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 meet the requirements of Good Laboratory Practice (GLP), Sichuan Institute for Drug Control (Sichuan Testing Center of Medical Devices, Sichuan Institute of Musk Deer Breeding) Safety Evaluation Center (hereinafter referred to as the center) conducts a targeted validation study to address the lack of supporting data for the specified validity periods of disinfectants, feed, and bedding during their use in laboratory animal facilities. The study summarizes practical experience in material management and provides a scientific basis for the standardized management of materials in the facility. MethodsUnder the routine operating conditions of the laboratory animal facility at the center, the disinfection efficacy of four commonly used disinfectants was confirmed using the quantitative suspension kill test, with the disinfectants tested on day 0, day 7, and at 1, 2, and 3 months after preparation and after opening; for laboratory animal feed, nutritional components, chemical contaminants, and microbial indicators were tested 7 days after opening; microbial indicators of laboratory animal corncob bedding were tested after storage for 7 days following opening and sterilization. ResultsUnder the GLP management system of our center, the disinfection efficacy log reduction values of prepared 0.04% sodium hypochlorite solution, 0.1% didecyldimethylammonium bromide solution, and 0.2% benzalkonium bromide solution were all ≥5 on days 0 and 7. The log reduction values of opened 75% ethanol were ≥5 on days 0 and 7 and at 1, 2, and 3 months after opening. All disinfectants were therefore qualified and effective. Compared with the factory inspection data, the nutritional components, chemical contaminants, and microbial indicators of SPF-grade rat and mouse maintenance feed, SPF-grade guinea pig growth and reproduction feed, conventional-grade guinea pig growth and reproduction feed, rabbit maintenance feed, and dog maintenance feed showed a slight overall downward trend but no significant differences 7 days after opening. The microbial indicators of specialized corncob bedding for SPF-grade laboratory animals stored for 7 days after opening and conventional-grade corncob bedding stored for 7 days after sterilization showed no significant fluctuations. All indicators still met the relevant requirements of GB/T 14924.2—2001 Laboratory Animals—Hygienic Standard for Formula Feeds and GB 14924.3—2010 Laboratory Animals—Nutrients for Formula Feeds. ConclusionBased on practical experience in managing the center's GLP laboratory animal facility and validation of core quality indicators, the specified validity periods of disinfectants, feed, and bedding meet the quality requirements, providing a practical reference for the standardized management of laboratory animal facilities.

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 establish and validate a multimodal MRI radiomics model based on intratumoral and peritumoral heterogeneity for prediction of spatial pattern of locally recurrent high-grade gliomas(HGGs).Methods A retrospective analysis was conducted on the clinical and imaging data of all HGGs patients who underwent maximum safe resection followed by postoperative radiotherapy combined with temozolomide treatment and experienced in local recurrence in Army Medical Center of PLA from 2012 to 2021.Two radiologists independently assessed the spatial patterns of locally recurrence HGGs through continuous follow-up MRI data,and primarily categorized the pattern into intra-resection cavity recurrence and extra-resection cavity recurrence.The subjected patients were randomly divided into a training set and a validation set in a 7∶3 ratio.In the training set,Pearson or Spearman correlation analysis and least absolute shrinkage and selection operator(LASSO)analysis were employed to screen radiomic features within the intratumoral and peritumoral regions,as well as to calculate radiomic scores.A radiomics model was established using logistic regression analysis.The performance of the model was assessed using calibration curves,Hosmer-Lemeshow goodness-of-fit test,and the area under the receiver operating characteristic curve(AUC).Validation of the model was performed in the validation set.Results A total of 121 patients with locally recurrent HGGs were enrolled in this study,including 54 in intra-resection cavity recurrence group and 67 in extra-resection cavity recurrence group.Among them,84 were assigned into the training set and 37 into the validation set.In the training set,the radiomics score for the extra-resection cavity recurrence group was 0.424(0.278,0.573),which was higher than that for the intra-resection cavity recurrence group[-0.030(-0.226,0.248),P<0.001].In the validation set,the radiomics score for the extra-resection cavity recurrence group was 0.369(0.258,0.487),which was higher than that for the intra-resection cavity recurrence group[0.277(0.103,0.322),P=0.033].The established radiomics model exhibited good calibration and performed well in predicting spatial recurrence patterns,with an AUC value of 0.844(95%CI:0.749～0.914)in the training set and 0.706(95%CI:0.534～0.844)in the validation set.Conclusion Our multimodal radiomics model combined with intratumoral and peritumoral heterogeneity can predict the spatial pattern of locally recurrent HGGs,providing a basis for individualized treatment of HGGs.

