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.

Xenotransplantation is one of the effective ways to overcome the shortage of donor organs. However, the molecular incompatibility between xenotransplantation donors and recipients can cause rejection, which greatly limits the clinical application of xenotransplantation. In recent years, researchers have deeply explored the mechanism of xenotransplantation rejection through xenotransplantation models of pig-to-monkey and pig-to-brain death recipients, and found that the innate immune system plays an important role in rejection. Macrophages, as phagocytes in the innate immune system, not only damage xenografts through phagocytosis but also interact with other immune cells to influence the immune microenvironment of xenotransplantation. However, due to the heterogeneity of macrophages, their phenotypes and functions in xenotransplantation rejection remain unclear. Therefore, it is necessary to further explore the role of macrophages in xenotransplantation rejection. This article reviews the latest research progress of macrophages in xenotransplantation rejection, aiming to explore the mechanisms of macrophages in xenotransplantation rejection and provide references for future research.

Hepatocellular carcinoma （HCC） with biliary duct tumor thrombus （BDTT） is currently not common in clinical practice and is easily misdiagnosed， and previously， it was often considered an advanced stage of the disease with a poor prognosis， making its treatment challenging. However， in-depth studies in recent years have gradually deepened our understanding of this disease， leading to significant changes in diagnostic and treatment concepts. Currently， comprehensive treatment， mainly surgery， is used for treatment， but there is still controversy over the selection of clinical treatment strategies. This article provides a detailed discussion on surgical methods and prognosis， in order to provide a reference for clinical treatment options.

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.

Organ transplantation faces the challenge of a shortage of donors. Although xenotransplantation holds great potential, it is limited by rejection. Extracellular histones, as key members of damage-associated molecular patterns, have been proven in recent years to play a crucial role in transplant rejection by activating innate immunity, regulating the coagulation-inflammation network, and modulating adaptive immune responses. However, the specific functions and key mechanisms remain to be clarified. Therefore, this article reviews the structural characteristics of histones, their release pathways, the biological functions of extracellular histones, and their potential roles in xenotransplantation. It summarizes the latest research progress of extracellular histones in xenotransplantation, analyzes the shortcomings of existing research and the direction for future research, with the expectation of providing references for the application of extracellular histones in xenogeneic kidney transplantation.

Objective To understand the clinical distribution characteristics and drug-resistance genotypes of carbapenem-resistant Pseudomonas aeruginosa(CRPA)in a tertiary hospital in Shanghai,so as to guide the rational use of antibiotics,reduce bacterial resistance and control nosocomial infections.Methods A total of 94 consecutive and non-redundant CRPA strains isolated from clinical specimens were collected in The First Affiliated Hospital of Naval Medical University between Jan.1,and Dec.31,2019.The distribution of CRPA across departments and sample sources were analyzed.Antimicrobial susceptibility testing against 13 antibiotics was determined using the VITEK 2 Compact automated microbiology analyzer and the Kirby-Bauer disk diffusion method.Polymerase chain reaction(PCR)was employed to detect genes encoding extended-spectrum β-lactamase resistance gene,carbapenemase resistance gene,and porin resistance gene.Homology analysis of selected isolates was performed using kSNP3,a k-mer-based software,for single nucleotide polymorphism(SNP)analysis.An evolutionary tree was constructed to assess genetic relationships.Additionally,multilocus sequence typing(MLST)was performed using the Pseudomonas aeruginosa typing scheme from the PubMLST database.Results Among the 94 CRPA isolates,high resistance rates were observed for carbapenems,including imipenem(92.6%,87 strains)and meropenem(87.2%,82 strains).In contrast,low resistance rates were detected for aminoglycosides,such as amikacin(10.6%,10 strains),gentamicin(20.2%,19 strains),and tobramycin(20.2%,19 strains).The top 3 departments in terms of isolate distribution were the Emergency Intensive Care Unit(9.6%,9 strains),Department of Cerebrovascular Surgery(8.5%,8 strains),and Department of Respiratory Medicine(8.5%,8 strains).PCR analysis of 94 CRPA strains detected outer membrane protein D2(OprD2)gene deletion in 47(50.0%)strains,13(13.8%)strains were positive for blaKPC,4(4.3%)strains for blaVIM,2(2.1%)strains for blaIMP,1(1.1%)strain for blaNDM,12(12.8%)strains for blaTEM,4(4.3%)strains for blaPER,and 2(2.1%)strains for blaGES,while blaOXA-48,blaBIC,blaSIM,blaVEB,and blaSHV were not detected.MLST identified 36 different sequence types(STs),with ST463 and ST274 being the most common,and 2 new ST(ST4023 and ST4024)were identified for the first time.Conclusion CRPA strains carry multiple resistance genes and exhibit concurrent resistance to several commonly used clinical antibiotics.The resistance is primarily associated with the presence of blaKPC,blaVIM and blaTEM genes and the deletion of OprD2 gene.Clinical monitoring of CRPA should be strengthened,and rational use of antimicrobial agents is essential to control its spread within the hospital.

