1.Antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center
Jiayu TIAN ; Tianyi YANG ; Jingen XIE ; Linlin CHEN ; Qian RAO ; Xiong XIAO ; Yongchun HOU ; Wenhong LI
China Pharmacy 2026;37(7):870-876
OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group, model group, dexamethasone group (positive control), and Ephedrae Herba-Armeniacae Semen Amarum 2∶1, 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g (crude drug)/kg], dexamethasone suspension (0.5 mg/kg), or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration, medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration, the nucleus tractus solitarius (NTS) was located using a stereotaxic apparatus. Histamine phosphate (1 μL) was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats; the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor (NGF), substance P (SP), norepinephrine (NA), 5-hydroxytryptamine (5-HT) and acetylcholine (Ach)] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor (NK-1R), p38 mitogen-activated protein kinase (MAPK), and c-fos in the medulla oblongata, as well as the protein expressions of NK-1R, p38 MAPK, and c-fos in the NTS region, were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine, pseudoephedrine, and methylephedrine. Compared with blank group, the contents of NGF, SP, NA, 5-HT and Ach, and the relative expression levels of NK-1R, p38 MAPK, and c-fos mRNA and protein were significantly increased in the model group ( P <0.01). Compared with model group, Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R, p38 MAPK, and c-fos mRNA and protein ( P <0.01), with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.
2.Construction of Organoid-on-a-chip and Its Applications in Biomedical Fields
Rui-Xia LIU ; Jing ZHANG ; Xiao LI ; Yi LIU ; Long HUANG ; Hong-Wei HOU
Progress in Biochemistry and Biophysics 2026;53(2):293-308
Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.
3.Construction of Organoid-on-a-chip and Its Applications in Biomedical Fields
Rui-Xia LIU ; Jing ZHANG ; Xiao LI ; Yi LIU ; Long HUANG ; Hong-Wei HOU
Progress in Biochemistry and Biophysics 2026;53(2):293-308
Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.
4.Camera inversion technique in laparoscopic sphincter-preserving surgery for mid to low rectal cancer
Rui HOU ; Ganbin LI ; Xiaoyuan QIU ; Xiao ZHANG ; Guole LIN
Chinese Journal of Gastrointestinal Surgery 2025;28(6):679-683
Objective:To explore the application of the camera inversion technique in laparoscopic sphincter-preserving surgery for mid to low rectal cancer.Methods:A retrospective study with historical controls was conducted on patients with non-metastatic mid to low rectal cancer which received laparoscopic total mesorectal excision at Peking Union Medical College Hospital from January 2019 to June 2024. The experimental group (2021.7-2024.6) utilized the camera inversion technique (rotating the lens 180° to position the bevel upward and switching the system to reverse display mode for improved visualization and operative angles) during key surgical steps (such as intraoperative mobilization of the mid-to-lower rectum and anastomosis), while the control group (2019.1-2021.6) did not. Clinical data and surgical videos were collected to analyze indicators like operative time, blood loss, mesorectal integrity, surgical complications, and postoperative hospital stay.Results:A total of 624 patients with non-metastatic mid to low rectal cancer were included, including 412 males and 212 females, with an average age of 59.8 years and an average tumor distance of 5.6 cm from the anal verge. The experimental group comprised 301 patients, while the control group had 323 patients.The proportion of abdominal ISR (intersphincteric resection) was significantly higher in the experimental group [19.3% (58/301) vs. 10.2%(33/323), χ 2=10.140, P=0.001], with a reduction in operative time [(161.8±67.8) minutes vs. (150.2±68.5) minutes, t=2.134, P=0.033] and a decrease in postoperative hospital stay [(7.8±2.1) days vs. (8.3±3.4) days, t=2.003, P=0.046]. The experimental group also demonstrated advantages in intraoperative blood loss, mesorectal integrity rate, and postoperative complications such as urinary retention, though these differences were not statistically significant (all P>0.05). Conclusion:In laparoscopic surgery for mid to low rectal cancer, using camera inversion technique during distal rectum dissection and transanal anastomosis can provide better surgical field exposure, facilitate precise operations within the correct anatomical plane, and minimize collateral damage. The camera inversion technique is safe and effective.
5.Assessment of Genotoxicity of Tissue Engineered Materials Based on Improved in vivo Hepatocyte Unscheduled DNA Synthesis(UDS)Assay
Luan-luan WANG ; Li HOU ; Xiang-yu CHU ; Zi-yi YANG ; Ling-xiao SUN ; Xiao-fei WANG ; Qiu-jin QU ; Jing XU ; Zeng-xiang LIU ; Xiao-xia SUN
Progress in Modern Biomedicine 2025;25(17):2740-2748
Objective:An in vivo mammalian hepatocyte Unscheduled DNA Synthesis(UDS)test was used to evaluate the genotoxicity of Cross-linked Sodium Hyaluronate Gel and Bone Repair Materials,providing experimental evidence for establishing a UDS testing method for medical devices and materials.Methods:0.9%sodium chloride injection and cottonseed oil were used as the solvent for test materials and negative control,respectively.N-dimethylnitrosamine(NDMA)was used as the positive control for the early sampling times,and 2-acetylaminofluorene(2-AAF)was used as the positive control for the late sampling times.SD rats were administered a single dose for toxic exposure,and liver tissues were collected at 4 h and 16 h,respectively.Hepatocytes were isolated using collagenase perfusion.After labeling with 5-ethynyl-2'-deoxyuridine(EdU),and the net average fluorescence intensity(NAFI)of cell nuclei and nucleoplasm was measured by fluorescence microscope.Data from 50 cells were used to analyze the DNA repair level.Results:Compared with the negative control groups,the positive control groups(NDMA and 2-AAF)showed highly statistically significant differences in NAFI(P<0.01),indicating successful induction of DNA damage.There was no statistically significant differences between the cross-linked sodium hyaluronate gel groups,bone repair material groups and the negative control group(P>0.05),suggesting that these materials did not significantly induce DNA damage under the experimental conditions.Conclusion:This study first applied EdU labeling technology to the in vivo hepatic UDS assay,achieving non-radioactive labeling through click chemistry reactions.Under the conditions of this study,cross-linked sodium hyaluronate gel and bone repair materials did not exhibit genotoxicity.In the follow-up,the sample range can be expanded and the observation period can be prolonged to further improve the genotoxicity evaluation system of medical devices.
6.Study on the distribution of FMR1 CGG repeat numbers among 16 610 women of childbearing age in China
Yahui SHEN ; Wei HOU ; Xiaolin FU ; Manli ZHANG ; Xiaoxiao XIE ; Chunyan ZHANG ; Jiaxin BIAN ; Xiao MAO ; Juan WEN ; Chunyu LUO ; Hua JIN ; Qian ZHU ; Qingwei QI ; Yeqing QIAN ; Jing YUAN ; Yanyan ZHAO ; Ailan YIN ; Shutie LI ; Yulin JIANG ; Rui XIAO ; Yanping LU
Chinese Journal of Reproduction and Contraception 2025;45(4):398-402
Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.
7.The trend of change in insulin resistance among Chinese adults from 2010 to 2018
Chunli YE ; Limin WANG ; Yanfang ZHAO ; Xiao ZHANG ; Chun LI ; Zhenping ZHAO ; Yue HOU ; Yanmei CHEN ; Mei ZHANG
Chinese Journal of Epidemiology 2025;46(2):179-187
Objective:To investigate the trends in insulin resistance, as represented by the triglyceride-glucose index (TyG index), among Chinese adult residents from 2010 to 2018 and to explore influencing factors.Methods:China Chronic Disease and Risk Factor Surveillance was conducted in 2010, 2013, and 2018, using a multi-stage stratified cluster random sampling method across all 31 provinces (autonomous regions and municipalities) in China. This study sampled 98 712 adults in 2010, 176 534 adults in 2013, and 184 876 adults in 2018, all aged ≥18 years, totaling 406 933 participants. Individuals with a TyG index > P75 were classified as having insulin resistance. The mean TyG index and the prevalence of insulin resistance were calculated for different years, sexes, age groups, provinces (autonomous regions and municipalities), and subgroups for 2018. Linear and logistic regression models were used to test trends in means and rates over time, and multivariate logistic regression models were conducted to analyze potential factors associated with insulin resistance. All analyses were adjusted for complex sampling weights based on the study design. Results:From 2010 to 2018, the mean TyG index among Chinese adults increased from 8.44±0.63 to 8.70±0.64, with significant upward trends observed across different age groups, sexes, and urban-rural residencies (all P<0.001). The mean TyG index was higher among males, urban residents, and those aged 45-59. There were significant differences in the mean TyG indices and prevalence of insulin resistance across provinces (autonomous regions and municipalities) (all P<0.05). Higher insulin resistance prevalence was independently associated with being male, aged ≥45 years, living in urban areas, excessive alcohol consumption, and insufficient physical activity (all P<0.05). Conclusions:From 2010 to 2018, the level of insulin resistance, as indicated by the TyG index, showed an increasing trend among Chinese adults. Males, individuals aged ≥45 years, urban residents, and individuals with unhealthy lifestyles such as excessive alcohol consumption or insufficient physical activity should be the focus of efforts to prevent and control metabolic diseases related to insulin resistance.
8.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
9.Necessity of blood hemocompatibility evaluation in medical devices with indirect contact with blood
Chun-xia QIAO ; Qiu-jin QU ; Li HOU ; Zeng-lin ZHAO ; Xiang-yu CHU ; Xiao-xia SUN
Chinese Medical Equipment Journal 2025;46(8):44-49
Objective To study the need for blood compatibility evaluation of medical devices that come into indirect contact with blood in order to accurately evaluate the risk of their interaction with blood.Methods Seven medical devices with indirect contact with blood were selected as samples including extension tubes of central venous catheters,port bodies of implantable drug delivery devices,infusion sets,receiving lines of dialysis equipment,auxiliary lines of left ventricular assist devices,blood monitors and catheter holders,with high-density polyethylene as the negative control,glass beads as the positive control and blank whole blood or plasma for the blank control.Partial thromboplastin time(PTT)test,platelet count test and hematology test(white blood cell and red blood cell count)were performed by direct contact method and indirect contact method,respectively.In the direct contact method,whole blood or plasma was in direct contact with the sample;while in the indirect contact method,whole blood or plasma was not in direct contact with the extraction solution,with no direct contact with the sample.Results With the indirect contact method the ratios(expressed as a percentage)of the PTT,platelate,WBC and RBC counts of the samples,positive and negative controls to those of the blank control were all higher than those with the direct contact method,and the indirect contact method had the sensitivity lower than that of the direct contact method.Conclusion Medical devices indirectly contacting blood have low risks for causing coagulation and platelet and hematologic adverse reactions,which are suggested to be evaluated for hemolysis testing only in case of the history of safe clinical use.[Chinese Medical Equipment Journal,2025,46(8):44-49]
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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