BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury （CLI） by inhibiting toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） pathway via regulating farnesol X receptor （FXR）. MethodsA total of 40 Wistar male rats were randomly selected， with 10 as a blank group，and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate （ANIT）. After modeling，they were randomly divided into the model group， the ursodeoxycholic acid （0.1 g·kg^-1） group and the Yinchenhao Tang （9.23 g·kg^-1） group，with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），γ-glutamyl transpeptidase （γ-GT），total bile acid （TBA），total bilirubin （TBil） and direct bilirubin （DBil） levels in serum were detected. Tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6） levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR，TLR4，MyD88，NF-κB，F4/80，TNF-α，IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR，TLR4，MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. ResultsCompared with those in the blank group，ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the model group were significantly increased （P<0.01）. The levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were significantly increased （P<0.01），and the mRNA and protein expressions of FXR in liver tissue were decreased （P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased （P<0.05，P<0.01）. Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group，ALT，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.05，P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased （P<0.05，P<0.01）. ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.01）. The mRNA and protein expressions of FXR in liver tissue were significantly increased，and the mRNA expressions of TLR4，MyD88，NF-κB，and F4/80， as well as the protein expressions of TLR4 and NF-κB were obviously decreased （P<0.05，P<0.01）. The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI，and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.

Hepatocellular carcinoma （HCC） is a common malignant tumor with a high fatality rate worldwide， with limited overall survival benefits and pronounced drug resistance issues， highlighting the urgent need for novel sensitization strategies and patient stratification systems. Ferroptosis， as an iron-dependent form of lipid peroxidation-driven cell death， is closely associated with tumor treatment responses. In addition to the classic glutathione peroxidase 4 （GPX4）/glutathione （GSH） pathway， the ferroptosis suppressor protein 1 （FSP1）-coenzyme Q10 （CoQ10） pathways and the dihydroorotate dehydrogenase （DHODH） pathway are two newly identified anti-ferroptosis pathways that function at the plasma membrane and mitochondria， respectively， and determine cellular sensitivity to ferroptosis in synergy with GPX4. This article systematically reviews the mechanism of action of the FSP1-CoQ10 and DHODH pathways in HCC and related research advances， proposes related therapeutic strategies， and look forward to its clinical translation and application prospects.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

