Gouty arthritis （GA） is an inflammatory disorder caused by monosodium urate （MSU） crystal deposition， accompanied by elevated oxidative stress and aberrant release of inflammatory cytokines， resulting in joint tissue damage and intense pain. Nuclear factor E₂-related factor 2 （Nrf2）， a key transcription factor regulating the antioxidant defence system， exerts cytoprotective effects through dissociation from Kelch-like ECH-associated protein 1 （Keap1） and activates downstream antioxidant response element （ARE）-mediated pathways. It can upregulate the expression of heme oxygenase-1 （HO-1）， NADH quinone oxidoreductase 1 （NQO1）， superoxide dismutase （SOD）， and glutathione transferase （GST） to preserve redox homeostasis. Moreover， Nrf2 can suppress activation of NOD-like receptor protein 3 （NLRP3） inflammasomes， reduce pro-inflammatory cytokine production and release， modulate nuclear factor-κB （NF-κB） transcriptional activity， regulate gut microbiota balance， enhance mitophagy， and inhibit apoptosis， so as to reduce joint inflammation and pain and promote body recovery. This review systematically examined recent advancements in traditional Chinese medicine （TCM） for GA prevention and treatment via regulating the Nrf2 signaling pathway. It delineated Nrf2's molecular mechanisms and its role in GA pathogenesis and elucidated how TCM intervenes in multiple pathways including Keap1/Nrf2/ARE， Nrf2/HO-1（NQO1）， and Nrf2/NF-κB/NLRP3 to exert therapeutic effects. The study demonstrated that TCM monomers and compounds effectively counteract oxidative damage， attenuate inflammatory responses， promote autophagy， and inhibit apoptosis via regulating the Nrf2 signaling pathway. These findings not only clarify the scientific basis of TCM in GA treatment but also offer strategic insights for developing novel Nrf2-targeted anti-gout drugs.

ObjectiveTo explore the effect of modified Lianpoyin formula （LPYJWF） in the treatment of Helicobacter pylori （Hp）-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control， model， high-dose LPYJWF （LPYJWF-H， 27.3 g·kg^-1·d^-1）， medium-dose LPYJWF （LPYJWF-M， 13.65 g·kg^-1·d^-1）， low-dose LPYJWF （LPYJWF-L， 6.83 g·kg^-1·d^-1）， and quadruple therapy groups. Except the control group， other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole （6.06 mg·kg^-1·d^-1） + amoxicillin （303 mg·kg^-1·d^-1） + clarithromycin （151.67 mg·kg^-1·d^-1） + colloidal pectin capsules （30.3 mg·kg^-1·d^-1） by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of gastric mucosa， and Warthin-Starry （W-S） silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue， and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A （TFAM） and translocase of the outer mitochondrial membrane member 20 （TOMM20）. The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA）， respectively， in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 （PINK1）， Parkin， p62， microtubule-associated protein 1 light chain 3 （LC3）， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time quantitative PCR was employed to assess the mRNA levels of PINK1， Parkin， p62， and LC3. ResultsCompared with the control group， the model group presented obvious gastric mucosal damage， colonization of a large number of Hp， severe mitochondrial damage， vacuolated structures due to excessive autophagy， reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue， and reduced SOD and increased MDA （P<0.01）. In addition， the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1， Parkin， and LC3 and down-regulated protein and mRNA levels of p62 （P<0.01， as well as increased expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa， reduced Hp colonization， mitigated mitochondrial damage， and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group （P<0.01）， and the MDA levels became lowered in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. Furthermore， the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1， Parkin， and LC3 and protein levels of PINK1 and Parkin， and up-regulated mRNA level of p62 （P<0.01）. The LPYJWF-M， LPYJWF-H， and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level （P<0.05， P<0.01） and up-regulated protein level of p62 （P<0.01）. The expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 were reduced in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice， which may be related to the inhibition of excessive mitochondrial autophagy， thereby inhibiting the activation of the NLRP3 inflammasome pathway.

