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.

OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.

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.

Xenotransplantation is an efficient pathway to solve the problem of transplant organ source deficiency in clinical settings. With the increasing progress of gene editing technique and immune suppression regimen, important development has been achieved on researches regarding pig to non-human primate kidney xenotransplantation, which provides a good condition for the introduction of the technique in the clinical application. In view of the substantial difference between human and non-human primate, and to meet the needs of current ethic requirements, it is necessary to perform subclinical studies for pig to human kidney xenotransplantation. In recent years, such subclinical studies with regard to the genetically modified pig to brain death recipient kidney xenotransplantation had been performed, indicating that kidney xenotransplantation gradually began to transit to the clinical development stage. However, donor/recipient selection and immune suppression regimen has not reached a consensus yet, and has to be clarified in subclinical studies. In this article, the current status and confronted problems of donor/recipient selection, immune suppression regimen and post transplantation management in the subclinical studies of kidney xenotransplantation were reviewed, aiming to promote the clinical transformation of kidney xenotransplantation to the clinical application.

BACKGROUND:Current studies have confirmed that Ganoderma lucidum polysaccharides can promote nerve regeneration in neurodegeneration-related diseases.The occurrence of neurodegenerative diseases is closely related to mitochondrial dysfunction,but the role of Ganoderma lucidum polysaccharides on the regulation of apoptosis and mitochondrial function in neurodegenerative diseases is not yet clarified. OBJECTIVE:To explore the regulatory effects and mechanisms of Ganoderma lucidum polysaccharides on apoptosis and mitochondrial dysfunction in H2O2-induced SH-SY5Y cells. METHODS:SH-SY5Y cells were divided into three groups:control group,H2O2 group,and Ganoderma lucidum polysaccharides group.Cells in the control group were normally cultured.Cells in the H2O2 group were treated with 300 μmol/L H2O2 for 24 hours.In the Ganoderma lucidum polysaccharides group,the intervention with 300 μg/L Ganoderma lucidum polysaccharides was conducted first for 1-2 hours,followed by the addition of 300 μmol/L H2O2 for 24 hours.The mitochondrial membrane potential was detected by JC-1 kit.Apoptosis was detected by TUNEL staining kit.The activities of malondialdehyde and superoxide dismutase were detected by malondialdehyde test kit and superoxide dismutase test kit,respectively.The apoptosis and expression of mitochondrial dynamics-related proteins were detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the mitochondrial membrane potential and superoxide dismutase activity were significantly reduced,as well as apoptotic rate and malondialdehyde levels were significantly increased in the H2O2 group(P<0.05).After treatment with Ganoderma lucidum polysaccharides,the membrane potential and superoxide dismutase activities were significantly increased,and apoptotic rate and malondialdehyde levels were significantly reduced compared with the H2O2 group(P<0.05).(2)The expression levels of pro-apoptotic proteins Bax and Caspase-3 were significantly increased,but the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the H2O2 group compared with the control group(P<0.05).Compared with the H2O2 group,the levels of Bax and Caspase-3 were significantly decreased,but the expression of anti-apoptotic protein Bcl-2 was significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(3)Compared with the control group,the expression of mitochondrial splitting proteins Fis1 and p-Drp1 was significantly increased,but the expression of mitochondrial fusion proteins OPA1,Mfn1,and Mfn2 was decreased in the H2O2 group(P<0.05).Compared with the H2O2 group,Fis1 and p-Drp1 expression was significantly reduced,but the expression levels of OPA1,Mfn1,and Mfn2 were significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(4)The above results confirm that Ganoderma lucidum polysaccharides can attenuate H2O2-induced oxidative stress damage and apoptosis in SH-SY5Y cells by ameliorating mitochondrial dysfunction.

Objective:To study the safety and efficiency of endovascular treatment in pediatric severe cerebral venous sinus thrombosis(CVST).Methods:This was a case series study.Data of pediatric severe CVST patients who received endovascular treatment in the Department of Neurointerventional, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023 were retrospectively analyzed.The technical success rate, periprocedural complications, neurologic and radiologic outcomes were collected to study the safety and efficacy of endovascular treatment in pediatric severe CVST.Results:A total of 15 patients were included in this study, including 6 males(40.0%) and 9 females(60.0%) with a mean age of(14.60±2.26) years.The modified Rankin Scale score(mRS) before endovascular treatment was(3.47±1.06) points, and the time from onset to endovascular treatment was 17(12-26) days.Thirteen patients(86.7%) received mechanical thrombectomy through catheter aspiration and/or stent-retriever thrombectomy followed or not followed by intrasinus thrombolysis(IST), and 2 patients(13.3%) received IST only.The technical success rate was 100%.Three patients(20.0%) had periprocedural complications.Ten patients(66.7%) had mRS≤2 points at discharge.Twelve patients(80.0%) had valuable neurologic and radiologic follow-ups with a duration of 9.5(3.5-19.0) months, and they all had mRS≤2 points.Among the 12 patients, 8(66.7%) had good cerebral venous recanalization.Conclusions:Endovascular treatment is technically feasible in pediatric severe CVST patients, with acceptable safety and efficacy.

