Ethnopharmacological relevance LingGui QiHua-3 decoction (LGQH-3) is a clinical formulation for heart failure with preserved ejection fraction (HFpEF) associated with fluid retention. As a derivative of Zhenwu Decoction, it embodies to the ethnopharmacological principles of warming “yang”, promoting “qi” transformation, and draining water to manage cardiorenal fluid dysregulation. However, its pharmacological underlying mechanisms remain unclear. Aim of the study This study aimed to determine whether LGQH-3 protects against HFpEF by restoring cardiorenal fluid metabolism, and to elucidate the underlying molecular mechanisms involved in coordinated cardiac and renal fluid regulation. Materials and methods HFpEF was induced in mice via high-fat diet and L-NAME administration. Mice model were evaluated by echocardiography, exercise tolerance, histopathology, and biochemical assays. Candidate pathways were identified through UHPLC-MS and network pharmacology, and subsequently validated by RT-qPCR, WB, ELISA, and immunohistochemistry. Mechanistic relevance was further examined in AC16 cardiomyocytes and HK-2 renal tubular epithelial cells using pharmacological inhibition. Results LGQH-3 improved diastolic function and exercise tolerance, attenuated cardiac hypertrophy/fibrosis and renal injury, reduced pulmonary congestion, and increased urine output. Mechanistically, LGQH-3 inhibited pathological p38 MAPK activation and associated normalized the aberrent expression of cardiac AQP4 and renal AQP2. In parallel, it restored the PCSK6/Corin axis and reactivated natriuretic peptide signaling to re-establish fluid homeostasis. The in vitro findings were consist with the in vivo results, and pharmacological inhibition of p38 MAPK further supported the critical role of the PCSK6/Corin-p38 MAPK/AQPs cascade. Conclusion LGQH-3 alleviates cardiorenal dysfunction in HFpEF by restoring fluid homeostasis through regulation of the PCSK6/Corin-p38 MAPK/AQPs network, providing a pharmacological basis for its traditional application and clinical translational potential.

Sweat is a complex biological fluid primarily responsible for thermoregulation, containing diverse organic and inorganic components derived from plasma and interstitial fluids. Its secretion is tightly regulated by hypothalamic-sympathetic pathways and reflects systemic physiological status. Recent studies reveal that sweat composition dynamically changes with various systemic diseases, providing diagnostic, mechanistic, and prognostic insights. Abnormalities in sweat components, such as electrolytes, glucose, lactate, amino acids, and proteins, mirror underlying metabolic, endocrine, immune, and neural dysregulation. This review synthesizes current evidence on how these alterations arise from specific physiological mechanisms-including transdermal diffusion, transporter-mediated secretion (e.g., GLUT2, CFTR), ductal reabsorption, and autonomic control-linking sweat gland biology to systemic homeostasis. These insights support the clinical development of sweat as a non-invasive biofluid for disease monitoring.

Background The stress hyperglycemia ratio (SHR) indicates how much glucose rises acutely relative to baseline, whereas glycemic variability (GV) captures short-term swings in glucose levels. However, the added value of their combined assessment, as well as the modulatory impact of different glucose metabolic states on their prognostic impact, remains unclear. Methods We performed a retrospective cohort analysis based on data obtained from the MIMIC-IV database. Adult critically ill patients with cerebrovascular disease were included and classified by glucose metabolic status. We calculated the SHR and GV, then grouped them by quantiles and by combined strata. Associations were evaluated using Kaplan–Meier survival analysis, multivariable Cox regression models, restricted cubic splines (RCS), subgroup analyses, and landmark analyses. Discriminative ability was compared through receiver operating characteristic curves. In addition, several machine learning models were built, key variables were selected using Boruta, and Shapley additive explanations were applied to explain the model with the highest performance. Result In total, 4,441 patients were enrolled, and the mortality rate within 28 days was 12.2%. Multivariable Cox analysis showed that higher SHR was associated with an increased risk of 28-day mortality, with the strongest association observed in the NGR group (HR 2.07, 95% CI 1.27–3.38, P = 0.004). Higher GV was also associated with increased mortality risk, mainly in the NGR group (HR 2.48, 95% CI 1.62–3.80, P < 0.001). After combined stratification, the risk gradient became clearer. Patients with both elevated SHR and increased GV showed the greatest risk (HR 1.84, 95% CI 1.43–2.37, P < 0.001). This association was even stronger in the NGR group (HR 2.87, 95% CI 1.79–4.61, P < 0.001). Landmark analysis indicated that there was no significant difference between the groups during the first 2 days following ICU admission (P = 0.130), while a significant difference emerged after 2 days (P = 0.008). In ROC analysis, the combined metric achieved a maximum AUC of 0.686 in the NGR group, whereas the best-performing machine learning model reached an AUC of 0.851. Conclusion Among critically ill patients with cerebrovascular disease, evaluating SHR together with GV enhances risk stratification for 28-day mortality.

