1.Effects of prostaglandin E2 injection into the median preoptic nucleus on body temperature in female mice and its mechanisms
Ya LI ; Yi’an SONG ; Qiaofeng JI ; Lei XU ; Jie ZHANG ; Jianhui XU ; Xiaoyu HOU
Acta Universitatis Medicinalis Anhui 2026;61(2):250-257
ObjectiveTo investigate the effects of prostaglandin E2 (PGE2) microinjection into the median preoptic nucleus (MnPO) on core body temperature in female mice, and to clarify its underlying mechanism. MethodsMicroinjection cannula were implanted into the MnPO of female mice using stereotaxic surgery.Subsequently, a multi-channel temperature acquisition system was used to simultaneously monitor rectal and brown adipose tissue (BAT) temperatures before and after intra-MnPO injections of different reagents.To investigate the thermoregulatory effects of the microinjection of PGE2 into the MnPO, 12 female C57BL/6 mice were randomly divided into a saline group (n=6) and a PGE2 group (n=6), which were injected with 0.1 μL saline and PGE2 (2.8 mmol/L), respectively.To determine whether E-series prostaglandin receptor (EP)1, EP3, and EP4 receptors mediate the thermoregulatory effects of PGE2, 15 female C57BL/6 mice were randomly divided into 3 groups (n=5 per group).Mice in each group first received an injection of 0.1 μL PGE2 (2.8 mmol/L) into the MnPO. After their body temperature returned to baseline levels, they were subsequently injected with a mixture of either EP1, EP3 or EP4 antagonist (ant) (20 mmol/L) + PGE2 (2.8 mmol/L). ResultsCompared with baseline level, the rectal temperature (P<0.01) and BAT temperature (P<0.001) of female mice both increased significantly after microinjection of PGE2 into the MnPO.Compared with the saline group, the increases in rectal temperature (P<0.001) and BAT temperature (P<0.000 1) were significantly greater in the PGE2 group of mice.Furthermore, following the injection of PGE2 into MnPO, the increase in BAT temperature was found to be significantly greater than that in rectal temperature in mice (P<0.001).Compared to the administration of PGE2 alone, co-injection of an EP3 ant + PGE2 into the MnPO of mice resulted in a significantly smaller increase in both rectal temperature (P<0.001) and BAT temperature (P<0.001).In contrast, the increases in rectal and BAT temperatures following MnPO injection of either EP1 ant + PGE2 or EP4 ant + PGE2 were not statistically significant (P>0.05). ConclusionInjection of PGE2 into the MnPO elevates BAT and core body temperature in female mice via the EP3 receptor.
2.Exploring Biological Characteristics of Rat Model of Atrial Fibrillation with Phlegm-heat and Blood Stasis Pattern Based on Metabolomics
Ailin HOU ; Yuxuan LIU ; Wenxi YU ; Xing JI ; Chan WU ; Dazhuo SHI ; Ying ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):245-255
ObjectiveTo establish an animal model of atrial fibrillation(AF) that accurately reflects the phlegm-heat and blood stasis(TRYZ) pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups:the control group, the TRYZ+AF group,the AF group and the TRYZ group, with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide(LPS) injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride(Ach-CaCl2) via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration, echocardiography evaluated left atrial dimensions and cardiac function, fully automated biochemical analyzer measured the levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C), hemoreometer analyzed the whole blood viscosity, plasma viscosity, and whole blood reduced viscosity, a coagulation analyzer assessed prothrombin time(PT), activated partial thromboplastin time(APTT), thrombin time(TT), and fibrinogen(FIB), enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of C-reactive protein(CRP), interleukin(IL)-1β, IL-6, IL-17, tumour necrosis factor(TNF)-α, matrix metalloproteinase-9(MMP-9), galectin-3(Gal-3), Collagen Ⅰ, and α-smooth muscle actin(α-SMA). Hematoxylin-eosin(HE) staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium, Western blot was employed to detect MMP-9, Collagen Ⅰ and α-SMA protein expression in myocardial tissue, real-time quantitative polymerase chain reaction(Real-time PCR) evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight, tongue color[red(R), green(G), and blue(B)], and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling, compared with the control group, rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight, dry faeces, elevated rectal temperature, dark red tongue, decreased RGB values on the tongue surface, and markedly elevated TC and LDL-C levels(P<0.05, P<0.01). The TRYZ+AF, TRYZ, and AF groups exhibited significantly decreased TT, APTT and PT, along with markedly elevated whole blood viscosity and FIB(P<0.05, P<0.01). Rats in the TRYZ+AF and AF groups exhibited AF rhythm, markedly decreased heart rate, prolonged RR intervals, enlarged left atrium, and significantly reduced ejection fraction and shortening fraction(P<0.05, P<0.01). Serum levels of CRP, IL-1β, IL-6, IL-17, TNF-α, MMP-9, Gal-3, Collagen Ⅰ, and α-SMA were elevated in rats from the TRYZ+AF, TRYZ, and AF groups compared to the control group, with the most pronounced increase observed in the TRYZ+AF group(P<0.05, P<0.01). Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF, TRYZ and AF groups was higher than that in the control group(P<0.05, P<0.01). Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9, Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups(P<0.05, P<0.01). Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group, primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome, demonstrating the pathological process where the interactions of phlegm, heat and stasis jointly trigger tremor, this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.
