OBJECTIVE To screen and quantitatively analyze the quality marker （Q-Marker） associated with anti-renal fibrosis in Shenqi shenshuai mixture （SQSS）， so as to provide references for the analysis of pharmacodynamic substances and new drug transformation of SQSS. METHODS The chemical components of SQSS were characterized by untargeted metabolomics. Combined with network pharmacology， gene expression omnibus （GEO） and connectivity map （CMAP） databases， the anti-renal fibrosis Q-Markers of SQSS were screened. HPLC-MS/MS was applied to determine the contents of Q-Markers in 10 batches of SQSS. RESULTS A total of 1 319 compounds were identified from SQSS via untargeted metabolomics，and 84 active ingredients with anti-renal fibrosis activity were further screened out， such as formononetin. Nine anti-renal fibrosis Q-Markers were obtained by network pharmacology and GEO database， including berberine， quercetin， honokiol， nicotinamide， daidzein， coumarin， kaempferol， formononetin and amygdalin. The quantitative results showed that the average contents of the above components （excluding amygdalin） in 10 batches of SQSS were 2.523， 1.942， 26.848， 1.415， 0.692， 0.171， 0.374， 7.401 μg/mL， respectively. CONCLUSIONS Nine anti-renal fibrosis Q-Markers of SQSS were screened in this study， and the contents of eight among them were determined. The results can provide a basis for elucidating the pharmacodynamic material basis and promoting the new drug transformation of SQSS.

Liver cancer is one of the world's serious diseases today because of its high frequency and fatality rate, genetic differences, and limited effectiveness of late-stage therapy. Although chemotherapy, targeted therapy, immunotherapy, ablation and transarterial chemoembolisation (TACE) have improved the disease control of some patients, recurrence and acquired resistance are still common, especially for tumors that are hypoxic, nutrient-deprived, acidic-stressed, vascularly insufficient and exposed to repeated drug pressure. A bad environment will cause a change in the quality-control system and metabolism of cancer cells, and as a result, lysosomes have started to alter. In addition to the above catabolic functions of lysosomes, they also take part in autophagic flux, substrate recycling, iron and lipid metabolism, nutrient sensing, drug distribution, membrane repair and cell death signalling. Under the stress of therapy in liver cancer cells, increased lysosomal acidification and enhanced terminal degradation lead to prolonged autophagy; TFEB/TFE3 promotes the formation of new lysosomes and lysophagosomes to sequester weakly basic drugs, thereby reducing the concentration of active drugs and mitigating proteotoxicity and oxidative stress to promote cell survival. The above processes produce a lysosome-dependent resistant phenotype that is particularly relevant to sorafenib and doxorubicin and other drugs whose effectiveness can be reduced by protective autophagy or changes in intracellular location. Conversely, the same dependency on lysosomal homeostasis is also a vulnerability. Natural products and monomeric compounds derived from Chinese herbal medicines have various structures, multiple target regulation capabilities, and the potential to act on several lysosome-related nodes simultaneously. Based on the evidence in this review, it is believed that such compounds may sensitise liver cancer cells by inhibiting V-ATPase-mediated acid hydrolysis, obstructing late-stage autophagy-mediated degradation, disrupting lysosomal calcium or membrane homeostasis, causing lysosomal membrane permeabilisation, reducing compensatory lysosomal biogenesis, promoting ferritin degradation and ferroptosis, or enhancing acid-responsive intracellular delivery. Agents that impair lysosomal function and protective autophagy, compounds that convert enlarged or drug-sequestering lysosomes into lethal targets, and nanodelivery systems that exploit the acidic environment of endolysosomes to co-deliver natural products with chemotherapeutic drugs are examples. Lysosome-targeted intervention will have different effects under different circumstances; for example, inhibiting autophagy may result in an increase in cytotoxic stress in some areas, whereas overstimulation of autophagy or iron release from lysosomes may induce autophagic cell death or ferroptosis in other areas. Therefore, the design of therapy should take into account the status of the tumour microenvironment, autophagic flux, lysosomal pH, TFEB/TFE3 activity, drug sequestration capacity, ferroptosis sensitivity, dosing sequence and delivery route. This review systematically examines the lysosomal homeostasis in the microenvironment of liver cancer, the mechanisms through which lysosomal adaptation contributes to chemoresistance, and the rationale for combining natural products with standard agents such as sorafenib and doxorubicin. Based on basic lysosome biology, pharmacodynamic and delivery data have also been collected; as a result, some applications for future studies have been proposed, such as dynamic monitoring of autophagy flux, in vivo spatial measurements of lysosomal functions, rational optimisation of combination therapy timings, and safety assessments in immunocompetent liver cancer models prior to clinical translation. Translation difficulties are also evident, such as insufficient tumour selectivity, pharmacokinetic limitations, compensatory lysosomal regeneration, toxicity to normal liver and immune cells, and a lack of validated predictive biomarkers. A new way will be found to use biomarkers to divide the patient group, optimize nanoparticles for better delivery, design specific schedules for combined treatments based on the problem they cause within the cell, etc., thereby overcoming drug resistance and reducing the harm patients suffer from toxic treatments. This system can help select biomarkers and rational drug pairs for the next round of lysosome-centred precision trials.