Background In heart failure with preserved ejection fraction (HFpEF), fluid volume overload constitutes a critical factor driving disease progression. Mahuang Decoction (MHD), a traditional Chinese medicine with diaphoretic and diuretic properties, has shown potential in improving HFpEF, yet its mechanisms remain unclear. Purpose This study aimed to explore the therapeutic effects of MHD on HFpEF and elucidate the mechanisms underlying its regulation of body fluid homeostasis. Study design A HFpEF mouse model was induced by feeding male C57BL/6J mice a high-fat diet combined with Nω-nitro L-arginine methyl ester (L-NAME) for 10 weeks, then received a 2-week MHD intervention. In vitro, AC16 cardiomyocytes and HK-2 renal tubular epithelial cells were employed for further validation. Methods The effects of MHD on HFpEF were evaluated by echocardiography, lung wet-dry ratio, exercise tolerance tests, sweating response assays, serum biomarkers, histopathology, and immunofluorescence staining. Molecular mechanisms were examined in vivo and in vitro using WB, RT-qPCR, ELISA and flow cytometry. In AC16 cells, pathway involvement was further probed using pharmacological inhibition of p38 MAPK (SB203580) and proprotein convertases (dec-RVKR-cmk). Results MHD significantly attenuated fluid retention, ameliorated cardiac remodeling and diastolic dysfunction. Mechanistically, MHD inhibited activation of p38 MAPK pathway, downregulated cardiac aquaporin (AQP) 4 and renal AQP2 to limit myocardial edema and water reabsorption, and upregulated dermal AQP5 to promote transcutaneous fluid excretion. Furthermore, MHD enhanced proprotein convertase subtilisin/kexin-6 (PCSK6) and Corin expression, thereby augmenting atrial natriuretic peptide (ANP)-mediated natriuresis and vascular remodeling Conclusion MHD ameliorated HFpEF through dual mechanisms involving p38 MAPK/AQPs regulation and PCSK6/Corin/ANP signaling, providing a promising approach for targeting the fluid retention in HFpEF therapy.

BackgroundHeart failure (HF) is a leading cause of global disease burden and mortality. Accurate prognosis assessment is critical for reducing the risk of adverse events. In recent years, numerous predictive models have been developed for different HF subtypes. However, the quality of existing models varies considerably, and there remains a lack of consensus on models suitable for widespread clinical application. This study systematically reviews the current landscape of HF prediction models, analyzes their strengths and limitations, and provides guidance for future research.MethodsThis review systematically retrieved studies on prognostic prediction models for HF from databases including PubMed and Embase, with a search period spanning from the inception of each database to 19 September 2025. The risk of bias of the included studies was assessed using the prediction model risk of bias assessment tool, and the performance of the prediction models was evaluated through metrics such as the C-index and calibration.ResultsA total of 46 prediction models from 38 studies were included. According to target population classification, 14 models were developed for predicting outcomes in HF patients with reduced ejection fraction, nine models were applicable to HF patients with preserved ejection fraction, one model targeted HF patients with mildly reduced ejection fraction, and the remaining 22 were designed for all HF patients regardless of subtype. The risk of bias assessment showed that 10 models had a high risk of bias, 21 models demonstrated an unclear risk of bias, and 15 models exhibited a low risk of bias. The study systematically summarized each model's study cohort, modeling methodology, predictors, outcomes, prediction performance, presentation format, as well as strengths and limitations.ConclusionRefining the methodological processes of model construction—including optimizing study cohort selection, updating predictor screening (such as incorporating novel biomarkers, imaging indicators, and multi-omics data), improving modeling strategies, and enhancing model presentation—will contribute to the development of more accurate and clinically applicable prediction models. Such advancements hold significant potential for improving clinical outcomes in patients across all types of HF. This review provides a substantive reference for future research in this field.

