Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

Chronic heart failure （CHF） is a group of complex clinical syndromes caused by abnormal changes in the structure and/or function of the heart due to various reasons， resulting in disorders of ventricular contraction and/or diastole. CHF is a condition where primary diseases such as coronary heart disease， hypertension and pulmonary heart disease recur frequently and persist for a long time， presenting blood stasis in meridians and collaterals， stagnation of water and dampness， and accumulation of Qi in collaterals. Its pathogenesis is complex and may involve myocardial energy metabolism disorders， oxidative stress responses， myocardial cell apoptosis， autophagy， inflammatory responses， etc. According to the theory of restraining hyperactivity to acquire harmony， we believe that under normal circumstances， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway functions normally， maintaining human physiological activities and energy metabolism. Under pathological conditions， the AMPK signaling pathway is abnormal， causing energy metabolism disorders， inflammatory responses， and myocardial fibrosis. Traditional Chinese medicine （TCM） can regulate the AMPK signaling pathway through multiple mechanisms， targets， and effects， effectively curbing the occurrence and development of CHF. It has gradually become a research hotspot in the prevention and treatment of this disease. Guided by the theory of TCM， our research group， through literature review， summarized the relationship between the AMPK pathway and CHF and reviewed the research progress in the prevention and control of CHF with TCM active ingredients， TCM compound prescriptions， and Chinese patent medicines via regulating the AMPK pathway. The review aims to clarify the mechanism and targets of TCM in the treatment of CHF by regulating the AMPK pathway and guide the clinical treatment and drug development for CHF.

Chronic heart failure （CHF） refers to a clinical syndrome in which the function or structure of the heart is changed due to damage to the original myocardium， resulting in reduced pumping and/or filling functions of the heart. In recent years， the mechanisms， pathways， and targets of traditional Chinese medicine （TCM） in the treatment of CHF have been continuously confirmed， and the application of TCM theories in guiding the syndrome differentiation and precise treatment of CHF is currently a research hotspot. On the basis of the syndrome differentiation and treatment in TCM， Professor LI Candong innovatively proposed the thinking of five differentiation： Disease differentiation， syndrome differentiation， pathogenesis differentiation， symptom differentiation， and individual differentiation. This article explores the clinical diagnosis and treatment of CHF from this thinking， emphasizing comprehensive syndrome differentiation， objective analysis， dynamic assessment， and individualized treatment. In terms of diagnosis， the first is to identify the disease name， cause， location， severity， and type of CHF， determine the type and its evolution， and clarify the process of transmission and transformation between deficiency and excess. Secondly， it is necessary to distinguish the authenticity， severity， primary and secondary， urgency and complexity of CHF syndromes， providing scientific guidance for syndrome differentiation and treatment. Thirdly， according to the symptoms and the principles of deficiency and excess， the physician should identify the core pathogenesis of CHF from the perspectives of Qi， blood， Yin， Yang， deficiency， stasis， phlegm， water， and toxins. Fourthly， from the macro， meso and micro levels， the physician should carefully distinguish the presence or absence， severity， authenticity， and completeness of the symptoms to guide the diagnosis and treatment process of CHF. Finally， personalized medication for CHF should be promoted based on the patient's gender， age， constitution， and living habits. In terms of treatment， based on the thinking of five differentiation， we propose that the treatment of CHF should integrate the disease and syndrome， clarify the pathogenesis， and apply precise treatment. The treatment should be people-oriented， staged， and typed， and the medication should be adjusted according to symptoms. This diagnostic and therapeutic approach is based on the holistic concept and syndrome differentiation and treatment， and combines the three causes for appropriate treatment， providing new ideas and insights for the diagnosis and treatment of CHF.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by various complications, and the exact etiology remains unclear. Treatments for SLE encompass hormone therapy, plasma exchange and immunoadsorption, and targeted biological therapies. Berbamine (BBM), a cellular immunopotentiator with diverse biological functions, has not been reported to have immunomodulatory and therapeutic effects on SLE. The mice were divided into control group, model group, positive control group, low, medium and high BBM groups. In control group, C57BL/6J wild mice received intraperitoneal injection of saline. In model group, MRL/lpr lupus mice were treated with intraperitoneal injection of saline. In positive control group, MRL/lpr lupus mice received intragastric administration of hydroxychloroquine sulfate tablets [Plaquenil, 150 mg/(kg·d)]. In BBM groups, MRL/lpr lupus mice received intragastric administration of different concentration of BBM respectively [20 mg/(kg·d), 50 mg/(kg·d), 100 mg/(kg·d)]. After 8 weeks of treatment, blood was collected from the retro-orbital venous plexus, and ELISA was used to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, antinuclear antibodies (ANA), and anti-small nuclear ribonucleoprotein/Sm (snRNP/Sm) antibodies. Spleen tissues were collected for analysis of Th1/Th2 ratio by flow cytometry. The RNA and protein of spleen were extracted, and the levels of T-box transcription factor T-bet and GATA3 (GATA binding protein 3) mRNA and protein were detected by qRT-PCR and Western blot. The proliferation of white blood cells in the blood was tested by blood routine test. The histopathological changes of kidneys of each group were detected by HE staining. Compared with the model group, the levels of ANA, anti-dsDNA, and anti-snRNP/Sm antibodies were significantly reduced in the BBM-treated groups. The Th1/Th2 ratio was significantly decreased in the model group, but reversed by BBM. Compared with the control group, T-bet expression was significantly downregulated, while GATA3 expression was significantly upregulated in the model group. After BBM intervention, T-bet expression significantly increased, while GATA3 expression decreased compared with the model group. The number of white blood cells significantly decreased in the model group, and increased in the BBM-treated groups. In the model group, the glomerular mesangial and endothelial cells showed significant hyperplasia, clear thrombus was observed in the dilated capillaries, and inflammatory cells infiltrated in the renal interstitium. In medium and high BBM groups, the infiltration of inflammatory cells and capillary thrombosis were significantly decreased. In conclusion, BBM exhibits certain immunomodulatory effects on SLE and promotes the proliferation of white blood cells.
Animals ; Lupus Erythematosus, Systemic/immunology* ; Mice ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Female ; Benzylisoquinolines/pharmacology*