OBJECTIVE To screen and quantitatively analyze the quality marker （Q-Marker） associated with anti-renal fibrosis in Shenqi shenshuai mixture （SQSS）， so as to provide references for the analysis of pharmacodynamic substances and new drug transformation of SQSS. METHODS The chemical components of SQSS were characterized by untargeted metabolomics. Combined with network pharmacology， gene expression omnibus （GEO） and connectivity map （CMAP） databases， the anti-renal fibrosis Q-Markers of SQSS were screened. HPLC-MS/MS was applied to determine the contents of Q-Markers in 10 batches of SQSS. RESULTS A total of 1 319 compounds were identified from SQSS via untargeted metabolomics，and 84 active ingredients with anti-renal fibrosis activity were further screened out， such as formononetin. Nine anti-renal fibrosis Q-Markers were obtained by network pharmacology and GEO database， including berberine， quercetin， honokiol， nicotinamide， daidzein， coumarin， kaempferol， formononetin and amygdalin. The quantitative results showed that the average contents of the above components （excluding amygdalin） in 10 batches of SQSS were 2.523， 1.942， 26.848， 1.415， 0.692， 0.171， 0.374， 7.401 μg/mL， respectively. CONCLUSIONS Nine anti-renal fibrosis Q-Markers of SQSS were screened in this study， and the contents of eight among them were determined. The results can provide a basis for elucidating the pharmacodynamic material basis and promoting the new drug transformation of SQSS.

Generative artificial intelligence(Gen-AI), an important branch of artificial intelligence(AI), has attracted increasing attention in medical image analysis and clinical decision support.Different from traditional discriminative models, Gen-AI can generate high-quality and diverse new data by learning the underlying distribution features of data. It exhibits unique advantages in alleviating insufficient training samples, mitigating uneven data distribution, and improving the generalization ability of models. Ophthalmology is highly dependent on multimodal imaging, making it a particularly suitable field for the application of Gen-AI. This review summarizes recent advances in major Gen-AI techniques, including generative adversarial networks, diffusion models, and large language models, and discusses their applications in ophthalmic disease screening and diagnosis, image synthesis and data augmentation, prognostic prediction, and individualized treatment planning. It also analyzes challenges in the course of clinical translation, including data quality, model credibility, ethical supervision and other issues, so as to provide references for its standardized application.

ObjectiveTo identify protein biomarkers and potential therapeutic targets associated with metabolic dysfunction-associated fatty liver disease （MAFLD） through an integrative multi-omics analysis. MethodsLarge-scale plasma protein quantitative trait locus data were integrated with MAFLD genome-wide association study data， and a proteome-wide Mendelian randomization analysis was performed. Summary data-based Mendelian Randomization （SMR）/heterogeneity in dependent instruments （HEIDI） test and colocalization analysis were used to assess significant proteins. The independent samples t-test was used for comparison of continuous data with homogeneity of variance between two groups， and the Welch-corrected t-test was used for comparison of continuous data with heterogeneity of variance. The transcriptomic validation results were compared with the Mendelian randomization results to evaluate the changing trends of gene expression， and boxplots were used to display the expression distribution of candidate genes between groups. ResultsAmong 7 130 proteins analyzed， 40 showed a causal relationship with MAFLD， among which 26 increased the risk of MAFLD and 14 exerted a protective effect against MAFLD （FDR<0.05）. Nine proteins were supported by SMR/HEIDI （P_SMR<0.05， P_HEIDI>0.05）， and 14 showed a strong colocalization signal （PPH₄>0.9）. The transcriptomic analysis identified 5 differentially expressed proteins （all P<0.05）， i.e.， adenosine diphosphate-ribosylation factor-like GTPase 2， insulin-like growth factor binding protein 2， casein kinase 1 delta （CSNK1D）， leucine-rich repeat neuronal 1， and moesin （MSN）. In vitro validation showed upregulated expression levels of MSN （1.612±0.346 vs 0.569±0.077， P<0.05）， 14-3-3 protein theta （YWHAQ） （1.267±0.126 vs 0.313±0.029， P<0.05）， and CSNK1D （0.871±0.025 vs 0.431±0.080， P<0.05） and a downregulated expression level of histone deacetylase 8 （0.637±0.059 vs 1.097±0.260， P<0.05） in the MAFLD cell model. Functional annotation showed that CSNK1D participated in circadian and metabolic regulation， YWHAQ modulated the Hippo pathway and lipid signal transduction， and MSN was associated with cytoskeletal remodeling and fibrogenic responses. ConclusionThe integrative proteogenomic analysis in this study shows that CSNK1D， YWHAQ， and MSN may be key mediators in the pathogenesis of MAFLD. These proteins have the potential to serve as novel biomarkers and therapeutic targets， providing new directions for research on disease mechanisms and the development of intervention strategies.

Virus-related lymphoma exhibits a dual nature as both a hematologic malignancy and a viral infectious disease， making it more resistant to treatment and associated with poorer prognosis. This paper analyzes the understanding and therapeutic advantages of traditional Chinese medicine （TCM） in virus-related lymphoma. It proposes a TCM-based approach centered around syndrome differentiation， using standardized measurements of the overall TCM condition， multi-omics research of hematologic tumors， and artificial intelligence technologies to identify the "pre-condition" of virus-related lymphoma. A risk warning model will be established to early identify high-risk populations with viral infections that may develop into malignant lymphoma， thereby establishing a risk warning system for virus-related lymphoma. At the same time， a TCM health management approach will be applied to manage and regulate virus-related lymphoma， interrupting its progression and forming a human-centered， comprehensive， continuous health service model. Based on this， a standardized， integrated clinical prevention and treatment decision-making model for virus-related lymphoma， recognized by both Chinese and western medicine， will be established to provide TCM solutions for primary prevention of major malignant tumors.