OBJECTIVE T o carry out the health economics evaluation and cost-benefit analysis of the type b Hae-mophilus influenzae(Hib)vaccination for the children who were hospitalized due to Hib infection so as to provide evidence for public health policies.METHODS The children who were diagnosed with Hib-related respiratory tract infections or meningitis and were hospitalized in respiratory medicine department,infection management depart-ment,emergency rooms and neurology department of Jiangxi Provincial Children's Hospital from Jan.1,2021 to Dec.31,2023 were recruited as the research subjects.Based on a 1∶1 matching condition,the matching variables included four items such as the same age for the admission to the hospital,same gender,same department and same grade of disease severity.The children for whom the primary immunization of Hib vaccination(including Hib monovalent vaccine and Hib-containing combination vaccine)were completed and the integrity of vaccination infor-mation could be checked out were assigned as the intervention group,while the children for whom the primary im-munization of Hib vaccination was not completed were chosen as the control group.The clinical data,vaccination data and the data such as length of hospital stay and hospitalization cost were collected from the children.The cost-benefit of the Hib vaccination among the children with Hib infection was observed.RESULTS A total of 622 hospi-talized children who were detected with Hib-positive respiratory tract infections or meningitis were enrolled in the study,and 73 children(20 children from infection management department,27 children from respiratory medi-cine department,26 children from emergency rooms)were finally included in the intervention group after matc-hing and multiple rounds of screening,73 children were chosen as the control group based on a 1∶1 matching con-dition.The male children accounted for 57.53％(42 cases)in both groups,and the female children accounted for 42.47％(31 cases)in both groups.With the respect to the length of hospital stay,it was 7.00(5.00,8.00)days in the intervention group,7.00(6.00,8.00)days in the control group(Z=-0.341,P=0.733).In terms of the hospitalization cost,it was 7 756.17(6 617.92,10 617.69)yuan in the intervention group,9 040.65(8 033.76,10 935.84)yuan in the control group(Z=-2.795,P=0.005).The cost of Hib vaccination was 343.03 yuan per capita in the intervention group,and the benefit-cost ratio(BCR)was 1∶3.74(343.03 yuan/1 284.48 yuan).CONCLUSIONS The Hib vaccination can save the hospitalization cost and has high cost effectiveness.It is sugges-ted that the Hib vaccination should be promoted and the coverage rate of Hib vaccination should be raised among the age-eligible children.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

Danggui Buxue decoction(DBD)is a classic prescription with immunomodulatory and hematopoietic effects.Previous studies have shown the DBD has potential to be used as an oral im-mune booster.However,its immunomodulatory effects and mechanism of action have not been thoroughly studied,especially the protective mechanism of immunomodulatory regulation in the state of immunosuppressive is still unclear.The aim of this study was to explore the protective mechanism of DBD in the immunosuppressive state using network pharmacology combined with animal experiments verification.The active components,core targets and signaling pathways of DBD in treating immunosuppression were obtained using network pharmacology tools.On this ba-sis,the active components of DBD were identified using HPLC-MS,and in vivo studies were con-ducted at the same time.The key active components of DBD obtained using network pharmacology included quercetin,kaempferol and formononetin.The core targets included TP53,RELA,TNF,AKT1,and IL-6.KEGG pathway enrichment analysis showed that phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT)may play an important role in the treatment of immunosuppres-sive diseases using DBD.Molecular docking confirmed that each core target had good binding activ-ity with its corresponding compounds.Animal experiments showed that after DBD intervention,the mRNA gene and protein expression of RELA,TNF,and IL-6 in the serum was significantly down-regulated.The mRNA expression of PI3K and AKT in the ileum and PI3K protein expression were also downregulated.In conclusion,DBD exerts its role in treating immunosuppressive diseases by regulating the PI3K-AKT signaling pathway.

Objective:To observe the effect of different degrees of decentration and tilt on the optical quality of the intraocular lenses (IOLs) with different focus designs.Methods:The UV 3300 PC UV-visible spectrophotometer was employed to measure the spectral transmittance of the monofocal IOL CT ASPHINA 509M (509M), bifocal IOL AT LISA 809M (809M), and trifocal IOL AT LISA Tri 839MP (839MP) within Zeiss MICS platform with a refractive power of + 20 D. The modulation transfer function (MTF) values at a spatial frequency of 50 lp/mm along with MTF curves and United States Air Force (USAF) resolution test charts for each IOL at the focal point were measured at apertures of 3.0 mm and 4.5 mm using the in vitro optical quality testing system OptiSpheric IOL R&D under centered, decentered (0.3, 0.5, 0.7, 0.9 and 1.1 mm) and tilted (3°, 5°, 7°, 9° and 11°) conditions. Results:All three IOLs filtrated the ultraviolet (UV) spectrum below 400 nm.When each IOL was in the centered position, at the 3.0 mm aperture, the MTF values were 0.772 at the far focus of the monofocal IOL 509M, 0.467 and 0.282 at the far and near focus of the bifocal IOL 809M, and 0.416, 0.147, and 0.229 at the far, intermediate, and near focus of the trifocal IOL 839MP, respectively.Whereas at the 4.5 mm aperture, the monofocal IOL 509M MTF value at the far focus was 0.664, the bifocal IOL 809M MTF values at the far and near focus were 0.506 and 0.264, and the trifocal IOL 839MP MTF values at the far, intermediate, and near focus were 0.392, 0.107, and 0.210, respectively.Among the three centered IOLs, the 509M demonstrated the highest MTF value at the far focus, followed by the 809M and then the 839MP; at the near focus, the MTF value of the 809M surpassed that of the 839MP.For decentration and tilt, the difference in MTF values of the three IOLs at the far and near focus was consistent with the differences observed when they were centered.At the same degree of decentration and tilt, all three IOLs exhibited superior optical quality at the 3.0 mm aperture compared to the 4.5 mm aperture.The optical quality of all three IOLs exhibited an overall decline as decentration and tilt increased.All three IOLs demonstrated a decrease in optical quality at the decentration of 0.3 mm or the tilt of 5°.Conclusions:The IOLs within the Zeiss MICS platform design exhibits identical spectral transmittance and UV filtering properties.Among the three IOLs, when centered, the 509M, the 839MP, and the 809M exhibit superior optical quality at the far, intermediate, and near focal points, respectively.Under decentered and tilted conditions, the 509M and the 809M demonstrate better resistance against decentration and tilt, respectively, at both far and near focuses.Additionally, all three IOLs demonstrate better optical quality at smaller apertures, given equivalent degrees of decentration or tilt.However, the optical quality at each focal point of the three IOLs decreases compared to the centered position when subjected to a decentration of 0.3 mm or a tilt of 5°.

To explore the effect of Macleaya cordata extract(MCE)on growth performance and serum biochemistry of Sichuan White Geese,and to analyze its mechanism of action by network pharmacology and molecular docking technology combined with animal experiments verification.A total of 90 1-day-old healthy goslings were randomly divided into 5 groups with 18 goslings per group after 5 d of adaptive feeding.The control group(CON)was fed with basal diet,the antibiotic group(CTC)was supplemented with 450 mg/kg chlortetracycline premix,and the low MCE group(MCEL),medium MCE group(MCEM)and high MCE group(MCEH)were supple-mented with 200,300 and 400 mg/kg MCE,respectively.The experimental period was 21 d.On the basis of the above experiments,Network pharmacology and molecular docking technology were used to predict the core targets and signaling pathways of MCE to promote geese growth from the levels of antioxidant,immune and apoptosis,and the expression levels of the core target genes were detected by Real-time fluorescence quantitative PCR.The results showed that compared with the CON group,MCE supplementation could increase the average daily weight gain,decrease the ratio of feed to gain,significantly increase the contents of serum GH,T3,T4,TP and ALB(P＜0.05),and significantly decrease the contents of serum AST and TG(P＜0.05).Network pharmacology analysis predicted 2 active ingredient and 237 active ingredient targets,and concluded that the mechanism of MCE promoting the growth of Sichuan White Geese may be related to the role of 5 key targets such as SRC,HSP90AA1,CASP3,ESR1 and MAPK14,and the action of MAPK,apop-tosis and other signaling pathways.Molecular docking results showed that the active ingredients of sanguinarine and chelerythrine in MCE could act through MAPK14.The validation results of core targets showed that MCE could significantly reduce the mRNA expression levels of CytC,CASP2,CASP3 and CASP9 in spleen(P＜0.05)and significantly increase the mRNA expression levels of Mcl-1(P＜0.05).These results indicated that MCE could promote the growth performance of Si-chuan White Geese by regulating apoptosis,promoting the secretion of serum growth-related hor-mones and improving biochemical indicators.

This paper reviews the current situation of massive open online course (MOOC) construction both domestically and internationally, highlighting the similarities, differences, and limitations of MOOC construction across nations. Based on the full-cycle MOOC construction of the "clinical epidemiology" course at Southern Medical University, including course design, resource integration, online deployment, and teaching evaluation, this study explored the significance, implementation path, and challenges of MOOC construction. This paper also reflects on the activation of teaching content, teacher-student interaction, and teaching mode, aiming to provide a reference for the construction and continuous enhancement of MOOC in China.