OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.

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.

AIM:To investigate the mechanism by which resveratrol(RSV)alleviates intestinal ischemia-re-perfusion(I/R)injury through modulation of the Wnt/β-catenin signaling pathway.METHODS:Twenty-four male C57BL/6J mice were randomly allocated into four experimental groups:the sham group,I/R group,I/R+RSV(treatment)group,and I/R+RSV+XAV939(inhibitor)group,with 6 mice per group.In the I/R,treatment,and inhibitor groups,the superior mesenteric artery was clamped for 45 minutes and then reperfused for 2 hours to establish the intestinal I/R injury model.The sham group underwent vascular dissection without occlusion.The treatment and inhibitor groups received dai-ly intraperitoneal injections of 15 mg/kg resveratrol for 5 d preoperatively,and the other two groups were intraperitoneally injected with an equal volume of 0.1%dimethyl sulfoxide.The inhibitor group additionally received 10 mg/kg XAV939 30 minutes pre-ischemia.HE staining was used to observe the pathological changes in the intestinal tissues,and the Chiu score standard was used to evaluate the pathological damage.Apoptosis was evaluated through TUNEL staining and the apoptotic index(AI).Diamine oxidase(DAO)level was measured by ELISA.The expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein,cleaved caspase-3,Wnt3a and β-catenin proteins were detected by Western blot.RESULTS:Compared with sham group,the mice in I/R group showed significantly increased Chiu score,elevated DAO level and AI(P<0.05),up-regulated cleaved caspase-3 and Bax protein levels,and down-regulated Bcl-2,Wnt3a and β-catenin protein levels(P<0.05).Treatment with RSV reversed these alterations(P<0.05).XAV939 co-administration abolished the protective effects of RSV(P<0.05).CONCLUSION:Resveratrol ameliorates intestinal I/R injury by acti-vating the Wnt/β-catenin signaling pathway and suppressing apoptosis.

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.

[Objective]To investigate the protective effect of overexpressed miRNA-200a&c on Angiostrongylus cantonensis-induced demyelinating optic neuritis in Balb/c mice.[Methods]SPF-grade Balb/c mice(2-3 weeks old)were divided into four groups:a normal group,and three A.cantonensis-infected groups at 7,14,and 21 days post-infection(dpi).Body weight,survival status,neurobehavioral scores,and visual function scores were recorded.Visual evoked potential(VEP)was used to detect visual damage,and transmission electron microscope(TEM)was applied to observe ocular structural changes.On day 7 post-infection,mice were stereotactically injected with exogenous miRNA-200a&c mimics into the lateral ventricle,and then divided into four groups:normal control,A.cantonensis-infected(AC-21 dpi),A.cantonensis-infected+negative control(AC+NC),and A.cantonensis-infected+overexpressed miRNA-200a&c(AC+miRNA-200a&c)mimics.VEP and TEM were repeated to assess visual damage and ocular structural changes.Immunofluorescence was performed to quantify retinal ganglion cells(RGCs)and oligodendrocytes(OLs)in the optic nerve.[Results]At 21 dpi,some mice exhibited complete eyelid closure(32.52±4.67)%or ocular atrophy(15.79±3.23)%,weight loss(P＜0.05)and altered consciousness.Neurobehavioral scores significantly decreased(P＜0.01),with a 68%decline in rotarod performance;some mice even displayed hemiplegia,slowed movement,ataxia,and directional deficits.Additionally,a subset of mice showed diminished sensory responses,unilateral vision loss(83%reduction in optokinetic threshold),and impaired visual function(P＜0.05).VEP results revealed a mild prolongation of latency in infected mice at 21 dpi(P＜0.05),predominantly affecting one eye.Following overexpression of miRNA-200a&c,compared with the 21 dpi group,VEP showed significantly shortened P1 latency(P＜0.05);TEM showed alleviated cytoplasmic swelling of RGCs,and improved compactness and uniformity of myelin sheath(P＜0.05);immunofluorescence showed increased numbers of RGCs and OLs with improved cell alignment(P＜0.05).[Conclusions]A.cantonensis infection induces demyelinating optic neuritis in Balb/c mice.Overexpression of miRNA-200a&c alleviates the resulting damage and ameliorates ocular injury.

