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.

As a cheap and effective antibiotic,sulfonamides are often used in animal husbandry.However,their residues in animal-derived foodstuffs will threaten human health.Consequently,a high-performance liquid chromatography(HPLC)method integrated with supramolecular solvent microextraction was successfully established for simultaneous quantification of sulfonamide residues sulfachlorpyridazine,sulfamethoxazole,sulfamethoxypyridazine and sulfadimethoxine in milk matrices.This approach exhibited prominent characteristics of operational simplicity,environmental sustainability,and high extraction efficiency.The supramolecular solvents prepared by tributyl octylphosphine tetrafluoroborate and tetrahydrofuran were employed as extraction solvents.The analytes underwent isolation and concentration via dispersive liquid-liquid microextraction(DLLME)prior to quantitative determination using high-performance liquid chromatography(HPLC).The composition and microscopic morphology of the supramolecular solvent were characterized through a series of analytical techniques,including phase diagram,Fourier transform infrared spectroscopy,scanning electron microscopy,and inverted fluorescence microscopy and so on.The density and pH value of supramolecular solvents were determined.The extraction conditions were optimized through the one-factor experiments.The experimental results demonstrated that under the optimal extraction conditions,the four kinds of sulfonamide antibiotics exhibited excellent linearity within respective detection range(R2 ≥ 0.9998)and the limits of detection(LOD)were 0.67-1.45 μg/L.Compared with literature methods,this approach offered some advantages such as simplicity of operation and less reagent consumption,and could be used for analysis and detection of sulfonamide antibiotic residues in milk samples.The present method provided technical support for food safety regulation and paved a new way for the application of supramolecular solvents in the field of extraction and separation.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

Objective:To investigate the clinical diagnosis and treatment of granulomatous prostatitis（GP）in patients with Prostate Imaging Reporting and Data System（PI-RADS）scores ≥ 4 on magnetic resonance imaging（MRI）.Methods:The data of 12 GP patients with PI-RADS score ≥ 4 who were admitted to Beijing Chaoyang Hospital，Capital Medical University，from February 2015 to February 2025，were retrospectively analyzed. The patients were aged 51?73 years（mean 66 years）. Presenting complaints included elevated prostate-specific antigen（PSA）levels in 6 cases，prostatic mass in 2 cases，urinary retention in 3 cases，and gross hematuria in 1 case. All 12 patients had concomitant lower urinary tract symptoms. Medical history revealed pulmonary tuberculosis in 2 cases，testicular tuberculosis in 1 case，close contact with tuberculosis in 1 case（spouse diagnosed with pulmonary tuberculosis 5 years earlier），allergic granulomatous vasculitis in 1 case，and intravesical bacillus Calmette-Guérin（BCG）instillation in 1 case. Digital rectal examination（DRE）showed gradeⅠprostatic hyperplasia in 2 cases，grade Ⅱ in 9 cases，and grade Ⅲ in 1 case. Nodules were palpable in 6 patients. The median PSA was 7.20 ng/ml（ranging 1.11?21.90 ng/ml），with 2 cases < 4 ng/ml. Transrectal ultrasound was performed in 10 patients，and prostate volumes were ranging from 29.48 to 109.78 cm3，with 6 cases > 45 cm3. All 12 patients underwent MRI，and all demonstrated PI-RADS scores ≥ 4，typically presenting as low signal intensity on T2-weighted imaging，high signal on diffusion-weighted imaging（DWI），and low apparent diffusion coefficient（ADC）values. Contrast-enhanced MRI in 8 cases revealed heterogeneous enhancement. One patient underwent 68Ga-prostate-specific membrane antigen positron emission tomography-computed tomography（ 68Ga-PSMA PET-CT），which showed band-like increased uptake in the central zone. All 12 patients were preoperatively suspected of prostate cancer，of whom 10 underwent transrectal biopsy and 2 underwent transperineal biopsy. Pathological characteristics and follow-up results were analyzed. Treatment outcomes were analyzed，The International Prostate Symptom Score（IPSS），quality of life（QOL）score，maximum urinary flow rate（Q max），and post-void residual urine（PVR）volume were compared before and 1 month after treatment. Results:Histopathology confirmed GP in all cases，with chronic inflammation in 11 cases and acute inflammation in 1 case. Immunohistochemistry demonstrated positivity for CD68（macrophage marker），high-molecular weight cytokeratin（HCK），and reticulin staining；periodic acid-Schiff（PAS）and acid-fast staining were positive in 2 cases，corresponding to 1 patient with a prior history of pulmonary tuberculosis and 1 with testicular tuberculosis. Two patients underwent thulium laser enucleation of the prostate，while 10 received conservative treatment，including 2 patients with tuberculosis infection who were referred for anti-tuberculosis therapy and 8 patients treated with oral tamsulosin 0.2 mg once daily. Follow-up was completed in 10 patients：9 were followed for 1 ? 3 months（mean 2.4 months），and 1 patient was followed for 9 years before being diagnosed with prostate cancer. Two additional patients，whose pathological findings suggested a possible diagnosis of tuberculous granulomatous prostatitis，were advised to undergo anti-tuberculosis treatment at another hospital and were subsequently lost to follow-up. Among the 2 patients who underwent thulium laser enucleation，IPSS decreased from 26 and 25 to 6 and 5 respectively，QOL scores decreased from 6 and 5 to 1 and 0 respectively，Q max increased from 4.5 and 4.3 ml/s to 23.0 and 21.9 ml/s respectively. In the 8 patients treated conservatively，IPSS decreased from 18.45±7.17 to 14.45±5.03，and QOL score decreased from 5.09±1.04 to 4.09±0.70 at 1 month after treatment，showing significant improvement（ P < 0.05）. Additionally，one patient initially diagnosed with GP and managed conservatively remained stable for 9 years，but subsequently developed urinary retention and underwent thulium laser enucleation，with postoperative pathology confirming prostate cancer. Conclusions:Clinical manifestations of GP are nonspecific，and the condition can easily be mistaken for prostate cancer due to elevated PSA levels and PI-RADS scores ≥4. Some patients may present with acute urinary retention，but definitive diagnosis still relies on prostate biopsy and immunohistochemistry. Treatment should be individualized according to the underlying etiology，with medication as the mainstay，while transurethral surgical intervention may be considered in cases with obstruction. Although GP is a benign lesion，its potential association with prostate cancer warrants vigilance and emphasizes the importance of long-term follow-up.

