1.Mechanistic Insights into The Role of LEPROTs and COPI Retrograde Transport in Regulating Golgi Morphology
Jing-Hu GAO ; Lin-Yue ZHAO ; Yu-Lu ZHANG ; Yan-Fang WU ; Bing YAN
Progress in Biochemistry and Biophysics 2026;53(6):1746-1757
ObjectiveThe Golgi apparatus serves as a central hub in the eukaryotic secretory pathway, responsible for the processing, sorting, and trafficking of proteins and lipids. In mammalian cells, the Golgi typically forms a perinuclear ribbon-like structure composed of laterally connected cisternae stacks.The maintenance of Golgi ribbon structure depends on the balance of membrane flux across multiple intracellular trafficking pathways, yet the specific contributions of distinct trafficking branches to Golgi macroscopic morphology remain elusive. In mammalian cells, the Golgi ribbon is typically organized as a perinuclear, laterally connected structure composed of stacked cisternae, and its integrity is highly dynamic and sensitive to perturbations in membrane trafficking. This study aims to elucidate the role of coat protein complex I (COPI)-mediated retrograde transport in maintaining the Golgi ribbon and to dissect the functional relationship between the transmembrane cargo receptors LEPROT/LEPROTL1 (LEPROTs) and the COPI adaptor GOLPH3. MethodsUsing siRNA interference and gene-deficient cell lines, we selectively perturbed COPI- or adaptor protein complex 1 (AP-1)-mediated trafficking pathways in HeLa cells. To quantitatively evaluate Golgi morphology, we employed a “Golgi Angle”-based measurement to assess its circumferential distribution around the nucleus. The spatial distribution of the Golgi ribbon was quantitatively analyzed using confocal microscopy, while Golgi ultrastructure and vesicle density were examined via transmission electron microscopy. Additionally, the subcellular distribution of COPI components was assessed by immunofluorescence co-localization. ResultsSelective inhibition of COPI retrograde transport significantly induced the circumferential extension of the Golgi ribbon around the nucleus, whereas blocking AP-1-mediated anterograde transport resulted in Golgi compaction, indicating opposing roles. These results suggest that different trafficking branches downstream of ARF1 exert distinct and even antagonistic effects on Golgi morphology. LEPROTs-deficient cells exhibited a Golgi extension phenotype highly consistent with COPI impairment. Furthermore, knockdown of GOLPH3 in a LEPROTs double-knockout background produced a significant additive effect on Golgi extension, suggesting that LEPROTs and GOLPH3 play non-redundant roles in regulating COPI-related trafficking processes. Mechanistically, loss of either LEPROTs or GOLPH3 led to the aberrant accumulation of COPI components at endoplasmic reticulum exit sites, accompanied by a reduction in COPI-like vesicles around the Golgi. This redistribution indicates a defect in COPI recycling between the ER-Golgi interface and the Golgi apparatus. Ultrastructural analysis revealed that Golgi cisternae in defective cells became shorter and thicker while maintaining a stable number of stacks. In parallel, the density of Golgi-associated vesicles was markedly decreased, further supporting an impairment in COPI vesicle formation or budding processes. ConclusionThis study demonstrates that active COPI retrograde transport is a critical factor in restricting the over-connection of the Golgi ribbon and maintaining its compactness. Rather than causing fragmentation, partial disruption of COPI function leads to a distinct morphological outcome characterized by Golgi ribbon extension at the light microscopy level and cisternal remodeling at the ultrastructural level. LEPROTs and GOLPH3 cooperatively promote the recycling and vesiculation of COPI components, thereby imposing a structural constraint on the Golgi periphery. Our findings support a model in which multiple adaptor proteins act in parallel to sustain efficient COPI cycling, thereby maintaining Golgi structural homeostasis. These findings provide new cell biological evidence for the membrane trafficking basis of Golgi morphological homeostasis.
