ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective To explore the bioactive components in Jiawei Xiaoyao Pills(JWXYP)and their mechanisms for alleviating depression-like behaviors.Methods The active compounds,key targets,and pathways of JWXYP were identified using TCMSP and TCMIP databases.Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress(CUMS)-induced depression groups.After modeling,the 5 model groups were treated with daily gavage of normal saline,1.8 mg/kg fluoxetine hydrochloride(positive control drug),or JWXYP at 1.44,2.88,and 4.32 g/kg.The depression-like behaviors of the rats were evaluated using behavioral tests,and pathological changes in the liver and hippocampus were examined with HE staining.The biochemical indicators in the serum and brain tissues were detected using ELISA.Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA,and gut microbiota changes were analyzed using 16S rDNA sequencing.Results Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system.In the rat models subjected to CUMS,treatment with JWXYP significantly improved body weight loss,sucrose preference and open field activities,reduced liver inflammation,alleviated structural changes in the hippocampal neurons,decreased serum levels of TNF-α,IL-1β,IL-6 and LBP,and increased 5-HT and VIP concentrations in the serum and brain tissue,and these effects were the most pronounced in the high-dose group.Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats,involving the pathways for bile acid biosynthesis and amino acid metabolism.16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.Conclusion JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters,inhibiting inflammation and oxidation,and modulating gut microbiota.

Objective To explore the prognostic value of glycolysis-related genes in colorectal cancer (CRC) patients and formulate a novel glycolysis-related prognostic risk model. Methods Single-cell and bulk transcriptomic data of CRC patients, along with clinical information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Glycolysis scores for each sample were calculated using single-sample Gene Set Enrichment Analysis (ssGSEA). Kaplan-Meier survival curves were generated to analyze the relationship between glycolysis scores and overall survival. Novel glycolysis-related subgroups were defined among the cell type with the highest glycolysis scores. Gene enrichment analysis, metabolic activity assessment, and univariate Cox regression were performed to explore the biological functions and prognostic impact of these subgroups. A prognostic risk model was built and validated based on genes significantly affecting the prognosis. Gene Set Enrichment Analysis (GSEA) was conducted to explore differences in biological processes between high- and low-risk groups. Differences in immune microenvironment and drug sensitivity between these groups were assessed using R packages. Potential targeted agents for prognostic risk genes were predicted using the Enrichr database. Results Tumor tissues showed significantly higher glycolysis scores than normal tissues, which was associated with a poor prognosis in CRC patients. The highest glycolysis score was observed in epithelial cells, within which we defined eight novel glycolysis-related cell subpopulations. Specifically, the P4HA1⁺ epithelial cell subpopulation was associated with a poor prognosis. Based on signature genes of this subpopulation, a six-gene prognostic risk model was formulated. GSEA revealed significant biological differences between high- and low-risk groups. Immune microenvironment analysis demonstrated that the high-risk group had increased infiltration of macrophages and tumor-associated fibroblasts, along with evident immune exclusion and suppression, while the low-risk group exhibited higher levels of B cell and T cell infiltration. Drug sensitivity analysis indicated that high-risk patients were more sensitive to Abiraterone, while low-risk patients responded to Cisplatin. Additionally, Valproic acid was predicted as a potential targeted agent. Conclusion High glycolytic activity is associated with a poor prognosis in CRC patients. The novel glycolysis-related prognostic risk model formulated in this study offers significant potential for enhancing the diagnosis and treatment of CRC.
Humans ; Colorectal Neoplasms/pathology* ; Glycolysis/genetics* ; Prognosis ; Transcriptome ; Tumor Microenvironment/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Kaplan-Meier Estimate