Ecological cultivation is an important way for the sustainable production of traditional Chinese medicine in the context of the carbon peaking and carbon neutrality goals. Facility cultivation and simulative habitat cultivation modes have been developed and applied to develop the endangered Dendrobium huoshanense on the basis of protection. However, the differences in the greenhouse gas emissions and global warming potential of these cultivation modes remain unexplored, which limits the accurate assessment of carbon-friendly ecological cultivation modes of D. huoshanense. Greenhouse gas emission flux monitoring based on the static chamber method provides an effective way to solve this problem. Therefore, this study conducted a field experiment in the facility cultivation and simulative habitat cultivation modes at a D. huoshanense cultivation base in Dabie Mountains, Anhui Province. From April 2023 to March 2024, samples of greenhouse gases were collected every month, and the concentrations of CO_2, CH_4, and N_2O of the samples were then detected by gas chromatography. The greenhouse gas emission fluxes, cumulative emissions, and global warming potential were further calculated, and the following results were obtained.(1)The two cultivation modes of D. huoshanense showed significant differences in greenhouse gas emission fluxes, especially the CO_2 emission flux, with a pattern of facility cultivation>simulative habitat cultivation [(35.60±11.70)mg·m~(-2)·h~(-1) vs(2.10±4.59)mg·m~(-2)·h~(-1)].(2) The annual cumulative CO_2 emission flux in the case of facility cultivation was significantly higher than that of simulative habitat cultivation[(3 077.00±842.00)kg·hm~(-2) vs(221.00±332.00)kg·hm~(-2)], while no significant difference was found in annual cumulative CH_4 and N_2O emission fluxes.(3) The facility cultivation mode had a significantly higher global warming potential than the simulative habitat cultivation mode [(3 053.00±847.00)kg·hm~(-2) vs(196.00±362.00)kg·hm~(-2)]. Overall, the simulative habitat cultivation of D. huoshanense has obvious carbon-friendly characteristics compared with facility cultivation, which is in line with the concept of ecological cultivation of medicinal plants. This study is of great reference significance for the implementation and promotion of the ecological cultivation mode of D. huoshanense under carbon peaking and carbon neutrality goals.
Dendrobium/chemistry* ; Greenhouse Gases/metabolism* ; Carbon/analysis* ; Ecosystem ; Carbon Dioxide/metabolism* ; China ; Global Warming

Hypertension is a major risk factor for cardiovascular diseases. Controlling blood pressure can reduce the incidence of cardiovascular events and mortality. The patients with hypertension are mainly treated with antihypertensive drugs. For the patients who can't achieve the target blood pressure with a single drug, comprehensive treatment strategies become particularly important. Chinese patent medicines are prepared by modern extraction and processing technology based on the basic theory of traditional Chinese medicine(TCM). Due to the stable antihypertensive effect, target organ protection, and synergistic effect with western medicine, Chinese patent medicines are becoming one of the effective options for the treatment of hypertension. At present, there are many systematic reviews on the treatment of hypertension with Chinese patent medicines, which makes it difficult for health policy makers and health service providers to choose the best evidence for the treatment. Umbrella review can integrate multiple systematic reviews to comprehensively assess the quality of evidence and potential bias, thereby providing high-quality evidence-based medicine basis for formulating clinical guidelines and optimizing treatment strategies. In this study, the systematic reviews/Meta-analysis of Chinese patent medicines in the treatment of essential hypertension were systematically searched. Sixty-nine articles were included for the umbrella review. Literature information was extracted, and the corrected covered area(CCA) was calculated to quantitatively evaluate the overlap degree of original studies in systematic reviews/Meta-analysis. The risk of bias in systematic reviews(ROBIS) tool and Cochrane RoB tool 2.0 were used to assess the risk of bias of the included studies. A Measure Tool to Assess Systematic Reviews 2(AMSTAR 2) was used to evaluate the methodological quality of systematic reviews/Meta-analysis. The quality of evidence was evaluated based on the Grade of Recommendations Assessment, Development and Evaluation(GRADE). The results showed that the Chinese patent medicines in the categories of treating wind, resolving stasis, and reinforcing healthy Qi were effective in lowering blood pressure. The Chinese patent medicines for resolving stasis combined with conventional treatment can lower blood pressure and the levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and total cholesterol in the treatment of hypertension complicated with coronary heart disease and hypertension complicated with left ventricular hypertrophy. Moreover, the combined therapy can recover the interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass index, left ventricular end diastolic diameter, and left ventricular ejection fraction in the case of left ventricular hypertrophy. The Chinese patent medicines for resolving stasis and for replenishing Qi and restoring pulse can be used in combination with conventional treatment for hypertension complicated with arrhythmia, which can lower blood pressure while improving the outcome indicators such as the P-wave dispersion of arrhythmia, left atrial diameter, ejection fraction, heart rate, and recurrence time. Due to the heterogeneity, the efficacy evidence obtained by the umbrella review needs to be further verified through precise clinical studies and long-term follow-up.
Hypertension/physiopathology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Antihypertensive Agents/therapeutic use* ; Nonprescription Drugs/therapeutic use* ; Blood Pressure/drug effects*

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste