The patient was a 56-year-old man who presented with abnormal urinalysis findings of over one month’s duration. Serological tests revealed an elevated serum free light chain κ/λ ratio, and immunofixation electrophoresis detected an IgG-κ monoclonal band. Renal biopsy demonstrated membranous nephropathy, with electron-dense deposits observed in the subepithelial space and mesangium on electron microscopy. Immunofluorescence confirmed glomerular deposits of IgG_1/IgG₃-κ. Based on clinical manifestation, bone marrow flow cytology, and lymph node pathology, the patient was diagnosed with small lymphocytic lymphoma (SLL), and membranous nephropathy with light chain-restricted deposition (IgG₁/IgG₃-κ) secondary to SLL. After receiving obinutuzumab treatment, the patient’s proteinuria partially remitted, the lymph nodes significantly shrank, and clinical remission was achieved.

N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl₄) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.

Objective: To evaluate the platelet transfusion requirements in children with high-risk stage Ⅳ neuroblastoma undergoing autologous hematopoietic stem cell transplantation (ASCT), and to identify risk factors for increased transfusion needs and prolonged time to platelet transfusion independence. Methods: This single-center retrospective clinical study included 96 children with high-risk stage Ⅳ neuroblastoma who underwent ASCT from January 2019 to May 2024 in our hospital. Relevant clinical data were collected and analyzed, including age, gender, body surface area, platelet count (PLT) on stem cell infusion day (day 0), conditioning regimen, CD34 stem cell dose, platelet transfusion requirements during transplantation, and time to platelet transfusion independence post-transplant. Results: All 96 (100%) children received transfusion after ASCT. From day 0 to transfusion independence, the median number of platelet transfusion was 3 (2, 4.50), and the median volume of platelet transfused was 3 (2, 4.25) units. Platelet transfusion was required in almost all children in pseudo-healing stage (day 4 to day 6) and polar stage (day 7 to day 14), with transfusion rates as high as 83.33%(n=80) and 100%(n=96), respectively. The median time to platelet transfusion independence post-transplant was 13(11,17) days. Multivariate analysis showed that PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, the use of “busulfan+ melphalan” conditioning regimen, and CD34 stem cell dose<4.0×10 /kg were associated with significantly increased platelet requirements and numbers of transfusion (P<0.05). PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, and CD34 stem cell dose<4.0×10 /kg were associated with significantly delayed platelet transfusion independence (P<0.05). Age, sex, and blood type showed no statistically significant association (P>0.05) with post-transplant platelet transfusion requirements or time to transfusion independence in neuroblastoma patients. Conclusion: This study provided quantitative data for platelet transfusion after ASCT in children with high-risk stage Ⅳ neuroblastoma, and identified PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, CD34 stem cell dose<4.0×10 /kg were risk factors for increased platelet transfusions and delayed transfusion independence. Furthermore, the use of the BuMel (busulfan-melphalan) conditioning regimen was also found to contribute to increased transfusion requirements.

Objective: To evaluate the platelet transfusion requirements in children with high-risk stage Ⅳ neuroblastoma undergoing autologous hematopoietic stem cell transplantation (ASCT), and to identify risk factors for increased transfusion needs and prolonged time to platelet transfusion independence. Methods: This single-center retrospective clinical study included 96 children with high-risk stage Ⅳ neuroblastoma who underwent ASCT from January 2019 to May 2024 in our hospital. Relevant clinical data were collected and analyzed, including age, gender, body surface area, platelet count (PLT) on stem cell infusion day (day 0), conditioning regimen, CD34 stem cell dose, platelet transfusion requirements during transplantation, and time to platelet transfusion independence post-transplant. Results: All 96 (100%) children received transfusion after ASCT. From day 0 to transfusion independence, the median number of platelet transfusion was 3 (2, 4.50), and the median volume of platelet transfused was 3 (2, 4.25) units. Platelet transfusion was required in almost all children in pseudo-healing stage (day 4 to day 6) and polar stage (day 7 to day 14), with transfusion rates as high as 83.33%(n=80) and 100%(n=96), respectively. The median time to platelet transfusion independence post-transplant was 13(11,17) days. Multivariate analysis showed that PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, the use of “busulfan+ melphalan” conditioning regimen, and CD34 stem cell dose<4.0×10 /kg were associated with significantly increased platelet requirements and numbers of transfusion (P<0.05). PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, and CD34 stem cell dose<4.0×10 /kg were associated with significantly delayed platelet transfusion independence (P<0.05). Age, sex, and blood type showed no statistically significant association (P>0.05) with post-transplant platelet transfusion requirements or time to transfusion independence in neuroblastoma patients. Conclusion: This study provided quantitative data for platelet transfusion after ASCT in children with high-risk stage Ⅳ neuroblastoma, and identified PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, CD34 stem cell dose<4.0×10 /kg were risk factors for increased platelet transfusions and delayed transfusion independence. Furthermore, the use of the BuMel (busulfan-melphalan) conditioning regimen was also found to contribute to increased transfusion requirements.