The risk prediction approach integrating disease and syndrome aligns more precisely with the clinical diagnosis and treatment needs of osteoporosis.Prior research has established a consensus on the model development methodology encompassing"Target outcome selection→ Key information collection→ Data mining and modeling →Model performance evaluation".Building on this foundation,a cohort of osteoporosis patients and syndrome cases with stable follow-up is established.Utilizing artificial intelligence algorithms,critical information in traditional Chinese medicine(TCM)symptoms and syndromes is objectively characterized and quantified alongside imaging data.Employing multi-omics sequencing technology,we seek to identify highly specific microscopic molecular information,analyze potential correlations among various dimensions of information,and develop a multidimensional risk prediction model for osteoporosis with distinctive TCM attributes.This model aims to identify biomarkers with both"disease"and"syndrome"characteristics,thereby advancing the precision diagnosis and treatment system for osteoporosis.

The dysregulation of cyclin-dependent kinase 12(CDK12),which may result from genomic alterations or modulation by upstream effectors,is implicated in cancer oncogenesis and progression.CDK12 over-expression or activation is sufficient to induce tumor initiation,recurrence,and therapeutic resistance.However,CDK12 may also exert tumor-suppressive functions in a context-dependent manner.Therefore,caution is warranted when targeting CDK12 in future clinical trials.A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance pre-cision oncology.This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer.Subsequently,we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts.Finally,we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology,offering insights into future directions for innovative cancer treatment strategies.