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

OBJECTIVE: To investigate the antidepressant effects of Xiaoyao Pill (XYP) by exploring its interactions with gut microbiota and tryptophan metabolism. METHODS: Utilizing network pharmacology, the functional substance groups, key targets, and pathways of XYP in the treatment of depression were identified. The chronic unpredictable mild stress (CUMS) protocol was implemented in male Sprague-Dawley rats to establish depression model. Thirty rats were randomly divided into 3 groups according to their body weight (10 for each): control, CUMS and XYP groups (1.8 g/kg). After 28-day interventions, behavioral phenotyping including sucrose preference test (SPT) and open field test (OFT) were performed. Biochemical validation encompassed enzyme-linked immunosorbent assay for serum cortisol, hematoxylin-eosin histopathology, and immunohistochemistry. Liquid chromatography-mass spectrometry was utilized to profile serum metabolites, while fecal samples underwent metagenomic sequencing for gut microbiota characterization. RESULTS: Network pharmacology studies predicted that key components can protect the nervous system by regulating inflammatory pathways through the blood-brain barrier. SPT and OFT showed that XYP treatment significantly ameliorated depressive-like behaviors (all P<0.05). XYP treatment also restored hippocampal neuronal density, increased serum neurotransmitter levels of neurotransmitters such as 5-hydroxytryptamine and vasoactive intestinal peptide, and while suppressing inflammatory markers such as tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β), and IL-6 (all P<0.05). Metagenomics revealed significant restructuring of gut microbiota, notably the regulation of Parabacteroides distasonis (P<0.05). Non-targeted metabolomics analysis showed that the level of metabolites in the tryptophan and kynurenine pathway significantly changed (variable importance in the projection >1, P<0.05), and the change of metabolic flux was significantly correlated with behavioral improvement (P<0.05). CONCLUSIONS XYP exerts antidepressant effects by increasing neurotransmitter levels, reducing inflammatory makers and modulating Parabacteroides distasonis. Through further exploration of metabolomics, we found that XYP may play a protective role in depression by regulating tryptophan metabolism.
Animals ; Tryptophan/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/blood* ; Male ; Stress, Psychological/drug therapy* ; Behavior, Animal/drug effects* ; Rats ; Chronic Disease ; Hippocampus/drug effects*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

Objective To investigate the correlation between dual-energy computed tomography angiography(CTA)parameters of carotid plaques and acute stroke events.Methods A retrospective analysis was conducted on the clinical and imaging data of patients who underwent dual-energy head and neck CTA and brain MRI scans.Utilizing the Siemens workstation(Syngo.Via VB40B),region of interest(ROI)were placed on the thickest slice of the carotid plaque in the axial plane to obtain parameters such as fat fraction(FF),virtual non-contrast(VNC)value,iodine concentration(IC),electron density(Rho),effective atomic number(Zeff),dual energy index(DEI),spectral curve,and corresponding CT values at 40 keV(40 keVHU)and 90 keV(90 keVHU).The slope of the energy spectrum curve(λ)was calculated within the 40 keV-90 keV range.Patients with acute cerebral infarction(ACI)in the ipsilateral anterior circulation territory were classified into the ACI group,while those without were classified into the non-acute cerebral infarction(NACI)(NACI group).Qualitative data were analyzed using the x2 test,and quantitative data were analyzed using the t-test.The predictive performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,and the differences between different ROC curves were compared using the DeLong test.Results A total of 72 patients were included,with 21 in the ACI group and 51 in the NACI group.The mean values of FF,Zeff,and 40 keVHU in the ACI group were greater than those in the NACI group.Statistically significant differences were observed between the groups for Zeff,DEI,40 keVHU,and λ(P＜0.05).40 keVHU demonstrated the highest predictive performance,and the AUC,sensitivity,and specificity was 0.789,81.0％,and 74.5％,respectively.A combined variable constructed through logistic regression analysis yielded an AUC,sensitivity,and specificity of 0.796,85.7％,and 70.6％,respectively,with no significant statistical differences compared to single factor variables.Conclusion Dual-energy CTA parameters of carotid plaques may aid in predicting intraplaque hemorrhage(IPH)and the occurrence of acute stroke events.