Ankylosing spondylitis(AS)is a chronic autoimmune disease characterized by inflammatory involvement of the axial skeleton and pathological bone formation.The T helper 17 cell(Th17 cell)subset of lym-phocytes plays a central role in mediating the inflammatory processes associated with AS.This review summarizes recent advances in the regulation of Th17 cell differentiation in AS,with a focus on the complex mechanisms governed by cytokine microenvironments,transcription factor networks,and metabolic and epigenetic regulatory pathways.Key regulatory components discussed include the IL-23/STAT3 signaling axis,the CCL20/CCR6 chemo-tactic axis,and the master transcription factor RORγt.Additionally,this review critically evaluates emerging thera-peutic strategies targeting metabolic reprogramming(e.g.,PKM2),epigenetic regulators(e.g.,JMJD3,EZH2),engineered exosome delivery systems,and modulators of metabolic enzymes.By analyzing the limitations of current treatment approaches,the review proposes future research directions emphasizing multi-target therapeutic strategies and highlights the importance of personalized medicine in achieving precise and effective treatment for AS.These developments reveal promising new avenues for modulating Th17-mediated immunity,offering transformative poten-tial for the clinical management of AS.

Objective:To analyze the influence of Internet + health coach technology (E-Coach) management mode on anticoagulant management and negative mood in patients with atrial fibrillation, and to provide intervention measures for improving anticoagulant management and alleviating negative mood in patients with atrial fibrillation.Methods:Using single-center randomized control study, 78 patients with atrial fibrillation from June 2022 to June 2023 in the Second Hospital, Jiaxing City by convenience sampling method was divided into intervention group (E-Coach management mode based on routine management) and control group (routine management) by random digits table method, 39 cases in each group. The intervention time was 6 months. The anticoagulant knowledge mastery situation, medication compliance, anxiety and depression scores were evaluated before and after the intervention in the two groups. The number of international normalized ratio (INR) full monitoring, days required for INR to reach the first standard (2.0-3.0), the rate of effective anticoagulation, the number of monitoring after INR≤3, bleeding and thrombosis were compared between the two groups.Results:One case was lost to follow-up in the intervention group, and three cases were lost to follow-up in the control group. The final trial intervention group consisted of 38 cases, while the control group consisted of 36 cases. There were 10 males and 26 females in the control group, aged (57.78 ± 10.50) years old, and 12 males and 26 females in the intervention group, aged (60.16 ± 9.86) years old. There were no significant differences in the anticoagulation knowledge mastery situation, medication compliance, anxiety and depression scores (all P>0.05). After the intervention, the scores of anticoagulation knowledge mastery and medication compliance were (13.68 ± 2.11), (7.39 ± 0.42) points in the intervention group, and (9.08 ± 1.93), (5.91 ± 0.85) points in the control group. There were significant differences between the two groups ( t=-9.77, -9.58, both P<0.01). The depression and anxiety scores were (48.74 ± 7.68), (50.61 ± 6.15) points in the intervention group, and (62.97 ± 9.66), (56.42 ± 7.13) points in the control group. There were significant difference between the two groups ( t=7.04, 3.76, both P<0.01). The number of INR full monitoring, days required for INR to reach the first standard, the rate of effective anticoagulation, and the number of monitoring after INR≤ 3 were (10.42 ± 2.04) times, (6.66 ± 1.70) times, 58.1%(25/38), 2.6%(1/38) in the intervention group, and (7.94 ± 1.76) times, (12.72 ± 2.45) times, 33.3%(12/36), 25.0%(9/36) in the control group. There were significant difference between the two groups ( t= -5.59, 12.45, χ2=4.84, 6.12, all P<0.05). Conclusions:E-Coach management mode effectively improves the anticoagulant management ability of patients with atrial fibrillation and reduces their negative emotions.