2.Comparative Study on the Effects of Qingchang Wenzhong Decoction (清肠温中方) on the Intestinal Mucus Barrier in Conventional and Pseudo-Germ-Free Model Mice of Acute Ulcerative Colitis
Mingxu GAO ; Leilei LIU ; Lijie LU ; Jiali WANG ; Juncong HU ; Yangzhe LIN ; Qirui LIU ; Yue DONG ; Luyue WANG ; Zeyu XUE ; Junxiang LI ; Lei SHI
Journal of Traditional Chinese Medicine 2026;67(14):1528-1537
ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction (清肠温中方, QWD) in treating ulcerative colitis (UC). MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group (n=45) and a conventional group (n=55) using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established, the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group, a pseudo-germ-free QWD group, and a pseudo-germ-free mesalazine group, with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group (n=10), as well as a conventional model group, a conventional QWD group, and a conventional mesalazine group, with 15 mice in each group. Except for the normal control group, acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment, mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/(kg·d) by gavage with deionized water, while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/(kg·d) by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment, six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight, and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota, including operational taxonomic units (OTUs), Shannon index, Observed_species index, and phylogenetic diversity (PD whole tree). On day 39, body weight was measured in all groups, and the disease activity index (DAI) was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin (HE) staining, and histological injury scores were determined. In addition, the expression levels of mucopolysaccharides and mucin 2 (MUC2) in colonic tissues were measured. ResultsOn day 25, there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group (P>0.05). Compared to the conventional microbiota group, the pseudo-germ-free group showed significantly reduced OTUs, Shannon index, Observed_species index, and PD whole tree (P<0.01). On day 39, compared to the normal control group, mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI, along with increased colon wet weight, shortened colon length, markedly elevated histopathological scores, and reduced expression of mucopolysaccharides and MUC2 (P<0.01). In contrast, no significant differences were observed in these parameters in the pseudo-germ-free model group (P>0.05). Compared to the conventional model group, the conventional QWD group showed significant improvement in all measured parameters, whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight (P<0.01). No statistically significant differences were observed among the pseudo-germ-free model group, the pseudo-germ-free QWD group, and the pseudo-germ-free mesalazine group (P>0.05). ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora, thereby exerting a therapeutic effect on acute UC.
3.Comparative Study on the Effects of Qingchang Wenzhong Decoction (清肠温中方) on the Intestinal Mucus Barrier in Conventional and Pseudo-Germ-Free Model Mice of Acute Ulcerative Colitis
Mingxu GAO ; Leilei LIU ; Lijie LU ; Jiali WANG ; Juncong HU ; Yangzhe LIN ; Qirui LIU ; Yue DONG ; Luyue WANG ; Zeyu XUE ; Junxiang LI ; Lei SHI
Journal of Traditional Chinese Medicine 2026;67(14):1528-1537
ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction (清肠温中方, QWD) in treating ulcerative colitis (UC). MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group (n=45) and a conventional group (n=55) using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established, the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group, a pseudo-germ-free QWD group, and a pseudo-germ-free mesalazine group, with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group (n=10), as well as a conventional model group, a conventional QWD group, and a conventional mesalazine group, with 15 mice in each group. Except for the normal control group, acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment, mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/(kg·d) by gavage with deionized water, while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/(kg·d) by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment, six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight, and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota, including operational taxonomic units (OTUs), Shannon index, Observed_species index, and phylogenetic diversity (PD whole tree). On day 39, body weight was measured in all groups, and the disease activity index (DAI) was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin (HE) staining, and histological injury scores were determined. In addition, the expression levels of mucopolysaccharides and mucin 2 (MUC2) in colonic tissues were measured. ResultsOn day 25, there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group (P>0.05). Compared to the conventional microbiota group, the pseudo-germ-free group showed significantly reduced OTUs, Shannon index, Observed_species index, and PD whole tree (P<0.01). On day 39, compared to the normal control group, mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI, along with increased colon wet weight, shortened colon length, markedly elevated histopathological scores, and reduced expression of mucopolysaccharides and MUC2 (P<0.01). In contrast, no significant differences were observed in these parameters in the pseudo-germ-free model group (P>0.05). Compared to the conventional model group, the conventional QWD group showed significant improvement in all measured parameters, whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight (P<0.01). No statistically significant differences were observed among the pseudo-germ-free model group, the pseudo-germ-free QWD group, and the pseudo-germ-free mesalazine group (P>0.05). ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora, thereby exerting a therapeutic effect on acute UC.
4.Comparison of the diagnostic value of 3.0 T MRI HASTE sequence and high-frequency color Doppler ultrasound for high-risk placenta previa combined with placenta accreta
Yue ZHAO ; Xueyang HU ; Lin SUN ; Rui ZHANG ; Zhibao WANG
Journal of Navy Medicine 2025;46(1):38-42
Objective To compare the value of high-field strength MRI half-Fourier single shot turbo spin-echo(HASTE)sequence with high-frequency color Doppler ultrasound for the diagnosis of placenta previa combined with placenta accreta.Methods A total of 116 pregnant women with suspected high-risk placenta previa and placenta accreta who underwent cesarean section at The No.2 Hospital of Baoding from December 2019 to December 2022 were selected as research objects.All parturients took examinations of ultrasound and high-field MRI before surgery.Pathological diagnosis after cesarean section was used as the gold standard for analysis of the consistency between MRI and ultrasound results and pathological results.The value of HASTE sequence and high-frequency ultrasound in diagnosing placenta accreta was compared.Results Pathological results confirmed that 86 patients had high-risk placenta previa and placenta accreta.The positive predictive values of ultrasound,MRI,and ultrasound+MRI in diagnosis of high-risk placenta previa combined with placenta accreta were 93.51%,97.62%,and 98.81%,respectively.The negative predictive values were 64.10%,87.50%,and 90.63%,respectively.The accuracies were 83.62%,94.83%,and 96.55%,respectively.The sensitivities were 83.72%,95.35%,and 96.51%,respectively.The specificities were 83.33%,93.33%,and 96.67%,respectively.The Kappa values for consistency were 0.611,0.868,and 0.912,respectively.The accuracy of MRI in diagnosis of high-risk placenta previa combined with placenta accreta was higher than that of ultrasound(P<0.05).Conclusion 3.0 T MRI HASTE sequence has greater efficacy and higher accuracy in diagnosis of high-risk placenta previa combined with placenta accreta.