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.

Hypoxia leads to persistent constriction and remodeling of pulmonary blood vessels,resulting in pulmonary hypertension(PH)and,in severe cases,right heart failure.Endothelial-mesenchymal transition(EndMT)is a biological process in which endothelial cells undergo functional and phenotypic transformation into mesenchymal cells,playing a critical role in pulmonary vascular remodeling.Recent studies have revealed that hypoxia promotes pulmonary vascular EndMT in PH through the mechanisms involving inflammation,transcription factors,signaling pathways,circular RNAs,and microRNAs.This article provides a review of recent research on the mechanisms of hypoxia-induced pulmo-nary vascular EndMT in PH,with the aim of offering insights for inhibiting pulmonary vascular remodeling in PH.

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.

OBJECTIVE To explore the clinical characteristics of Mycoplasma pneumoniae pneumonia(MPP)after COVID-19 epidemic so as to offer help for early clinical diagnosis and treatment.METHODS The clinical data that were collected from the MPP patients who were treated in the fever clinic of the First Medical Center of Chinese PLA General Hospital from Jul.2023 to Aug.2024 were retrospectively analyzed.The results of laboratory tests for the different age groups of patients complicated with other pathogens were statistically analyzed.RESULTS Of totally 161 MPP patients who were enrolled in the study,78(48.85％)were male,and 83(51.55％)were fe-male;the average age was(32.98±14.35)years old,and the patients aged between 20 and 40 years old accoun-ted for 43.48％(70 cases).The enrolled patients were divided into the simple MPP group with 92(57.14％)ca-ses and the MPP+mixed group with 69(42.86％)cases according to the result of etiological test of sputum;the patients of MPP+mixed group were divided into the MPP+bacteria group with 42(60.87％)cases,the MPP+fungi group with 10(14.49％)cases,and the MPP+viruses group with 17(24.64％)cases.There was significant difference in the age among the groups(P＜0.05);there were no significant differences in the sex,white blood cell counts and percentage of mononuclear cells among the groups,the percentage of lymphocytes was highest in the simple MPP group,the levels of C-reactive protein(CRP)and interleukin-6(IL-6)were highest in the MPP+bacteria group,and there were significant differences(P＜0.05).All of the patients were divided into three groups:the ≤20-year-old group the＞20-40-year old group and the＞40-year-old group.There were no sig-nificant differences in the white blood cell counts,percentage of lymphocytes,percentage of mononuclear cells and IL-6 level among the three groups,and the CRP level was highest in the＞20-40-year old group(P=0.025).Ran-dom forest model analysis showed that the weight of CRP was highest(22.65％)among the clinical characteristics of the MPP patients,which played a key role in construction of model.As for other factors,the weight of age was 17.02％,the percentage of lymphocytes 15.34％,the white blood cells counts 14.86％,the percentage of mono-nuclear cells 14.39％,the IL-6 13.61％,the gender 2.13％.CONCLUSION MPP maintains common among the patients aged less than 40 years old after the COVID-19 epidemic,nearly half of the patients are complicated with the infections of other pathogens,and CRP is more helpful for the clinical diagnosis and treatment of the MPP in early stage.