ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

In this study,we aim to evaluate the immunogenicity of the whole-cell proteins isolated from Mycobacterium marinum(MM).The findings of this research may provide scientific basis for the development of new candidate tuberculosis vaccines.Both MM 95014 and Mycobacteriumtuberculosis(MTB)H37Rv cells were routinely cultured and collected.After inactivation,whole-cell proteins were extracted by low-temperature ultrasonic fragmentation and mixed with DDA/Poly:IC adjuvant.The mixture was administered to BALB/c mice subcutaneously with 50 mg/mouse twice with an interval of 10 days.Blood sample was collected before each immunization,as well as 10 days after the last immunization.Blood samples and spleen tissue extracts were measured for serum antibody potency and cytokine levels by an enzyme-linked immunosorbent assay.An in vitro growth inhibition assay(MGIA)was used to assess the ability of mouse bone marrow-derived macrophages,collected after immunization with MM whole-cell proteins,to inhibit MTB growth.A MTB whole mycobacterium proteome microarray was applied to analyze the interaction between the serum in MM immunization group and MTB proteins.Our results indicated that,compared with the adjuvant group,MM whole-cell proteins induced higher levels of Th1 cytokines(IL-2,IFN-γ,IL-12,TNF-α)in the mice.The IgG and IgM antibody titers induced by MM immunization group reached 1∶608 874 and 1∶304 437,respectively.The MGIA results showed that the MM immunization group was able to significantly inhibit MTB growth in vitro.The MTB proteome microarray results indicated that there were 226 and 324 cross-proteins with IgG and IgM antibodies,respectively.This study suggested that MM whole-cell proteins can induce high levels of cellular and humoral immune responses in mice and exhibit strong inhibition of MTB growth in vitro.The results may suggest potential application value of MM whole-cell proteins as a novel candidate vaccine for tuberculosis.

Objective:To explore the cognitive characteristics, influencing factors, and treatment needs regarding biologic agents among patients with psoriasis.Methods:A cross-sectional study was conducted. Patients with psoriasis attending the Department of Dermatology, Xijing Hospital, Air Force Medical University were selected from October to December 2022, and from June to December 2023. A self-designed electronic questionnaire was used for investigation, covering demographic characteristics, psoriasis history (disease types, disease duration, previous treatments, etc.), biologics knowledge (sources of awareness, core cognitive dimensions), and treatment needs.Results:The valid questionnaire response rate reached 93.2% (439/471). The ages of enrolled patients were 35.95 ± 12.57 years, and the disease duration was 7.90 ± 3.26 years. Psoriasis vulgaris was the predominant type (363 cases, 82.69%). The overall awareness rate of biologics slightly increased from 68.62% (105/153) in 2022 to 72.38% (207/286) in 2023 ( P > 0.05). Primary information sources included new media (WeChat/internet) platforms (168 cases, 53.84%) and peer-to-peer sharing (115 cases, 36.86%), while physician counseling merely accounted for 9.29% (29 cases) ( P < 0.001). Insufficient knowledge of biologics was manifested primarily as poor awareness of comorbidities (47.60%, 209/439) and treatment monitoring protocols (22.32%, 98/439). Core concerns regarding biologic therapy included safety (73.34%, 322/439), economic burden (65.14%, 286/439), and long-term efficacy (63.55%, 279/439) ; 60.13% (264/439) of the patients expected rapid improvement of skin symptoms. As for treatment modalities, 90.20% (396/439) of the patients preferred regimens with extended dosing intervals. Conclusions:The patients with psoriasis demonstrated an imbalance in their cognitive structure regarding biologic agents. Their treatment needs exhibited multidimensional characteristics, emphasizing not only rapid clearance of skin lesions but also greater importance of treatment safety and cost-effectiveness.

40 patients with choronic periodontitis underwent periodontal basic treatment were randomly divided into 2 groups(n=20).The patients in control group used special toothpaste and toothbrush to brush their teeth after meals,those in the experimental group brushed their teeth with special toothpaste and toothbrush in the morning,evening and after meals,and wore personalized film pressing trays containing cymene care solution while sleeping at night.Gingival bleeding,periodontal pocket depth and attachment loss were ob-served after 4,6 and 10 weeks respectively.The personalized tray combined with cymbidium reduced the depth of periodontal pocket(P＜0.05)and the rate of probing bleeding sites(P＜0.05)more effectively,and showed no statistical significance in the change of attachment loss(P＜0.05).Cymene care solution is effective in the improvement of periodontal health.

Objective:To verify the efficacy of VELscope autofluorescence examination technology in the early warning of potential oral malignant diseases.Methods:80 patients with suspected dysplasia were included and underwent oral examination,visually en-hanced lesion scope(VELscope)autofluorescence examination and histopathology examination respectively,the fluorescence imaging results were compared with the histopathological results.Results:Pathological reports showed 64 cases with mild or no dysplasia,9 cases with moderate or severe dysplasia,1 case with moderate dysplasia without malignant transformation and 6 cases with cancer.The results of VELscope showed that there were 73 positive cases and negative 7 cases of fluorescence deletion.The sensitivity and specificity of VELscope were 93.75％and 9.37％respectively,and the sensitivity could reach 100％in the cancerous tissue.Con-clusion:As a non-invasive examination method,VELscope is highly sensitive but lowly specific.

OBJECTIVE: To measure and analyze the relationships among the posterior tibial slope (PTS), meniscal slope (MS), and meniscus posterior horn thickness (MPHT) of the medial and lateral tibial plateau in healthy people and patients with anteromedial osteoarthritis (AMOA) in Heilongjiang province, so as to provide reference basis for appropriate tibial osteotomy and prosthesis placement angles in knee joint surgeries. METHODS: A retrospective collection of imaging data from knee joint MRI examinations conducted prior to AMOA for various reasons was performed. A total of 103 healthy individuals (healthy group) and 30 AMOA patients (AMOA group) were included. There was no significant difference in the gender composition ratio, side, and body mass index between the two groups ( P>0.05); however, the comparison of ages between the two groups showed a significant difference ( P<0.05). The collected DICOM format image data was imported into the RadiAnt DICOM Viewer software and measured the medial PTS (MPTS), lateral PTS (LPTS), medial MS (MMS), lateral MS (LMS), medial MPHT (MMPHT), and lateral MPHT (LMPHT) with standard methods. The differences of the above indexes between the two groups and between different genders and sides in the two groups were compared, and Pearson correlation analysis was carried out. At the same time, the measured data of healthy group were compared with the relevant literature reported in the past. RESULTS: Compared to the healthy group, the AMOA group exhibited significantly smaller MPTS and LPTS, as well as significantly greater MMPHT and LMPHT, with significant differences ( P<0.05). However, there was no significant difference in the MMS and LMS between the two groups ( P>0.05). The differences in various indicators between genders and sides within the two groups were not significant ( P>0.05). The correlation analysis and regression curves indicated that both MPTS and LPTS in the two groups were positively correlated with their respective ipsilateral MS and MPHT ( P<0.05); as PTS increased, the rate of increase in MS and MPHT tend to plateau. Compared to previous related studies, the MPTS and LPTS measured in healthy group were comparable to those of the Turkish population, exhibiting smaller values than those reported in other studies, while MMS and LMS were relatively larger, and MMPHT and LMPHT were smaller. CONCLUSION In healthy people and AMOA patients in Heilongjiang province, PTS has great individual differences, but there is no significant individual difference in MS. MPHT can play a certain role in retroversion compensation, and its thickness increase may be used as one of the indicators to predict the progression of AMOA. The above factors should be taken into account when UKA is performed, and the posterior tilt angle of tibial osteotomy should be set reasonably after preoperative examination and evaluation.
Humans ; Osteoarthritis, Knee/surgery* ; Retrospective Studies ; Tibia/pathology* ; Male ; Female ; Adult ; Menisci, Tibial/anatomy & histology* ; China ; Knee Joint/pathology* ; Magnetic Resonance Imaging ; Middle Aged ; Aged ; Osteotomy

Objective:This study aimed to integrate RNA-seq data to identify key genes associated with macrophage-ferroptosis and develop a prognostic model for hepatocellular carcinoma(HCC).Methods:We retrieved a dataset from the GEO database containing transcriptome data and clinical information for 163 samples.Macrophage-related genes were identified using WGCNA and immune infiltration analyses.Ferroptosis-related genes from the FerrDbV2 database were intersected with differentially expressed genes to obtain significant macrophage-ferroptosis-related genes.Hub genes were screened via protein interaction network construction,and key genes were identified using four machine learning algorithms.These genes exhibited significant expression differences between cancer and normal tissues and were closely linked to patient prognosis.ROC curve and KM survival analyses were performed,and expression levels were validated at the transcriptome and proteome levels.Results:Four key genes RRM2,KIF20A,PCK2,and PDK4 were identified and evaluated.RRM2 and KIF20A demonstrated high importance in classification prediction models and reliable performance in ROC and KM analyses(AUC＞0.9,P＜0.05).These genes regulate cancer cell proliferation/survival and macrophage polarization/function,influencing the tumor microenvironment and HCC progression.Conclusion:RRM2 and KIF20A regulate cancer cell proliferation and survival,modulate macrophage polarization and function,and influence the immune response in the tumor microenvironment.They can serve as prognostic biomarkers and potential immunotherapy targets for hepatocellular carcinoma.

In this study,we aim to evaluate the immunogenicity of the whole-cell proteins isolated from Mycobacterium marinum(MM).The findings of this research may provide scientific basis for the development of new candidate tuberculosis vaccines.Both MM 95014 and Mycobacteriumtuberculosis(MTB)H37Rv cells were routinely cultured and collected.After inactivation,whole-cell proteins were extracted by low-temperature ultrasonic fragmentation and mixed with DDA/Poly:IC adjuvant.The mixture was administered to BALB/c mice subcutaneously with 50 mg/mouse twice with an interval of 10 days.Blood sample was collected before each immunization,as well as 10 days after the last immunization.Blood samples and spleen tissue extracts were measured for serum antibody potency and cytokine levels by an enzyme-linked immunosorbent assay.An in vitro growth inhibition assay(MGIA)was used to assess the ability of mouse bone marrow-derived macrophages,collected after immunization with MM whole-cell proteins,to inhibit MTB growth.A MTB whole mycobacterium proteome microarray was applied to analyze the interaction between the serum in MM immunization group and MTB proteins.Our results indicated that,compared with the adjuvant group,MM whole-cell proteins induced higher levels of Th1 cytokines(IL-2,IFN-γ,IL-12,TNF-α)in the mice.The IgG and IgM antibody titers induced by MM immunization group reached 1∶608 874 and 1∶304 437,respectively.The MGIA results showed that the MM immunization group was able to significantly inhibit MTB growth in vitro.The MTB proteome microarray results indicated that there were 226 and 324 cross-proteins with IgG and IgM antibodies,respectively.This study suggested that MM whole-cell proteins can induce high levels of cellular and humoral immune responses in mice and exhibit strong inhibition of MTB growth in vitro.The results may suggest potential application value of MM whole-cell proteins as a novel candidate vaccine for tuberculosis.

Objectives:This study aims to investigate the expression changes of transient receptor potential vanilloid type 1 (TRPV1) channel and inflammatory factors in the peripheral blood of patients with schizophrenia, and to evaluate their potential value for diagnostic prediction.Methods:This cross-sectional study was conducted at Renmin Hospital of Wuhan University from September 2023 to June 2024. A total of 35 patients with schizophrenia (patient group) from the outpatient/inpatient departments and 35 age-and sex-matched healthy individuals (control group) were recruited. Psychiatric symptoms and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The between-group comparisons of the total scores of these two instruments were calculated using independent samples t-tests. Fasting peripheral blood samples were collected from all participants. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated for subsequent analysis. TRPV1 protein expression was quantified by Western blotting, while inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10), were measured using enzyme-linked immunosorbent assay (ELISA). The between-group differences in TRPV1 and inflammatory cytokines were analyzed using the analysis of covariance (ANCOVA), controlling for age and sex. Pearson correlation analysis was employed to examine relationships between continuous variables, controlling for years of education, age, and sex. The diagnostic performance of TRPV1 and inflammatory cytokines for schizophrenia was assessed using receiver operating characteristic (ROC) curve analysis. Results:Significant between-group differences were observed in BACS total and subscale scores ( t=2.57-9.72, all P<0.01). Compared with the control group, the patient group exhibits significantly decreased expression of TRPV1, IL-4, and IL-10 ( t=6.78, 2.75, 2.53, all P<0.01), increased expression of TNF-α, IL-2, and IL-6 ( t=4.08, 2.64, 2.63, all P<0.01), and an increased IL-6/IL-10 ratio ( t=3.18, P<0.01). Correlation analyses revealed that in the patient group, the TRPV1 expression level was negatively correlated with levels of TNF-α and IL-6, and positively correlated with levels of IL-4 and IL-10 ( r=-0.589, -0.234, 0.341, 0.293, all P<0.05). In the patient group, the TRPV1 expression level was negatively correlated with the negative symptom score of PANSS ( r=-0.299, P<0.05), and the IL-6 level was positively correlated with the negative symptom score, the general pathology score, and the total score of PANSS ( r=0.387, 0.356, 0.321, all P<0.05). The TRPV1 level was positively correlated with the total score of BACS in both the control group and the patient group ( r=0.144, 0.828, all P<0.01). The IL-6/IL-10 ratio was positively correlated with the total score of PANSS and negatively correlated with the total score of BACS in the patient group ( r=0.623, -0.333, all P<0.05). The area under the ROC curve for the combination of TRPV1 level and IL-6/IL-10 ratio was 0.98 (95% confidence interval=0.96 to 1.00). Conclusions:Patients with schizophrenia exhibit reduced expression levels of TRPV1 along with an imbalanced inflammatory response. The combined assessment of TRPV1 level and IL-6/IL-10 ratio has demonstrated a high predictive and diagnostic value for schizophrenia.