The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

The philosophy of “treating disease before its onset” is a fundamental concept of traditional Chinese medicine (TCM), permeating its diagnostic and therapeutic framework, and is central to clinical practice. However, current TCM diagnostic and treatment models for the “pre-disease to disease” window period face several limitations, including the lack of comprehensive clinical parameters, difficulties in characterizing and integrating heterogeneous multimodal data, and insufficient dynamic precision in interventions and efficacy evaluations. To address these issues, guided by Professor Candong Li’s theory of TCM stateology, this study focuses on integrating objective multimodal data. It proposes a new model for personalized TCM diagnosis and treatment targeting the “pre-disease to disease” window period. This approach first proposes the idea of restructuring the conceptual framework of “symptom” and integrating multi-source heterogeneous data at macroscopic, mesoscopic, and microscopic levels to form a three-dimensional assessment indicator system. By integrating graph neural networks, convolutional neural networks, attention mechanisms, and knowledge graph-guided weight allocation, this approach enables collaborative representation, alignment, and fusion of multi-source data. Subsequently, it plans to construct a multimodal fusion model at both feature and decision levels, in order to establish mappings between indicators and TCM state elements, and to screen key indicators characterizing pathological evolution during the window period. Furthermore, it proposes a technical path for enhancing model interpretability using methods such as SHapley Additive exPlanations (SHAP) and Ablation-CAM++. Finally, with state assessment as the core, it proposes the concept of constructing a dynamic evaluation method for individualized diagnosis and treatment based on time-series data analysis using algorithms such as long short-term memory (LSTM) networks and gated recurrent units (GRUs). Moreover, a causal inference framework and semi-supervised learning strategies are introduced to enable quantitative evaluation of individual intervention effects and to provide interpretable therapeutic feedback, forming a complete technical path from data representation and fusion, weight adjustment, and interpretability analysis, to dynamic diagnosis feedback. This study aims to address deficiencies in the current TCM diagnosis and treatment model during the “pre-disease to disease” window period and to provide an operational framework for the clinical practice of TCM’s “treating disease before its onset”.

Ulcerative colitis （UC） is a chronic intestinal autoimmune disease， with clinical manifestations including abdominal pain， diarrhea， mucus and bloody stools， and its pathogenesis is complex. The classic prescription Xianglian pills （XLP） has been widely used in the clinical treatment of UC in recent years. It has few adverse reactions， good patient tolerance， and shows significant potential for clinical application. However， there is currently no comprehensive integration of evidence on its clinical research and molecular mechanisms. Through a systematic review of the clinical research and molecular mechanisms of XLP in the treatment of UC， it is found that XLP and its modified formulas， when used in combination with chemical drugs， can significantly improve the symptoms of UC patients and reduce intestinal inflammation， with superior efficacy compared to chemical drugs alone. Its mechanism of action involves regulating pan-apoptosis， immune response， signaling pathways （hypoxia-inducible factor-1α， nuclear factor-κB， etc.）， intestinal flora， and repairing the intestinal mucosal barrier. Its medicinal materials， monomers and active components can also prevent the differentiation of helper T cells 17 and restore the balance of M1/M2 cells through regulating multiple pathways such as Wnt/β -catenin and Janus kinase/signal transducer and activator of transcription， thereby reducing intestinal damage in UC.

Objective To analyze the epidemiological characteristics of mumps in Guangxi from 2012 to 2024, and to provide a scientific basis for formulating prevention and control strategies. Methods Descriptive epidemiological methods were used to analyze the incidence data of mumps in Guangxi from 2012 to 2024. Results A total of 159 873 mumps cases were reported from 2012 to 2024 in Guangxi, with an average annual reported incidence of 25.41/100 000, and no death. Mumps occurred every month, with the peak incidence mainly concentrated in April to July and October to January of the next year. There were 96,118 male cases (29.43 /100 000), and 63 755 female cases (21.07 /100 000). The male to female ratio was 1.40:1, and the difference between male and female was significant (χ²=4 321.276，P＜0.05). The annual incidence of mumps showed a certain periodic change, with the incidence peak and trough alternating every 4 - 5 years. The majority of patients were under 15 years old, accounting for 85.32% of the total number of cases. The patients mainly included students, preschool children and scattered children. The highest average incidence was in Nanning City with 40 231 cases (42.08/100 000), and the lowest was in Qinzhou City with 3 466 cases (8.16/100 000). From 2012 to 2024, a total of 210 mumps outbreaks with 4 483 cases were reported in Guangxi. Conclusion The incidence of mumps in Guangxi from 2012 to 2024 shows a periodic change and obvious seasonality. People under 15 years old are the key group at risk of mumps. The prevention and control of the epidemic of mumps in schools and kindergartens should be strengthened. It is suggested to carry out long-term monitoring of mumps as well as immune effect research, and continue to maintain a high vaccination rate of 2 doses of mumps-containing vaccines.

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

BACKGROUND: P16 inactivation is frequently accompanied by telomerase reverse transcriptase ( TERT ) amplification in human cancer genomes. P16 inactivation by DNA methylation often occurs automatically during immortalization of normal cells by TERT . However, direct evidence remains to be obtained to support the causal effect of epigenetic changes, such as P16 methylation, on cancer development. This study aimed to provide experimental evidence that P16 methylation directly drives cancer development. METHODS: A zinc finger protein-based P16 -specific DNA methyltransferase (P16-Dnmt) vector containing a "Tet-On" switch was used to induce extensive methylation of P16 CpG islands in normal human fibroblast CCD-18Co cells. Battery assays were used to evaluate cell immortalization and transformation throughout their lifespan. Cell subcloning and DNA barcoding were used to track the diversity of cell evolution. RESULTS: Leaking P16-Dnmt expression (without doxycycline-induction) could specifically inactivate P16 expression by DNA methylation. P16 methylation only promoted proliferation and prolonged lifespan but did not induce immortalization of CCD-18Co cells. Notably, cell immortalization, loss of contact inhibition, and anchorage-independent growth were always prevalent in P16-Dnmt&TERT cells, indicating cell transformation. In contrast, almost all TERT cells died in the replicative crisis. Only a few TERT cells recovered from the crisis, in which spontaneous P16 inactivation by DNA methylation occurred. Furthermore, the subclone formation capacity of P16-Dnmt&TERT cells was two-fold that of TERT cells. DNA barcoding analysis showed that the diversity of the P16-Dnmt&TERT cell population was much greater than that of the TERT cell population. CONCLUSION P16 methylation drives TERT -mediated immortalization and transformation of normal human cells that may contribute to cancer development.
Humans ; Telomerase/genetics* ; DNA Methylation/physiology* ; Fibroblasts/cytology* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Cell Line ; Cell Transformation, Neoplastic/genetics*

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

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans ; Liver/drug effects* ; Animals ; Chemical and Drug Induced Liver Injury/metabolism* ; Membrane Transport Proteins/metabolism* ; Biological Transport ; Liver Diseases/drug therapy* ; Pharmaceutical Preparations/metabolism*

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*