed that,except for the 14-d improvement in abdominal pain/discomfort,the observation group showed better improvement in all other symptoms at 14 d and in all symptoms at 28 d compared to the control group(all P<0.05).No adverse reactions were observed in either group.The CER for the observation group was 283.78 yuan/efficacy rate at 14 d and 128.57 yuan/efficacy rate at 28 d,while the control group's CER was 729.93 yuan/efficacy rate at 14 d and 290.22 yuan/efficacy rate at 28 d.Conclusion:Compound azinomide enteric-coated tablets demonstrated good clinical efficacy in treating dyspepsia symptoms after LC with excellent safety and high cost-effectiveness.Despite some limitations,the results provide a new treatment option for dyspepsia after LC.Larger-scale randomized controlled trials are needed to validate this study's conclusions further.

Objective To characterize the features of patent foramen ovale(PFO)-related cryptogenic stroke using diffusion-weighted imaging(DWI)and to investigate the correlation between infarct size and cardiac CT characteristics of PFO.Methods A retrospective,consecutive cohort study was conducted on acute ischemic stroke patients admitted to Neurology Department of Xuanwu Hospital,Capital Medical University from January 2022 to September 2024.Patients were categorized into PFO group,arterio-arterial embolism(AAE)group,and atrial fibrillation(AF)group based on etiological diagnosis.Baseline clinical data,including age,height,body mass index,admission National Institutes of Health stroke scale(NIHSS)score,history of old cerebral infarction,hypertension,diabetes mellitus,coronary heart disease,dyslipidemia,and smoking history were collected and compared.All patients underwent head MR within 24 h of admission.DWI was used to analyze and compare infarct characteristics across the three groups,including lesion number(single or multiple),location(cortical+subcortical,deep white matter,cortical+subcortical+deep white matter,cerebellum+thalamus+brainstem),size(≥15 mm or＜15 mm,based on maximum transverse diameter;for multiple lesions,if any lesion had a maximum diameter≥15 mm,it was categorized as≥15 mm),infarcted vascular territory(anterior,posterior,or both circulations),and specific arterial supply(anterior cerebral artery,middle cerebral artery,posterior cerebral artery,basilar artery,posterior inferior cerebellar artery,superior cerebellar artery,anterior choroidal artery,or multiple arteries).Patients in the PFO group additionally underwent cardiac CT to measure PFO-related parameters:tunnel length,width,height,septum secundum thickness,and fossa ovalis length.Spearman correlation analysis was performed to evaluate the relationship between infarct size and PFO cardiac CT features.Results A total of 232 acute ischemic stroke patients were included(mean age[57±17]years,ranged 19-86 years;141 males,91 females),comprising 116 in the PFO group,36 in the AAE group,and 80 in the AF group.(1)The proportion of males in the PFO group was higher than that in the AF group,it was lower than that in the AAE group.The age,body mass index and proportions of patients with hypertension,diabetes,hyperlipidemia,coronary heart disease were all lower than those in the other two groups(both P＜0.016 7),while other baseline characteristics showed no significant differences(all P＞0.05).(2)The PFO group exhibited a higher proportion of multiple infarcts compared to the AAE group(83.62％[97/116]vs.61.11％[22/36],P＜0.016 7),but a lower proportion than the AF group(83.62％[97/116]vs.98.75％[79/80],P＜0.016 7).The PFO group also showed a significantly higher proportion of cortical+subcortical infarcts(47.41％[55/116]vs.11.11％[4/36]and 6.25％[5/80],respectively,both P＜0.016 7)and infarcts with a maximum diameter＜15 mm compared to both AAE and AF groups(66.38％[77/116]vs.36.11％[13/36]and 11.25％[9/80],respectively,both P＜0.016 7).Furthermore,the PFO group had a lower proportion of anterior circulation infarcts(27.59％[32/116]vs.69.44％[25/36]in AAE group and 67.50％[54/80]in AF group,both P＜0.016 7),but a higher proportion of posterior circulation infarcts(62.07％[72/116]vs.16.67％[6/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).Specifically,middle cerebral artery infarcts were less common in the PFO group(18.97％[22/116]vs.66.67％[24/36]in AAE group and 52.50％[42/80]in AF group,both P＜0.016 7),while posterior cerebral artery infarcts were more common(48.28％[56/116]vs.8.33％[3/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).(3)Spearman correlation analysis revealed that infarct size was negatively correlated with PFO tunnel length(rs=-0.429,P=0.029),fossa ovalis length(rs=-0.408,P=0.038),and septum secundum thickness(rs=-0.525,P=0.006),but not correlated with PFO width or height(both P＞0.05).Conclusions PFO-related cryptogenic stroke is predominantly characterized by multiple small infarcts,primarily located in the cortical+subcortical regions and posterior circulation.Infarct size was found to be negatively correlated with PFO tunnel length,fossa ovalis length,and septum secundum thickness.Comprehensive assessment integrating DWI and cardiac CT features may facilitate the identification of PFO-related stroke.These findings warrant further validation through larger,prospective studies.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.