Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

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:It has been found that abnormal apoptosis of bone tissue cells induced by abnormal iron metabolism plays an important role in the progression of osteoporosis. OBJECTIVE:To investigate the effect of naringin on iron metabolism and cell apoptosis in bone tissue of rats with osteoporosis. METHODS:Fifty 2-month-old female Sprague-Dawley rats were randomly divided into five groups with 10 rats in each group:sham group,osteoporosis group,naringin low-dose group,naringin high-dose group,and naringin high-dose+DKK-1 group.Except for the sham group,rat models of osteoporosis were established by removing bilateral ovarian tissues in the other groups.At 8 weeks after modeling,rats in the naringin low-and high-dose groups were given 100 and 400 mg/kg/d naringenin by gavage,respectively,and rats in the naringenin high dose+DKK-1 group were given 400 mg/kg/d naringin by gavage and subcutaneous injection of 25 mg/kg/d DKK-1,an inhibitor of the Wnt1 signaling pathway,for 7 consecutive days.Relevant indexes were detected after administration. RESULTS AND CONCLUSION:Compared with the osteoporosis group,naringin could enhance the bone mineral density and serum calcium and superoxide dismutase levels in rats(P<0.05),and reduce the serum levels of osteocalcin,malondialdehyde,and phosphorus(P<0.05),while DKK-1 could partially inhibit the interventional effect of naringin(P<0.05).Results from Micro-CT scanning,hematoxylin-eosin and TUNEL staining showed that compared with the osteoporosis group,naringin significantly improved bone microstructure and reduced the rate of cell apoptosis,while DKK-1 partially inhibited the interventional effect of naringin.Immunofluorescence staining results showed that compared with the osteoporosis group,naringin could reduce the oxygen content,anti-tartaric acid phosphatase expression,and elevate the expression of alkaline phosphatase in active tibia tissues(P<0.05),while DKK-1 could partially inhibit the interventional effect of naringin(P<0.05).Results from Prussian blue staining and immunohistochemical staining showed that compared with the osteoporosis group,naringin reduced iron deposition in bone and liver tissues as well as the expression of transferrin receptor 1(P<0.05),and elevated the protein expression of ferroportin 1(P<0.05)in bone tissue,and DKK-1 partially inhibited the intervention of naringin(P<0.05).PCR and western blot assay of tibia specimens showed that compared with the osteoporosis group,naringin decreased the expression of anti-tartrate acid phosphatase,transferrin receptor 1 and Bax(P<0.05),and elevated the expression of alkaline phosphatase,ferroportin 1,Bcl-2,Wnt1 and β-catenin(P<0.05),while DKK-1 partially inhibited the interfering effect of naringin(P<0.05).To conclude,naringin inhibits the progression of osteoporosis by reducing iron deposition and apoptosis rate in bone tissue,which may be related to the activation of the Wnt1 signaling pathway.

Di-(2-ethylhexyl)phthalate(DEHP)is an environmental pollutant commonly found in plastic products and has toxic effects on female reproductive system.DEHP can interfere with the synthesis of progesterone,testosterone and estradiol through female hypothalamic-pituitary-ovarian axis,aggravate insulin resistance and obesity by affecting glucose and lipid metabolism,and cause ovarian damage through inducing oxidative stress,excessive autophagy and pyroptosis of oocyte or granulosa cells.It can also alter epigenetic genes relating to follicular development and prevent follicles from mature.These factors are closely contribute to the pathogenesis of polycystic ovary syndrome.We systematically summarizes the mechanism of DEHP interfering with ovarian function and inducing polycystic ovary syndrome,in order to provide help for the prevention and treatment of female reproductive injury from environmental pollutant.

Objective This research was performed to identify rodent-borne pathogens in Hekou Port,Yunnan Province.Methods Rodents were captured using cages and dissected to collect their lungs,liver,spleen,and other viscera.Eight pathogens,including Yersinia pestis,Leptospira,Bartonella,and Anaplasmataceae,were identified using polymerase chain reaction amplification.Amplified pathogen sequences from positive samples were sequenced,and BLAST homology searches were conducted using GenBank to confirm pathogen identities.A phylogenetic tree of the identified pathogens was constructed using the neighbor joining method.Results The total of 31 rodents,identified as Rattus tanezumi,R.norvegicus,and Mus musculus,were captured.Among these,R.tanezumi was the dominant species,accounting for 64.52％of the total.Two pathogens,Leptospira interrogans and Neoehrlichia mikurensis,were detected,with positivity rates of 9.68％and 29.03％,respectively.No other pathogens were detected.The overall positivity rate for rodent-borne pathogens was 35.48％.Conclusions The single 16S rRNA gene fragment is insufficient for the molecular identification of all Neoehrlichia species.Accurate species identification should be based on a combined analysis of multiple genes.The prevalence of rodent-borne pathogens in Hekou Port indicates the necessity for enhanced surveillance of rodent-borne diseases and implementation of additional prevention and control measures in border ports.

Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury. After injury, Schwann cells produce an inflammatory response and secrete various chemokines, inflammatory factors, and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages, enhancing their phagocytotic ability, and thus play an important role in promoting nerve regeneration. Macrophages have also been found to promote vascular regeneration after injury, promote the migration and proliferation of Schwann cells along blood vessels, and facilitate myelination and axon regeneration. Therefore, there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration, but this has not been systematically summarized. In this review, the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other, to provide directions for research on accelerating nerve injury repair.
Schwann Cells/metabolism* ; Peripheral Nerve Injuries/physiopathology* ; Animals ; Macrophages/immunology* ; Nerve Regeneration/physiology* ; Humans ; Cell Movement/physiology*

Objective:To investigate the effect of FOXQ1 expression on chemoresistance in colorectal cancer and analyze its regulatory role in SIRT1 expression and p53 deacetylation under DNA damage response(DDR)condi-tions.Methods:qRT-PCR was used to detect FOXQ1 mRNA expression levels in SW620 cells and SW620 cells stimulated with cisplatin(CDDP).Lentiviral vectors were constructed for FOXQ1 overexpression and RNA interference.The cells were divided into three groups:FOXQ1 overexpression group(oe-FOXQ1),FOXQ1 RNA interference group(sh-FOXQ1),and a control group transfected with an empty vector(NC).The half-maximal inhibitory concentration(IC50)of CDDP in each group was determined using the CCK-8 assay.Apoptosis level and cell viability were assessed using the Annexin V-APC/7-ADD apoptosis detection kit and Calcein/PI staining.Western blot analysis was performed to evaluate the effect of FOXQ1 on SIRT1 expression and acetylated p53 levels.The SIRT1 pathway inhibitor(S)-Selisi-stat was introduced to observe changes in p53 acetylation levels.Results:Compared to normal colon tissues,FOXQ1 expression was significantly upregulated in SW620 cells(P＜0.05),and low-dose CDDP stimulation further en-hanced its expression(P＜0.05).After 24 hours of CDDP treatment,the IC50 values for the oe-FOXQ1,sh-FOXQ1,and NC groups were 58.3 μmol/L,36.4 μmol/L,and 43.7 μmol/L,respectively,with statistically significant differences among the groups(P＜0.05).Compared to the NC group,the oe-FOXQ1 group showed a decrease in late apoptotic cell count(P＜0.05),while the sh-FOXQ1 group exhibited an increase(P＜0.05).Cytotoxic fluorescence staining re-vealed that the proportion of cell death was lower in the oe-FOXQ1 group and higher in the sh-FOXQ1 group com-pared to the NC group(P＜0.05).Protein expression analysis showed that FOXQ1 and SIRT1 levels were higher in the oe-FOXQ1 group and lower in the sh-FOXQ1 group compared to the NC group(P＜0.05).FOXQ1 overexpression pro-moted p53 deacetylation,while the addition of the SIRT1 pathway inhibitor(S)-Selisistat restored p53 acetylation levels(P＜0.05).Conclusion:FOXQ1 promotes p53 deacetylation by upregulating SIRT1 expression,thereby inhibiting DDR-induced apoptosis.

OBJECTIVE: To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods. METHODS: In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator. RESULTS: The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups. CONCLUSION This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans ; Female ; Propensity Score ; Embryo Transfer ; Adult ; Acupuncture Therapy ; Retrospective Studies ; Pregnancy ; Live Birth ; Birth Rate ; Cohort Studies

