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.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

Objective To investigate the protective effect of benzoylaconine(BAC)on H9c2 cardio-myocytes after oxygen glucose deprivation/reoxyenation(OGD/R)injury.Methods After an in vitro model of OGD/R injury was established in H9c2 cells,the cells were treated with BAC at different concentrations(0,25,50,75,100 μmol/L)to determine its optimal dose.Then,H9c2 cells were randomly divided into control group,OGD/R group,OGD/R+BAC group(75 μmol),OGD/R+LY294002 group(PI3K/Akt inhibitor),and OGD/R+LY294002+BAC group.Corre-sponding reagent kits were used to determine cell viability and LDH level,as well as the expres-sion levels of TNF-α,IL-6,IL-1β,MDA and GSH-Px in the cells.Western blotting was applied to detect the expression of the PI3K/Akt pathway proteins,as well as autophagic proteins such as LC3,Beclin1,and P62.Results Compared to the control group,the cell viability was significantly decreased,and LDH level was obviously increased in the OGD/R group(P＜0.01).Treatment of 75 μmol/L BAC significantly increased the cell viability(0.87±0.06 vs 40.49±0.06,P＜0.01)and decreased the LDH level(86.75±7.79 U/L vs 234.42±6.20 U/L,P＜0.01)when compared to the levels of the OGD/R group.OGD/R injury induced notable increases in TNF-α,IL-6,IL-1β,and MDA expression levels,while decrease of GSH-Px expression level(P＜0.01),and down-regulation of p-PI3K,p-Akt and P62 and up-regulation of LC3 Ⅱ/LC3 Ⅰ and Beclin-1(P＜0.01)when compared with the control group.Treatment of 75 μmol/L BAC increased the levels of p-PI3K,p-Akt,and P62 proteins(0.90±0.07 vs 0.58±0.04,1.02±0.02 vs 0.49±0.01,1.48±0.05 vs 0.87±0.04)and decreased those of LC3 Ⅱ/LC3 Ⅰ and Beclin-1(0.52±0.01 vs 1.24±0.04,0.12±0.01 vs 0.32±0.02)when compared with the OGD/R group(P＜0.01).Conclusions BAC attenu-ates the inflammatory response and oxidative stress of myocardial cells after OGD/R injury,regu-lates autophagy homeostasis,and reduces myocardial cell damage.Its regulatory effect on myocar-dial autophagy homeostasis may be related to the activation of the PI3K/Akt pathway.

Objective:To investigate the effects of glimepiride on cerebral edema and apoptosis in a rat model of sub-arachnoid hemorrhage(SAH).Methods:An SAH model was established in rats using the internal carotid artery punc-ture method.Low-dose glimepiride was administered via intraperitoneal injection.Neurological deficits were assessed u-sing the modified Neurological Severity Score(mNSS),and brain water content was evaluated by measuring the wet-dry weight ratio of brain tissue.Cortical tissue from the surgical side was collected to measure the mRNA expression of sul-fonylurea receptor 1(SUR1)and transient receptor potential melastatin 4(TRPM4)using RT-qPCR,while the protein expression of Bcl-2 and Bax was detected by Western blot.Results:SAH rats exhibited impaired neurological function,increased brain water content,upregulation of SUR1 and TRPM4 mRNA expression,and a decreased Bcl-2/Bax ratio.Low-dose glimepiride did not affect blood glucose levels but significantly improved neurological function and reduced cerebral edema in SAH rats.Although glimepiride had no significant effect on SUR1 and TRPM4 mRNA expression,it increased the Bcl-2/Bax ratio.Conclusion:Glimepiride alleviates cerebral edema and inhibits apoptosis in SAH model rats by suppressing the SUR1-TRPM4 channel.

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 investigate the application effect of curved incision surgery in the treatment of hammock finger tendon.Methods:45 patients with hammock finger tendon who were admitted to Pingle Orthopedics and Traumatology Hospital in Shenzhen were selected from May 2022 to May 2023,all of whom were treated with curved incision surgery.Wound healing,functional recovery and complication rate were observed after surgery.Results:In this study,45 patients with hammock finger tendon were successfully followed up for 3 to 18 months,with an average follow-up of 1 year.The results of follow-up showed that all the incisions healed in one stage,and there were no complications such as skin infection and necrosis,exposed knots and skin irritation.X-ray reexamination before and after the operation showed,no complications such as loosening of the Kirkner needle,redisplacement of bone mass and nonunion of bone.During the follow-up period,there was no significant recurrence of vertical deformity.Crawford grading showed that,35 cases were excellent,9 were good,and 1 was fair.Conclusion:Using curved incision surgery to treat hammock finger tendon,which has the advantages of less trauma,faster recovery and fewer complications,and the effect is good.

Objective:To investigate the effects of glimepiride on cerebral edema and apoptosis in a rat model of sub-arachnoid hemorrhage(SAH).Methods:An SAH model was established in rats using the internal carotid artery punc-ture method.Low-dose glimepiride was administered via intraperitoneal injection.Neurological deficits were assessed u-sing the modified Neurological Severity Score(mNSS),and brain water content was evaluated by measuring the wet-dry weight ratio of brain tissue.Cortical tissue from the surgical side was collected to measure the mRNA expression of sul-fonylurea receptor 1(SUR1)and transient receptor potential melastatin 4(TRPM4)using RT-qPCR,while the protein expression of Bcl-2 and Bax was detected by Western blot.Results:SAH rats exhibited impaired neurological function,increased brain water content,upregulation of SUR1 and TRPM4 mRNA expression,and a decreased Bcl-2/Bax ratio.Low-dose glimepiride did not affect blood glucose levels but significantly improved neurological function and reduced cerebral edema in SAH rats.Although glimepiride had no significant effect on SUR1 and TRPM4 mRNA expression,it increased the Bcl-2/Bax ratio.Conclusion:Glimepiride alleviates cerebral edema and inhibits apoptosis in SAH model rats by suppressing the SUR1-TRPM4 channel.

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 investigate the application effect of curved incision surgery in the treatment of hammock finger tendon.Methods:45 patients with hammock finger tendon who were admitted to Pingle Orthopedics and Traumatology Hospital in Shenzhen were selected from May 2022 to May 2023,all of whom were treated with curved incision surgery.Wound healing,functional recovery and complication rate were observed after surgery.Results:In this study,45 patients with hammock finger tendon were successfully followed up for 3 to 18 months,with an average follow-up of 1 year.The results of follow-up showed that all the incisions healed in one stage,and there were no complications such as skin infection and necrosis,exposed knots and skin irritation.X-ray reexamination before and after the operation showed,no complications such as loosening of the Kirkner needle,redisplacement of bone mass and nonunion of bone.During the follow-up period,there was no significant recurrence of vertical deformity.Crawford grading showed that,35 cases were excellent,9 were good,and 1 was fair.Conclusion:Using curved incision surgery to treat hammock finger tendon,which has the advantages of less trauma,faster recovery and fewer complications,and the effect is good.