5.Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in anterior mediastinal masses
Junmin ZHU ; Junjie WANG ; Jianming YUE ; Yixin SUN ; Yichen LIU ; Lei WANG ; Lin LIN ; Jie LI ; Jinlan ZHAO ; Xuehua TU ; Ningying DING ; Jianrong HU ; Chunmei HE ; Leilei TIAN ; Hongtao TANG ; Jiasheng ZHAO ; Cheng CHEN ; Yongxiang SONG ; Yunwei TIAN ; Yong XIAO ; Kaidi LI ; Lin MA ; Yun WANG ; Longqi CHEN ; Dong TIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1603-1609
Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.
6.Feasibility of deep learning reconstruction algorithm combined with adual-low protocol for thoracoabdominal aortic CT angiography
Yingying HU ; Yunpeng GAO ; Yan CHEN ; Nanxue LIANG ; Yue LIN ; Tongxi LIU ; Peiyao ZHANG ; Hongliang SUN
Chinese Journal of Radiology 2025;59(10):1149-1154
Objective:To investigate the feasibility of deep learning reconstruction (DLR) algorithm combined with a dual-low protocol (low radiation dose and low contrast medium dose) for thoracoabdominal aortic CT angiography (CTA).Methods:This cross-sectional study prospectively enrolled 56 patients suspected of aortic diseases who underwent aortic CTA at China-Japan Friendship Hospital from June 2023 to June 2024. All patients were randomly divided into two groups: Group A (28 cases) underwent CTA with a tube voltage of 100 kVp, automatic tube current modulation (noise index=10), and a contrast agent dose of 80 ml (flow rate 5 ml/s), with images reconstructed using the three-dimensional adaptive iterative dose reduction algorithm (AIDR). Group B (28 cases) underwent CTA with a tube voltage of 80 kVp, automatic tube current modulation (noise index=25), and a contrast agent dose of 40 ml (flow rate 3.5 ml/s), with images reconstructed using either the deep learning reconstruction algorithm-Advanced intelligent Clear-IQ Engine (AiCE subgroup) or the AIDR (AIDR subgroup). Two physicians evaluated the image quality of the three groups subjectively and objectively. Objective evaluation metrics included CT values, image noise (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) at the ascending aorta, carina-level descending aorta, celiac trunk-origin abdominal aorta, and common iliac bifurcation abdominal aorta carina. Subjective evaluation metrics included image quality and noise scores. Comparisons among the three datasets (Group A, AiCE subgroup, AIDR subgroup) were performed using one-way ANOVA or the Kruskal-Wallis test, with appropriate post-hoc tests for pairwise comparisons.Results:No significant differences were observed in CT values of the ascending aorta, descending aorta, and abdominal aorta between Group A and the AiCE subgroup or the AIDR subgroup ( P0.05). However, significant overall differences were found in SD, SNR, and CNR values for the ascending aorta, descending aorta, and abdominal aorta ( P0.05). Pairwise comparisons revealed that, except for no significant differences in SD, SNR, and CNR values of the ascending and descending aorta between Group A and the AiCE subgroup, and no significant difference in SNR values of the ascending and abdominal aorta between Group A and the AIDR subgroup ( P0.05), all other intergroup comparisons showed statistically significant differences ( P0.05). Significant overall differences were also observed in image quality and noise scores between Group A and the AiCE and AIDR subgroups ( P0.05). Except for no significant differences in image quality and noise scores between Group A and the AiCE subgroup ( P0.05), all other pairwise comparisons showed statistically significant differences ( P0.05). Conclusions:The application of deep learning reconstruction algorithm combined with a dual-low protocol in thoracoabdominal aortic CTA can reduce radiation dose and contrast agent dose while maintaining diagnostic image quality, demonstrating significant clinical value for widespread adoption.
7.Effects of High Temperature on Antioxidant,Carbon Metabolism Physiological Indicators and Transcriptome of Mytilus coruscus
Zhi YANG ; Yuan-Yue ZHANG ; Jian-Xin WANG ; Zhi LIAO ; Qun-Ju HU ; Qiao-Mei YANG ; Xiao-Lin ZHANG ; Mei-Hua FAN
Chinese Journal of Biochemistry and Molecular Biology 2025;41(3):446-459
The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P<0.05),de-creased the ATP content of digestive glands(P<0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P<0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.