Objective:To discuss the clinical application value of echocardiography in evaluating the early outcomes of transcatheter aortic valve replacement(TAVR)via the transapical approach,and to clarify the role of echocardiography in assessing the efficacy of the surgery.Methods:The clinical data of 85 patients who received J-Valve prosthetic valves via the transapical TAVR were retrospectively analyzed.The patients were divided into AS group(simple aortic stenosis,n=20),AR group(simple aortic regurgitation,n=37),and AS&AR group(aortic stenosis with regurgitation,n=28).Echocardiographic examination was performed on all the patients before operation,1 week after operation,3 months after operation,and 6 months after operation.The parameters including left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),interventricular septal thickness(IVST),left ventricular posterior wall thickness(LVPWT),aortic valve peak flow velocity(AV Vmax),aortic valve mean transvalvular pressure gradient(AV PGmean),and paravalvular leak(PVL)width were measured to evaluate the cardiac function and the function of the prosthetic valve;the occurrence of postoperative complications of the patients in various groups was also analyzed.Results:J-Valve prosthetic valves were successfully implanted in all 85 patients.There were no significant differences in age,gender,New York Heart Association(NYHA)heart function classification,history of hypertension,history of diabetes,history of hyperlipidemia,and history of coronary artery disease among various groups befor operation(P＞0.05),ensuring comparability.Compared with before operation,1 week after operation,the AV Vmax and AV PGmean of the patients in AS group and AS&AR group were decreased(P＜0.05);there were no significant differences in various parameters of the patients in AR group(P＞0.05).Compared with before operation,3 months after operation,the LVEF and LVFS of the patients in AS group were increased(P＜0.05),while the AV Vmax and AV PGmean were decreased(P＜0.05);the LVEDV and LVESV of the patients in AR group were decreased(P＜0.05),while the LVEF and LVFS were increased(P＜0.05);the LVEDV,LVESV,AV Vmax,and AV PGmean of the patients in AS&AR group were decreased(P＜0.05),while the LVEF and LVFS were increased(P＜0.05).Compared with before operation,LVEDV,LVESV,IVST,and LVPWT of the patients in all three groups 6 months after operation were decreased(P＜0.05),while LVEF and LVFS were increased(P＜0.05);the AV Vmax and AV PGmean of the patients in AS group and AS&AR group were decreased(P＜0.05);the AV PGmean of the patients in AR group was decreased(P＜0.05).The postoperative complications included 3 cases of permanent pacemaker implantation(2 cases in AS group,1 case in AR group),1 case of stroke(in AS group),and 13 cases of PVL(4 cases in AS group,5 cases in AR group,4 cases in AS&AR group).No deaths occurred during follow-up.Conclusion:Echocardiography can accurately and quantitatively evaluate early changes in cardiac function and the functional state of prosthetic valves after transapical TAVR,providing objective evidence for evaluating surgical outcomes and postoperative complications.

Objective: To explore the mechanism of Buzhong Yiqi Decoction in modulating macrophage polarization and intervening in autoimmune thyroiditis (AIT) mice. Methods: Using the random number table method, 48 SPF-grade NOD.H-2h4 mice were assigned to the normal, model, low-dose (4.10 g/kg), medium-dose (8.19 g/kg), high-dose group (16.38 g/kg) of Buzhong Yiqi Decoction, and selenium yeast tablet (0.026 mg/kg) groups, with eight mice in each group. All groups, except the normal group, were free to drink high iodine water (0.05% sodium iodide) to prepare AIT mouse models for 8 consecutive weeks. After the modeling was complete, each treatment group was orally administered with the corresponding medication, while the normal and model groups were orally administered with an equal volume of distilled water once a day for 8 consecutive weeks. High-performance liquid chromatography with an oscillometric refractive detector was used to analyze the content of Astragaloside Ⅳ in Buzhong Yiqi Decoction. Hematoxylin and eosin staining was used to observe the pathological morphology of mouse thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). An immunofluorescence assay was used to detect the positive area percentage of M1 and M2 macrophages in mouse thyroid tissue. Flow cytometry assay was used to detect macrophage polarization in mouse spleen tissue. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), nuclear factor kappa B inhibitory protein α (IκBα), and nuclear factor-κB (NF-κB) p65 in mouse spleen tissue. Western blotting was used to detect the expression of the phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), and NLRP3 protein in mouse spleen tissue. Results: The content of Astragaloside Ⅳ in Buzhong Yiqi Decoction was (7.09±0.06) g/L. Compared to the normal group, significant lymphocyte infiltration was observed in the thyroid tissue of mice in the model group. The levels of serum TPO-Ab, TgAb, IL-6, and TNF-α increased (P<0.05). The positive area percentage of M1 macrophages in thyroid tissue increased (P<0.05). The proportion of M1 macrophages and M1/M2 in spleen tissue increased (P<0.05). The relative expression levels of NF-κB p65 and NLRP3 mRNA in spleen tissue increased (P<0.05). The relative expression of p-IκBα, p-NF-κB p65, and NLRP3 proteins increased (P<0.05). Compared to the model group, the inflammation infiltration degree in the thyroid tissue of mice in each dose group of Buzhong Yiqi Decoction and selenium yeast tablet group was reduced, the serum TPO-Ab, TgAb, IL-6, TNF-α content was decreased, the spleen tissue M1/M2 was reduced, the expression of NF-κB p65 mRNA was reduced, and the relative expression levels of p-IκBα, p-NF-κB p65 protein were reduced (P<0.05). The Buzhong Yiqi Decoction high-dose and selenium yeast tablets groups showed an increase in IL-10 content, an increase in positive area percentage of M2 macrophages in thyroid tissue, an increase in M2 macrophages proportion in spleen tissue, and a decrease in NLRP3 mRNA and protein relative expression levels (P<0.05). Conclusion Buzhong Yiqi Decoction may regulate macrophage polarization by inhibiting the NF-κB/NLRP3 signaling pathway, thus improving the inflammatory damage in mice with AIT.