Objective:To investigate the impact of correcting rotational subluxation through circumferential fusion and transforaminal lumbar interbody fusion (TLIF) on postoperative coronal plane imbalance in degenerative scoliosis.Methods:A retrospective analysis was conducted on the data of 108 patients with type A degenerative scoliosis in the Nanjing classification who underwent primary multi-segment posterior column osteotomy (PCO) with deformity correction and internal fixation at Nanjing Gulou Hospital from June 2017 to June 2021. Patients were divided into two groups based on the presence of preoperative rotational subluxation: the rotational subluxation group and the non-rotational subluxation group. The rotational subluxation group consisted of 60 patients, with 8 males and 52 females, aged 63.7±5.5 years (range, 56-75 years). The non-rotational subluxation group included 48 patients, with 5 males and 43 females, aged 64.4±5.2 years (range, 53-72 years). Within the rotational subluxation group, depending on whether TLIF was performed on the rotational subluxation segment, they were further categorized into the TLIF group and the PCO group. The TLIF group comprised 28 patients, while the PCO group had 32 patients. Full-spine anteroposterior and lateral X-rays were taken preoperatively, postoperatively, and at the last follow-up to measure coronal balance types and radiographic parameters. The differences in the lumbar Cobb angle, coronal balance distance (CBD), and the Cobb angle of the lumbosacral curve (Cobb-Fra angle) were compared between the rotational subluxation group and the non-rotational subluxation group, as well as between the TLIF group and the PCO group.Results:The average surgery duration ranged from 200 to 310 min, with a mean of 235±47 min. The intraoperative blood loss ranged from 700 to 2,400 ml, with an average of 950±355 ml. The number of fused segments in the rotational subluxation group was 7.6±2.1, ranging from 5 to 11 segments, while in the non-rotational subluxation group, it was 7.4±2.0, ranging from 5 to 10 segments. Postoperatively, 13%(8/60) of patients in the rotational subluxation group developed type C coronal imbalance, significantly higher than the 2%(1/48) in the non-rotational subluxation group. The immediate postoperative and final follow-up lumbar Cobb angles, CBD, and Cobb-Fra angles in the rotational subluxation group were 20.60°±10.73° and 20.33°±10.92°, 22.53±16.45 mm and 18.53±17.31 mm, 13.14°±4.40° and 11.23°±4.92°, respectively, which were higher than those in the non-rotational subluxation group (13.92°±7.02° and 12.92°±6.64°, 18.62±17.44 mm and 8.83±8.95 mm, 11.91°±3.03° and 9.52°±3.30°), with statistical significance ( P<0.05).. Among patients in the rotational subluxation group, the probability of new-onset coronal imbalance postoperatively was 4%(1/28) in the TLIF group, which was lower than the 22%(7/32) in the PCO group, with a statistically significant difference (χ 2=4.330, P=0.037). The immediate postoperative and final follow-up lumbar Cobb angles, CBD, and Cobb-Fra angles in the PCO group were 25.63°±11.00° and 25.13°±11.04°, 27.37±18.95 mm and 25.25±18.67 mm, 15.50°±3.62° and 14.08°±4.77°, respectively, which were significantly higher than those in the TLIF group (14.86°±6.96° and 14.86°±5.37°, 17.08±10.94 mm and 10.86±7.86 mm, 10.14°±3.37° and 8.46°±2.66°), with statistical significance ( P<0.05). Conclusion:For patients with Type A degenerative scoliosis combined with rotational subluxation according to the Nanjing classification, performing a 360-degree circumferential release and interbody fusion at the segment with rotatory subluxation can reduce the risk of developing new postoperative coronal imbalances.