To evaluate the effectiveness and safety of Qishen Yiqi Dripping Pill (QSYQ) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). This multicentre prospective cohort study was conducted at 40 centers in China. Patients with ACS after PCI entered either the QSYQ or Western medicine (WM) groups naturally based on whether they had received QSYQ before enrollment. QSYQ group received QSYQ (0.52 g, 3 times a day for 12 months) in addition to WM. The primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, and other thrombotic events. Quality of life was assessed by the Seattle Angina Questionnaire (SAQ). A total of 936 patients completed follow-up of the primary endpoint from February 2012 to December 2018. Overall, 487 patients received QSYQ and WM. During a median follow-up of 566 days (inter quartile range, IQR, 517–602), the primary endpoint occurred in 46 (9.45

BackgroundDanlou tablets (DLTs) have been widely used to treat coronary heart disease in China. However, the benefits associated with DLT for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in routine practice require further investigation.PurposeTo investigate the effectiveness of DLT in patients with ACS undergoing PCI.MethodsThis multicenter prospective cohort study for patients with ACS undergoing PCI was conducted in 40 centers in mainland China from February 2012 to December 2018. This trial is registered under ChiCTR-OOC-14005552. Patients were assigned to either the DLT group or the conventional medicine (CM) group based on whether they used DLT prior to enrollment. The duration of DLT use (1.5 g, three times a day) was 12 months. The primary endpoint comprised of cardiac death, non-fatal myocardial infarction, and urgent revascularization. Secondary endpoint included rehospitalization owing to ACS, heart failure, stroke, and other thrombotic events. The Seattle Angina Questionnaire (SAQ) was used to assess quality of life (QOL). Primary and secondary endpoints were followed up for 36 months, and the SAQ was followed up for 12 months. The Cox proportional hazards regression model was used to analyze the independent effect of DLT on primary and secondary endpoints. Propensity score matching (PSM) analyses were performed to mitigate bias. Survival estimation was performed using Kaplan–Meier survival curves and log-rank tests in the PSM cohort, and landmark analyses were used for further evaluation of primary and secondary endpoints. Subgroup analyses and interactions confirmed the robustness of the findings. Linear mixed effects models were used to assess the QOL.ResultsOverall, 936 patients were enrolled in this cohort study, of whom 875 completed follow-up. The primary and secondary endpoints had no significantly difference between the DLT and CM groups after Cox proportional hazards models. Kaplan–Meier survival curves and log-rank tests performed in the PSM cohort also found no significant differences between the two groups on primary and secondary endpoints. However, landmark analysis showed significant benefit in the primary endpoint for the DLT group after 200 days (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.22–0.93, P = 0.03). Landmark analysis also showed a significant benefit in the secondary endpoint in the DLT group within 200 days (HR 0.33, 95% CI 0.15–0.73, P = 0.006). Moreover, DLT improves the SAQ summary score, and scores in the physical limitation, treatment satisfaction, and disease perception domains for patients with ACS undergoing PCI.ConclusionsDLT combined with conventional treatment reduced the risk of the primary endpoint after 200 days and the secondary endpoint within 200 days during the 3-year follow-up. Additionally, DLT can improve the QOL without adverse effects.