Objective:To explore the mechanism of Ginkgo biloba extract(EGb)on cerebral ischemia reperfusion injury(CIRI)in rats via the advanced glycation end products(AGEs)/receptor for AGEs(RAGE)pathway.Methods:SD rats were randomly divided into sham operation group(Sham group),CIRI group,CIRI+EGb pretreat-ment group(CIRI+EGb group),CIRI+AGEs inhibitor alagebrium chloride(ALT711)group(CIRI+ALT711 group)and CIRI+EGb+ALT711 group.HE,Nissl and Prussion blue staining were used to observe pathological chan-ges in the cerebral cortical area.The expression of AGEs,RAGE and nicotinamide adenine dinucleotide phosphate oxi-dase 4(NOX4)in the cerebral cortical area was detected by immunohistochemistry,the expression of AGEs,RAGE,NOX4,ferritin heavy chain 1(FTH),glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)in the cerebral cortical area was detected by Western blot,and the expression of RAGE and NOX4 mRNA in the cerebral cortical area was detected by RT-qPCR.Results:Compared with the Sham group,the pathological dam-age in the brain tissue of rats in the CIRI group was observed;the expression of AGEs,RAGE and NOX4 was increased(P<0.01),the expression of FTH,GPX4 and SLC7A11 was reduced(P<0.01),the expression of RAGE and NOX4 mRNA was increased(P<0.01);compared with the CIRI group,the pathological damage in the brain tissue of rats in the CIRI+EGb group and CIRI+ALT711 group was reduced,the expression of AGEs,RAGE and NOX4 was reduced(P<0.01),the expression of FTH,GPX4 and SLC7A11 was increased(P<0.01),the expression of RAGE and NOX4 mRNA was reduced(P<0.05);compared with the CIRI+ALT711 group,the pathological damage in the brain tissue of rats,as well as the expression of AGEs,RAGE and NOX4 in the CIRI+EGb+ALT711 group were re-duced(P<0.01),the expression of FTH,GPX4 and SLC7A11 was increased(P<0.01),the expression of RAGE and NOX4 mRNA was reduced(P<0.01).Conclusion:EGb could protect CIRI by inhibiting NOX4 and ameliorating ferroptosis through the AGEs/RAGE pathway.

Objective:To explore the mechanism of Ginkgo biloba extract(EGb)on cerebral ischemia reperfusion injury(CIRI)in rats via the advanced glycation end products(AGEs)/receptor for AGEs(RAGE)pathway.Methods:SD rats were randomly divided into sham operation group(Sham group),CIRI group,CIRI+EGb pretreat-ment group(CIRI+EGb group),CIRI+AGEs inhibitor alagebrium chloride(ALT711)group(CIRI+ALT711 group)and CIRI+EGb+ALT711 group.HE,Nissl and Prussion blue staining were used to observe pathological chan-ges in the cerebral cortical area.The expression of AGEs,RAGE and nicotinamide adenine dinucleotide phosphate oxi-dase 4(NOX4)in the cerebral cortical area was detected by immunohistochemistry,the expression of AGEs,RAGE,NOX4,ferritin heavy chain 1(FTH),glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)in the cerebral cortical area was detected by Western blot,and the expression of RAGE and NOX4 mRNA in the cerebral cortical area was detected by RT-qPCR.Results:Compared with the Sham group,the pathological dam-age in the brain tissue of rats in the CIRI group was observed;the expression of AGEs,RAGE and NOX4 was increased(P<0.01),the expression of FTH,GPX4 and SLC7A11 was reduced(P<0.01),the expression of RAGE and NOX4 mRNA was increased(P<0.01);compared with the CIRI group,the pathological damage in the brain tissue of rats in the CIRI+EGb group and CIRI+ALT711 group was reduced,the expression of AGEs,RAGE and NOX4 was reduced(P<0.01),the expression of FTH,GPX4 and SLC7A11 was increased(P<0.01),the expression of RAGE and NOX4 mRNA was reduced(P<0.05);compared with the CIRI+ALT711 group,the pathological damage in the brain tissue of rats,as well as the expression of AGEs,RAGE and NOX4 in the CIRI+EGb+ALT711 group were re-duced(P<0.01),the expression of FTH,GPX4 and SLC7A11 was increased(P<0.01),the expression of RAGE and NOX4 mRNA was reduced(P<0.01).Conclusion:EGb could protect CIRI by inhibiting NOX4 and ameliorating ferroptosis through the AGEs/RAGE pathway.