ObjectiveTo explore the effect of modified Lianpoyin formula （LPYJWF） in the treatment of Helicobacter pylori （Hp）-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control， model， high-dose LPYJWF （LPYJWF-H， 27.3 g·kg^-1·d^-1）， medium-dose LPYJWF （LPYJWF-M， 13.65 g·kg^-1·d^-1）， low-dose LPYJWF （LPYJWF-L， 6.83 g·kg^-1·d^-1）， and quadruple therapy groups. Except the control group， other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole （6.06 mg·kg^-1·d^-1） + amoxicillin （303 mg·kg^-1·d^-1） + clarithromycin （151.67 mg·kg^-1·d^-1） + colloidal pectin capsules （30.3 mg·kg^-1·d^-1） by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of gastric mucosa， and Warthin-Starry （W-S） silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue， and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A （TFAM） and translocase of the outer mitochondrial membrane member 20 （TOMM20）. The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA）， respectively， in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 （PINK1）， Parkin， p62， microtubule-associated protein 1 light chain 3 （LC3）， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time quantitative PCR was employed to assess the mRNA levels of PINK1， Parkin， p62， and LC3. ResultsCompared with the control group， the model group presented obvious gastric mucosal damage， colonization of a large number of Hp， severe mitochondrial damage， vacuolated structures due to excessive autophagy， reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue， and reduced SOD and increased MDA （P<0.01）. In addition， the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1， Parkin， and LC3 and down-regulated protein and mRNA levels of p62 （P<0.01， as well as increased expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa， reduced Hp colonization， mitigated mitochondrial damage， and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group （P<0.01）， and the MDA levels became lowered in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. Furthermore， the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1， Parkin， and LC3 and protein levels of PINK1 and Parkin， and up-regulated mRNA level of p62 （P<0.01）. The LPYJWF-M， LPYJWF-H， and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level （P<0.05， P<0.01） and up-regulated protein level of p62 （P<0.01）. The expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 were reduced in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice， which may be related to the inhibition of excessive mitochondrial autophagy， thereby inhibiting the activation of the NLRP3 inflammasome pathway.

BACKGROUND: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis. METHODS: Restenosis and atherosclerosis rat models of type 2 diabetes ( n   =  20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t -test and one-way analysis of variance were used for statistical analysis. RESULTS: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells. CONCLUSION Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
Animals ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Muscle, Smooth, Vascular/metabolism* ; Rats ; DNA Methylation/physiology* ; CCAAT-Enhancer-Binding Protein-beta/genetics* ; Male ; Myocytes, Smooth Muscle/cytology* ; Rats, Sprague-Dawley ; RNA-Binding Proteins/genetics* ; Cells, Cultured ; Coronary Restenosis/metabolism*

Objective To investigate the clinical features of thyroid dysfunction in lung cancer patients treated with programmed cell death receptor-1(PD-1)or programmed cell death receptor-ligand 1(PD-L1)and their value for predicting therapeutic efficacy.Methods Lung cancer patients treated with PD-1/PD-L1 inhibitors at West China Hospital,Sichuan University between March 2018 and September 2022 were retrospectively enrolled.Data concerning the medical records,therapeutic efficacy,and thyroid function indicators of the patients were retrieved from the hospital electronic medical record information system.The data were then analyzed to identify risk factors and predictive factors for immune-related adverse events(irAEs)of the thyroid.The predictive value of thyroid irAEs for treatment efficacy and prognosis was assessed.Objective response rate(ORR)was defined as the indicator for therapeutic efficacy and progression-free survival(PFS)was defined as the prognostic indicator.Results A total of 368 lung cancer patients were enrolled.Among them,31.5％(116/368)developed thyroid irAEs.According to the results of logistic regression analysis,baseline thyroid stimulating hormone(TSH)concentration and baseline positive results for thyroglobulin antibody(TGAb)and thyroid peroxidase antibody(TPOAb)were risk factors for thyroid dysfunction caused by PD-1/PD-L1 inhibitors.Among the three measures,baseline TPOAb concentration demonstrated good predictive value for thyroid irAEs,with an area under the receiver-operating characteristic(ROC)curve(AUC)of 0.745.Patients with thyroid irAEs had a longer median PFS(16.0 months vs.9.7 months,P＜0.001)and a higher ORR(55.2％vs.34.9％,P＜0.001)compared to those without thyroid irAEs.Patients with thyroid irAEs had a better ORR than those without thyroid irAEs did.It was more likely for patients with thyroid irAEs to achieve an objective response compared to those without thyroid irAEs(odds ratio[OR]=2.29;95％CI,1.46-3.60).Conclusion In lung cancer patients treated with the PD-1/PD-L1 inhibitors,the TPOAb antibody demonstrates good predictive value for thyroid irAEs.Patients who develop thyroid irAEs have better treatment outcomes and prognosis.