目的:系统评价中药治疗射血分数降低型心力衰竭(HFrEF)的有效性及安全性.方法:计算机检索中国知网(CNKI)、万方(WanFang)、维普(VIP)、中国生物医学文献数据库(CBM)、PubMed、the Cochrane Library 和 EMbase,检索时限为 2011 年 1 月 1日—2020年 10月 1日,纳入中药治疗 HFrEF的随机对照试验,利用 Cochrane协作网偏倚风险评价标准对纳入的文献进行质量评价,采用 RevMan 5.4.1软件对主要结局指标左室射血分数(LVEF)、临床总有效率及次要结局指标 Lee氏心力衰竭计分有效率、脑钠肽(BNP)/N末端脑钠肽前体(NT-proBNP)、6 min步行试验(6MWT)、明尼苏达心力衰竭生活质量评分(MLHFQ)进行 Meta分析.结果:共纳入 30项研究,涉及 3 291例病人.Meta分析结果显示,与对照组比较,试验组可提高临床总有效率[OR=2.85,95%CI(2.29,3.56),P<0.000 1],改善 LVEF[MD=6.75,95%CI(5.65,7.84),P<0.000 01],降低 BNP[MD=-137.94,95%CI(-203.26,-72.63),P<0.000 01]、NT-proBNP水平[MD=-302.25,95%CI(-412.26,-192.24),P<0.000 01],提高 6MWT[MD=64.93,95%CI(51.88,77.97),P<0.000 01]、MLHFQ[MD=-6.78,95%CI(-8.56,-5.01),P<0.000 01]、Lee氏心力衰竭计分有效率[OR=3.08,95%CI(1.78,5.35),P<0.000 1].结论:现有证据表明,中西医结合治疗可提高HFrEF病人临床疗效、LVEF,降低BNP、NT-proBNP水平,提高生活质量及运动耐力,且安全性较高.

Pre-heart failure with preserved ejection fraction (Pre-HFpEF) is a critical link to the development of heart failure with preserved ejection fraction (HFpEF). Early recognition and early intervention of pre-HFpEF will halt the progression of HFpEF. This article addresses the concept proposal, development, and evolution of pre-HFpEF, the mechanisms and risks of pre-HFpEF, the screening methods to recognize pre-HFpEF, and the treatment of pre-HFpEF. Despite the challenges, we believe more focus on the topic will resolve more problems.

Objective Heart failure with preserved ejection fraction (HFpEF), an increasing public health concern, is increasing in prevalence and is associated with an elevated risk of hospitalization and mortality. Currently, data on the clinical application value of left ventricular global longitudinal strain (LV GLS) in HFpEF are contradictory. Therefore, we performed the following meta-analysis to appraise the diagnostic and prognostic value of LV GLS in HFpEF.Methods PubMed, Medline, Scopus, and Web of Science were retrieved exhaustively from their inception until December 20, 2022, to obtain literature assessing the diagnostic and prognostic value of LV GLS in HFpEF.Results Forty-one studies (including 14,543 patients) published from 2008 to 2022 were included. The results of the meta-analysis were as follows: First, the LV GLS values in HFpEF patients were significantly lower than in healthy individuals (SMD:1.21; 95% CI (0.94, 1.47), p<0.00001, I2=85%; P<0.00001), but substantially higher than in HErEF patients (SMD: -2.03; 95% CI (−2.23, -1.72), p<0.00001, I2=92%; P<0.00001). Second, the pooled diagnostic parameters of LV GLS for HFpEF were as follows: sensitivity, 0.77 (95% CI: 0.71–0.82); specificity, 0.66 (95% CI: 0.58–0.74); DOR, 7.53 (95% CI: 3.19–17.74); AUC for the SROC, 0.81 (95% CI: 0.79–0.87). Finally, the low LV GLS values were correlated with a higher risk of all-cause death (HR: 1.12; 95% CI: 1.01-1.25; p=0.000, I2=84%; P = 0.031) in HFpEF patients.Conclusions LV GLS is impaired in HFpEF patients despite a normal left ventricular ejection fraction, indicating the existence of mild LV contractile dysfunction. Moreover, LV GLS might be an auxiliary indicator for diagnosing HFpEF and predicting all-cause death in HFpEF patients.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementNo### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll relevant data are within the paper.

