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.

The pathogenesis of obesity-associated kidney disease (OAKD) involves many aspects,including the overactivation of the renin-angiotensin-aldosterone system,insulin resistance,chronic inflammation,disorder of lipid metabolism and imbalance of gut microecology.Treatment strategies for OAKD focus on lifestyle adjustments,pharmacotherapy,bariatric surgery,and fecal microbiota transplantation.A deeper understanding of the hazards of OAKD and its pathogenesis will contribute to the development of personalized and precise strategies for prevention,diagnosis and treatment of OAKD in the future.
Humans ; Obesity/complications* ; Kidney Diseases/therapy* ; Renin-Angiotensin System ; Insulin Resistance

Objective To investigate the effects of laparoscopic sleeve gastrectomy(LSG)on the cardiac structure and function in obese patients with heart failure(HF)and compare the efficacy of LSG across obese patients with different HF types.Methods This study included 33 obese patients with HF who underwent LSG.The clinical indicators were compared between before operation and 12 months after operation.Repeated measures analysis of variance was employed to evaluate the changes in echocardiographic parameters before operation and 3,6,and 12 months after operation.Patients were allocated into a HF with preserved ejection fraction group(n=17),a HF with mildly reduced ejection fraction group(n=5)and a HF with reduced ejection fraction(HFrEF)group(n=11)based on left ventricular ejection fraction(LVEF)before operation for subgroup analyses of the effects of LSG on the cardiac structure and function of obese patients with HF.The paired samples t-test was conducted to assess the degree of cardiac structural and functional alterations after LSG.Results The 33 patients included 69.7% males,with an average age of(35.3±9.9)years,and a body mass index(BMI)of(51.2±9.8)kg/m².The median follow-up was 9.0(5.0,13.3)months.Compared with the preoperative values,the postoperative BMI(P=0.002),body surface area(BSA)(P=0.009),waist circumference(P=0.010),hip circumference(P=0.031),body fat content(P=0.007),and percentage of patients with cardiac function grades Ⅲ-IV(P<0.001)decreased.At the 12-month follow-up left atrial diameter(P=0.006),right atrial long-axis inner diameter(RAD1)(P<0.001),right atrial short-axis inner diameter(RAD2)(P<0.001),right ventricular inner diameter(P=0.002),interventricular septal thickness at end-diastolic(P=0.002),and left ventricular end-diastolic volumes(P=0.004)and left ventricular end-systolic volumes(P=0.003) all significantly reduced compared with preoperative values.Additionally,left ventricular fractional shortening and LVEF improved(both P<0.001).Subgroup analyses revealed that cardiac structural parameters significantly decreased in the HF with preserved ejection fraction,HF with mildly reduced ejection fraction,and HFrEF subgroups compared with preoperative values.Notably,the HFrEF group demonstrated the best performance in terms of left atrial diameter(P=0.003),left ventricular inner diameter at end-diastole(P=0.008),RAD1(P<0.001),RAD2(P=0.004),right ventricular inner diameter(P=0.019),left ventricular end-diastolic volume(P=0.004)and left ventricular end-systolic volume(P=0.001),cardiac output(P=0.006),tricuspid regurgitation velocity(P=0.002),and pulmonary artery systolic pressure(P=0.001) compared to preoperatively.Postoperative left ventricular fractional shortening(P<0.001,P=0.003,P<0.001)and LVEF(P<0.001,P=0.011,P=0.001)became higher in all the three subgroups than the preoperative values.Conclusions LSG decreased the body weight,BMI,and BSA,improved the cardiac function grade,reversed the enlargement of the left atrium and left ventricle,reduced the right atrium and right ventricle,and enhanced the left ventricular systolic function.It was effective across obese patients with different HF types.Particularly,LSG demonstrates the best performance in improving the structures of both atria and ventricles in obese patients with HFrEF.
Humans ; Male ; Female ; Gastrectomy/methods* ; Heart Failure/complications* ; Adult ; Obesity/physiopathology* ; Laparoscopy ; Middle Aged ; Heart/physiopathology* ; Stroke Volume