3.Effect of Compatibility of Effective Monomer Components of Fujin Shengjisan on Angiogenesis of HUVEC Based on Uniform Design
Xianying LU ; Jing GAO ; Dingxi BAI ; Chaoming HOU ; Wenting JI ; Huan CHEN ; Chenxi WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):9-20
ObjectiveTo determine the optimal combination of the effective monomer components "quercetin-kaempferol-abietic acid-boswellic acid" in Fujin Shengjisan for promoting diabetic ulcer (DU) wound healing through uniform design, thereby achieving the modern application of the ancient formula. MethodsFollowing the principle of "uniform design-pharmacodynamic experiment-mathematical modeling and model verification", the U14(145) uniform design table was adopted.The four monomer components of Chinese medicine were considered as the independent variables, and the proliferation rate of human umbilical vein endothelial cells (HUVECs) induced by glucose was used as the pharmacodynamic indicator. A mathematical model was constructed using DPS software to correlate the effective monomer components with the pharmacodynamic indicator. The results of uniform design were verified through CCK-8 assay, cell scratch healing, tube formation, Western blot, and Real-time PCR. ResultsAmong the 14 compatibility groups, compared with the high-glucose model group, compound compatibility group 6 showed the strongest proliferation effect and statistical significance (P<0.05). Four quadratic polynomial regression equations (Y1-Y4) were obtained through DPS modeling. Considering the model's fit, stability, and practical application, equations Y1-Y3 were selected for the follow-up verification. To ensure experiment reproducibility, group 6 was used for validation. Group 6 and equations Y1-Y3 were renamed as compound prescription ① to compound prescription④, respectively, to represent the modern application of the ancient FJSJ Powder through compatibility of monomer components. Verification experiments showed that in the CCK-8, scratch healing, and tube formation assays, the cell viability, wound healing rate, and tube formation number of HUVECs stimulated with 50 mmol·L-1 glucose were significantly reduced compared with the blank group. Moreover, the expression levels of angiogenesis-related cytokines, vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2), and CD31 secretion were significantly down-regulated. However, after intervention with compound prescriptions ① to ④, compound prescriptions ① and ③ significantly improved the biological functions of HUVECs induced by 50 mmol·L-1 glucose. Further analysis of the regression coefficients of compound prescriptions ① and ③, and the relative dose ratios of each monomer component, indicated that abietic acid, quercetin, and boswellic acid promoted angiogenesis of HUVECs in the high glucose environment, with a major effect (positive partial correlation coefficients, all > 0.9). Abietic acid and boswellic acid, as well as kaempferol and boswellic acid, promoted angiogenesis in HUVECs through interaction (positive partial correlation coefficients). ConclusionCompound prescriptions ① and ③ are the optimal combinations. They can reverse the inhibitory effects of high glucose, stimulate the proliferation, migration, and tube formation abilities of HUVECs in a high glucose environment, and promote the expression of vascular endothelial growth factorA(VEGFA), FGF2, and CD31, thereby promoting angiogenesis and facilitating DU wound healing. This finding not only confirms the good reproducibility and feasibility of compound prescriptions ① and ③ but also provides new insights and methods for the rational construction of mathematical models to further study the compatibility theory of Chinese medicine.
