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.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

A 65-year-old male was admitted to Peking Union Medical College Hospital. The patient had intermittent fever for 2 months with a maximum body temperature of 39.3 ℃ and elevated serum creatinine levels for 1 week. He had no other suggestive symptoms or positive signs. Laboratory test results suggested acute kidney injury and a sharp elevation in serum lactic dehydrogenase levels. Abdominal enhanced computed tomography (CT) revealed multiple low-density lesions, and further biopsy pathology demonstrated chronic inflammation. Thereafter, positron emission tomography (PET)/CT showed abnormally elevated uptake value for the bones throughout the entire body, in addition to the liver and brain. Repeated bone marrow biopsy finally confirmed metastatic bone cancer, which possibly originated from the kidney according to immunohistochemical staining. In this rare case of fever of unknown origin, the primary lesion was a renal tumor with bone, liver, and brain metastases. Enhanced CT and PET/CT provided negative results, and the diagnosis was eventually confirmed by repeated bone marrow pathology.

A 65-year-old male was admitted to Peking Union Medical College Hospital. The patient had intermittent fever for 2 months with a maximum body temperature of 39.3 ℃ and elevated serum creatinine levels for 1 week. He had no other suggestive symptoms or positive signs. Laboratory test results suggested acute kidney injury and a sharp elevation in serum lactic dehydrogenase levels. Abdominal enhanced computed tomography (CT) revealed multiple low-density lesions, and further biopsy pathology demonstrated chronic inflammation. Thereafter, positron emission tomography (PET)/CT showed abnormally elevated uptake value for the bones throughout the entire body, in addition to the liver and brain. Repeated bone marrow biopsy finally confirmed metastatic bone cancer, which possibly originated from the kidney according to immunohistochemical staining. In this rare case of fever of unknown origin, the primary lesion was a renal tumor with bone, liver, and brain metastases. Enhanced CT and PET/CT provided negative results, and the diagnosis was eventually confirmed by repeated bone marrow pathology.

Objective:To explore the effect and safety of mesenchymal stem cell exosome microneedle introduction in the treatment of melasma.Methods:Thirty cases of female patients with stable melasma in the Department of Dermatology, Changsha Meilai Medical Beauty Hospital, aged (36±5) years and with a disease duration of (42.4±20.7) months, from July 2021 to July 2022, were retrospectively included. According to Fitzpatrick skin typing, 23 cases of type Ⅲ and 7 cases of type Ⅳ were included. All patients were locally anesthetized with lidocaine cream for 30 min, and rolled with a 0.5 mm needle in a zigzag pattern with even force, in the order of the right cheek, the left cheek, the forehead, the nose, the mandible, and the upper lip. During the rolling process, 3 ml of MSC exosome medical liquid wound dressing was applied to the facial skin, and after it was fully absorbed, exosome was locally readministered in the area of melasma. Treatment ended with a slight redness at the site of application. 1 MSC exosome wound dressing was appllied as a cold compress for 15 min after treatment. Treatment was given once every 2 weeks for 6 consecutive sessions. All the patients were followed up at 4 and 12 weeks after the last session, and the area and severity index of melasma (MASI) were scored before and after the treatment, the clinical efficiency and patient satisfaction rate and the incidence of adverse reactions were also counted.Results:At 4 and 12 weeks after the end of treatment, the skin color of all 30 patients was brighter than that before treatment, and no recurrence of melasma symptoms seen. At 12 weeks after the end of treatment, the decrease rate of MASI score was 66.1%, among which the decrease rate of MASI score in patients with type Ⅲ melasma was 63.9%, and the decrease rate of MASI score in patients with type Ⅳ melasma was 63.9%. Among the 30 patients, 1 case was cured, 25 cases showed obvious improved, 4 cases were improved, and no cases were ineffective, with an effective rate of 86.7% (26/30). Five patients were very satisfied, 18 patients were satisfied, 6 patients were generally satisfied, and 1 patient was dissatisfied; the patient satisfaction rate was 76.7% (23/30). No serious adverse reactions occurred in all patients.Conclusions:MSC exosome microneedle introduction is safe and effective in the treatment of melasma without serious adverse reactions.

