Background: The heterogeneity in the health burden and non-infectious risk factors of Burkitt lymphoma (BL) across sex, age, and geographic distribution remain inadequately understood. Methods: Based on Global Burden of Disease study 2021, we estimate the health burden of BL from four metrics: incidence, mortality, prevalence, and disability-adjusted life years. Subgroups were stratified by age, sex, region, and socio-demographic index (SDI). Joinpoint regression was used to evaluate the average annual percentage change (AAPC) to quantify trends in the health burden. Predictions were performed using the Bayesian age-period-cohort model. Non-infectious risk factors were identified and analyzed utilizing summary exposure values (SEVs) to assess their impact on BL incidence and mortality. Results: The estimated global incident number of BL was 19,073 (95% CI: 9651 to 32,509) in 2021, nearly threefold that of 1990. The health burden of BL was markedly higher in males than females, especially among individuals aged under 20 years. From 1990 to 2021, the most significant increasing trend in BL health burden was observed in Cabo Verde, while Georgia exhibited the most notable decline. From 2021 to 2040, the global age-standardized incidence and mortality rates were projected to decline by 14.7% and 24.7%, respectively. Conversely, the health burden on individuals aged 20 to 54 years was anticipated to rise through 2040. In our study, low bone mineral density was found to be linked with elevated risk for males aged over 54 years, while childhood sexual abuse exhibited a paramount positive association with BL risk for females, regardless of age. Notably, tobacco use, particularly secondhand smoking, were inversely associated with BL risk across all age groups and sexes. Conclusion: Burkitt lymphoma demonstrated unique distribution patterns in terms of age, sex, and region. Further investigations into the heterogeneity of the risk factors for BL are essential for the development of more effective health policies and clinical practices.

BackgroundRural communities in Southwest China are undergoing rapid nutrition and lifestyle transitions, with sustained positive energy balance and long-term weight gain. These settings are often ethnic minority-dominant and characterized by higher habitual alcohol consumption than most other Chinese populations. Evidence on how life-course adiposity relates to metabolic liver fat burden in such a rural community with varying alcohol drinking frequency remains limited. We examined associations of current BMI, life-course BMI trajectories, and long-term BMI change with controlled attenuation parameter (CAP)-defined hepatic steatosis.MethodsWe conducted a retrospective cohort analysis embedded within a routine health examination program in Ning’er County, Yunnan Province, China. Adults who underwent an index examination including vibration-controlled transient elastography (VCTE) were included. Hepatic steatosis and severe steatosis were defined as CAP ≥238 and ≥292 dB/m, respectively. Body weight and height at ages 18, 30 and 40 years were extracted from prior health examination records, and BMI at each time point was calculated and categorized using Chinese cut-offs to construct life-course trajectory patterns. Multivariable logistic regression estimated odds ratios (ORs) for CAP-defined outcomes adjusting for age, sex, ethnicity, smoking, and past-year alcohol drinking frequency, with further adjustment for waist circumference and metabolic and liver biomarkers. Restricted cubic splines evaluated dose–response associations between long-term BMI change (ΔBMI from age 18 to the index examination) and steatosis.ResultsAmong 956 adults (predominantly ethnic minorities), the prevalence of CAP-defined steatosis and severe steatosis was 52.9 and 18.2%, respectively. Higher current BMI and weight-gain or persistent-obesity trajectory patterns were associated with greater odds of steatosis and severe steatosis. After additional adjustment, BMI ≥ 28.0 kg/m2 remained independently associated with steatosis (OR 2.08; 95% CI 1.05–4.14), whereas associations with severe steatosis were attenuated. Long-term BMI gain was monotonically associated with steatosis, with the OR becoming statistically significant at ΔBMI 6.64 kg/m2. Alcohol drinking frequency showed no strong independent association with CAP-defined outcomes.ConclusionIn this ethnic minority-dominant rural population with relatively frequent self-reported alcohol use, sustained weight gain across adulthood and adverse life-course BMI trajectories were associated with a higher burden of CAP-defined hepatic steatosis and severe steatosis. These findings support the importance of life-course weight maintenance for reducing liver fat accumulation in rural community settings.

