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.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Objective:To investigate the effects of prognostic nutritional index (PNI) on the readmission rate, complication rate, mortality rate and survival of patients with liver cirrhosis.Methods:From January 1, 2020 to December 31, 2022, 395 hospitalized patients with liver cirrhosis at Tianmen Hospital Affiliated to Wuhan University of Science and Technology were retrospectively enrolled. The clinical data were collected from the patients at their first hospitalization (baseline period) and re-hospitalization during follow-up period. The 18-month follow-up was divided into 4 periods, including the first period (from the 0th to the 3rd month), the second one was from the 4th to the 6th month, the third one was from the 7th to the 12th month, and the fourth one was from the 13th to the 18th month of follow-up. The prognostic value of PNI for patients with liver cirrhosis was evaluated through the receiver operating characteristic curve (ROC) of the baseline PNI. The 395 patients were divided into the low PNI group and the high PNI group based on the optimal cut-off value of PNI on the ROC. Patients readmitted during each follow-up period were divided into the PNI improvement group (PNI at follow-up -PNI at baseline>0) and the PNI non-improvement group (PNI at follow-up-PNI at baseline ≤0). Independent sample t-test, one-way analysis of variance (ANOVA), Mann-Whitney U test, chi-square test or Fisher′s exact test were used for statistical analysis. Survival curves depicting the relationship between PNI and overall survival rate of patients with liver cirrhosis were constructed using the Kaplan-Meier method. Results:The ROC analysis indicated that the optimal cut-off value of PNI at baseline was 32.65, with an area under the curve of 0.639 (95% confidence interval: 0.541 to 0.738, P=0.011), with a sensitivity of 0.567 and a specificity of 0.701. There were 269 cases in the high PNI group and 126 cases in the low PNI group. The readmission rate, complication rate and mortality rate in the low PNI group were all higher than those in the high PNI group at the first and fourth follow-up periods (32.5% (41/126) vs. 22.3% (60/269), 31.7% (40/126) vs. 20.4% (55/269), 6.3% (8/126) vs. 1.1% (3/269), 25.0% (29/116) vs. 16.2% (42/260), 25.0% (29/116) vs. 15.4% (40/260), 6.0% (7/116) vs. 1.5% (4/260)), and the differences were statistically significant ( χ2=4.72, 6.00, 6.86, 4.10, 4.95, and 4.24; P=0.030, 0.014, 0.009, 0.043, 0.026, and 0.040). The mortality rates of the PNI improvement group at the first and fourth follow-up periods were both lower than those of the PNI non-improvement group (4.3% (2/47) vs. 16.7% (9/54), 0 (0/24) vs. 23.4% (11/47)), and the differences were statistically significant ( χ2=3.99, Fisher′s exact test; P=0.046 and 0.012). There were no statistically significant difference in the incidence of complications between the PNI improvement group and the PNI non-improvement group at each follow-up period (all P>0.05). The Kaplan-Meier survival curve demonstrated that the average survival time of the high PNI group was longer than that of the low PNI group (17.54 months (95% confidence interval: 17.26 to 17.83 months) vs. 16.74 months (95% confidence interval: 16.96 to 17.52 months), and the difference was statistically significant ( χ2=9.18, P<0.001). The survival rate of the high PNI group at the 18th month of follow-up period was higher than that of the low PNI group (95.2% (256/269) vs. 86.5% (109/126), and the difference was statistically significant ( χ2=9.17, P=0.002). Conclusions:PNI has certain predictive efficacy for the survival period of patients with liver cirrhosis. Low-level PNI may increase the readmission rate, complication rate, and mortality of patients with liver cirrhosis, and shorten the survival period, indicating poor prognosis.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

Objective:To compare the etiological characteristics between influenza-like illness (ILI) cases in outpatient and emergency departments and those with severe acute respiratory infection (SARI) in Guangdong Province, hoping to provide scientific evidence for the treatment, prevention, and control of respiratory infectious diseases.Methods:Laboratory testing for multiple respiratory pathogens was conducted on 6 090 specimens collected from ILI and SARI cases in Guangdong Province from August to December 2023. Chi-square test was used to analyze the differences in positive rates. Results:The overall positive rate of respiratory pathogens was 49.5% (3 016/6 090). The positive rate was 54.5% (2 260/4 145) in ILI cases and 38.9% (756/1 945) in SARI cases. The overall positive rate was higher in ILI cases than in SARI cases across all genders and age groups, and in most cities of the province, with statistically significant differences ( P<0.05). No significant difference was found in the overall positive rate between different genders. However, the difference between different age groups was statistically significant( P<0.001), with the highest rate identified in children aged 5-14 years (57.2%, 957/1 673). The main pathogens detected in ILI cases were influenza virus, human rhinovirus/enterovirus, and Streptococcus pneumoniae, while in SARI cases they were Mycoplasma pneumoniae, human rhinovirus/enterovirus, and influenza virus. The positive rates of adenovirus, human parainfluenza virus, SARS-CoV-2, human coronavirus, influenza virus, and Streptococcus pneumoniae were significantly higher in ILI cases than in SARI cases, while the positive rate of Mycoplasma pneumoniae was significantly higher in SARI cases ( P<0.05). Moreover, ILI cases were characterized by a higher risk of coinfection compared with SARI cases, especially in males or those aged 25-59 years. Conclusions:There are differences in the detection rates and spectrum of respiratory pathogens between ILI and SARI cases in Guangdong Province. Case features should be considered when developing strategies for preventing and treating respiratory infections.

Objective:To explore the efficacy and safety of vagus nerve stimulation (VNS) combined with rehabilitation training in recovery of upper limb function in patients with ischemic stroke (IS) through Meta-analysis.Methods:Randomized controlled trials on upper limb motor dysfunction in IS patients accepted VNS published in PubMed, Web of Science, Embase, CNKI, Wanfang and VIP databases, and Chinese Biomedical Literature Database were retrieved. The retrieval period was from establishment of the databases to April 2025. Quality of the trials was assessed according to Cochrane handbook for systematic reviews of interventions (version 5.1). Two researchers independently screened the literature, extracted the data and evaluated the risk of bias of the included articles; and then, Meta-analysis was conducted by RevMan 5.4 software.Results:Eleven articles of randomized controlled trails were chosen, including 495 patients. Three articles were rated as A-level in terms of quality, and 8 were rated as B-level. Overall bias risk of the included studies was low. Results of Meta-analysis showed that compared with the control group (rehabilitation training alone), the intervention group (VNS combined with rehabilitation training) had significantly improved upper limb motor function (Fugl-Meyer assessment of upper limb motor function: standardized mean difference [ SMD]=0.77, 95% CI: 0.24-1.30, P<0.001) and activities of daily living (modified Barthel index: SMD=0.86, 95% CI: 0.56-1.16, P<0.001). Meanwhile, compared with those in the control group, incidence of adverse events ( RR=1.12, 95% CI: 0.95-1.33, P=0.170) and incidence of severe adverse events ( RR=1.67, 95% CI: 0.51-5.50, P=0.400) in the intervention group did not significantly increase. Results of subgroup analysis showed that compared with that in the control group, more significantly improved upper limb motor function was noted in patients from the non-invasive VNS intervention sub-group ( SMD=1.09, 95% CI: 0.46-1.72, P<0.001), intervention sub-group with a frequency of 5 times per week ( SMD=1.73, 95% CI: 0.58-2.87, P<0.001), and intervention sub-group with a duration of 4 weeks ( SMD=1.09, 95%CI: 0.72-1.47, P<0.001). Conclusion:VNS combined with rehabilitation training has good safety and efficacy in upper limb motor dysfunction after IS.

The aim of this study is to establish an gene editing method of Mesomycoplasma hyo-pneumoniae(Mhp)based on the homologous recombination principle.The restriction enzyme di-gestion and ligation method combined with gene synthesis were used to construct a shuttle plasmid to achieve replication in both Mhp and Escherichia coli(E.coli).The pGEM?-T vector was used as the skeleton.The oriC sequence of Mhp which can achieve the replication of the plasmid in Mhp was inserted into the vector.Sequences of the Spiroplasma promoter and puromycin resistance gene were then inserted into the above constructed plasmid to screen recombinant clones.The up-stream and downstream homologous arms of p97 were constructed to initiate homologous recombination.The recA gene of E.coli is inserted to improve the efficiency of homologous recom-bination.The obtained shuttle plasmid was then delivered into Mhp by electro-transformation or chemical transformation.A shuttle plasmid,pGEM?-Mhp-oriC-p 97,which can replicate in both Mhp and E.coli was constructed.With the transformation of this plasmid,the carried puromycin gene and recA gene can be expressed,the p97 gene can be edited.Finally,the genetically unstable p97 gene mutant was initially obtained.In this study,a tool for Mhp gene editing based on the principle of homologous recombination was established,which laid a foundation for the develop-ment of tools for studying the pathogenesis of Mhp.

The advantages of deep learning(DL)over the traditional imaging evaluation methods were introduced for tumor prognosis prediction and efficacy assessment.The research progress of DL applied in prognosis and efficacy prediction of head and neck squamous cell carcinoma was reviewed in terms of survival prediction,local recurrence and distant metastasis,cervical lymph node metastasis,therapeutic efficacy and molecular markers of tumors.The defficiencies of DL for prognosis and efficacy prediction of head and neck squamous cell carcinoma were explored,and the future research directions were envisioned.[Chinese Medical Equipment Journal,2025,46(6):97-104]

Objective: To determine the expression of melanoma-associated antigens D4(MAGED4) and SIRT7 in human glioma, and to analyze the potential effects of MAGED4 and SIRT7 on glioma cell proliferation. Methods: The MAGED4 and SIRT7 expression levels and their correlation were compared by the China glioma genome atlas(CGGA), human protein atlas(HPA), and UALCAN databases. Survival analysis, ROC curve analysis, and Cox regression analysis were used to predict the outcome of MAGED4 and SIRT 7 in glioma patients. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) signaling pathway enrichment analysis were used to explore the biological functions of MAGED4 and SIRT7 in glioma. Western blot experiment was used to investigate whether MAGED4 protein exerted its regulatory effects on the activity of the PI3K/AKT signaling pathway via SIRT7. The effect of MAGED4 on cell proliferation in glioma through SIRT7 was explored by CCK-8. Results: The analysis results of CGGA, UALCAN, and HPA databases showed that the expression levels of MAGED4 and SIRT7 in glioma tissues were higher than those in normal brain tissue, and the expression were positively correlated. Results of survival, ROC, and Cox analysis showed that high expression of MAGED4 and SIRT7 mRNA were risk factors for poor prognosis in glioma. Results of KEGG enrichment analysis showed that MAGED4 and SIRT7 were associated with the PI3K/AKT signaling in glioma, and Western blot results showed that MAGED4 activated the PI3K/AKT signaling pathway by regulating SIRT7. The CCK-8 results showed that MAGED4 promotes the proliferation of glioma cells through SIRT7. Conclusion MAGED4 and SIRT7 are highly expressed in glioma and associated with poor prognosis, and MAGED4 promotes glioma cell proliferation through activation of the PI3K/AKT signaling pathway by SIRT7.