Aim To explore the effect and mechanism of annexin A1 mimic peptide Ac2-26 on ferroptosis in hu-man umbilical vein endothelial cells(HUVEC).Methods Induction of HUVEC ferroptosis was achieved by the clas-sical ferroptosis agonist RSL3,with subsequent intervention by the annexin A1 mimtic peptide Ac2-26.The cell number and viability were detected by CCK-8 kit,the levels of malondialdehyde(MDA)and glutathione(GSH)were detected by ELISA,the expression of ferroptosis-related molecules and adhesion molecules was detected by Western blot,the lipid re-active oxygen species(ROS)levels were detected by C11-BODIPY fluorescent probe,and the mitochondrial reactive oxy-gen species(mtROS)levels were detected by MitoSOX probe.FeRhoNOX-1 fluorescent probe was used to detect intra-cellular Fe2+content,perspective microscopy was used to observe mitochondrial morphology,JC-1 fluorescent probe was used to detect mitochondrial membrane potential,kit was used to detect ATP levels,the Scratch assay was used to detect cell migration ability,and nitrate reductase assay was used to detect nitric oxide(NO)level.Results Ac2-26 inhibi-ted RSL3-induced decrease in HUVEC viability,up-regulated the expression of suppressor of ferroptosis proteolytic carrier family 7 member 11(SLC7A11),GPX4,and ferritin heavy chain 1(FTH1),increased the GSH content,decreased the MDA content,reduced the generation of intracellular lipid ROS,and decreased the intracellular Fe2+aggregation(P＜0.05 or P＜0.01);Ac2-26 inhibited RSL3-induced damage to HUVEC mitochondrial morphology and function,up-regulated ATP content(P＜0.05)and mitochondrial membrane potential(P＜0.001);Ac2-26 inhibited RSL3-induced decrease in HUVEC migratory ability,up-regulated NO levels,inhibited intercellular adhesion molecule-1(ICAM-1)and interleukin-1β(IL-1β)protein expression(P＜0.05 or P＜0.01).Conclusion Ac2-26 inhibits RSL3-induced ferroptosis in HUVEC and maintains mitochondrial morphology and function,as well as HUVEC function.

Objectives:QT interval prolongation during treadmill test exercise is one of the clinical feature of patients with long QT syndrome(LQTS).This study aimed to explore the feasibility and efficacy of treadmill exercise testing as an auxiliary diagnosis tool for LQTS in clinical practice.Methods:We enrolled normal healthy individuals,common cardiovascular disease patients,and clinically diagnosed or suspected LQTS patients,who underwent treadmill exercise test from July 2023 to July 2024 at Fuwai Hospital.A special treadmill exercise testing procedure was designed to record the QT interval correction(QTc)intervals of the twelve lead electrocardiogram at 6 time points when performing the exercise tablet,including supine,sitting,standing,peak exercise,and recovery at 1-minute and 4-minute.The differences in QTc intervals among healthy group,cardiovascular diseases group,and suspected LQTS group were compared.Results:A total of 80 cases were consecutively enrolled,including 37 normal healthy controls,25 patients with common cardiovascular disease,and 18 patients with suspected LQTS.The QTc intervals at 6 points did not differ significantly between normal healthy controls and patients with cardiovascular disease,with QTc intervals less than 480 ms at all measurement.For patients with suspected LQTS,67.7%(12/18)of these patients presented a QTc interval≥480 ms at the 4-minute during recovery period.Among them,5 cases were confirmed to have pathogenic gene mutations of LQTS by genetic testing(including 1 case with a lying electrocardiogram QTc interval of 489 ms diagnosed with LQTS 1 type and a QTc interval of 636 ms during the 4-minute recovery period after exercise);5 clinically diagnosed patients(negative or undetectable in genetic testing)with a Schwartz score≥4,and the remaining 2 patients had a Schwartz score of 3.The remaining 5/18 patients,include 2 patients with clinical Schwartz scores≥4 and 3 patients with clinical suspicion(Schwartz scores 2-3)had a 4 min QTc interval of 445-480 ms during exercise recovery.Another patient with clinical suspicion(Schwartz score 3)had a 4 min QTc interval of<445 ms during exercise recovery and a negative genetic test at a later stage.Receiver operating characteristic curve analysis showed a sensitivity of 83.3%and specificity of 98.4%for QTc interval≥482 ms during the 4-minute recovery period of exercise as the LQTS diagnostic cutoff.Conclusions:This study results suggest that this special treadmill exercise testing protocol is effective in identifying LQTS and has strong feasibility and generalizability for clinical practice.