Ultrasound-based computer-aided diagnosis (CAD) has indicated effectiveness for developmental dysplasia of the hip (DDH). Recently, foundation models have shown promising potential to further improve the performance of a CAD model. However, their deployment in clinical applications remains challenging due to the high computational cost and overfitting risk of full fine-tuning. To address this issue, a new memory-efficient adaptation framework, named External Spatial Adapter Tuning (ESAT), is proposed for the CAD of DDH. The ESAT develops spatial adapters based on lowrank depthwise separable convolution at each layer of foundation model, so as to extract and refine hierarchical spatial features. These adapter outputs are further fused externally for the classification task, so that the gradient flow is fully decoupled from the foundation model. In real-world DDH diagnosis experiments, the ESAT requires only 30.16 % and 0.304 % of the memory and parameter usage on ViT-Base (as foundation model) compared with the full fine-tuning, yet achieves higher diagnostic accuracy than the full fine-tuning and other parameter-efficient tuning methods.

Background:Although obesity is a well-established risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the impact of long-term weight trajectories on MASLD risk remains unclear. We aimed to examine the association between weight change trajectories across adulthood and the risk of ultrasound-defined MASLD. Methods:We analysed data from 4999 participants from the Healthy Happy Aging Community Cohort. Weight trajectories were assessed using body mass index (BMI) at age 25 years, ten years before baseline, one year before baseline, and at baseline. MASLD was defined as a median (MD) controlled attenuation parameter (CAP) of ≥274 dB/m and severe steatosis as a MD CAP of ≥302 dB/m via vibration-controlled transient elastography. Results:There were 2247 (44.9%) patients with MASLD, of whom 1468 (29.4%) had severe steatosis. Compared with stable normal weight, sustained obesity (BMI ≥ 30 kg/m2 at all time points) demonstrated a strong association with MASLD risk (adjusted odds ratio (aOR) = 2.17; 95% confidence interval (CI) = 1.64-2.86), particularly for severe steatosis (aOR = 2.52; 95% CI = 1.74-3.66). The transition from non-obese to obese status was associated with a 2.5-fold increase in risk (aOR = 2.51; 95% CI = 1.81-3.48), with a more pronounced effect observed in men (P-interaction <0.05). Weight gain of ≥5 kg between ages 25-40 years showed particularly strong associations (aOR = 2.20; 95% CI = 1.70-2.86), while baseline severe obesity (BMI ≥ 35 kg/m2) remained the strongest independent predictor (aOR = 4.12; 95% CI = 2.70-6.29). Conclusions:Long-term obesity and weight gain, especially in early adulthood, significantly increase MASLD risk. Sustained obesity and progression to obesity were key risk factors, with severe obesity showing the strongest association. Early weight management is crucial for MASLD prevention.

Large granular lymphocytic leukemia (LGLL) represents a rare, indolent T-cell lymphoproliferative disorder. Clinically, it frequently manifests as cytopenia and organ infiltration. First-line immunosuppressive therapy induces clinical remission in approximately one-third to one-half of patients. Nevertheless, a significant proportion of patients experience a chronic disease course, necessitating long-term disease management. Precision medicine emerges as the pivotal future direction for this disease, with advances in molecular biology serving as the most potent driving force. In recent years, facilitated by the widespread adoption of next-generation sequencing technologies, the diagnostic and prognostic significance of gene mutations – such as those in STAT3 and STAT5B – has become increasingly elucidated within LGLL. These discoveries concurrently provide a rational foundation for exploring targeted therapeutic approaches, notably JAK inhibitors. However, the molecular landscape of LGLL remains substantially uncharted territory, warranting dedicated research efforts. This review synthesizes current progress in the molecular biology of LGLL, aiming to stimulate further investigation and offer insights for researchers in the field.

INTRODUCTION:Splenic marginal zone Lymphoma (SMZL) is a rare, chronic B lymphocyte proliferative disease. Generally, SMZL is accompanied by circulating atypical villous lymphocytes, known as SMZL with villous lymphocytes. Rituximab is a chimeric monoclonal antibody to CD20; recent but limited studies have confirmed its effectiveness in treating SMZL. Given the low incidence and selection of treatment, statistical comparisons of rituximab monotherapy with other available treatment options with the full range of data from previous clinical studies remain sparse. Here, we report a case of SMZL with villous lymphocytes treated by rituximab monotherapy, which is especially infrequently reported. CASE REPORT:A 63-year-old Chinese female was presented to the hospital with complaints of splenomegaly and pain in the spleen area. Immunohistochemistry analysis was positive for IGH, IGK, and IGL clonal rearrangement. Villous lymphocytes were found in peripheral blood and bone marrow, along with further immunotyping results. The case was considered as SMZL with villous lymphocytes. Based on the SMZLSG prognosis assessment, we applied rituximab monotherapy. After eight cycles of rituximab treatment, the patient's condition improved markedly, with blood constituent and size of the spleen returning to normal levels, achieving complete response, with no significant side effect observed. DISCUSSION:The patient provides a typical SMZL with villous lymphocytes case treated with rituximab monotherapy. Currently, the main treatment options include splenectomy and rituximab. After synthesizing a series of current views, we put forward our opinion about the selection of therapy for SMZL patients in order to gain maximum benefits for patients in need of treatment. CONCLUSION:Our analysis found no statistically significant difference between rituximab monotherapy and rituximab combined with chemotherapy, while rituximab treatments resulted in better therapeutic effects than chemotherapy. Rituximab monotherapy has favorable therapeutic effects and minor adverse effects (AEs) in treating SMZL.

ObjectiveTo explore the correlation between the quantitative analysis curve of renal contrast-enhanced ultrasound and the anatomical location of renal cortical microcirculation associated with acute kidney injury.MethodsThis study included a 1-year-and-11-month-old female child with acute kidney injury caused by drug overdosed and a 14-year-old female child with acute kidney injury caused by drug intentional, who were treated at Shanghai Children's Medical Center affiliated with Shanghai Jiao Tong University School of Medicine. Both patients underwent renal contrast-enhanced ultrasound and quantitative analysis. In addition, their clinical medical history data were recorded.ResultsThe first child developed acute kidney injury owing to cyclosporine A overdosed. Contrast-enhanced ultrasound revealed poor cortical blood flow perfusion in both kidneys, with abnormally prolonged cortical perfusion times and possible obstruction of vascular inflow pathways. The second child experienced acute kidney injury owing to ibuprofen intentional. Contrast-enhanced ultrasound showed good cortical blood wash-in/perfusion but significantly delayed wash-out/excretion.ConclusionThe structure and function of the glomerulus significantly influence the perfusion rate and intensity of the rising branch of the curve. Furthermore, the descending branch of the curve is affected by the interplay of the capillaries surrounding the renal tubules. Exploration of these anatomical structures aids in understanding the renal microcirculation pathways and provides further insight into renal perfusion dynamics.

Indolent T-cell lymphoma of the gastrointestinal tract (iTCL-GI) is rare, lacking standardized treatments. We report a successful venetoclax treatment in one patient with indolent T-cell lymphoma of the gastrointestinal tract. A 35-year-old male was admitted due to complaints of anemia and hematochezia. He was diagnosed with iTCL-GI according to histopathology and next-generation sequencing (NGS). He received the first cycle of CHOP-E chemotherapy, but he continued to have intermittent blood in stools. After starting oral Bcl-2 inhibitor venetoclax, the results of peripheral hemogram and the body temperature gradually turned normal, with no symptoms of hematochezia occurring again. In addition, colonoscopy showed improved ulcers in the ascending and transverse colon. Routine blood tests returned to normal without adverse effects. Therefore, venetoclax may represent a potential treatment approach for iTCL-GI. This report might provide clues for the future management of similar cases.

Cutaneous T-cell lymphoma (CTCL) is a type of lymphoma that affects the skin and has various subtypes with different features. It can be either slow-growing or aggressive and currently has limited treatment options, causing a significant impact on patients' quality of life. However, more research is needed to fully understand the underlying causes of the disease. Single-cell sequencing technology shows promise in comprehending the complex genome and microenvironment of CTCL. By analyzing the molecular status of each tumor cell, this approach can provide insights into tumor heterogeneity, microenvironment composition, and cell state transitions, tailoring treatment strategies to individual patients. In this review, we highlight recent research progress in CTCL via single-cell sequencing, focusing on gene alterations and related biomarkers, disease origin and progression, and the tumor microenvironment. We aim to provide examples of single-cell studies that can help inform new drug discovery and contribute to improved treatment strategies for patients with CTCL.

Accurate quantitative assessment using gadolinium-contrast magnetic resonance imaging (MRI) is crucial in therapy planning, surveillance and prognostic assessment of primary central nervous system lymphoma (PCNSL). The present study aimed to develop a multimodal artificial intelligence deep learning segmentation model to address the challenges associated with traditional 2D measurements and manual volume assessments in MRI. Data from 49 pathologically-confirmed patients with PCNSL from six Chinese medical centers were analyzed, and regions of interest were manually segmented on contrast-enhanced T1-weighted and T2-weighted MRI scans for each patient, followed by fully automated voxel-wise segmentation of tumor components using a 3-dimenstional convolutional deep neural network. Furthermore, the efficiency of the model was evaluated using practical indicators and its consistency and accuracy was compared with traditional methods. The performance of the models were assessed using the Dice similarity coefficient (DSC). The Mann-Whitney U test was used to compare continuous clinical variables and the χ2 test was used for comparisons between categorical clinical variables. T1WI sequences exhibited the optimal performance (training dice: 0.923, testing dice: 0.830, outer validation dice: 0.801), while T2WI showed a relatively poor performance (training dice of 0.761, a testing dice of 0.647, and an outer validation dice of 0.643. In conclusion, the automatic multi-sequences MRI segmentation model for PCNSL in the present study displayed high spatial overlap ratio and similar tumor volume with routine manual segmentation, indicating its significant potential.

The B-mode ultrasound based computer-aided diagnosis (CAD) has shown its effectiveness for diagnosis of Developmental Dysplasia of the Hip (DDH) in infants within 6 months. Hip landmark detection is a feasible way for the CAD of DDH according to the Graf's method. However, existing landmark detection algorithms mainly focus on designing special models to capture the features from hip ultrasound images, but generally ignore the important spatial relations among different landmarks. To this end, a novel weakly supervised learning-based algorithm, the Topological Graph Convolutional Network (TGCN) guided Improved Conformer (TGCN-ICF), is proposed for detecting landmarks from hip ultrasound images. The TGCN-ICF includes two subnetworks: an Improved Conformer (ICF) subnetwork to generate heatmaps and constraint vectors from ultrasound images, and a TGCN subnetwork to additionally explore topological relations among hip landmarks with the guidance of class labels for further refining and improving the detection accuracy. Moreover, a new Mutual Modulation Fusion (MMF) module is developed to fully exchange and fuse the extracted feature information from the convolutional neural network (CNN) and Transformer branches in ICF. Meanwhile, a novel Mutual Supervision Constraint (MSC) strategy is designed to provide a constraint for detection of each hip landmark. The experimental results on two real-world DDH datasets demonstrate that the TGCN-ICF outperforms all the compared algorithms, suggesting its potential applications.

Developmental dysplasia of the hip (DDH) is the most common congenital joint disease in infant. The B-mode ultrasound (BUS) based computer-aided diagnosis (CAD) can help sonologists improve diagnostic accuracy for DDH. The routine CAD models mainly developed based on convolutional neural network or Transformer, which cannot fully learn the inherent structural and texture properties in the hip BUS images. The newly proposed Mamba model has shown its superior performance for learning feature representation with linear computation complexity. However, the scanning mechanism still effect the performance of state space model in Mamba to learns sequence information. To this end, a novel Hybrid Symmetry Mamba Network (HSMN) is proposed to improve the diagnostic performance of CAD model for DDH. The HSMN conducts both the symmetry convolution operation and symmetry scanning in Mamba to more effectively extract inherent information to represent the symmetrical structure in hip BUS images for DDH. The experimental results indicate that the proposed HSMN achieves a diagnostic accuracy of 89.28±2.32%, and outperforms all the compared algorithms, suggesting its effectiveness.Clinical RelevanceThis CAD model has the potential to be applied in clinical practice for help sonologist improve diagnostic accuracy of DDH.

