Uveal melanoma(UM)is the most common primary intraocular malignancy in adults and arises predominantly from the choroid. Mitochondria, as essential organelles, not only fuel energy metabolism, but also orchestrate signal transduction and apoptosis. Recent studies have progressively uncovered the multifaceted roles of mitochondria in UM, including mitochondrial DNA copy-number alterations, reprogramming of mitochondria-related metabolic genes, and mitochondria-dependent autophagy. Moreover, mitochondria modulate UM progression partly through the PI3K/AKT axis. Natural compounds and small-molecule drugs that impair mitochondrial function have also shown promising activity in inducing UM cell dysfunction. These findings provide new insights into UM pathogenesis and highlight mitochondria as potential therapeutic targets.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Gentiopicroside(GPS)is the main active ingredient extracted from Gentiaceae.It has anti-inflammatory,antioxidant,analgesic,anti-fibrosis,inhibition of tumor cell proliferation and improvement of glucose and lipid metabolism.Gentiaceae shows a wide range of application prospects in the treatment of diabetes,liver diseases,bone and joint diseases and other diseases.This paper reviewed the pharmacokinetics of gentiopicrin,including its pharmacokinetic properties in different animal models,and its mechanism and targets in the treatment of diabetes mellitus and its complications,liver injury,bone and joint diseases.Studies have shown that gentiopictin exerts its therapeutic effects by regulating various signaling pathways,such as PI3K/AKT,FOXO1,PPAR-γ,NF-κB,etc.Although the current research has made some progress,there are still limitations,such as most studies focused on animal models and in vitro experiments,lack of high-quality clinical evidence-based trials support.Future studies should further explore the new targets and signal transduction pathways of gentiopicroside,improve its bioavailability,and strengthen the research of traditional Chinese medicine compounds,so as to give full play to the advantages of holistic treatment of traditional Chinese medicine.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

OBJECTIVE: To investigate the effects of the combined Yiqi Huoxue Jiedu formula (YHJF) on intestinal microbiota in elderly patients with pulmonary-derived sepsis and identify potential microbial targets. METHODS: A prospective randomized double-blind controlled trial was conducted. Elderly patients with pulmonary infection-induced sepsis admitted to the emergency department of Guangdong Provincial Hospital of Traditional Chinese Medicine (TCM), intensive care unit (ICU) of Fangcun Hospital, and ICU of Daxuecheng Hospital, from November 2020 to October 2021 were enrolled and randomized into two groups. Both groups received conventional Western medicine treatment. The observation group additionally received YHJF (composed of 15 g of Panax ginseng, 9 g of Panax notoginseng, and 3 g of Rheum palmatum, dissolved in 50 mL warm water) orally or via nasogastric tube twice daily for 7 days; while the control group received a placebo. Clinical data and fresh fecal samples were collected before treatment and on days 5-7 of treatment. Intestinal microbiota diversity and structure were analyzed via 16S rDNA sequencing and bioinformatics [α diversity, β diversity, and linear discriminant analysis effect size (LEfSe)]. RESULTS: Fifty-five patients were included (29 in the control group, 26 in the observation group). There were no significantly differences in gender, age, comorbidities, and baseline sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), acute gastrointestinal injury (AGI) classification score, and gastrointestinal failure (GIF) score between the two groups. Compared to the control group, the observation group showed significantly lower serum procalcitonin, APACHE II score, and greater reduction in GIF score by day 7. Thirty fecal samples were collected pre-treatment (baseline group), 29 post-treatment from the control group, and 26 from the observation group. Gut microbiota α diversity analysis revealed that Simpson index in the observation group and control group were significantly decreased compared to the baseline group [0.75 (0.53, 0.91), 0.81 (0.32, 0.91) vs. 0.88 (0.87, 0.89), both P < 0.05], but there was no significantly difference between the observation group and the control group. There were no significantly differences in Chao1, Ace, and Shannon indices among three groups. β diversity analysis indicated that distinct microbiota structures among three groups (R² = 0.096, P = 0.026). Species difference analysis showed that, at the phylum level, Firmicutes (53.69%), Actinobacteria (16.23%), Proteobacteria (15.39%), and Bacteroidetes (9.57%) dominated, with no significant intergroup differences. At the genus level, 38 taxa showed significant differences. Compared to the control group, the observation group exhibited increased Erysipelatoclostridium (P = 0.014) and Faecalibacterium (P = 0.013), and decreased Bacteroides (P = 0.009), Bilophila (P = 0.005), Eggerthella (P = 0.002), and Collinsella (P = 0.043). LEfSe analysis highlighted Lactobacillus salivarius, Erysipelatoclostridium, Collinsella, Cloacibacillus, and Bacteroides as key discriminators. CONCLUSION YHJF combined with conventional therapy alters intestinal microbiota structure in patients with elderly pulmonary-derived sepsis, with Bacteroides, Erysipelatoclostridium, and Collinsella identified as potential microbial targets.
Humans ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Double-Blind Method ; Sepsis/drug therapy* ; Aged ; Prospective Studies ; RNA, Ribosomal, 16S/genetics* ; Male ; Female ; Panax notoginseng ; Rheum