Heart failure with preserved ejection fraction (HFpEF) represents a multifaceted syndrome related to complex pathologic mechanisms. Sacubitril/valsartan (Sac/val) has demonstrated therapeutic efficacy in HFpEF treatment. However, additional research is required to elucidate its pharmacological mechanisms. Accordingly, this study aimed to explore the potential therapeutic effects of Sac/val in HFpEF rats and the underlying molecular mechanisms. In this study, rats with HFpEF were induced by subjecting spontaneously hypertensive rats to a diet rich in fats, salts, and sugars, along with administering streptozotocin. Subsequently, they were administered Sac/val at a daily dosage of 18 mg/kg. Finally, cardiac structure and function were assessed using echocardiography; Hematoxylin and eosin staining and Masson's trichrome staining were employed to evaluate the pathological changes; Quantitative real-time polymerase chain reaction and Western blot analysis were conducted to determine the expression of pertinent mRNA and proteins. Sac/val treatment attenuated left ventricular (LV) remodeling and diastolic dysfunction in HFpEF rats, possibly related to its anti-inflammatory, anti-hypertrophic, and anti-fibrotic efficacy. Mechanistically, Sac/val might inhibit inflammation by down-regulating cell adhesion molecule (intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial cell adhesion molecule-1 (VCAM-1)) expression. Additionally, it blocked the phosphorylation of glycogen synthase kinase 3β (GSK-3β) to prevent cardiomyocyte hypertrophy. Furthermore, it effectively suppressed myocardial fibrosis by inhibiting the transforming growth factor-beta1 (TGF-β1)/Smads pathway. Our findings suggest that Sac/val improved LV remodeling and diastolic dysfunction, potentially attributed to its anti-inflammatory, anti-hypertrophic, and anti-fibrotic effects. These results provide a sound theoretical rationale for the clinical application of Sac/val in patients with HFpEF.

Aiming at the common problem of heart failure with preserved ejection fraction（HFpEF） in the cardiovascular field, from the perspective of "Sanjiao Qi movement",combining the clinical manifestations of HFpEF at different stages, it is proposed to analyze the early, middle and late stages of HFpEF dynamically according to dysfunctional gasification of upper, middle and lower Jiao, and put forward the treatment plan: dispersing the upper Jiao in the early stage, unblocking the middle Jiao in the middle stage, warming the lower Jiao in the late stage, dredging Sanjiao in the acute stage. It analyzed the pathogenesis of HFpEF from "Sanjiao Qi movement",which could dynamically reveal the location, nature and trend of disease in different stages and guide the clinical treatment more effectively and accurately.