Objective To investigate the expression changes of iron autophagy-mitochondrial ferric ion transport protein families(SFXNs)in acute kidney injury(AKI)and chronic kidney disease(CKD)mouse models induced by cisplatin(Cis)and ischemia reperfusion(IR).Methods C57BL/6 mice were randomly divided into control group(control),Cis-AKI group,Cis-CKD group,sham-operated group(sham),IR-AKI group,and IR-CKD group.Serum and kidney tissue samples were collected from mice.Serum creatinine(Cr)and blood urea nitrogen(BUN)levels were detected.Pathological changes in renal tissues were observed by HE staining.Western blot was used to detect the expression of renal SFXNs and kidney injury related proteins.Results Compared with the control or sham group,the levels of BUN and Cr in the serum of the model group were significantly increased(P＜0.05),the renal tissue showed significant pathological damage,with the kidney injury molecule-1(KIM-1),neutrophil gelatinase-associated lipocalin(NGAL),and pro-apoptotic protein Bax significantly upregulated(P＜0.05),while the anti-apoptotic protein Bcl-2 was significantly downregulated(P＜0.05).Compared to the control or sham group,the Cis-AKI group showed a significant downregulation of SFXN4(P＜0.05);The SFXN4 and SFXN5 subtypes were significantly downregulated in the IR-AKI group and Cis-CKD group(P＜0.05);All five subtypes of SFXN in the IR-CKD group were significantly downregulated(P＜0.05).Conclusions Cis or IR in-duces renal tissue damage and tubular mitochondrial injury in mice and affects the expression of SFXN family pro-teins,suggesting their potential role in renal injury of animal models.

Iron is an essential element for living organisms that plays critical roles in the process of bacterial growth and metabolism. However, it remains to be elucidated whether piuB encoding iron-uptake factor is involved in iron uptake and pathogenicity of Xanthomonas axonopodis pv. glycines (Xag). To investigate the function of piuB, we firstly generated a piuB deletion mutant (ΔpiuB) by homologous recombination. Compared with the wild-type, the piuB mutant exhibited significantly reduced growth and virulence in host soybean. The mutant displayed markedly increased siderophore secretory volume, and its sensitivity to Fe³⁺, Cu²⁺, Zn²⁺ and Mn²⁺ was significantly enhanced. Additionally, the H₂O₂ resistance, exopolysaccharide yield, biofilm formation, and cell mobility of ΔpiuB were significantly diminished compared to that of the wild-type. The addition of exogenous Fe³⁺ cannot effectively restore the above characteristics of ΔpiuB. However, expressing piuB in trans rescued the properties lost by ΔpiuB to the levels in the wild-type. Taken together, our results demonstrated that PiuB is a potential factor for Xag to assimilate Fe³⁺, and is necessary for Xag to be pathogenic in host soybean.
Iron ; Glycine max ; Virulence ; Xanthomonas axonopodis/genetics* ; Hydrogen Peroxide

The acupoint sensitization theory,a breakthrough in acupuncture and moxibustion over the past two decades,has greatly enhanced the understanding of meridians and acupoints while increasing the effectiveness of clinical diagnosis and treatment in acupuncture and moxibustion practices.The number of studies on surface sensitization site detection for different diseases is increasing.However,systematic sorting and a summary of the detection mode of surface sensitization points are lacking.Therefore,this study categorizes the method of surface sensitization point detection into two modes:pan-scanning and focused scanning.The classification is based on the characteristics of the openness of the research purpose,the precision of the target range,and the degree of variation during detection.The two modes have considerable differences in the exploration efficiency and the presentation of result.The pan-scanning mode can be further subdivided into holistic and localized pan-scanning modes,whereas the focused-scanning mode can be subdivided into fixed-and variable-focused scanning modes.This study analyzes the application scenarios,characteristics,advantages,and limitations of each detection mode and presents opinions on mode selection,mode innovation,and future development directions.This study aims to provide valuable insights and guidance for the follow-up research on surface sensitization site detection of various diseases.

[Abstract] Blood transfusion is a common therapeutic measure with indispensable role in clinical medicine. However, there is a risk of transmitting diseases during blood transfusion, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), etc. To reduce these risks and ensure blood transfusion safety, detection of disease markers in blood transfusion is particularly important. Biological sensing technology, with its advantages of high sensitivity, rapid response and portability, has broad application prospects in the detection of disease markers in blood transfusion. However, the biological sensing strategies for detection of disease markers in blood transfusion have not yet been systematically classified or fully discussed. Therefore, this paper first elucidates the common disease markers in blood transfusion and their importance. Then, it focuses on the application of biological sensors in the detection of disease markers in blood transfusion and discusses the challenges faced and the direction of future development in this field.

Cells within tissues are subject to various mechanical forces,including hydrostatic pressure,shear stress,compression,and tension.These mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes,shaping the microenvironment and maintaining cellular physiological balance.Several studies have demonstrated the roles of Yes-associated protein(YAP)and its homolog transcriptional coactivator with PDZ-binding motif(TAZ)as mechanotransducers,exerting dynamic influence on cellular phenotypes including differentiation and disease pathogenesis.This regulatory function entails the involvement of the cytoskeleton,nucleoskeleton,integrin,focal adhesions(FAs),and the integration of multiple signaling pathways,including extracellular signal-regulated kinase(ERK),wingless/integrated(WNT),and Hippo signaling.Furthermore,emerging evidence substantiates the implication of long non-coding RNAs(lncRNAs)as mechanosensitive molecules in cellular mechanotransduction.In this review,we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical stimuli.Additionally,we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.