BackgroundTumor genetic anomalies and immune dysregulation are pivotal in the progression of multiple myeloma (MM). Accurate patient stratification is essential for effective MM management, yet current models fail to comprehensively incorporate both molecular and immune profiles.MethodsWe examined 776 samples from the MMRF CoMMpass database, employing univariate regression with LASSO and CIBERSORT algorithms to identify 15 p53-related genes and six immune cells with prognostic significance in MM. A p53-TIC (tumor-infiltrating immune cells) classifier was constructed by calculating scores using the bootstrap-multicox method, which was further validated externally (GSE136337) and through ten-fold internal cross-validation for its predictive reliability and robustness.ResultsThe p53-TIC classifier demonstrated excellent performance in predicting the prognosis in MM. Specifically, patients in the p53low/TIChigh subgroup had the most favorable prognosis and the lowest tumor mutational burden (TMB). Conversely, those in the p53high/TIClow subgroup, with the least favorable prognosis and the highest TMB, were predicted to have the best anti-PD1 and anti-CTLA4 response rate (40%), which can be explained by their higher expression of PD1 and CTLA4. The three-year area under the curve (AUC) was 0.80 in the total sample.ConclusionsOur study highlights the potential of an integrated analysis of p53-associated genes and TIC in predicting prognosis and aiding clinical decision-making in MM patients. This finding underscores the significance of comprehending the intricate interplay between genetic abnormalities and immune dysfunction in MM. Further research into this area may lead to the development of more effective treatment strategies.

Background: As the second most prevalent hematologic malignancy, multiple myeloma (MM) affects plasma cells and is characterized by chromosomal abnormalities, particularly involving the immunoglobulin heavy chain switch region. MM represents a biologically and clinically heterogeneous hematological malignancy that serves as a clonal evolution model, exhibiting clonal heterogeneity throughout all stages from monoclonal gammopathy undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM. Although significant progress has been made in the treatment of MM, leading to improved patient outcomes, concerns are arising regarding disease relapse due to the presence and selection of pre-existing resistant clones or selective pressure during therapy. Case Presentation: We present a case of multiple myeloma (MM) in a female patient, who underwent an 8-year course of treatment, including chemotherapy, immunomodulators, hematopoietic stem cell transplantation, CD38 monoclonal antibody, and chimeric antigen receptor T-cell (CAR-T), and was recently diagnosed with concurrent progressive MM and acute myeloid leukemia (AML). This patient has witnessed the evolution of MM treatment paradigms. Conclusion: In this course, disease relapses occurred twice, one of which was manifested by a light chain escape (LCE). Moreover, through the course of the disease in this patient, we review the process of clonal evolution that may be relevant.

Adverse events of atrial fibrillation (AF) have been commonly reported in lymphoma patients in treating Bruton's tyrosine kinase inhibitors (BTKi). The incidence rate of AF can vary depending on the specific types of BTKi and the patient population. Totally 45 published studies have revealed that the overall incidence rate of AF is 5% (95% CI 4%–7%). By performing a subtype single-rate analysis, the second-generation BTKi shows a lower AF incidence rate and lower cardiovascular toxicity. In the subtype single-rate analysis, we conclude the different AF incidence rates of Ibrutinib (10%, 95% CI 7%–13%), Acalabrutinib (4%, 95% CI 1%–6%), Orelabrutinib (0%, 95% CI 0%–1%), and Zanubrutinib (0%, 95% CI 0%–1%). The comprehensive analysis of AF inspires us to better predict and manage AF and other cardiovascular events in treating lymphoma. Meticulous evaluation, collaboration between cardiologists and hematologists, and discovery of new biomarkers are essential for its management.

Abstract Aim To investigate the expression and clinical relevance of the alpha- 1,3- mannosyltransferasegene (ALG3) gene in Multiple Myeloma through intensive mining of the Oncomine database and CCLE database. Methods Meta-analysis was performed on all MM datasets included in the Oncomine database. The ALG3 gene was identified and the expression changes in MM patients were analyzed. Download the source files of MM datasets containing survival information and perform survival analysis depending on the level of ALG3 mRNA expression. Correlation analysis and Cox multifactor regression analysis were performed using SPSS statistical analysis software for factors including ALG3 expression and 1q21 + status. The expression of ALG3 in each tumor cell line was evaluated with CCLE database. Co-expression analysis, as well as KEGG and GO enrichment analysis, were performed for ALG3 through the STRING online data analysis tool. Results The Oncomine database contains 33 MM datasets with 3157 samples. Meta-analysis of two datasets containing 207 samples labeled "Multiple Myeloma vs Normal" showed that ALG3 was the 18th most significantly hyper-expressed molecule. Survival analysis indicated that ALG3 expression was negatively associated with overall survival of MM patients. High ALG3 expression was a poor prognostic factor independent of 1q21 amplification. KEGG and GO enrichment analysis of molecules co-expressed with ALG3 revealed the correlation of ALG3 with pathways involving RNA degradation, proteasome regulation, HIF- 1 signaling pathway and shear body formation. Conclusion ALG3 is highly expressed in multiple myeloma and negatively correlates with survival prognosis of patients. ALG3 is a poor prognostic marker in MM patients, associated with upregulation in myeloma with pathways including proteasome regulation, RNA degradation and shedder formation, which is promising as a precise therapeutic target for MM.