目的 观察复方芪丹方对高血压和糖尿病致射血分数保留心力衰竭(HFpEF)模型大鼠心脏功能及糖脂代谢的影响.方法 选择SPF级 14 周龄自发性高血压大鼠(SHR),持续高脂高糖饲料喂养 16 周,高脂高糖饲料喂养 2 周后腹腔注射 1%链脲佐菌素(25 mg/kg)复制高血压、糖尿病致HFpEF大鼠模型.将大鼠按随机数字表法分为HFpEF模型组、阳性药物对照组[沙库巴曲缬沙坦钠(诺欣妥)组,给予诺欣妥 18 mg/kg]、复方芪丹方低剂量组(芪丹低剂量组,给予复方芪丹方含生药 4.90 g/kg)、复方芪丹方高剂量组(芪丹高剂量组,给予复方芪丹方含生药 9.80 g/kg);另设SHR模型组(SHR组,给予等体积纯净水)和正常对照组[Wistar-Kyoto(WKY)组,给予等体积纯净水].灌胃 8 周后采用超声评估大鼠心脏功能;心脏超声结束后,腹主动脉取血,分离血浆和血清,检测空腹血糖(FPG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)水平和糖化血清蛋白(GSP)、胰岛素(FINS)、瘦素(LEP)、胰高血糖素(GCG)、C肽,以及血浆心钠素(ANP)和脑钠肽(BNP)水平;同时取心脏组织行苏木素-伊红(HE)染色,光镜下观察心肌组织病理学变化.结果 与WKY组比较,HFpEF模型组舒张早期二尖瓣血流峰值速度(E)、二尖瓣心房收缩期最大血流(A)、E/舒张早期二尖瓣环心肌运动速度(e')比值、ANP、BNP、TC、TG、LDL-C、FPG、GSP、C肽、GCG、LEP、FINS、IRI水平均明显升高,e'、左房射血分数(LAEF)、胰岛素敏感指数(ISI)自然对数(IAI)均明显降低(均P＜0.05);与HFpEF模型组比较,芪丹低、高剂量组E、A、E/e'比值、TC、FPG、C肽、GCG、LEP、FINS、IRI水平均明显降低[E(m/s):0.78±0.13、0.81±0.15 比 1.02±0.15,A(m/s):0.46±0.06、0.43±0.04 比 0.67±0.07,E/e'比值:15.34±4.58、15.01±3.56 比 24.47±6.38,TC(mmol/L):3.16±1.00、2.40±0.69 比 4.61±0.73,FPG(mmol/L):13.92±1.80、12.65±2.13比17.05±3.44,C肽(μg/L):1.84±0.42、1.46±0.42比2.75±0.70,GCG(ng/L):132.79±28.69、122.33±31.47比161.23±21.43,LEP(μg/L):5.77±1.82、5.37±1.02比9.30±1.42,FINS(pmol/L):104.13±27.65、83.57±32.62 比 133.10±32.78,IRI:10.85±3.87、7.73±3.16 比 17.19±5.80,均P＜0.05],e'和IAI明显升高[e'(m/s):5.20±0.52、5.53±0.70 比 4.30±0.62,IAI:-5.45±0.34、-5.07±0.48 比-5.88±0.45,均P＜0.05],芪丹高剂量组LAEF、左室射血分数(LVEF)均显著升高(LAEF:0.52±0.05 比 0.46±0.06,LVEF:0.82±0.05 比 0.75±0.08),ANP、BNP含量和LDL-C水平显著降低[ANP(μg/L):0.48±0.16 比 0.70±0.11,BNP(ng/L):15.87±4.18比21.08±3.23,LDL-C(mmol/L):1.33±0.72比2.47±0.86,均P＜0.05].HE染色显示,复方芪丹方可显著改善心肌细胞形态.结论 复方芪丹方可改善高血压、糖尿病致HFpEF模型大鼠的糖脂代谢,增加胰岛素敏感性,降低心房内压及心室压力,改善心肌病理形态和心脏舒张功能.