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective:Previous studies have shown that insomnia is closely related to erectile dysfunction(ED).However,the causal relationship between them is still unclear.Mendelian randomization(MR)provides a new method for studying the relationship between the two,and the theory of heart-kidney interaction in TCM provides a new idea for exploring the causal relationship between them.Methods:Based on the statistical data collected by genome-wide association studies(GWAS),the causal relationship be-tween insomnia and ED was discussed by MR.Inverse variance weighted(IVW)is the main analysis method,and weighted median(WME),simple mode(SM),weighted mode(WM)and MR Egger method were the supplementary analysis to evaluate the causal effect.MR-Egger intercept test,Cochran Q test and leave-one-out method were used in sensitivity analysis to verify the reliability of MR results.Results:Thirty-nine SNPs significantly related to insomnia were finally included for MR analysis.The results of IVW method in MR analysis showed that insomnia had a significant causal relationship with the increased risk of ED(OR=3.111,95％CI=1.566-6.181,P=1.193 × 10-3).The results obtained by MR-Egger method,WME method,WM method and SM method were consistent with IVW method in the direction of effect.The sensitivity results suggested that the results of this study were robust.Conclusion:Our study reveals the causal relationship between insomnia and ED,which provides a new basis for future clinical practice and prevention and treatment of ED.

Objective To evaluate the pharmacokinetics(PK)and pharmacodynamics(PD)of propofol injectable emulsion,and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.Methods Thirty-two healthy Chinese adult volunteers were recruited and randomly assigned to a fasting.single-dose,two-period and double-crossover study.Propofol was given to eligible subjects at a speed of 30 μg·kg-1·min-1 for 30 min.The concentration of propofol in plasma was determined by avalidated high performance liquid chromatography-tandem mass spectrometery(HPLC-MS/MS)method.The PK parameters of the two preparations were calculated.Bispectral index(BIS)was measured to calculate the PD parameters of two formulations.Adverse events during the trial were recorded.Results Thirty-one volunteers were included in the pharmacokinetic parameter set.The mean values of PK parameters of test andreference formulations were as follows:Cmax were(660.87±110.25)and(683.13±125.75)ng·mL-1;AUC0-t were(473.50±86.03)and(478.40±80.25)h·ng·mL-1;AUC0-∞ were(500.45±96.49)and(507.84±88.00)h·ng·mL-1;tmax were 0.47(0.25,0.53)and 0.50(0.40,0.54)h;t1/2 were(2.97±1.74)and(3.08±1.82)h.Thirty-one volunteers were included in the bioequivalence set.The 90％confidence intervals(CI)for the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ were 92.64％-101.39％,96.43％-101.00％,95.67％-100.70％,respectively.The mean values of PD parameters of test and reference formulations were as follows:BISmin were(75.94±13.66)and(74.39±12.32);BISAUC0-60minwere 5 569.85±182.78 and 5 575.68±166.19;T-BISmin were 23.00 and 29.00 min,respectively.There were no serious adverse events.Conclusion Two formulations of propofol injectable emulsion were bioequivalent and both of them exhibited good safety.

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

In recent years, with the development of single-cell sequencing technology, spatial transcriptome technology and in vivo tracing technology, scientists have a deeper understanding of scientific issues about the in vivo development, functional regulation and ex vivo expansion of hematopoietic stem cells (HSCs). Among them, epigenetic modification plays an important role in the development and fate decisions, function maintenance and ex vivo expansion of HSCs, which has become a research hotspot in the field of stem cells in recent years. This article reviews the recent research progress of epigenetic modification in the development, functional regulation and expansion of HSCs.
Hematopoietic Stem Cells ; Epigenesis, Genetic ; Humans ; DNA Methylation