The B-mode ultrasound based computer-aided diagnosis (CAD) has demonstrated its effectiveness for diagnosis of Developmental Dysplasia of the Hip (DDH) in infants, which can conduct the Graf's method by detecting landmarks in hip ultrasound images. However, it is still necessary to explore more valuable information around these landmarks to enhance feature representation for improving detection performance in the detection model. To this end, a novel Involution Transformer based U-Net (IT-UNet) network is proposed for hip landmark detection. The IT-UNet integrates the efficient involution operation into Transformer to develop an Involution Transformer module (ITM), which consists of an involution attention block and a squeeze-and-excitation involution block. The ITM can capture both the spatial-related information and long-range dependencies from hip ultrasound images to effectively improve feature representation. Moreover, an Involution Downsampling block (IDB) is developed to alleviate the issue of feature loss in the encoder modules, which combines involution and convolution for the purpose of downsampling. The experimental results on two DDH ultrasound datasets indicate that the proposed IT-UNet achieves the best landmark detection performance, indicating its potential applications.

Purpose: Systemic light chain (AL) amyloidosis arises from the aberrant folding of monoclonal immunoglobulin light chains, resulting in the formation of amyloid proteins. These proteins are subsequently deposited in various tissues and organs, instigating structural damage, organ impairment, and relentless disease progression. Daratumumab, a fully human IgG1κ monoclonal antibody engineered to target CD38, serves as both a depleting agent for plasma cells and an immunomodulator. In 2021, daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (D-VCd regimen) became the first formally licensed treatment for AL amyloidosis. Our study, an observational investigation involving five patients diagnosed with AL amyloidosis, aims to demonstrate the efficacy and safety of daratumumab based treatment. Methods: This clinical observation encompasses five patients, with four undergoing renal biopsies and one undergoing a fat biopsy. All patients were diagnosed with confirmed and symptomatic AL amyloidosis and received treatment with the D-VCd regimen at our institution between August 2021 and August 2023. The treatment protocol involved administering daratumumab at a dose of 16 mg/kg, bortezomib 1.3 mg/m2, cyclophosphamide 300 mg/m2 (500 mg maximum weekly dose), and dexamethasone 20 mg intravenously. Treatment was initially administered once weekly for weeks 1 to 8, followed by every 2 weeks from weeks 9 to 24 (for all patients), and subsequently extended to every 4 weeks for up to 12 months (only for Pt 3 and Pt 4). Results: The case series comprises five male individuals with a median age of 66 years (range, 43-73 years). Among these individuals, four patients achieved a hematologic very good partial response (VGPR), two of whom achieved a complete response (CR). The mean difference of serum free light chain (dFLC) value changed from 384.2 mg/L (range, 81.1-926.1) to 95.72 mg/L (range, 0.73-447). Conversely, one patient exhibited no discernible improvement following six months of therapy, prompting the discontinuation of daratumumab. Four patients showed cardiac and renal responses after six cycles of treatment. Remarkably, after 6 cycles of treatment, according to common terminology criteria for adverse events, (CTCAE) assessment, no patients experienced adverse reactions of grade 3 or above. Conclusions: This study presents our clinical observation of daratumumab based immunochemotherapy for AL amyloidosis, unveiling its safety and efficacy. Notably, 80% (4/5) of patients exhibited hematologic response following six cycles of treatment, devoid of any discernible side effects. Simultaneously, an equivalent proportion of patients 80% (4/5) showcased cardiac and renal responses, underscoring the treatment's effectiveness in preserving organ function and extending patient survival.