Objective: To investigate the distribution of traditional Chinese medicine (TCM) syndromes and syndrome elements in lymphoma, as well as the correlation between TCM syndromes and Western clinical indicators, in order to analyze associations between TCM syndromes and these indicators. Methods: From January 2023 to May 2024, 216 patients with lymphoma who met the inclusion criteria in the Department of Hematology, Third People′s Hospital Affiliated to Fujian University of Traditional Chinese Medicine were enrolled. Four diagnostic methods were applied to perform TCM syndrome differentiation and extract syndrome elements. The correlations between various syndromes and blood test indicators of lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), white blood cell (WBC), hemoglobin (Hb), platelet count (PLT), neutrophil (NEUT), immunohistochemical markers of B-cell lymphoma-6 (BCL6), B-cell lymphoma-2 (BCL2), proto-oncogene MYC, and Ki67 protein expression, Ann Arbor staging, international prognostic index (IPI) score, bone marrow infiltration, concurrent infections during chemotherapy, and post-chemotherapy bone marrow suppression rate were analyzed. Results: Five TCM syndromes, ranked by frequency, were syndromes of yin deficiency with phlegm accumulation(41.67%), qi depression with phlegm obstruction(30.56%), cold-phlegm congelation and stagnation(12.96%), phlegm-blood stasis toxin(12.04%), and lingering pathogen due to deficient vital qi(2.77%). Yin deficiency(50.93%) and phlegm(45.37%) were the more prevalent syndrome elements. The TCM syndromes were correlated with β2-MG, PLT, MYC, BCL2/MYC, Ki67 protein expression, and bone marrow infiltration (P<0.05). No statistically significant differences were observed in Ann Arbor staging or IPI score across the syndromes. Compared to the syndrome of cold-phlegm congelation and stagnation, the syndrome of qi depression with phlegm obstruction exhibited higher levels of NEUT, MYC, BCL2/MYC, and Ki67 protein expression, as well as a higher rate of post-chemotherapy bone marrow suppression (P<0.05); the syndrome of phlegm-blood stasis toxin showed higher MYC and BCL2/MYC protein expression and a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05); the syndrome of yin deficiency with phlegm accumulation demonstrated higher MYC and BCL2/MYC protein expression and bone marrow infiltration rates, whereas PLT level was lower (P<0.05); the syndrome of lingering pathogen due to deficient vital qi had higher MYC, BCL2/MYC, and Ki67 protein expression levels, as well as a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05). Compared to the syndrome of qi depression with phlegm obstruction, the syndrome of phlegm-blood stasis toxin exhibited lower Ki67 protein expression (P<0.05); the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, bone marrow infiltration rate, and rate of concurrent infections during chemotherapy, whereas PLT and NEUT levels and the rate of post-chemotherapy bone marrow suppression rate were lower (P<0.05). Compared to the syndrome of phlegm-blood stasis toxin, the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, whereas NEUT and the rate of post-chemotherapy bone marrow suppression were lower(P<0.05); the syndrome of lingering pathogen due to deficient vital qi exhibited a higher Ki67 protein expression (P<0.05). Compared to the syndrome of yin deficiency with phlegm accumulation, the syndrome of lingering pathogen due to deficient vital qi also showed a higher Ki67 protein expression(P<0.05). Conclusion The syndrome of yin deficiency with phlegm accumulation is relatively common in lymphoma. There is a correlation between TCM syndromes and Western medicine clinical indicators. The presence of heat signs in the syndromes may indicate active disease and poor prognosis, while the presence of strong pathogenic factors and weak vital qi in the syndromes may indicate a severer chemotherapy-related bone marrow suppression.

Chronic eczema is clinically characterized by pruritus and skin lesions such as macules,exudation,desquamation,and lichenification.Traditional Chinese medicine(TCM)typically attributes its pathogenesis to wind,dampness,and heat pathogens,and TCM treatment for chronic eczema focused on dispelling wind,eliminating dampness,and clearing heat.However,there were fewer reports about the treatment of accompanying emotional changes and sleep disturbances in chronic eczema patients.This paper integrated the physique-qi-spirit trinity life view with zang-fu organ differentiation,and proposed that the disorder of spleen transportation and transformation contributed to the pathological foundation of chronic eczema,while the dysfunction of heart and liver was the factor that significantly influenced disease progression after analyzing the clinical features of chronic eczema.For the treatment of chronic eczema,the establishment of strategies should consider clinical characteristics,duration of disease,and skin lesion patterns.The combination of physique-qi-spirit regulation with heart-liver-spleen treatment approaches aims to alleviate clinical symptoms,improve quality of life,and enhance therapeutic efficacy for chronic eczema patients.

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*

Heat acclimation provides cardiovascular protection in high-temperature environments through multilevel mechanisms; however, the complete molecular basis of its effects remains unclear. In this paper, we systematically review the effects of heat acclimation on blood volume, vascular function, cardiac structure, energy metabolism, and anti-stress regulation, revealing their potential mechanisms in cardiovascular adaptive protection. We also summarizes the multilevel responses induced by heat stress and heat acclimation, including the modulatory effects of heat acclimation on heat shock proteins (HSPs), hypoxia inducible factor 1 (HIF-1), and apoptotic pathways. Additionally, we highlights the comprehensive protective effects of heat acclimation across various stressors (e.g., hypoxia, heat stress). This review provides a significant physiological basis for cardiovascular disease management and sports medicine, emphasizing the potential application of heat acclimation in response to multiple stressors and supporting its role as an effective tool in cardiovascular health management and stress protection interventions.
Humans ; Acclimatization/physiology* ; Hot Temperature ; Heat-Shock Proteins/metabolism* ; Animals ; Heat-Shock Response/physiology* ; Hypoxia-Inducible Factor 1/metabolism* ; Apoptosis/physiology*