Objective To explore the functional connectivity(FC)changes of hippocampus and amygdala in type 2 diabetes mellitus(T2DM)patients with erectile dysfunction(DMED),and the central pathological neural mechanisms underlying DMED.Methods 61 T2DM patients who visited Department of Endocrinology,Nanjing First Hospital,Nanjing Medical University from January 2020 to December 2021 were selected and divided into a simple T2DM group(n=30)and a combined DMED group(n=31).Another 47 healthy individuals were selected as control group(NC).The international erectile function scale(IIEF-5)was used to evaluate the erectile function.Resting-state functional magnetic resonance imaging(rs-fMRI)data were acquired from all participants.MRI data were preprocessed by the DPABI software package.Bilateral hippocampus and amygdala were selected as regions of interest(ROI)and the whole brain FC values were calculated.The FC values of brain regions between groups were tested by two-sample t-test with REST software package.Results Left hippocampus as ROI:compared with the NC group,FC values of the left superior temporal gyrus increased in the T2DM group,FC values of the left superior frontal gyrus,left inferior temporal gyrus,left posterior central gyrus and rectus gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left inferior parietal gyrus,left supramarginal gyrus,left middle occipital gyrus and right posterior central gyrus decreased in the DMED group.Right hippocampus as ROI:compared with the NC group,FC values of the right middle temporal gyrus and right rolandic operculum increased while FC values of the right calcarine fissure decreased in the T2DM group;FC values of bilateral anterior cingulate gyrus,right middle temporal gyrus and left rectus gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus,left inferior parietal gyrus and right inferior temporal gyrus decreased in the DMED group.Left amygdala as ROI:compared with the NC group,FC values in the left parahippocampal gyrus,left fusiform gyrus and right insula increased in the T2DM group;FC value of the left middle temporal gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus and left supramarginal gyrus decreased in the DMED group.Right amygdala as ROI:compared with the NC group,FC values of the left insula,right parahippocampal gyrus,right superior temporal gyrus and right supramarginal gyrus increased while FC values in the right caudate decreased in the T2DM group;FC values of the right middle frontal gyrus,left rectus gyrus and left middle occipital gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus and left inferior parietal gyrus decreased in the DMED group.Conclusions DMED patients have abnormalities in the hippocampus,amygdala and other brain regions,especially the frontal lobe functional cortex,which may be related to changes in their brain function.

Objective To investigate the stability and reproducibility of the treatment fractions during the intensity-modulated radiotherapy(IMRT)for breast cancer and the effect of respiratory motion on the dose irradiation of breast cancer radiotherapy by comparing the results of breast cancer dosimetric verification based on fractionated images by an electronic portal imaging device(EPID).Methods A total of 28 IMRT patients admitted to some hospital from January to June 2023 were grouped according to the pathological results and effects of respiratory motion on the accuracy of radiotherapy during clinical treatment,including 14 cases in a breast group and 14 cases in a non-breast group with 8 ones of head and neck tumors,5 ones of esophageal cancer and 1 case of cervical cancer.All the patients underwent a scan with cone beam computed tomography(CBCT)before the first radiotherapy,and image registration was carried out with a positioning CT.An EPID was used to acquire transmission dose images of 10 fractions of radiotherapy,and γ analysis was performed using the RIT 113 QA software to compare the images of the subsequent 9 fractions with those of the first fraction,with the images of the first fraction of radiotherapy as the baseline values.Absolute maximum dose normalization was implemented under the condition of 10％dose assessment threshold,and the γ-pass rates under the 3 criteria of 2％/2 mm,3％/2 mm and 3％/3 mm were counted separately.The fraction dose verification results of the 28 patients were divided into 3 treatment phases of 2-4 times(T1),5-7 times(T2)and 8-10 times(T3)to analyze the stability of dose irradiation during the radiotherapy.SPSS 22.0 software was used for statistical analysis.Results Under the condition of 10％dose assessment threshold,the breast and non-breast groups had the γ-pass rates being(95.80±2.65)％and(94.60±6.59)％under the 2％/2 mm criterion and(98.46±1.31)％and(97.50±3.30)％under the 3％/2 mm criterion respectively,and the differences were statistically significant(all P<0.05).Under the assessment criteria of 2％/2 mm,3％/2 mm and 3％/3 mm,the breast group had the γ-pass rates of fractions of treatment significantly lower than those of the non-breast group(all P<0.05),while the γ-pass rates showed no significant differences at T1,T2 and T3 treatment phases(all P>0.05).Conclusion EPID fraction images contribute to evaluating IMRT accuracy effectively.IMRT has high stability and reproducibility during the treatment cycle,while respiration may result in dose deviation during the fraction radiotherapy for breast cancer,and optical surface tracking technology or active breathing control technology is suggested to be involved in to relieve dose deviation.[Chinese Medical Equipment Journal,2025,46(6):54-58]