Background The thyroid gland is one of the organs sensitive to ionizing radiation, and there are few studies on the effects of long-term exposure to low doses of ionizing radiation on the thyroid gland of radiation workers. Objective To investigate thyroid abnormalities in workers in medical radiology departments in Guangdong Province and to identify potential influencing factors of thyroid abnormalities. Methods A total of 1657 radiation workers from 48 hospitals in Guangdong Province were selected as survey subjects using convenience sampling, and their personal dose monitoring results and health examination information were retrospectively analyzed to determine the factors affecting thyroid abnormalities. Results The M (P₂₅, P₇₅) of thyroid absorbed dose (D_T) was 1.55 (0.65, 3.96) mGy in the 1657 investigated workers. The attribute-specific medians of D_T were 1.29, 1.38, 1.99, and 3.51 mGy for departments of diagnostic radiology, interventional radiology, radiotherapy, and nuclear medicine, respectively; and 1.10, 1.55, and 1.80 mGy for job titles of nurse, technician, and physician, respectively. Differences in D_T by gender, age, years of radiological work, age of radiation exposure onset, occupational category, and job title were statistically significant (Z=−6.35, H=708.52, 918.20, 31.19, 95.64, 39.28, P<0.05). The positive rate of thyroid abnormalities in investigated workers was 46.53% (771/1657). Among them, the positive rate of abnormal thyroid function was 22.87% (379/1657), that of abnormal thyroid morphology was 33.98% (563/1657), and that of thyroid nodule was 26.55% (440/1657). The differences in thyroid abnormality rates by gender, age, years of radiation work, age of radiation exposure onset, D_T, and job title of radiation workers were statistically significant (χ²=51.89, 49.64, 20.54, 18.29, 12.07, 16.16, P<0.05). The differences in abnormal thyroid function positive rate by gender, age of radiation exposure onset, and job title were statistically significant (χ²=26.21, 6.21, 8.32, P<0.05). The differences in the positive rates of abnormal thyroid morphology and nodules were statistically significant by gender, age, years of radiological work, age of radiation exposure onset, D_T, and job title (abnormal thyroid morphology, χ²=40.24, 64.17, 37.63, 15.17, 19.28, 15.05; nodules, χ²=31.41, 77.98, 42.11, 19.16, 21.70, 13.52, P<0.05). The positive rates of thyroid abnormality, thyroid morphology abnormality, and nodules all showed a linear increasing trend with increasing age, years of radiation work, and age of radiation exposure onset (P<0.05). The results of logistic regression analysis indicated that the factors influencing thyroid abnormalities were female (OR=2.17, 95%CI: 1.72-2.74), increased years of radiological work (OR=1.04, 95%CI: 1.03-1.06), onset of radiation exposure in age groups of 30-34 and ≥35 years (OR=1.63, 95%CI: 1.12-2.37; OR=2.58, 95%CI: 1.74-3.29), and working in department of diagnostic radiology (OR=1.40, 95%CI: 1.07-1.84). Conclusion Long-term exposure to low doses of ionizing radiation has an effect on thyroid abnormalities in medical radiation workers. Among them, being female, physicians, and working in department of diagnostic radiology are at a higher risk of abnormal thyroid function; being female, increased years of radiation work, and radiation exposure onset at age ≥30 years are associated with a higher risk of reporting abnormal thyroid morphology.

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.
Cross-Sectional Studies ; HIV Infections/epidemiology* ; HIV-1 ; Homosexuality, Male ; Humans ; Immunoenzyme Techniques ; Incidence ; Male ; Sexual and Gender Minorities

ObjectiveTo explore the potential mechanism of Polygonati Rhizoma on the treatment of osteoporosis （OP） based on network pharmacology and molecular docking method and to verify the mechanism by experiments. MethodThe main active ingredients and corresponding targets of Polygonati Rhizoma were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） 2.3 by conditional searching. The treatment targets were obtained from the genes related to OP and DisGeNET 7.0. The potential target genes of Polygonati Rhizoma for treating OP were obtained by the crossing of the corresponding targets and the treatment targets. Cytoscape 3.7.1 was used to construct the “Polygonati Rhizoma-active ingredient-potential target” network. The protein-protein interaction （PPI） analysis was carried out by STRING 11.0， and the PPI network was constructed. Metascape 3.5 was used to conduct Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses of the key targets. The core ingredients and key targets of Polygonati Rhizoma were selected for molecular docking by AutoDock Vina 1.1.2. Finally， the effect of β-sitosterol on osteogenic differentiation of MC3T3-E1 cells in rats was observed. ResultTwelve active ingredients and 32 potential targets of Polygonati Rhizoma for OP treatment were screened out. Six active ingredients including baicalein and β-sitosterol and key targets including protein kinase 1 （Akt1）， tumor suppressor p53 （TP53）， vascular endothelial growth factorA （VEGFA）， proto-oncogene Jun （JUN）， matrix metalloproteinase-9 （MMP-9）， and proto-oncogene c-Fos （FOS） were obtained by Cytoscape 3.7.1 topological analysis. A total of 995 GO entries and 181 signaling pathways involving the response to reactive oxygen species and regulations of growth were obtained from GO and KEGG enrichment analyses. The results of molecular docking showed that the core active ingredients possessed good binding activities with the respective key targets. The results of cell experiments showed that β-sitosterol promoted the osteogenic differentiation at the concentration of 2.5 μmol·L^-1 and 5 μmol·L^-1. ConclusionPolygonati Rhizoma had the therapeutic effect on treating OP by regulating inflammation， oxidative stress， apoptosis， and metabolism. The β-sitosterol significantly promoted the osteogenic differentiation of MC3T3-E1 cells.