Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

This paper reviews the published articles of recent years on the application of deep learning methods in automatic localization of acupoint, and summarizes it from 3 key links, i.e. the dataset construction, the neural network model design, and the accuracy evaluation of acupoint localization. The significant progress has been obtained in the field of deep learning for acupoint localization, but the scale of acupoint detection needs to be expanded and the precision, the generalization ability, and the real-time performance of the model be advanced. The future research should focus on the support of standardized datasets, and the integration of 3D modeling and multimodal data fusion, so as to increase the accuracy and strengthen the personalization of acupoint localization.
Deep Learning ; Acupuncture Points ; Humans ; Neural Networks, Computer

This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods* ; Male ; Animals ; Swine ; Acupuncture Points ; Humans ; Swine, Miniature ; Needles

Objective To observe the value of 2D SECara-Net and 3D U2-Net models constructed based on 2D maximal intensity projection(MIP)and 3D time-of-flight MR angiography(3D TOF-MRA)images,respectively,also of their combination for MRA detecting unruptured saccular intracranial aneurysms(USIA).Methods Totally 973 patients with single USIA and 300 subjects who underwent healthy physical examination were retrospectively collected and divided into training set(n=923,containing 723 cases of USIA and 200 healthy subjects)and test set(n=350,containing 250 cases of USIA and 100 healthy subjects)at the ratio of 7:3.Pre-processed 3D TOF-MRA and the obtained 2D-MIP images in training set were imported into 3D U2-Net and 2D SECara-Net models for training and adjusting parameters,respectively.The efficiency of 2 models and their combination for detecting USIA were evaluated.Results The sensitivity,specificity and accuracy of 2D SECara-Net model for detecting USIA in test set was 78.80％(197/250),95.00％(95/100)and 83.43％(292/350),of 3D U2-Net model was 82.80％(207/250),86.00％(86/100)and 83.71％(293/350),respectively.The specificity of 2D SECara-Net model was higher than that of 3D U2-Net model(P=0.030),while no significant difference of sensitivity nor accuracy was found between 2 models(both P＞0.05).The specificity of the combination of the 2 models was 99.00％(99/100),higher than that of 3D U2-Net model(P＜0.05),and the sensitivity and accuracy of the combination was 91.20％(228/250)and 93.43％(327/350),respectivelty,both higher than those of 2 single models(all P＜0.05).Conclusion 2D SECara-Net and 3D U2-Net models had similar,sensitivity and accuracy for MRA detecting USIA.Combination of them could improve the detecting efficacy.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the short-term efficacy of the retrograde semi-retrieval technique(RESET)in the treatment of patients with acute intracranial large vessel occlusion.Methods This retrospective study involved 286 patients with acute intracranial large vessel occlusion who underwent mechanical thrombectomy using RESET at Tianjin Huanhu Hospital from November 2017 to March 2019.The patients were divided into two groups based on the presence or absence of intracranial atherosclerotic stenosis(ICAS):ICAS group(n=186,65％)and non-ICAS group(n=100,35％).Baseline characteristics,procedural outcomes,and 90-day modified Rankin Scale(mRS)scores were compared between the two groups.Results The two groups did not significantly differ in baseline characteristics,including age,gender,past medical history,on-admission National Institutes of Health Stroke Scale(NIHSS)score,and Alberta Stroke Program Early CT(ASPECT)score(all P＞0.05).Successful vascular recanalization was achieved in 272 patients(95.1％),with 209 patients(73.1％)achieving complete recanalization with a single thrombectomy attempt.Rescue therapy was required in 33 patients(11.5％).Two patients in the ICAS group died due to postoperative symptomatic intracranial hemorrhage,and one patient in the non-ICAS group died due to postoperative multiple organ failure.Compared with the non-ICAS group,the ICAS group had a significantly longer puncture-to-recanalization time[141.36(124.11,156.53)min vs.65.17(53.92,83.25)min,P＜0.001]but a significantly smaller number of thrombectomy attempts[1.00(1.00,1.00)vs.1.00(1.00,2.00),P=0.002].However,there were no significant differences between the two groups in terms of final recanalization rate,complete recanalization rate with a single thrombectomy attempt,distal embolism or embolization of new territory,symptomatic intracranial hemorrhage,perioperative death,or 90-day mRS score(all P＞0.05).Conclusion RESET demonstrates satisfactory short-term efficacy in the treatment of acute intracranial large vessel occlusion.The number of thrombectomy attempts required for complete recanalization is significantly lower in the ICAS group than in the non-ICAS group,suggesting that RESET is particularly suitable for patients with ICAS.

Objective:To study the comparative genomic characteristics of Marmota himalayana-derived (referred to as marmota-derived) Brucella abortus (B.ab). Methods:The species and types of one strain of marmota-derived Brucella and one strain of human-derived Brucella isolated from the brucellosis epidemic area in Qinghai Province in the same year were identified. Meanwhile, DNA was extracted for whole genome sequencing and comparative genomics analysis (including phylogenetic tree construction, gene family clustering analysis, common/specific gene analysis, and genomic structural variation analysis, etc.). Results:Two Brucella strains from different hosts were identified as B.ab. By constructing a phylogenetic tree, the marmota-derived B.ab strain was grouped with strains from Heilongjiang Province and showed genetic correlation with strains from Russia. Human-derived B.ab strain was classified as a strain in Inner Mongolia Autonomous Region, Hebei Province, Beijing City, and Gansu Province. The multilocus sequence typing (MLST) of the two strains belonged to the ST2 type. Multiple locus variable-number tandem repeat analysis (MLVA) belonged to two new MLVA-8 and MLVA-11 genotypes, which were clustered in two subclusters of the same cluster and clustered with the strains from Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, and Hebei Province. The pan-genome numbers of the marmota-derived B.ab and human-derived B.ab were 283 and 8, respectively; the number of core genes (common genes) was 68 and 2, respectively; and the number of unique genes was 3 and 4, respectively. The unique gene encoded proteins were inconsistent. In marmota-derived B.ab, the main ones were the ABC transporter ATP-binding protein, N-terminal acetyltransferase, and glucose/galactose transporter. The number of homologous genes of the marmota-derived B.ab and human-derived B.ab was 16 and 20, respectively; the number of translocation and inversion genes was 13 and 8, respectively; the number of deletion mutation genes was 11 and 14, respectively. Pathogenicity analysis showed that both strains had the mprF resistance gene, and the marmota-derived B.ab strain also carried bacitracin and macrolide resistance genes. Conclusions:Brucella exhibits cross-species genetic diversity. The proteins encoded by the unique genes of the marmota-derived B.ab mainly play a role in metabolic and epigenetic regulation. The strains cluster with B.ab strains from northern China, providing a reference for molecular epidemiology and pathogen tracing of B.ab infection.

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.