Ethnopharmacological relevance: Ling-Qui-Qi-Hua (LGQH) decoction, composed of Poria cocos (Schw.) Wolf, Cinnamomum cassia (L.) J. Presl, Paeonia veitchii Lynch, and Atractylodes macrocephala Koidz., is a compound formula derived from Ling-Gui-Zhu-Gan decoction recorded in the Treatise on Febrile and Miscellaneous. It has shown cardioprotective effects on patients or rats with heart failure with preserved ejection fraction (HFpEF). Nevertheless, the active ingredients of LGQH and its anti-fibrotic mechanism remain unknown.Aim of the study: To determine the active ingredients in LGQH decoction and verify that LGQH decoction may inhibit left ventricular (LV) myocardial fibrosis in HFpEF rats by blocking the transforming growth factor-81 (TGF-81)/Smads signaling pathway from the perspective of animal experiments.Materials and methods: First, liquid chromatography-mass spectrometry (LC-MS) technology was used to identify active components in the LGQH decoction. Secondly, a rat model of the metabolic syndrome-associated HFpEF phenotype was established and subsequently received LGQH intervention. The mRNA and protein expression of targets in the TGF-81/Smads pathway were detected by quantitative real-time polymerase chain reaction and western blot analysis. Finally, molecular docking was conducted to examine the interactions between the active ingredients in the LGQH decoction and key proteins of the TGF-81/Smads pathways.Results: According to LC-MS analysis, the LGQH decoction contained 13 active ingredients. In animal experiments, LGQH attenuated LV hypertrophy, enlargement, and diastolic function in HEpEF rats. Mechanically, LGQH not only down-regulated TGF-81, Smad2, Smad3, Smad4, a-SMA, Coll I, and Coll III mRNA expressions and TGF-81, Smad2, Smad3, P-Smad2/Smad3, Smad4, a-SMA, and Coll I protein expressions, but also upregulated Smad7 mRNA and protein expressions, which ultimately led to myocardial fibrosis. Furthermore, molecular docking confirmed that 13 active ingredients in the LGQH decoction have excellent binding activities to the critical targets of the TGF-81/Smads pathway.Conclusion: LGQH is a modified herbal formulation with multiple active ingredients. It might alleviate LV remodeling and diastolic dysfunction and inhibit LV myocardial fibrosis by blocking TGF-81/Smads pathways in HFpEF rats.

BackgroundHeart failure with preserved ejection fraction (HFpEF) represents a syndrome involving multiple pathophysiologic disorders and clinical phenotypes. This complexity makes it challenging to develop a comprehensive preclinical model, which presents an obstacle to elucidating disease mechanisms and developing new drugs. Metabolic syndrome (MetS) is a major phenotype of HFpEF. Thus, we produced a rat model of the MetS-related HFpEF phenotype and explored the molecular mechanisms underpinning the observed pathological changes.MethodsA rat model of the MetS-related HFpEF phenotype was created by feeding spontaneously hypertensive rats a high-fat-salt-sugar diet and administering streptozotocin solution intraperitoneally. Subsequently, pathological changes in the rat heart and their possible molecular mechanisms were explored.ResultsThe HFpEF rats demonstrated primary features of MetS, such as hypertension, hyperglycemia, hyperlipidemia, insulin resistance, and cardiac anomalies, such as left ventricular (LV) remodeling and diastolic impairment, and left atrial dilation. Additionally, inflammation, myocardial hypertrophy, and fibrosis were observed in LV myocardial tissue, which may be associated with diverse cellular and molecular signaling cascades. First, the inflammatory response might be related to the overexpression of inflammatory regulators (growth differentiation factor 15 (GDF-15), intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial cell adhesion molecule-1 (VCAM-1)). Secondly, phosphorylated glycogen synthase kinase 3β (GSK-3β) may stimulate cardiac hypertrophy, which was regulated by activated -RAC-alpha serine/threonine-protein kinase (AKT). Finally, the transforming growth factor-β1 (TGF-β1)/Smads pathway might regulate collagen production and fibroblast activation, promoting myocardial fibrosis.ConclusionThe HFpEF rat replicates the pathology and clinical presentation of human HFpEF with MetS and may be a reliable preclinical model that helps elucidate HFpEF pathogenesis and develop effective treatment strategies.