8.Party building-guided initiatives in colorectal cancer screening and support for primary healthcare in-stitutions
Xueqing YAO ; Chengzhi HUANG ; Zhiyuan LIU ; Zhanyan GUO ; Yue ZHOU ; Weixian HU ; Xiaowu LI ; Zhenbin LIN ; Yuemei ZHONG ; Dailan XIONG ; Zejian LYU ; Junjiang WANG
Modern Hospital 2025;25(8):1274-1276
With the advancement of China's healthcare reform,enhancing the capacity of primary healthcare services has become a pivotal task.Colorectal cancer,one of the most prevalent malignancies in China,highlights the critical importance of early screening and diagnosis to improve patient survival rates.This study,guided by the principles of Party building and Xi Jinping Thought on Socialism with Chinese Characteristics,examines the implementation and outcomes of a rural outreach program focused on colorectal cancer screening and diagnostic technologies.By promoting the dissemination of colorectal cancer screening initiatives,the paper aims to provide empirical evidence to support the deepening of primary-care services,foster high-quality ad-vancement of grassroots health services,and align with the national Healthy China Initiative,thereby more effectively safeguarding population health.
9.Effects of different dressing methods on wound healing after cosmetic suturing for facial trauma
Bin HOU ; Shuling ZHANG ; Guangqin MA ; Lehao WU ; Sixun LIN ; Hu XIAO ; Changbo YUE
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(4):355-361
Objective:To evaluate the effects of two dressing methods on wound healing and patient satisfaction after cosmetic suturing for pediatric facial trauma.Methods:A prospective randomized controlled trial was conducted at Dongying People′s Hospital from October 2022 to October 2023. A total of 180 pediatric patients [105 males, 75 females, aged 3-7 (3.9±1.4) years] with facial trauma requiring cosmetic suturing were enrolled in this study. Participants were randomly divided into the study group ( n=91) and control group ( n=89) using a random number table. During the first postoperative dressing change at 24 hours, the study group received saline cleaning followed by erythromycin ointment coverage, while the control group underwent iodine disinfection with gauze coverage. Pain intensity during the second dressing change was assessed using the Chinese version of the Children′s Hospital of Eastern Ontario pain scale (CHEOPS). Wound healing at 6-7 days post-suturing was evaluated using the Chinese version of the redness, edema, ecchymosis, discharge, and approximation (REEDA) scale. Scar appearance at 14 days was measured via the Stony Brook scar evaluation scale (SBSES). Complication rates (infection, dehiscence) and satisfaction rates were statistically analyzed. Results:During the second dressing change, the CHEOPS score was significantly lower in the study group (6.27±1.32) than that in the control group (6.89±1.21) ( P=0.001). At 6-7 days, the REEDA score in the study group (2.26±1.91) was significantly lower than that in the control group (3.07±2.13) ( P=0.008). At 14 days, the SBSES score was significantly lower in the study group [2.60±1.42) vs (3.89±1.50), P<0.001]. The infection rate was 1.09% (1/91) in the study group and 1.12% (1/89) in the control group, with two cases of epidermal dehiscence observed in the control group. The satisfaction rate in the study group was 93.41% (85/91), which was higher than that in the control group [85.49% (76/89), P=0.020]. Conclusion:Saline cleaning combined with erythromycin ointment coverage reduces pain during wound dressing change, facilitates early wound healing, and improves patient′s satisfaction.
10.The influence of two-way referral model on treatment and prognosis of patients with chronic heart failure
Yijun SUN ; Xinyu ZHANG ; Yue HU ; Zongwei LIN ; Jie XIAO ; Peng LI ; Xin ZHAO ; Huafang ZHANG ; Bo QIN ; Dequan JIA ; Tao ZHANG ; Jian MA ; Hongping CHEN ; Chunju ZHANG ; Xinwei GENG ; Kaiyan ZHANG ; Man ZHENG ; Fenglei ZHANG ; Yan LANG ; Hegong HOU ; Peng LIU ; Haifeng JIA ; Jianjun LU ; Kai ZHAO ; Hui ZHAO ; Jiechang XU ; Mi ZHANG ; Xiuxin LI ; Dongxia ZHANG ; Lin ZHONG ; Hui ZHAO ; Fangfang LIU ; Yan LIU ; Dongxia MIAO ; Chengwei WANG ; Hui ZHANG ; Chen WANG ; Fen WANG ; Xuejuan ZHANG ; Huixia LYU ; Xiaoping JI
Chinese Journal of Cardiology 2025;53(11):1244-1253
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.

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