Objective Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA)guidelines,to obtain precise and reliable comprehensive effect conclusions by quantitatively combining pharmacodynamic results from animal experiments investigating Astragali Radix(single-entity Astragali Radix preparation)or its ingredients for treatment of acute pancreatitis(AP)in literature reports through meta-analysis.Methods Databases including China National Knowledge Infrastructure(CNKI),VIP Database for Chinese Technical Periodicals(VIP),Wanfang Data Knowledge Service Platform,China Biomedical Literature Database(CBMdisc),PubMed,and Web of Science(WOS)were searched from inception to March 2025 for animal studies related to Astragali Radix(single-entity Astragali Radix preparation)or its ingredients for AP treatment.Risk of bias for included studies was assessed with SYRCLE tool.Heterogeneity among studies was evaluated according to Cochrane Handbook using Cochrane's Qtest and/2statistic.Sensitivity analysis was performed using the leave-one-out method,and publication bias risk was detected using Egger's test.Results A total of 297 articles were retrieved,and after screening and evaluation,19 animal studies were finally included for meta-analysis.These 19 publications cover SD rats,as well as three breeds of mice:C57BL/6 mice,BALB/c mice,and Kunming mice.SYRCLE scores ranged from 3 to 4.The results of the sensitivity analysis showed that no study significantly affected the heterogeneity index.The results of Egger's test showed a significant publication bias with P＜0.05.Cochrane's Qtest and I2statistic indicated substantial heterogeneity among studies.Meta-analysis results of 19 animal studies showed that single-entity Astragali Radix preparation(Astragali Radix injection)could reduce serum amylase(AMY)levels,an AP-specific indicator.The Astragali Radix ingredients could decrease both AMY and lipase(LPS)levels.Astragali Radix injection or its ingredients could reduce serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1 β,while increasing IL-10 levels;could increase serum levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),and decrease malondialdehyde(MDA)levels.High-dose groups of Astragali Radix injection or Astragali Radix ingredients were more effective than low-dose groups in reducing AMY,TNF-α,and IL-6 levels and increasing SOD levels,but dosage effect on MDA levels was not demonstrated.Conclusion Evidence-based analysis of animal experiment results shows that in various animal models including SD rats,C57BL/6 mice,BALB/c mice,and Kunming mice,Astragali Radix injection or its ingredients can effectively reduce expression or secretion levels of AP-specific indicators(AMY and LPS).The mechanisms may be related to some inflammatory mediators,including reducing TNF-α,IL-6,and IL-1 β levels and increasing IL-10 levels;They may also intervene in oxidative/antioxidative equilibrium,such as increasing SOD and GSH-Px levels and reducing MDA levels.Except for MDA,dose-response relationships are shown for reducing AMY,TNF-α,and IL-6 levels and increasing SOD levels with Astragali Radix injection or its ingredients.However,due to high heterogeneity,potential publication bias risk,and species differences between animal models and human diseases in existing studies,further high-quality clinical trials or animal experiments are still needed in the future.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA)guidelines,to obtain precise and reliable comprehensive effect conclusions by quantitatively combining pharmacodynamic results from animal experiments investigating Astragali Radix(single-entity Astragali Radix preparation)or its ingredients for treatment of acute pancreatitis(AP)in literature reports through meta-analysis.Methods Databases including China National Knowledge Infrastructure(CNKI),VIP Database for Chinese Technical Periodicals(VIP),Wanfang Data Knowledge Service Platform,China Biomedical Literature Database(CBMdisc),PubMed,and Web of Science(WOS)were searched from inception to March 2025 for animal studies related to Astragali Radix(single-entity Astragali Radix preparation)or its ingredients for AP treatment.Risk of bias for included studies was assessed with SYRCLE tool.Heterogeneity among studies was evaluated according to Cochrane Handbook using Cochrane's Qtest and/2statistic.Sensitivity analysis was performed using the leave-one-out method,and publication bias risk was detected using Egger's test.Results A total of 297 articles were retrieved,and after screening and evaluation,19 animal studies were finally included for meta-analysis.These 19 publications cover SD rats,as well as three breeds of mice:C57BL/6 mice,BALB/c mice,and Kunming mice.SYRCLE scores ranged from 3 to 4.The results of the sensitivity analysis showed that no study significantly affected the heterogeneity index.The results of Egger's test showed a significant publication bias with P＜0.05.Cochrane's Qtest and I2statistic indicated substantial heterogeneity among studies.Meta-analysis results of 19 animal studies showed that single-entity Astragali Radix preparation(Astragali Radix injection)could reduce serum amylase(AMY)levels,an AP-specific indicator.The Astragali Radix ingredients could decrease both AMY and lipase(LPS)levels.Astragali Radix injection or its ingredients could reduce serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1 β,while increasing IL-10 levels;could increase serum levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),and decrease malondialdehyde(MDA)levels.High-dose groups of Astragali Radix injection or Astragali Radix ingredients were more effective than low-dose groups in reducing AMY,TNF-α,and IL-6 levels and increasing SOD levels,but dosage effect on MDA levels was not demonstrated.Conclusion Evidence-based analysis of animal experiment results shows that in various animal models including SD rats,C57BL/6 mice,BALB/c mice,and Kunming mice,Astragali Radix injection or its ingredients can effectively reduce expression or secretion levels of AP-specific indicators(AMY and LPS).The mechanisms may be related to some inflammatory mediators,including reducing TNF-α,IL-6,and IL-1 β levels and increasing IL-10 levels;They may also intervene in oxidative/antioxidative equilibrium,such as increasing SOD and GSH-Px levels and reducing MDA levels.Except for MDA,dose-response relationships are shown for reducing AMY,TNF-α,and IL-6 levels and increasing SOD levels with Astragali Radix injection or its ingredients.However,due to high heterogeneity,potential publication bias risk,and species differences between animal models and human diseases in existing studies,further high-quality clinical trials or animal experiments are still needed in the future.