4.Application of a rapid rehabilitation nursing model under the theoretical framework of Rogers' Science of Unitary Human Beings in children undergoing radical operation on Hirschsprung's disease
Huabing LI ; Xianghua JI ; Xianjie GENG ; Liang ZHOU ; Chunxia ZHANG ; Guangjun HOU
Chinese Journal of Modern Nursing 2025;31(29):4020-4024
Objective:To investigate the effect of a rapid rehabilitation nursing model under the theoretical framework of Rogers' Science of Unitary Human Beings in the postoperative care of children undergoing radical operation on Hirschsprung's disease.Methods:A total of 91 children with Hirschsprung's disease and their parents who underwent radical surgery at the Children's Hospital Affiliated to Zhengzhou University (Henan Children's Hospital, Zhengzhou Children's Hospital) between January 2022 and January 2024 were selected by convenience sampling. Using a computer-generated random number table, they were randomly divided into an intervention group ( n=46) and a control group ( n=45). The control group received routine surgical nursing, while the intervention group received a rapid rehabilitation nursing model based on Rogers' theoretical framework in addition to routine care. Postoperative pain stress, anorectal function, gastrointestinal functional recovery, and parental satisfaction were compared between the two groups. Results:On the third postoperative day, the intervention group had lower scores on the FLACC scale, better anorectal function, and shorter times to first bowel sound, first anal exhaust, and first defecation than the control group. The overall parental satisfaction rate in the intervention group was 86.96% (40/46), higher than 51.11% (23/45) in the control group, and the differences were statistically significant (all P<0.05) . Conclusions:The rapid rehabilitation nursing model under the theoretical framework of Rogers' Science of Unitary Human Beings showed significant effectiveness in children undergoing radical operation on Hirschsprung's disease. It reduced postoperative pain, promoted recovery of anorectal and gastrointestinal function, and improved parental satisfaction.
5.Feasibility analysis of bilateral uterine artery embolization via distal radial artery access
Faliang DAI ; Chunhai LI ; Jun HOU ; Tianshu LIU ; Yongqi JI ; Fangfang ZHANG ; Yan JIAO ; Guoning TIAN ; Yixing LIU
Journal of Practical Radiology 2025;41(9):1549-1552
Objective To explore the feasibility and safety of bilateral uterine artery embolization(UAE)via distal radial artery access.Methods Thirty patients who underwent bilateral UAE were selected.They were divided into distal radial artery group(14 cases)and femoral artery group(16 cases).The clinical signs,puncture times,operation time,compression hemostasis time,discomfort scores,microcatheter non-use rates,and complication rates of the two groups were analyzed,the feasibility and safety of bilateral UAE via distal radial artery access were evaluated.Results The mean number of puncture times in the distal radial artery group was 1.6 times that of the femoral artery group,and the puncture pain score was 1.5 times that of the femoral artery group(P<0.05).The operation time and puncture point compression hemostasis time in the distal radial artery group were shorter than those in the femoral artery group,and the discomfort score of compression hemostasis in the distal radial artery group was lower than that in the femoral artery group(P<0.01).The proportions who did not use microcatheters in the two groups accounted for 28.6%and 6.3%,respectively,the difference was not statistically significant(P>0.05).Four patients with poor access vessels were found in the distal radial artery group(P<0.05).Conclusion Bilateral UAE via distal radial artery access is safe and feasible.
6.Effect and prognosis of thoracolumbar fracture combined with incomplete spinal cord injury on male sexual function
Gao SI ; Yuexin WANG ; Daole HU ; Guojin HOU ; Zhongwei YANG ; Yan GUO ; Zhishan ZHANG ; Hongquan JI ; Fang ZHOU ; Yun TIAN ; Yang LYU
Chinese Journal of Orthopaedics 2025;45(9):552-560
Objective:To investigate the effects of thoracolumbar vertebral fracture with incomplete spinal cord injury on male sexual function and postoperative prognosis.Methods:A retrospective review was conducted on data from 144 male patients with thoracolumbar vertebral fractures and incomplete spinal cord injuries treated between May 2009 and May 2021 in the Department of Traumatology and Orthopedics at Peking University Third Hospital. Patients ranged in age from 19 to 55 years (mean: 38.6±10.6 years) and underwent posterior incision and reduction internal fixation. The International Index of Erectile Function-5 (IIEF-5), the Premature Ejaculation Diagnostic Tool (PEDT), and the International Spinal Cord Injury Male Sexual Function Basic Data Set were used for sexual function evaluation. Based on the American Spinal Injury Association (ASIA) Spinal Cord Injury classification, changes in neurological and sexual function were assessed at the pre-injury stage, 3 months post-injury, 2 years postoperatively, and at the final follow-up. Factors influencing sexual dysfunction and recovery were analyzed. Spearman correlation analysis was used to identify factors affecting sexual function injury and recovery.Results:A total of 117 patients were included in the final analysis. Follow-up duration ranged from 26.2 to 161.7 months (mean: 74.6±40.5 months). After injury, ASIA grades were distributed as follows: 43 patients with grade B, 41 with grade C, and 33 with grade D. At the 2-year follow-up, 30 patients were grade E, 63 grade D, 19 grade C, and 5 grade B. Improvement in ASIA classification was observed in 90.6% (106/117) of