As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

Kidney transplantation is an effective treatment for end-stage renal disease.However,post transplantation diabetes mellitus(PTDM)is a common complication after kidney transplantation,affecting 10%to 40%of recipients and increasing the risk of cardiovascular disease,infections,sepsis and other conditions.The pathogenesis of PTDM is complex,including pancreatic β-cell dysfunction and insulin resistance.Tacrolimus,a commonly used immunosuppressive drug,is an independent risk factor for PTDM.Its mechanisms include damaging pancreatic β-cells,mediating impaired mitochondrial autophagy,etc.In addition,tacrolimus also raises blood glucose levels through various pathways,such as affecting gut microbiota metabolism and activating bile acid signaling pathways.In recent years,some new anti-diabetic drugs have shown certain application prospects in kidney transplant recipients,but the evidence-based medical evidence for their combined use still needs further exploration.In the future,it is necessary to conduct in-depth research on the multiple sites of action of tacrolimus to reduce the occurrence of PTDM and improve the prognosis of kidney transplant recipients.

Talaromyces marneffei is a rare opportunistic pathogen.Talaromyces marneffei infection is characterized by insidious onset,atypical clinical manifestations,low early diagnosis rate,and high misdiagnosis and fatality,and has received widespread attention in recent years.Organ transplant recipients become a high-risk group for Talaromyces marneffei infection due to postoperative immunosuppressive therapy.Metagenomic next-generation sequencing,targeted antifungal therapy,and immunosuppression regimen adjustment are key to improving the prognosis of Talaromyces marneffei infection patients.This article reviews the epidemiology,pathogenesis,diagnosis and treatment of Talaromyces marneffei infection in organ transplant recipients,explores current challenges and future research directions,and aims to inform the diagnosis and treatment of Talaromyces marneffeiinfection.

Periodontitis, a common chronic inflammatory disease, progressively damages the supporting tissues of teeth, ultimately resulting in tooth loss. The rising incidence of periodontitis in adults has prompted researchers to observe a frequent co-occurrence of mental health disorders (such as anxiety disorders, depression disorders) in patients undergoing periodontitis onset and treatment. The existence of severe periodontitis can even aggravate the mental and psychological disorders of patients. Furthermore, the long-term fast-paced, high-pressure modern life is easy to cause a series of psychological problems, in turn affecting the occurrence and development of periodontitis. At present, researchers have reported the correlation between periodontitis and anxiety disorders/depression disorders. However, due to the lack of systematic understanding, most of them are clinical investigations or epidemiological statistics without deep mechanism studies. In view of the above problems, this article elucidates the bidirectional relationship between periodontitis and depression/anxiety disorders in recent years by examining recent epidemiological findings, exploring potential bidirectional pathogenic mechanisms, and discussing current treatment strategies. Ultimately, this review seeks to provide new perspectives for improving both oral and mental health outcomes in patients affected by periodontitis and anxiety/depression disorders.

BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However， the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder， and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently， 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory （BDI） and Beck Anxiety Inventory （BAI） were used for assessment， and decision-making behavior was evaluated using Probabilistic Reversal Learning （PRL） task. Indicators assessed included the number of trials to criterion， perseverative errors， win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group （t=3.684， P<0.01）. There were no statistically significant differences between two groups in trials to criterion， perseverative errors and win-stay rate （t=0.329， 0.132， 0.609， P>0.05）. In depression group， BDI and BAI scores were positively correlated with the win-stay rate（r=0.450， 0.398， P<0.01）. ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore， the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. ［Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University （number， 2019LZXNYDJ39］

Objective:To analyze the drug resistance status of Mycobacterium tuberculosis（MTB）at a hospital in Xiamen over the past decade. Methods:Sputum culture-positive specimens of tuberculosis patients from Xiamen Xinglin Hospital from 2015 to 2024 were collected retrospectively. Isolates were identified as MTB complex and subjected to drug susceptibility testing. Drug resistance patterns and trends over the study period were analyzed using descriptive statistics and Chi-square trend tests in SPSS 27.0 and GraphPad Prism 8.0.Results:Among 3 883 MTB isolates analyzed，1 132（29.15%）exhibited resistance to at least one drug. The highest rates of resistance to individual first-line drugs were observed for isoniazid（INH，16.04%），streptomycin（SM，15.43%），and rifampicin（RFP，12.28%）. Multidrug-resistant tuberculosis（MDR-TB）was identified in 380 isolates（9.79%）. The predominant MDR resistance patterns were INH+RFP+SM（2.34%），INH+RFP（1.65%），and INH+RFP+SM+ethambutol（EMB）（1.03%）. Polyresistance was found in 188 isolates（4.84%），the predominant patterns were INH+SM（1.49%），INH+fluoroquinolone（FQs）（0.31%），and INH+para-aminosalicylic acid（PAS）（0.31%）. Extensively drug-resistant tuberculosis（XDR-TB）was detected in 49 isolates（1.26%）. From 2015 to 2024，significant decreasing trends were observed for overall drug resistance（ χ2=8.858， P=0.003），MDR（ χ2=15.692， P<0.001），and RFP resistance（ χ2=21.627， P<0.001）. In contrast，fluoroquinolone（FQs）resistance showed no significant trend（ χ2=0.149， P=0.699）. Among RFP resistant and MDR isolates，FQs resistance rates were notably high at 33.12%（158/477）and 36.84%（140/380），respectively. Conclusions:The MTB resistance situation in the hospital has gradually declined in the past 10 years，but the resistance situation remains severe，and clinical attention needs to be strengthened on the use of FQs.