In order to establish a simple,sensitive and specific diagnostic method for the simultane-ous detection of Mycoplasma hyorhinis(Mhr)and Mycoplasma hyopneumoniae(Mhp)in swine,specific primers and probes were designed using the Mhr p37 and Mhp p36 gene sequences as the target genes,and the dual LFD-RPA rapid test was established by screening the primers and probes,optimizing primer ratios and evaluating its effectiveness through the sensitivity,reproduc-ibility and clinical sample testing.The sensitivity,specificity,reproducibility and clinical samples were evaluated.The results showed that the established dual LFD-RPA assay could complete the amplification in 15 min at 39 ℃,and its optimal primer ratio was 1.6∶0.8,and the lowest detection limits were up to 3.63 and 3.60 copies/μL,respectively;the reproducibility was stable;and there was no cross-reactivity with Pasteurella multocida,Bordetella bronchiseptica,Haemophilus pa-rasuis,Actinobacillus pleuropneumoniae,Escherichia coli.The test successfully established a dual LFD-RPA assay,which can detect Mhr and Mhp simultaneously,and is simple,sensitive and spe-cific without relying on specialized equipment,and is suitable for carrying out on-site rapid diagno-sis of Mhr and Mhp.

Objective To reveal the detailed histological characteristics of pyramidal neuron cell bodies and their axonal projections along the corticospinal tract in the primary motor cortex(M1)of the brain,by using the biotinylated dextran amine(BDA)neural tracing technique combined with panoramic and local microscopic imaging technologies.Methods A total of 100 nL of 10％BDA(10,000 molecular weight)was injected into M1 region using stereotaxic system.The distribution of BDA labeling along the corticospinal tract was continuously tracked with panoramic tissue scanning analysis system.Detailed observations of the histological characteristics of BDA labeling were carried out with laser confocal microscope.Results It is more convenient to observe the overall distribution of BDA neural labeling by using the panoramic tissue scanning analysis system.Around the injection site in M1,the BDA labeling was shown in the somas of pyramidal neurons in layer V.In the M1 region corresponding to the contralateral site of the injection site and ipsilateral primary sensory cortex,BDA showed predominantly the anterograde labeled nerve fibers accompanied by a few retrograde labeled neurons.Besides,BDA labeled nerve fibers-including bundles and terminals-projecting to regions such as the ipsilateral striatum,thalamus,internal capsule,cerebral peduncle,and pons,and further reaching the contralateral spinal cord via the brainstem pyramidal decussation.Confocal microscopy and its 3D reconstruction system facilitated detailed analysis of the local microscopic features of BDA labeling,revealing retrograde labeled neuron cell bodies,dendrites and their spines,as well as anterograde labeled nerve fibers and their terminals.Conclusions These findings demonstrated that the integration of traditional BDA neural tracing with panoramic tissue scanning analysis and confocal microscopy provided an effective approach to the observation and analysis of long-projection neural circuits from panoramic to local perspectives,with broad application prospects.

Objective: To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1). Methods: The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential. Results: Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05). Conclusion YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.

Chronic obstructive pulmonary disease(COPD)is a common disease with a high global incidence and mortality rate.It is charac-terized by chronic inflammation and structural airway obstruction that is not fully reversible,leading to shortness of breath caused by air trapping and increased physical exertion.Over the past few decades,the incidence of COPD has continued to rise.Although commonly used therapeutic agents,such as glucocorticoids and bronchodilators,have demonstrated significant symptomatic relief,they primarily target symptoms rather than halting disease progression.Therefore,further research is needed to better understand the underlying mechanisms of COPD and to develop novel therapeutic strategies for its prevention and management.Early studies on the pathogenesis of COPD primarily focused on airway epithelial cell injury,while relatively less attention was given to pulmonary vascular endothelial cells(PVECs).However,recent evidence indicates that COPD is not only an airway and systemic inflammatory disorder but also a vascular disease,with PVECs playing a critical role in its pathogenesis.PVECs are among the main cellular targets damaged in COPD and are involved in mediating its initiation and progression.In this review,we summarize emerging evidence that highlights the close association between PVEC injury and COPD pathogenesis.We also explore the roles and mechanisms of various therapeutic interventions targeting PVECs,including chemical agents and traditional Chinese medicine,in the treatment of COPD.