建立符合中医药自身规律的疗效评价体系是中医药发展的关键环节之一,近年来中医药临床疗效评价体系的构建取得了一些进展,但已经形成的评价体系或者共识并没有得到广泛应用,其主要原因与疗效评价缺乏客观化、标准化有关,此外,还与固定的疗效评价体系很难满足不同临床研究目的的需求有关.以心力衰竭(HF)临床疗效评价的发展现状为切入点,探讨以中西医病证结合思想为指导、医患共同报告的临床结局为主体、采用1+N模式构建HF中医临床疗效评价体系的具体方法、优势和难点.建立中西医病证结合的疗效评价体系可以搭建与西医疗效对接的桥梁;医患共同报告的临床结局可以体现中医以人为本的理念和整体观念;构建1+N疗效评价模式,通过固定为"1"的核心指标集满足一般的临床研究需求,搭配不同的"N"的疗效评价指标以满足不同研究目的的临床需求.构建中医HF疗效评价体系的难点在于需要统一HF的证候诊断、规范纳入的HF标准,还要区分证候疗效标准和证候诊断标准的不同.通过构建既符合中医自身特点又体现西医循证理念的1+N模式的HF疗效评价体系,以期为中医临床疗效评价的发展提供思路.

[Objective] To observe the effect of ginger-partitioned moxibustion and navel therapy on clinical symptoms and quality of life in patients with chronic heart failure. [Methods] From March 2021 to July 2021,80 patients with heart failure who were hospitalized in the cardiovascular department of our hospital were selected and divided into observation group and control group by a simple random number table method,with 40 cases in each group. The control group was treated with standard drugs for heart failure and nursing,and the observation group was treated with ginger-partitioned moxibustion on the navel on the basis of routine treatment and nursing,three columns a day,14 days as a course of treatment. The cardiac function,NT-proBNP level,traditional Chinese medicine（TCM） symptom score and the improvement of the Minnesota Heart Failure Quality of Life Scale（MLHFQ） were compared between the two groups.[Results] Both groups of patients completed the study,and the improvement of cardiac function in the observation group was better than the control group,with statistical significance（P＜0.05）;the levels of NT-proBNP in the two groups were significantly decreased after treatment（P＜0.05）,and compared with the control group,the levels of plasma NT-proBNP in the observation group were significantly decreased after treatment（P＜0.05）;the MLHFQ scale score of the observation group decreased significantly after treatment（P＜0.05）.[Conclusion] Ginger-partitioned moxibustion and navel theraphy can help improve the cardiac function,TCM symptoms and the quality of life of patients with chronic heart failure. The operation is simple and easy to operate,and worthy of clinical promotion.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.

目的 观察高脂、高盐、高糖饲料等多种危险因素结合高血压大鼠(SHR)造成认知障碍复合模型大鼠的脑组织病理形态和铁沉积的变化.方法 14周龄SPF级大鼠,每组8只,正常对照组(同遗传背景WKY大鼠,WKY组),SHR大鼠随机分4组:对照组(SHRs组)、高脂组(HFAT-SHRs组)、高盐组(HSAIL-SHRs组)、高糖-脂组(DM-SHRs组,同时给予1％的链脲佐菌素腹腔注射,以血糖含量检测在11.1 mmol/L以上作为糖尿病模型标准),WKY组和SHRs组予普通饲料,模型组分别予高脂、高盐和高糖饲料,干预32周.检测大鼠血清及脑组织铁含量的变化、光镜下观察大鼠脑组织病理形态和亚铁含量(普鲁士蓝染色)变化,ELISA法检测大鼠炎症因子水平、胆碱能水平和β-AP的含量.结果 与WKY组比较,各模型组大鼠脑组织存在细胞排列紊乱,细胞核固缩,尼氏小体减少或消失的情况,铁染色显示铁的面积增加,以DM-SHRs组更为显著;SHRs组与3个模型组大鼠乙酰胆碱(ACh)、乙酰胆碱酯酶(AChE)水平降低,白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平升高(P＜0.05,P＜0.05),血清和脑组织铁含量不同程度增加(P＜0.05,P＜0.05),组间比较无统计学意义(P＞0.05).结论 高脂、高盐和高糖因素能改变脑细胞组织形态,促使铁沉积,抑制内源性抗氧化活性,铁含量超载是高血压脑损害中导致认知障碍的可能因素之一.