Aim To explore the mechanism of Epimedii folium-Astmgali radix activating the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way and its effect on sperm production and vitality in oligoasthenospermia.Methods Sixty male SD rats were used to establish a model of oligoasthenospermia with cyclophosphamide.They were randomly divided into six groups:experimental group(further divided into high,medium,and low dose group),model group,control group and blank group.The oligoasthenosper-mia model was established by using cyclophosphamide in experimental group,levocarnitine group and model group.The rats in the high,medium,and low dose group of the experimental group were orally adminis-tered Epimedii folium-Astmgali radix extract at doses of 800,400,and 200 mg·kg-1,respectively,Once daily for 35 days.Rats of the control group were orally ad-ministered 250 mg·kg-1·d-1 of levocarnitine,Once daily for 35 days.ELISA was used to detect serum of T,E2,FSH,and LH.Western blot and IHC staining were used to detect the expression of SCF,c-kit,Bcl-2,Bax,PI3K,and Akt proteins in rat testicular tissues.Sperm activity is examined by microscopy.The testicu-lar tissue structure and cell morphology of rats in each group were observed.Results Compared with the model group,Epimedii folium-Astmgali radix increased the sperm density,total viability rate,and vitality(P＜0.05,P＜0.01),decreased sperm apoptosis rate and LH,T,and E2 levels(P＜0.05,P＜0.01),decreased Bax protein expression in testicular tissue(P＜0.01),and increased Bcl-2,SCF,c-Kit,PI3K,and Akt protein expression(P＜0.05,P＜0.01);it increased the number of germ cells,thickened basement membrane,and significantly improved seminiferous tubule mor-phology,even showing germ cells at different develop-mental stages and mature sperm.Conclusions Epi-medii folium-Astmgali radix has a significant therapeu-tic effect on oligoasthenospermia in rats.Its mechanism may be related to the activation of the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way promoting the proliferation and differentiation of germ cells,and promoting sperm production,maturation and motility.

Objective:To apply artificial intelligence（AI）in classifying ovarian tumors on ultrasound images，and compare the diagnostic results of several sonographers with varying seniority levels.Methods:A total of 645 patients diagnosed with adnexal masses via gynecological ultrasound examination at Qilu Hospital of Shandong University from January 2021 to December 2024 were enrolled. Three deep learning architectures，i.e.，Alexnet，Densenet121，and Resnet50 were developed and used to internally test the classification effectiveness of ovarian tumors，while the optimal model was selected for external testing. Two junior sonographers and two senior sonographers were recruited to independently diagnose ovarian tumors in the external test dataset. Subsequently，the benign and malignant results of the model's predictions were disclosed to each sonographer，and their revised diagnoses on the same external test data in combination with the best AI model were recorded.Results:The optimal model achieved an accuracy of 0.941，sensitivity of 0.936，and specificity of 0.944 on the internal test dataset，and maintained robust performance on the external test dataset with accuracy of 0.891，sensitivity of 0.880，and specificity of 0.907. Compared to junior sonographers，the optimal model demonstrated significantly higher sensitivity in discriminating benign from malignant ovarian tumors（0.880 vs. 0.723，0.602；all P<0.05）. No statistically significant difference was observed in diagnostic accuracy between the optimal model and senior sonographer 1（ P=0.05）. With assistance from the optimal model，junior sonographers achieved significant improvements in both sensitivity and specificity（sensitivity：0.723 vs. 0.843，0.602 vs. 0.819；specificity：0.778 vs. 0.833，0.685 vs. 0.741；all P<0.05）. Conclusions:The optimal model achieves comparable performance to that of senior sonographers in ovarian tumor classification. With model assistance，the diagnostic performance of junior sonographers is significantly improved.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

TAFRO syndrome is an idiopathic systemic inflammatory disease that overlaps with idiopathic multicentric Castleman disease (iMCD). The clinical features of TAFRO syndrome include thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis/renal insufficiency (R) and organomegaly (O). The paper reports a special clinical subtype of iMCD—TAFRO syndrome in a patient, manifested as multiple-system involvement including serous effusion (ascites), fever, thrombocytopenia, anemia, multiple lymphadenopathies, pancreatitis and renal insufficiency. Bone marrow biopsy pathology showed active bone marrow hyperplasia. Renal biopsy revealed renal thrombotic microangiopathy, acute renal tubular interstitial injury combined with chronic lesions. Lymph node biopsy demonstrated lymphoproliferative lesions consistent with Castleman disease (hyaline vascular type). Following diagnosis, glucocorticoids, tacrolimus, rituximab and lenalidomide were administered, resulting in significant symptomatic improvement: ascites disappeared, and urinary findings, erythrocyte counts, renal function and hematological indexes normalized. The paper describes the patient's clinical manifestations, diagnosis and treatment process, and prognosis, and reviews relevant literature, to improve clinicians' understanding of this rare disease.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.