BackgroundMetabolic syndrome （MetS） is highly prevalent in patients with mental disorders， including elevated diastolic or systolic blood pressure， elevated fasting glucose， hypercholesterolemia， abdominal obesity and so on. As an important component of MetS， the relationship between hypercholesterolemia and mental disorder has been extensively reported， whereas few genome-wide association studies （GWAS） have been conducted to identify the causal role of mental disorders in hypercholesterolemia. ObjectiveTo explore the potential causal relationship between mental disorders and hypercholesterolemia by two-sample Mendelian randomization （MR） method. MethodsSummary data from GWAS were analyzed. Single nucleotide polymorphisms （SNPs） strongly associated with mental disorders were chosen as instrumental variables， and hypercholesterolemia was used as outcome variable. MR analysis utilized inverse-variance weighted （IVW）， MR-Egger regression and weighted median estimation （WME） as the primary analytical tool， and supplemented by simple mode （SM） and weighted mode （WM）. The causal relationship between mental disorders and the risk of hypercholesterolemia was illustrated in terms of odds ratio （OR）. ResultsA total of 36 SNPs associated with mental disorders were identified as instrumental variables. The primary findings from IVW revealed existence of a causal relationship between mental disorders and hypercholesterolemia （IVW： OR=1.067， 95% CI： 1.026~1.109， P=0.001）. Findings from the additional methods （MR-Egger regression， WME， SM， WM） were basically consistent with those reported in IVW method. Further verification indicated that the causal relationship between mental disorders and the risk of hypercholesterolemia was not affected by genetic polymorphism （P>0.05）. The absence of heterogeneity was confirmed through Cochran's Q test and MR-Egger regression （P>0.05）. Furthermore， no causal association in the reverse direction was found （P>0.05）. ConclusionThere is a causal relationship between mental disorders and hypercholesterolemia， and patients with mental disorders may have an increased probability of suffering from hypercholesterolemia.

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 analyze the diagnostic and prognostic value of platelet aggregation rate in sepsis-related coagulation disorders. Methods: A total of 238 patients with sepsis were enrolled from Xinjiang Uygur Autonomous Region People's Hospital between June 2021 to June 2024. Patients were divided into coagulation dysfunction group (n=142) and non-dysfunction group (n=96) based on the occurrence of sepsis-related coagulation dysfunction. The general data, platelet aggregation rate and coagulation-related indicators of the two groups were compared. The 28-day survival outcomes were evaluated, and platelet aggregation rates were compared between survivors and non-survivor groups. Factors influencing the occurrence of sepsis-related coagulation dysfunction were analyzed. ROC curves were used to evaluate the predictive value of platelet aggregation rate for the prognosis of sepsis-related coagulation dysfunction. Results: Compared to the non-dysfunction group, APACHE II score, procalcitonin (PCT), activated partial thromboplastin time (APTT), platelet aggregation rate, and SOFA score were higher in the dysfunction group, while fibrinogen (Fib) was lower in the dysfunction group (P<0.05). The values were: (18.30±2.00) points vs (10.76±1.42) points, (7.27±2.10) ng/mL vs (3.87±1.62) ng/mL, (46.78±3.22) s vs (40.43±0.90) s, (69.07±6.32)% vs (55.78±2.96)%, (7.91±2.21) points vs (4.72±1.76) points, (243.23±40.91) mg/dL vs (342.09±46.58) mg/dL, respectively. The APTT、PCT level, platelet aggregation rate, APACHE II score and SOFA score were all risk factors for the development of sepsis-related coagulation dysfunction (OR>1, P<0.05). The platelet aggregation rate was higher in the non-survivor group compared to the survivor group (74.10±5.19 vs 66.05±4.87, P<0.05). The combination of platelet aggregation rate and PCT yielded the highest AUC for prediction, which was significantly greater than that of either single indicator (platelet aggregation rate: AUC=0.868; PCT: AUC=0.854, P<0.05). Conclusion: Platelet aggregation rate is an independent risk factor for the development of sepsis-associated coagulation dysfunction, and also an effective predictor for the prognosis of patients with sepsis coagulation dysfunction.