Objective:To analyze the expression levels and clinical significance of interferon (IFN)-α/β in the renal cortex and serum of children with lupus nephritis (LN).Methods:A total of 32 children with LN diagnosed in the pediatric nephrology department of the Second Xiangya Hospital of Central South University from December 2017 to September 2020 were selected as the study subjects (LN group). The normal kidney control group consisted of 3 normal kidney transplant volunteers who underwent biopsy of kidney tissue (normal kidney control group), while 14 healthy children who underwent physical examination were collected as the normal control group. According to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), LN patients were divided into mild activity group ( n=8), moderate activity group ( n=9), and severe activity group ( n=15). According to the International Society of Nephrology/Society of Nephrology (ISN/RPS) 2003 LN classification criteria, pathological classification was performed (3 cases in the mild pathological damage group, 8 cases in the moderate pathological damage group, and 11 cases in the severe pathological damage group); Immunohistochemistry was used to detect the expression and distribution of IFN-α/β in glomeruli and renal interstitium; Enzyme linked immunosorbent assay (ELISA) was used to detect the concentration of IFN-α/β in serum samples and analyze its correlation with the pathological classification and disease activity of LN patients. Results:The serum and renal cortex IFN-α/β levels in the LN group were higher than those in the normal control group and normal kidney control group, respectively (all P<0.05). The average level of serum IFN-α/β in the heavy activity group was higher than that in the light and moderate activity groups (all P<0.05). The serum and renal cortex IFN-α/β levels in the severe pathological damage group were significantly higher than those in the mild and moderate pathological damage groups (all P<0.05). Conclusions:IFN-α/β in the renal cortex is closely related to renal injury in LN; Serum IFN-α/β can assist in evaluating the disease activity level of LN to a certain extent.

Public hospitals stand in need of strengthening cost control and improving operational efficiency to balance public welfare and economic benefits.Taking practice and exploration of ultrasound department as an exam-ple,it integrates the advantages of TDABC with cost management.Take the merits of time driver and activity driver,realizes direct cost accounting under the clinical pathway,strengthen capacity management capabilities un-der the integration of industry and finance,with a view to providing a powerful cost control tool for public hospitals to sensibly respond to pricing reform and reasonably make operational decisions.

Objective:To analyze the clinical characteristics and management strategy of carotid web (CW)-related stroke and improve the understanding of CW.Methods:The clinical data of 6 patients with CW-related stroke treated at Xuanwu Hospital, Capital Medical University, from January 2018 to September 2022 were retrospectively analyzed. Relevant data included clinical manifestations, bronchial magnetic resonance imaging (MRI), CT angiography (CTA)/digital subtraction angiography (DSA), carotid ultrasonography, and transcranial color-coded Doppler sonography (TCCD). Treatments and follow-ups were also reported.Results:All 6 patients were middle-aged or young, without traditional risk factors for cerebrovascular disease. The male-to-female ratio was 2∶4. All patients had recurrent strokes, with a score of 2-4 on the National Institutes of Health Stroke Scale at the time of onset. Head MRI showed 5 patients with cerebral infarction in the middle cerebral artery supply area; 1 patient had no intracranial infarction. No significant stenosis of the vessels at the site of the CW was observed in any of the 6 patients. Four patients had ipsilateral stenosis or occlusion of the middle cerebral artery, 1 patient had microembolic signals in the middle cerebral artery, and 1 patient had no significant abnormalities in the intracranial artery. All 6 patients were initially diagnosed by ultrasound. Diagnoses were confirmed by CTA/DSA in 5 cases; the other patient did not show any significant abnormalities. All 6 patients underwent a carotid endarterectomy after a pathological examination to confirm the diagnosis. Postoperatively, regular antiplatelet aggregation and statin lipid-lowering therapies were administered. A follow-up of 0.5 to 5.2 years showed no stroke recurrence in any patient.Conclusions:CW-related stroke is a rare cause of cryptogenic stroke and has a high recurrence rate. For stroke patients who do not have traditional risk factors for cerebrovascular disease while repeatedly experiencing embolic events of the internal carotid artery system, attention should be paid to the combination of the carotid and cerebral arteries, and comprehensive hemodynamic characteristics should be checked for the presence of a CW. Carotid artery ultrasound and TCCD combined with other imaging methods can improve the detection rate of a CW. Simple antiplatelet aggregation therapy cannot effectively prevent stroke recurrence. For patients with confirmed CW-related cerebral infarction, surgical resection can be performed, and the treatment effect can be evaluated using ultrasonography.