Objective:To investigate the clinical diagnosis and treatment of granulomatous prostatitis（GP）in patients with Prostate Imaging Reporting and Data System（PI-RADS）scores ≥ 4 on magnetic resonance imaging（MRI）.Methods:The data of 12 GP patients with PI-RADS score ≥ 4 who were admitted to Beijing Chaoyang Hospital，Capital Medical University，from February 2015 to February 2025，were retrospectively analyzed. The patients were aged 51?73 years（mean 66 years）. Presenting complaints included elevated prostate-specific antigen（PSA）levels in 6 cases，prostatic mass in 2 cases，urinary retention in 3 cases，and gross hematuria in 1 case. All 12 patients had concomitant lower urinary tract symptoms. Medical history revealed pulmonary tuberculosis in 2 cases，testicular tuberculosis in 1 case，close contact with tuberculosis in 1 case（spouse diagnosed with pulmonary tuberculosis 5 years earlier），allergic granulomatous vasculitis in 1 case，and intravesical bacillus Calmette-Guérin（BCG）instillation in 1 case. Digital rectal examination（DRE）showed gradeⅠprostatic hyperplasia in 2 cases，grade Ⅱ in 9 cases，and grade Ⅲ in 1 case. Nodules were palpable in 6 patients. The median PSA was 7.20 ng/ml（ranging 1.11?21.90 ng/ml），with 2 cases < 4 ng/ml. Transrectal ultrasound was performed in 10 patients，and prostate volumes were ranging from 29.48 to 109.78 cm3，with 6 cases > 45 cm3. All 12 patients underwent MRI，and all demonstrated PI-RADS scores ≥ 4，typically presenting as low signal intensity on T2-weighted imaging，high signal on diffusion-weighted imaging（DWI），and low apparent diffusion coefficient（ADC）values. Contrast-enhanced MRI in 8 cases revealed heterogeneous enhancement. One patient underwent 68Ga-prostate-specific membrane antigen positron emission tomography-computed tomography（ 68Ga-PSMA PET-CT），which showed band-like increased uptake in the central zone. All 12 patients were preoperatively suspected of prostate cancer，of whom 10 underwent transrectal biopsy and 2 underwent transperineal biopsy. Pathological characteristics and follow-up results were analyzed. Treatment outcomes were analyzed，The International Prostate Symptom Score（IPSS），quality of life（QOL）score，maximum urinary flow rate（Q max），and post-void residual urine（PVR）volume were compared before and 1 month after treatment. Results:Histopathology confirmed GP in all cases，with chronic inflammation in 11 cases and acute inflammation in 1 case. Immunohistochemistry demonstrated positivity for CD68（macrophage marker），high-molecular weight cytokeratin（HCK），and reticulin staining；periodic acid-Schiff（PAS）and acid-fast staining were positive in 2 cases，corresponding to 1 patient with a prior history of pulmonary tuberculosis and 1 with testicular tuberculosis. Two patients underwent thulium laser enucleation of the prostate，while 10 received conservative treatment，including 2 patients with tuberculosis infection who were referred for anti-tuberculosis therapy and 8 patients treated with oral tamsulosin 0.2 mg once daily. Follow-up was completed in 10 patients：9 were followed for 1 ? 3 months（mean 2.4 months），and 1 patient was followed for 9 years before being diagnosed with prostate cancer. Two additional patients，whose pathological findings suggested a possible diagnosis of tuberculous granulomatous prostatitis，were advised to undergo anti-tuberculosis treatment at another hospital and were subsequently lost to follow-up. Among the 2 patients who underwent thulium laser enucleation，IPSS decreased from 26 and 25 to 6 and 5 respectively，QOL scores decreased from 6 and 5 to 1 and 0 respectively，Q max increased from 4.5 and 4.3 ml/s to 23.0 and 21.9 ml/s respectively. In the 8 patients treated conservatively，IPSS decreased from 18.45±7.17 to 14.45±5.03，and QOL score decreased from 5.09±1.04 to 4.09±0.70 at 1 month after treatment，showing significant improvement（ P < 0.05）. Additionally，one patient initially diagnosed with GP and managed conservatively remained stable for 9 years，but subsequently developed urinary retention and underwent thulium laser enucleation，with postoperative pathology confirming prostate cancer. Conclusions:Clinical manifestations of GP are nonspecific，and the condition can easily be mistaken for prostate cancer due to elevated PSA levels and PI-RADS scores ≥4. Some patients may present with acute urinary retention，but definitive diagnosis still relies on prostate biopsy and immunohistochemistry. Treatment should be individualized according to the underlying etiology，with medication as the mainstay，while transurethral surgical intervention may be considered in cases with obstruction. Although GP is a benign lesion，its potential association with prostate cancer warrants vigilance and emphasizes the importance of long-term follow-up.

Objective: To investigate the causes and characteristics of immune hemolytic transfusion reactions (HTRs) triggered by anti-E antibodies, so as to provide a scientific reference for guaranteeing clinical blood transfusion safety. Methods: Five patients who experienced HTRs in our hospital from November 2023 to October 2024 were selected as the research subjects. ABO/RhD blood grouping, antibody screening, antibody identification, and the direct antiglobulin test (DAT) were conducted using the column agglutination method. The causes of HTRs in these patients were investigated using multiple techniques such as the two-step enzyme method, polyethylene glycol (PEG), acid elution technique, and capillary centrifugation method. Results: All five patients tested negative for antibody screening prior to transfusion. However, after transfusion of E+ phenotyped blood, patients 1, 2, 3, and 5 developed delayed haemolytic transfusion reaction (DHTR), while patient 4 experienced acute haemolytic transfusion reaction (AHTR). Anti-E antibodies were detected in all blood samples from the patients after the hemolytic transfusion reaction, including the enzyme-only anti-E antibody in two cases. Conclusion: Anti-E antibody can trigger both intravascular and extravascular hemolysis. It is recommended to conduct ABO/RhD and RhE antigen-matched transfusions and establish a regional blood transfusion database to reduce immune hemolytic transfusion reactions caused by anti-E antibody.