Autoimmune diseases of the nervous system are a category of conditions in which a malfunction of the body's immune system leads to damage of nerve tissues, with B cells playing a critical role in their pathogenesis. Currently, the therapeutic approaches used in clinical practice (such as monoclonal antibodies targeting B cells) can effectively control the progression of these diseases, but fail to achieve a radical cure. Chimeric antigen receptor (CAR)-T cell therapy uses genetic engineering to modify T cells derived from either patients or donors, enabling them to specifically target and durably eliminate peripheral B cells, which might remit or even functionally cure these diseases. Currently, multiple clinical studies on efficacy and safety of CAR-T cell therapy in neurological autoimmune diseases have been carried out successively, and initial results have been achieved. This article reviews the clinical research progress in this field, discusses its application prospects and challenges, aiming to provide some references for in-depth research in this area.

Objective:To propose a semi-supervised learning method for dynamic generation of organ geometric contours, leveraging bladder volume variations and its relative position to the uterus to accurately generate uterine contours in cervical cancer radiotherapy.Methods:A total of 120 sets of pelvic planning CT images (including both full and empty bladder scans) from 60 patients with cervical cancer treated at the Department of Radiation Oncology, Nanfang Hospital of Southern Medical University between January and December 2023 were retrospectively collected. A conditional generative adversarial network (CGAN) based on a squeeze-and-excitation channel attention mechanism was proposed to accurately generate uterine geometric contours under varying bladder filling states. By emphasizing the critical spatial relationships between the bladder and uterus, the model learned the relative anatomical positions of pelvic organs and their motion correlations. The generative performance was quantitatively evaluated using the average Dice similarity coefficient (DSC), intersection over union (IoU), and the 95 th percentile Hausdorff distance (HD95), and was compared with GAN model, CGAN model, and Pix2Pix model. Pairwise comparisons were perfomed by paired-sample t-test. Results:The proposed SE-CGAN model achieved the best performance on the test set, with DSC of 0.83±0.09, IoU of 0.71±0.05, HD95 of (6.74±1.23) mm, improving DSC by 7.5%, 4.9%, and 3.6% compared to the GAN, CGAN, and Pix2Pix models, respectively (all P<0.001), and reducing the mean HD95 by 32.9%-45.3%. Statistical analysis revealed significant differences between SE-CGAN model and the other 3 baseline models, whereas no significant difference was observed between CGAN model and Pix2Pix model. The visualization results further demonstrated that the GAN model produced uterine contours deviated greatly from the real shape, and the edge was fuzzy; CGAN and Pix2Pix model achieved better overlap but lacked of precision in boundary reconstruction. In contrast, the contours generated by SE-CGAN model closely matched the ground truth with clearly defined edges, indicating superior reconstruction accuracy. Conclusions:In this study, we propose a generative adversarial network method that establishes a dynamic modulation mechanism by which the bladder state influences the uterine geometric contour, enabling accurate generation of the uterine contours from the bladder contours of any given localization CT scan. This approach effectively addresses the uncertainty in radiotherapy target delineation caused by pelvic organ motion.

Traditional Chinese medicine (TCM) plays an important role in preventing and treating diseases and improving human health. However, the complex bioactive components and regulation of signaling pathway and network restrict the elucidation of the mechanisms of action of TCM. A human being is regarded as a super "symbiont" composed of body cells and commensal microorganisms. Gut microbiota is the core commensal microorganism system of a human body, being considered as "the second genome" and the new "organ". Alterations in gut microbiota reflect the state of body health and progression of diseases. Recent investigations have revealed that the TCM rich in polysaccharides and polyphenols can modulate gut microbiota metabolites to rehabilitate gut homeostasis, thus ameliorating diseases via regulating gut-liver axis or gut-brain axis. This review summarizes the causal relationship and mechanisms of action of TCM in the treatment of diseases from the perspective of gut microbiota metabolites. Our findings are expected to provide new insights into the mechanisms of TCM in preventing and treating diseases and guidance for TCM-based drug discovery in the future.
Humans ; Gastrointestinal Microbiome/physiology* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Polyphenols/pharmacology* ; Polysaccharides/pharmacology*