Objective:To investigate the mechanism of Polygonati Rhizoma-Angelicae Sinensis Radix in the treatment of prediabetes based on network pharmacology and animal experiments.Methods:The active components of Polygonati Rhizoma and Angelicae Sinensis Radix were retrieved from the TCMSP database. The potential targets of the active components were predicted using the Swiss Target Prediction database. The "drug-active component-target" network was constructed by Cytoscape 3.10 software. The disease targets were obtained from OMIM, Genecards, TTD and the U.S. National Library of Medicine. The common targets of drugs and diseases were screened by Venny 2.1.0 platform and imported into STRING database to construct the PPI network. The DAVID database was employed to perform Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on the common targets of drugs and diseases. The prediabetes model was established by feeding C57BL/6J mice with high-fat diet. 24 high-fat fed mice were divided into four groups using a random number table: the model group, Polygonati Rhizoma group, Angelicae Sinensis Radix group and Polygonati Rhizoma-Angelicae Sinensis Radix group (herb pair group), with 6 mice in each group. Another 6 normal mice were set as the normal group. Polygonati Rhizoma group was intragastrically administered with Polygonati Rhizoma granule solution at 2.055 g/kg, the Angelicae Sinensis Radix group was intragastrically administered with Angelicae Sinensis Radix granule solution at 2.055 g/kg, and the herb pair group was intragastrically administered with Polygonati Rhizoma-Angelicae Sinensis Radix herb pair at 4.11 g/kg, once daily. The model group and the normal group were intragastrically administered with an equal volume of deionized water for 10 weeks. Fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were regularly performed. After 10 weeks of intragastric administration, the levels of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting insulin (FINS) were measured; glycogen deposition in liver tissues was observed using periodic acid-Schiff (PAS); the mRNA expression levels of FGF1, FGF2, PGF, KDR, IGF1R, INSR, PI3Kca, PI3Kcb, PI3Kcg, Akt1, Akt2 and GSK-3β in liver tissues were detected by Real-time PCR; the protein expression levels of PI3K, phosphorylated (p)-Akt, Akt, p-GSK-3β and GSK-3β in liver tissues of mice were detected by Western blot.Results:205 core targets of Polygonati Rhizoma-Angelicae Sinensis Radix in the treatment of prediabetes were identified; KEGG enrichment analysis revealed that the herb pair may exert hypoglycemic effects by activating the PI3K-Akt signaling pathway. Compared with the model group, the FBG level and AUC values in the herb pair group decreased ( P<0.05), the levels of LDL-C and HDL-C decreased ( P<0.01), the FINS and HOMA-IR levels decreased ( P<0.05), the mRNA expression levels of FGF1, FGF2, PGF, KDR, IGF1R, INSR, PI3Kca, PI3Kcb, PI3Kcg, Akt1, Akt2 and GSK-3β in liver tissues were elevated significantly ( P<0.01), and the protein expression levels of PI3K/β-actin, p-Akt/Akt and p-GSK-3β/GSK-3β in liver tissues of the herb pair group significantly increased ( P<0.01). Conclusion:Polygonati Rhizoma-Angelicae Sinensis Radix may activate PI3K/Akt/GSK-3β signaling pathway by up-regulating FGF1, FGF2, PGF, etc., and affect insulin resistance, glycogen synthesis and other processes, so as to treat prediabetes.

Objective:In order to advance the upgrade of the Traditional Chinese Medicine(TCM)"preventive healthcare"project and develop high-quality TCM preventive healthcare services.Methods:Utilizing stakeholder theory to identify the stakeholders of current TCM health preservation services,and analyze the core stakeholders'interest relationships,influence,connection strength,policy impact,and the recognition degree for TCM"preventive healthcare".Results:It describes the economic connotations and current development status of TCM"preventive healthcare"services,where the core stakeholders include government and functional departments,medical insurance departments,medical institutions,medical and health technicians,and patient groups.By comparing the interest descriptions of core stakeholders,the existing problems are analyzed.Conclusion:The government should improve policy management and promote departmental collaboration.Medical insurance departments need to strengthen policy coordination and product development.Medical institutions should establish a multi-level service system,optimize the service model,improve the incentive mechanism for medical and health technicians,and enhance service capabilities.The patient group should enhance health awareness and optimize the service experience.Through the management strategy driven by interests,it can promote the high-quality development of TCM preventive treatment services and meet the health needs of the residents.

Objective:To investigate the relation between temporal expression changes of proline-rich transmembrane protein 2 ( PRRT2) gene and clinical progression of PRRT2-related paroxysmal disorders (PRPDs). Methods:A retrospective analysis was performed; 19 patients with PRPDs admitted to Department of Neurology, Second Affiliated Hospital of Guangzhou Medical University from July 2021 to July 2024 were enrolled; their clinical data, including onset age and disease progression, were collected. Using Bgee database, the PRRT2 gene expressions in different age groups were analyzed to explore their relations with clinical progression. Results:Among the 19 patients, 8 were diagnosed as having infantile convulsion with choreoathetosis (ICCA), 1 patient as having infantile convulsion, and 10 as having paroxysmal kinesigenic dyskinesia (PKD). Among patients with ICCA, the disease course was divided into two stages: in infantile period, it manifested as infantile convulsions at the onset, with an onset age of (5.75±1.03) months, ranged 4-7 months; in early childhood, no seizures were noted, enjoying a silent period and lasting for a period ranged 7-15 years; subsequently, the disease relapsed during adolescent, presenting as dyskinesia, with an onset age of (11.75±3.11) years, ranged 8-16 years. Among patients with PKD, onset age was (10.40±3.17) years, ranged 5-17 years. PRRT2 expression peaked before 1 year old, declined to the lowest level at 10 years old, and then gradually increased, reaching a second peak at 17 years old; PRRT2 expression demonstrated bimodal peaks during early childhood and adolescence. Conclusion:PRPDs progression shows a certain consistency with the temporal change of PRRT2 gene expression.