Objective: To genotype 50 RhD variant samples from Guangzhou, China, using our previously established genotyping strategy, thereby providing guidance for transfusion management and antenatal monitoring in RhD-variant individuals. Methods: Between June and August 2024, fifty samples identified as RhD variants during RhD-negative confirmation testing at Guangzhou Blood Center were collected. Serological testing for the D antigen was performed with two different anti-D reagents, and the epitope profiles of the D antigen were determined using a commercial panel of monoclonal anti-D reagents containing nine kinds of monoclonal anti-D. Genomic DNA was extracted, and high-resolution melting (HRM) analysis was applied to detect the Asian-type DEL (RHD 1227A). Subsequently, RHD genotyping was carried out using Multiplex Ligation-dependent Probe Amplification (MLPA) and Sanger sequencing. Results: Among the 50 D variant samples, 17 (34.0%) Asian type DEL samples were detected by HRM, including 13 cases with RHD DEL1/01N.01 genotype and 4 cases with RHD DEL1/DEL1 genotype. Eleven (11/50, 22.0%) samples were typed as DVI by the epitope profiles of D antigen. The epitope profiles of D antigen combined with Sanger sequencing of exon 6 identified 5 (5/50, 10.0%) cases of RHD weak partial 15/01N.01. MLPA combined with Sanger sequencing identified two cases of RHD DVI.3/DEL1, representing 4.0% (2/50) of the samples. Additionally, the following RHD genotypes were each detected in one case: RHD weak D type 18/01N.04, RHD weak D type 72/01N.01, RHD weak D type 95/DEL1, RHD weak D type 114/DEL1, RHD weak D type 136/DEL1, RHD weak D type 147/01N.01, RHD 496G/496G, RHD 536C/01N.01, RHD 689A/689A, RHD 689A/DEL1, RHD DEL32/DEL1, RHD DV.1/01N.01, RHD DV.5/01N.01, RHD 01.01/01N.01, and RHD 01/01N.01. Conclusion: Fifty D variant individuals were typed using our previously established serological and molecular approach. These findings provide guidance for precision transfusion therapy in RhD variant patients and inform evidence-based decisions regarding anti-D immunoglobulin prophylaxis for RhD variant pregnant women.

Objective: To investigate the distribution characteristics of Kidd blood group antigens, phenotypes and genotypes in Xinjiang and their influence on the risk of coronary heart disease. Methods: Samples from 7 981 patients treated at People's Hospital of Xinjiang Uygur Autonomous Region from August 1, 2023 to May 31, 2024 were collected for Jk(a-b-) phenotype screening via urea hemolysis test, followed by the third-generation sequencing (TGS). Kidd blood group Jk and Jk antigens in 1 081 patients with coronary heart disease and 1 021 healthy people were detected, and their phenotype frequency distribution was analyzed and corresponding gene frequencies were calculated. Correlation analysis and logistic regression were used to evaluate the influence of Kidd blood group antigen expression on coronary heart disease risk. Results: Two Jk(a-b-) phenotype samples were detected, both resulting from novel gene mutation combinations. Comparative analysis of two groups revealed a higher proportion of the Jk(a-b+) phenotype in the case group (22.5%, 243/1 081) than in the control group (18.5%, 189/1 021). Moreover, Kidd blood group phenotype distribution varied significantly across all ethnic groups in the case group (P<0.05). In the control group, the Hui ethnic group exhibited the highest JK JK genotype frequency 64.15% (34/53). In the case group, the highest JK allele frequency was observed in Mongol ethnic group 56.31% (125/222), and the lowest in Han patients 45.71% (341/746). The expression of Jk antigen was negatively correlated with coronary heart disease (P<0.05). Conclusion: The distribution of Kidd blood group system varied across ethnic groups in Xinjiang. The expression of Jk antigen may have protective effect on coronary heart disease, which provides a basis for future clinical blood transfusion treatment and the mechanism study of the correlation between Kidd blood group and coronary heart disease.