patients: 79 improved by one grade, 27 by two grades, 8 remained unchanged, 1 worsened by one grade, and 2 worsened by two grades. Mean IIEF-5 scores were 19.5±6.4 pre-injury, 8.7±8.0 at 3 months post-injury, and 17.5±7.1 at 2 years postoperatively, with statistically significant differences ( F=123.247, P<0.001). Differences between 3 months post-injury vs. pre-injury and 2 years postoperatively vs. 3 months post-injury were statistically significant ( P<0.05). Mean PEDT scores were 5.3±3.1 pre-injury, 6.9±5.2 at 3 months post-injury, and 6.4±5.1 at 2 years postoperatively, with statistically significant differences ( F=17.014, P<0.001). The difference between 3 months post-injury and pre-injury was statistically significant ( P<0.05), but not between 2 years postoperatively and 3 months post-injury ( P>0.05). At the 2-year follow-up, 96 patients had their IIEF-5 classification restored to pre-injury levels, 85 restored PEDT classifications, and 83 restored both. Post-injury ASIA classification was positively correlated with a decrease in IIEF-5 score and an increase in PEDT score at 3 months post-injury ( P<0.05). Injury segment was positively correlated with the decrease in IIEF-5 score ( P<0.05). Time from injury to surgery showed a positive correlation with increased PEDT score at 3 months ( P<0.05). Post-injury ASIA grade, injury segment, time to surgery, age, intraoperative decompression, and spinal cord function recovery all showed significant correlations with changes in IIEF-5 and (or) PEDT scores at 2 years postoperatively ( P<0.05). According to the International Spinal Cord Injury Male Sexual Function Basic Data Set, the proportion of patients willing to discuss sexual issues increased from 29.9% at 3 months post-injury to 47.9% at 2 years postoperatively ( P<0.05). The proportion of patients with absent or diminished psychogenic erections remained stable (48.7% vs. 48.9%, P>0.05), while those with normal reflexive erections increased from 34.2% to 65.0% ( P<0.05). Conclusion:Thoracolumbar fractures with incomplete spinal cord injury result in reduced erectile function and increased incidence of premature ejaculation. The degree of spinal cord injury and the level of the injured segment are strongly correlated with the extent of sexual dysfunction. At the 2-year postoperative follow-up, 70.9% of patients had recovered sexual function to pre-injury levels.
7.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.
8.Construction and practice of digital medical laboratory management system: taking National Clinical Research Center for Aging and Medicine (HuaShan) as an example
Feng JI ; Jianping MAO ; Di HOU ; Wei LIU ; Huaizhou YOU ; Jing CHEN
Chinese Journal of Medical Science Research Management 2025;38(4):340-346
Objective:To address the inefficiency, safety hazards, and resource wastage in traditional medical laboratory management, this study proposes a digital laboratory information management system (LIMS) based on Total Quality Management (TQM) principles. The LIMS has been implemented at the National Center for Geriatric Medicine (Huashan) affiliated with Fudan University.Methods:Centered on the principles of " all-staff participation, whole-process control, and comprehensive management", a multidimensional management framework was developed to integrate personnel, equipment, reagents, and safety protocols. The system incorporated IoT, digital twin, and artificial intelligence (AI) technologies to achieve end-to-end digital control. A layered architecture (physical layer, data layer, model layer, etc.) was designed to integrate functional modules such as full lifecycle equipment management, dual-authentication for hazardous chemicals, and intelligent resource scheduling. A 3D digital twin model was deployed to visualize real-time laboratory operations.Results:Post-implementation, equipment reservation frequency and usage duration at the National Center increased by 114% and 124%, respectively, with no safety incidents reported. Equipment sharing utilization reached 85%, and reagent expiration waste decreased by 30%.Conclusions:The system transforms laboratory management from experience-driven to data-driven by breaking data silos and optimizing collaboration mechanisms. It provides a replicable technical pathway and practical insights for the healthcare industry′s digital transformation. However, further improvements are needed in mobile support and system scalability.
9.Advances in mechanism of dihydromyricetin in treatment of digestive system diseases
Yelin JI ; Zijuan HOU ; Chuoyi LIANG ; Xi JING ; Fengxia YAN
Chinese Journal of Pathophysiology 2025;41(11):2243-2249
Dihydromyricetin(DMY),a flavonoid compound extracted from Ampelopsis grossedentata,exhibits diverse pharmacological activities,including anti-inflammatory,antioxidant,antitumor,neuroprotective,and immuno-modulatory effects.Recent studies have demonstrated that DMY can suppress inflammatory responses and oxidative stress through multiple molecular pathways,as well as regulate bile acid metabolism and maintain intestinal microbiota balance.These actions help reduce histopathological damage,improve gastrointestinal barrier function,and alleviate the symptoms of digestive system diseases.DMY has shown significant therapeutic effects in the treatment of gastrointestinal inflamma-tion,liver diseases,and digestive tract tumors.This review systematically summarizes the mechanisms of action and thera-peutic potential of DMY in digestive system diseases,providing a scientific basis and theoretical support for its clinical ap-plication and the development of new drugs.
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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