This report presents two cases of penicillium marneffei infection occurring after kidney transplantation. Both recipients presented initially with gastrointestinal symptoms and were diagnosed early by metagenomic next generation sequencing (mNGS). Treatment included amphotericin B combined with voriconazole, adjustment of immunosuppressive therapy, and nutritional support, resulting in favorable outcomes. This study aims to characterize the clinical presentation, diagnostic challenges, and individualized treatment strategies for penicillium marneffei infection in kidney transplant recipients, providing valuable insights for clinical management.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

OBJECTIVES: To investigate the mechanism by which circ_EPHB4 regulates temozolomide (TMZ) sensitivity of glioma cells through the miR-424-5p/Wnt3 signal axis. METHODS: We detected the expression levels of circ_EPHB4, miR-424-5p and Wnt3 mRNA in glioma specimens from 25 patients with primary glioma and 25 patients experiencing relapse following temozolomide-based chemotherapy and in TMZ-sensitive and -resistant glioma A172 and SHG44 cells with circ_EPHB4 knockdown using qRT-PCR, and Wnt3 protein expression level was detected with Western blotting. Cell viability, colony-forming ability, and apoptosis of the cells with circ_EPHB4 knockdown were assessed, and the targeted regulation relationship between circ_EPHB4, miR-424-5p, and Wnt3 was verified by dual luciferase reporter assay and RNA immunoprecipitation (RIP) experiments. The effect of circ_EPHB4 knockdown on tumorigenesis of glioma cells was evaluated in subcutaneous tumor-bearing nude mouse models. RESULTS: The expression of circ_EPHB4 was significantly increased in glioma tissues and cells as compared with normal neural tissues and astrocytes (P=0.014). In TMZ-resistant glioma cells, circ_EPHB4 knockdown resulted in an obvious reduction of IC50 value of TMZ, inhibited cell colony formation, and promoted cell apoptosis, and these effects were reversed by miR-424-5p knockdown. The expressions of miR-424-5p and circ_EPHB4 were negatively correlated in glioma tissues (P=0.011). MiR-424-5p knockdown also attenuated the effect of circ_EPHB4 knockdown on expressions of PCNA, P-gp, MRP1 and bax. CONCLUSIONS Circ_EPHB4 regulates Wnt3 expression through "sponge adsorption" of miR-424-5p, thereby modulating TMZ-resistant glioblastoma cell clonogenesis, apoptosis, and TMZ sensitivity, suggesting the potential of circ_EPHB4 as a therapeutic target for reversing drug resistance of gliomas.
MicroRNAs/genetics* ; Humans ; Temozolomide ; Glioma/genetics* ; Animals ; Mice, Nude ; Cell Line, Tumor ; Wnt3 Protein/metabolism* ; Mice ; Apoptosis ; RNA, Circular ; Drug Resistance, Neoplasm ; Brain Neoplasms/pathology* ; Signal Transduction

OBJECTIVES: To investigate the oncogenic role of circular RNA circ_EPHB4 in glioma and its molecular mechanism. METHODS: Microarray analysis was performed to identify the differentially expressed circRNAs in glioma tissues. The effects of circ_EPHB4 on glioma cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and tumorigenicity in vivo were assessed using scratch wound healing assay, Transwell invasion assay and nude mouse models bearing subcutaneous tumors. RNA immunoprecipitation (RIP), RNA stability assays, and gene overexpression and silencing techniques were employed to validate the synergistic regulatory effect of circ_EPHB4 and the N6-methyladenosine (m⁶A) reader protein YTHDF3 on Wnt3 expression. RESULTS: Circ_EPHB4 was significantly overexpressed by 2.3 folds (|log2FC|=1.2, P<0.01) in glioma tissues compared to the adjacent tissues, and by 2.5 folds in glioma cell line U373 compared to normal cells (P<0.001). Overexpression of circ_EPHB4 significantly enhanced migration and invasion of glioma cells, and promoted the expressions of EMT markers N-cadherin and vimentin. In the tumor-bearing mouse models, the tumor volume in circ_EPHB4 overexpression group was significantly greater than that in the control group, and the lung metastatic foci increased by 4.2 folds. Overexpression of circ_EPHB4 promoted oncogenesis by upregulating Wnt3 expression, while YTHDF3 extended the half-life of Wnt3 mRNA in an m⁶A-dependent manner. Simultaneous knockdown of circ_EPHB4 and YTHDF3 resulted in an obvious reduction of Wnt3 mRNA expression by up to 47% compared to its level following knocking down either circ_EPHB4 or YTHDF3 alone. CONCLUSIONS Circ_EPHB4 and YTHDF3 promote glioma progression by jointly targeting the Wnt3 signaling pathway, which may provide a new therapeutic strategy for gliomas.
Glioma/genetics* ; Humans ; Animals ; Cell Line, Tumor ; RNA-Binding Proteins/genetics* ; RNA, Circular ; Epithelial-Mesenchymal Transition ; Mice, Nude ; Cell Movement ; Wnt3 Protein/genetics* ; Mice ; Disease Progression ; Adenosine/metabolism* ; Brain Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic