Podocyte injury is central to glomerular diseases, but protective mechanisms unique to human podocytes remain largely unknown. Integrin-associated protein (CD47) is a membrane protein with multiple functions, and it is absent in mouse podocytes but enriched in human podocytes. We investigated whether CD47 has a specific protective role in human podocytes. We analyzed CD47 expression in human and mouse podocytes using public single-cell RNA-sequencing datasets, cultured cells, and kidney biopsy samples from patients with glomerular disease. To explore potential roles of CD47 in human podocytes, we generated a humanized mouse model with podocyte-specific expression of human CD47 and evaluated glomerular injury in nephrotoxic serum- and adriamycin-induced experimental nephropathies. In addition, CD47 knockdown by siRNA was performed in cultured human podocytes and its effects were analyzed. CD47 is highly expressed in human, but not mouse, podocytes. However, in patients with glomerular disease, CD47 expression in podocytes is downregulated and inversely correlates with disease severity. Humanized mice with podocyte-specific expression of human CD47 exhibited attenuated glomerular injury in both nephrotoxic serum- and adriamycin-induced experimental nephropathies. Consistently, CD47 knockdown by siRNA was sufficient to induce injury in cultured human podocytes. These results demonstrate a protective effect of CD47 on human podocytes. Mechanistically, CD47 can bind to integrin αV (ITGAV) and likely disrupt its ability to activate the latent transforming growth factor-beta (TGF-β), thereby protecting podocytes from injury, including CDC42 downregulation, cytoskeletal disruption, and dedifferentiation under stress. CD47 operates as a previously unrecognized, human-specific protective machinery that limits TGF-β signaling likely through preventing the activation of latent TGF-β by ITGAV in podocytes. Its downregulation in glomerular diseases suggests that maintenance of CD47 expression may represent a potential therapeutic approach.

This meta-analysis compared chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs) for relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL), focusing on efficacy and safety. We analyzed 59 phase I/II trials involving 2,914 patients. CAR-T achieved higher ORR (72% [95% CI 67-77%] vs. 50% [38-62%]) and CR (54% [49-59%] vs. 33% [23-46%]) than BsAbs. However, it was associated with higher rates of grade ≥3 CRS (8% [6-11%] vs. 4% [3-7%]), ICANS (12% [9-16%] vs. 6% [2-18%]), and neurotoxicity (8% [6-10%] vs. 6% [2-13%]). Among CAR-T constructs, dual-targeting products (CD19/20 and CD19/22) showed higher efficacy with more varied toxicity profiles; among BsAbs, CD3×CD20 had a more favorable safety profile relative to CD3×CD19. These results suggest CAR-T may be preferable when deep remission is the priority, whereas BsAbs could be a better fit for frail patients or those seeking outpatient care with lower toxicity risks. Treatment selection should be tailored to patient characteristics, including age, tumor burden, and comorbidities. Together, these results provide a comprehensive, evidence-based framework to guide individualized treatment and sequencing in clinical practice.

Background Treatment interruptions and prolongation of overall radiotherapy duration are clinically meaningful process metrics during definitive chemoradiotherapy for esophageal cancer. We examined whether longitudinal trajectories of weekly body weight and time-varying nutrition support utilization were associated with treatment tolerance. Methods We conducted a retrospective cohort study of consecutive adults with esophageal carcinoma treated with definitive concurrent chemoradiotherapy (50.4 Gy in 28 fractions) between August 1, 2020 and December 31, 2025. Weekly body weight and prescription records for oral nutritional supplements and enteral nutrition were used to construct joint trajectory groups. The primary endpoint was radiotherapy schedule disruption, operationalized as prolongation of overall radiotherapy duration (delay time). Multivariable models adjusted for prespecified clinical and treatment covariates. Results Among 286 eligible patients, joint trajectory modeling identified three subgroups: Stable course (n = 123), Late deterioration (n = 109), and Early sustained deterioration (n = 54). Delay time exceeded 3 days in 23.4% of patients, and overall radiotherapy duration exceeded 45 days in 8.7%. Compared with the Stable course subgroup, Early sustained deterioration was associated with higher odds of delay time greater than 3 days (adjusted odds ratio, 3.12; 95% CI, 1.66–5.88) and overall radiotherapy duration greater than 45 days (adjusted odds ratio, 3.96; 95% CI, 1.62–9.64). Early sustained deterioration was also associated with grade 3 or higher acute toxicity (adjusted odds ratio, 2.85; 95% CI, 1.53–5.30) and unplanned hospitalization (adjusted odds ratio, 2.41; 95% CI, 1.24–4.68). Conclusions Distinct longitudinal trajectories of body weight and nutrition support utilization during definitive esophageal chemoradiotherapy were associated with treatment tolerance. Early sustained deterioration identified a high-risk subgroup with substantially higher risk of schedule disruption and severe acute events.

Background: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive non-Hodgkin lymphoma. Currently, high-dose methotrexate (HD-MTX)-based chemotherapy remains the standard first-line treatment. Previous clinical trials have reported that fotemustine-containing regimens offer promising efficacy and tolerability as an alternative option. Objectives: To compare the efficacy, safety, and feasibility of fotemustine-containing regimens with HD-MTX-containing regimens for newly diagnosed PCNSL. Design: A single-center, retrospective cohort study. Methods: We retrospectively analyzed 114 newly diagnosed PCNSL patients treated between April 2011 and December 2021. Patients were classified into two cohorts: those receiving fotemustine-containing regimens ( n = 72) and those receiving HD-MTX-containing regimens ( n = 42). The primary efficacy endpoint was the objective response rate (ORR). Secondary endpoints included complete response rate, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: No significant difference in ORR was observed between the fotemustine-containing group and HD-MTX-containing group (68% vs 67%, p = 0.879). At a median follow-up of 28.5 months, the survival outcomes were comparable, with no statistically significant differences in either PFS (hazard ratio (HR) = 0.887, 95% confidence interval (CI): 0.522–1.508; p = 0.654) or OS (HR = 0.966, 95% CI: 0.494–1.888; p = 0.918). Notably, fotemustine-based therapy was associated with significantly fewer AEs, including leukopenia, thrombocytopenia, digestive tract toxicity, and mucositis (all p < 0.05). Conclusion: Fotemustine-containing chemotherapeutics appear to confer a safer profile with comparable efficacy relative to HD-MTX-based regimens in newly-diagnosed PCNSL patients.

Luteolin, a flavonoid present in botanical drugs, plants, and dietary sources, has demonstrated anticancer properties against various tumors, yet its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to uncover the molecular mechanism of luteolin in DLBCL treatment using a combination of in vitro and in vivo experiments and computational analysis. Human DLBCL cell lines U2932 and OCI-LY10 were utilized to assess luteolin’s impact on cell growth, apoptosis, cell cycle progression, and the modulation of JAK2/STAT3 pathway proteins. In vivo, a U2932 tumor-bearing nude mice model was employed to evaluate luteolin’s antitumor efficacy and its effects on JAK2/STAT3 pathway protein expression. Additionally, molecular dynamics simulations were conducted to explore the interaction between luteolin and JAK2. The findings revealed that luteolin significantly suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase in both cell lines. In the mouse model, luteolin effectively inhibited tumor growth and downregulated the expression of phosphorylated JAK2 and STAT3 without altering the total protein levels of JAK2 and STAT3. Computational analysis indicated stable binding of luteolin to JAK2. Collectively, these results suggest that luteolin’s anti-DLBCL activity may be mediated through the regulation of the JAK2/STAT3 signaling pathway, positioning it as a potential therapeutic agent for DLBCL.

Background:While carfilzomib has shown effectiveness in treating relapsed or refractory multiple myeloma (RRMM), the best frequency of dosing is still debated. This meta-analysis aims to investigate the differences in safety and effectiveness between once-weekly and twice-weekly carfilzomib treatment schedules for patients with RRMM. Methods:A thorough search of five databases was performed. We calculated pooled relative risks (RRs), hazard ratios (HRs), and 95% confidence intervals (95% CIs), and conducted heterogeneity and sensitivity analyses using StateMP 18 software. Results:Five studies met the inclusion criteria. Analysis indicated that once-weekly carfilzomib significantly enhanced progression-free survival (HR: 0.80, 95% CI: 0.69-0.94, p = 0.007). However, no statistical difference was observed in the pooled RRs for overall response rate (RR: 1.13, 95% CI: 0.94-1.38, p = 0.198) and complete response or better (RR: 2.08, 95% CI: 0.65-6.65, p = 0.217). The once-weekly regimen was notably associated with a reduction in adverse events (RR: 0.98, 95% CI: 0.96-1.00, p = 0.047) relative to the twice-weekly regimen. Conclusion:The results propose once-weekly carfilzomib as a viable alternative treatment option for RRMM.

PURPOSE:The objective of this study was to explore the relationship among serum levels of the growth-stimulating expressed gene 2 protein (ST2), Galectin-3 (GAL-3), N-terminal pro-Btype natriuretic peptide (NT-proBNP) in elderly hypertensive patients and heart failure with preserved ejection fraction (HFpEF). MATERIALS AND METHODS:Eighty-five elderly hypertensive patients with HFpEF were registered as the HFpEF group, and 46 hypertensive patients without HF were registered as the Non-HF group. The levels of serum sST2 (soluble ST2), Galectin-3, and NT-proBNP were measured, and related indexes of heart function were performed with echocardiography in two groups, respectively.The obtained variables were applied to statistical software for analysis. RESULTS:Age, BMI, SBP, DBP, TC, LDL-C, HCY, sST2, Galectin-3, NT- proBNP, LVEDD, IVSD, LVEF, and E/A were obviously different between the two groups (p < 0.05). The levels of sST2, Galectin- 3 and NT- proBNP in the HFpEF group were higher than in the Non-HF group (P < 0.05). ANOVA results indicated that sST2, Galectin-3, and NT- proBNP levels increased gradually with the increasing NYHA grades (P<0.05). BMI, SBP, DBP, TC, LDL-C, FBG, UA, HCY, LVEDD, IVSD, LVEF, and E/A were significant differences in patients with different NYHA classes (P < 0.05). Spearman indicated that sST2, Galectin-3, and NT-proBNP were positively correlated with BMI, SDP, DBP, LDL-C, FBG, and HCY (P < 0.05). Logistic analysis indicated that BMI, SBP, DBP, FBG, HCY, sST2, Galectin-3, NT-proBNP, LVEDD, LVEF, and E/A were risk factors for hypertension with HFpEF (P < 0.05). ROC indicated that the AUC of the diagnostic performance of sST2, Galectin-3, and NT-proBNP were all above 0.7, which may have some forecasting value for elderly hypertensive patients with HFpEF. CONCLUSION:The levels of sST2, Galectin-3, and NT-proBNP were closely related to cardiac function grades. sST2, Galectin-3, and NT-proBNP have similar diagnostic performance and predictive value for elderly hypertensive patients with HFpEF. sST2 was more sensitive than NT-proBNP. It is recommended that measurements of sST2, Galectin-3 and NT-proBNP levels in elderly hypertensive patients may be useful in classifying early HFpEF.

Relapsed/refractory B-cell non-Hodgkin's lymphoma (R/R B-NHL) remains challenging to treat, and durable remission is often difficult to achieve with conventional therapies. Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs), as emerging immunotherapeutic strategies, have shown promising therapeutic prospects in several early-stage clinical trials in recent years, mainly targeting B-cell antigens such as CD19 or CD20. However, a systematic comparison of their relative efficacy and safety is lacking. The aim of this study was to systematically evaluate and compare the efficacy and safety of CAR-T cell therapy with bispecific antibodies in the treatment of patients with R/R B-NHL. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.A systematic search for single-arm phase I/II clinical trials was performed to indirectly compare efficacy and safety using a random-effects single-arm meta-analysis.We searched PubMed, Embase, Web of Science, and Cochrane databases up to February 8, 2025. The primary outcome was the objective response rate (ORR), and the secondary outcome was the complete response rate (CR); meta-regression analyses were performed to adjust for relevant covariates. Among pre-established search criteria, 59 trials involving 2,914 pts met the eligibility criteria and were included in the analysis. A total of 59 clinical studies were included, comprising 46 CAR-T and 13 BsAbs trials (ratio ≈2:1). Among CAR-T studies, 32 targeted CD19, 7 dual CD19/CD20, 3 CD20, and 4 dual CD19/CD22; among BsAbs studies, 7 used a CD3×CD20 configuration and 6 a CD3×CD19 configuration. In terms of study design, 17 were multicenter trials, and 43 (71.7%) were single-center studies. CAR-T cell therapy was significantly more efficacious than BsAbs, with an ORR of 72% (95% CI: 67%–77%) and a CR of 54% (49%–59%), which were significantly higher than those of BsAbs in terms of ORR 50% (38%–62%) and CR 33% (23%–46%) (both p<0.01). Among these, CD20 targeted CAR-T therapies demonstrated a higher ORR 85% (95% CI: 5%–100%) than CD3×CD20 BsAbs 54% (37%–71%) (p<0.01), although the wide confidence interval reflects limited available data. Among grade ≥3 adverse events, the CAR-T group had an overall higher incidence than the BsAbs group, including cytokine release syndrome (CRS, 8% vs. 4%; p<0.01), neurotoxicity (8% vs. 6%; p<0.01), and infection (14% vs. 15%; p<0.01). Specifically, grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) was more common in the CAR-T group (12%, 95% CI: 9%–16%) vs. the BsAbs group (6%, 2%–18%; p<0.01). In addition, dual-target CAR-T constructs may be associated with a higher risk of adverse events. Among different generations of CAR-T products, the ORR of third-generation products was 79% (49%–93%), slightly higher than that of second-generation products 72% (67%–77%). In second-generation CAR-T, the 4-1BB co-stimulation conformation 74% (69%–79%) was slightly more efficacious than the CD28 conformation 67% (54%–78%). Among the FDA approved CAR-T products, Axicabtagene ciloleucel demonstrated a high ORR 78% (71%–83%); among the BsAbs, Epcoritamab had the highest ORR 76% (wide CI due to limited studies). CAR-T cell therapy demonstrates superior efficacy, while BsAbs exhibit a more favorable safety profile. Both modalities offer distinct advantages that provide valuable guidance for clinical decision-making in R/R B-NHL.

Objective: Despite the significant clinical efficacy of PD-1 blockade in relapsed or refractory classical Hodgkin lymphoma (R/R cHL), its underlying mechanisms remain incompletely understood, largely due to the complex tumor microenvironment (TME). Reliable predictive biomarkers are currently lacking. This study investigated potential TME-based prognostic indicators for response to PD-1 antibody therapy in cHL to advance personalized treatment strategies. Methods: We conducted a retrospective analysis of 40 R/R cHL patients treated with PD-1 antibodies at the First Affiliated Hospital of Zhengzhou University. Clinical data and follow-up information were collected. The expression of key immune markers (CD8+ cytotoxic T cells, CD68+ macrophages, FOXP3+ Tregs, PD-1, PD-L1, PD-L2) in pretreatment tumor tissues was quantified using immunohistochemistry and average optical density (AOD) measurements. Results: AOD values for all six markers (CD8, CD68, FOXP3, PD-1, PD-L1, PD-L2) showed no significant association with baseline clinical characteristics (age, gender, histology, stage, B symptoms, IPS score, LDH level, bulky disease, number of involved nodal areas, EBER status). However, higher CD68 AOD was significantly associated with improved objective response rate (ORR) (P=0.013). AOD values for CD8, FOXP3, PD-1, PD-L1, and PD-L2 showed no association with ORR. Using median AOD values to distinguish patients into high expression and low expression groups, univariate survival analysis revealed that high CD68 expression was significantly associated with prolonged progression-free survival (PFS) following PD-1 inhibitor therapy (P=0.046). Conclusion: Quantitative assessment of CD68+ tumor-associated macrophage density via AOD measurement is associated with improved treatment response and PFS in R/R cHL patients receiving PD-1 inhibitors. Pretreatment evaluation of CD68 expression in pathological tissues may serve as a valuable prognostic biomarker to guide PD-1 inhibitor therapy selection in cHL.

One of the major limitations of cancer therapy is the emergence of drug resistance. This review amis to provide a focused analysis of the multifactorial mechanisms underlying therapy resistance,with an emphasis on actionable insights for developing novel therapeutic strategies. It concisely outlines key factors contributing to therapy resistance, including drug delivery barriers, cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), cancer heterogeneity, tumor microenvironment (TME), genetic mutations, and alterlations in gene expression. Additionally, we explore how tumors evade targeted therapies through pathway-specific mechanisms that restore disrupted signaling pathways. The review critically evaluates innovative strategies designed to sensitize resistant tumor cells, such as targeted protein dedgradation, antibody-drug conjugates, structure-based drug design, allosteric drugs, multitarget drugs, nanomedicine and others We also highlight the importance of understanding the pharmacological actions of these agents and their integration into treatment regimens. By synthesizing current knowledge and identifying gaps in our understanding, this review aims to guide future research and improve patient outcomes in cancer therapy.

Natural cell-inspired nanoparticles (NCINPs) represent a transformative innovation in nanomedicine, featuring a core-shell structure coated with isolated natural cell membranes (NCMs) that effectively mimic the functions of native cells. The development of NCINPs achieves molecular-level emulation of native cells by precisely reconstructing the hierarchical architecture of the bio-interface, including the structure of the phospholipid bilayer, lipid rafts, protein matrix, and polysaccharide interactions. This advanced biomimetic strategy not only retains the inherent biocompatibility and targeting precision of natural cells but also enables programmable functionalities that surpass those of natural systems, offering enhanced therapeutic potential. In this review, an in-depth introduction to the background of natural cell-inspired research is provided, the current prevalent synthesis methods of NCINPs is delineated, and the application mechanisms based on various types of NCMs, as well as their applications in both benign and malignant diseases are elucidated. However, clinical translation faces significant challenges: complex synthesis, compromised membrane functionality, and unpredictable in vivo behavior. The work comprehensively synthesizes the progress, limitations, and challenges encountered throughout the development of NCINPs, while delineating future prospects. Bridging the translational gap from bench to bedside accelerates the clinical translation of NCINPs and fully realizes their therapeutic potential across diverse medical applications.

Ethnopharmacological relevance: Xiao-Ai Jie-Du decoction (XAJDD) has been used in clinical practice to treat diffuse large B-cell lymphoma (DLBCL); its prescriptions vary based on the pathogenesis of patients. Aim of the study: We aimed to determine the core formula of XAJDD and investigate its mechanism of action against DLBCL. Materials and methods: Apriori data mining of 187 clinical cases (including 421 Traditional Chinese Medicines, TCMs) was conducted to retrieve the core formula of XAJDD. Comprehensive in silico modeling was used to identify potential active components and corresponding targets. The potential targets of 16 compounds were identified based on network pharmacology using in silico modeling. Thereafter, experimental determination of the active compounds and their mechanism of action in treating DLBCL was performed using different assays (including CCK-8, Annexin V-FITC/PI double-staining, Western blot, and flow cytometry assays). Results: The core formula of XAJDD included six herbs: Astragalus mongholicus Bunge (Huangqi, family: Fabaceae), Scutellaria barbata D. Don (Banzhilian, family: Lamiaceae), Prunella vulgaris L. (Xiakucao, family: Lamiaceae), Smilax glabra Roxb. (Tufuling, family Smilacaceae) and Fritillaria thunbergii Miq. (Dabei, family: Liliaceae), and Curcuma zanthorrhiza Roxb. (Ezhu, family: Zingiberaceae); Databases including 62 druggable compounds and 38 DLBCL-related structural targets were constructed; similar to 0.3 million data points produced by computational modeling based on potential compounds and targets six components from XAJDD, including astibin, folic acid, baicalin, kaempferol, quercetin, and luteolin, significantly inhibited DLBCL cell proliferation, induced apoptosis, and suppressed the expression of key oncogenes. Conclusion: This study provides an integrated strategy for determining the core formula of XAJDD and reveals the molecular mechanisms underlying the treatment of DLBCL, which were consistent with the principle of "monarch (Jun), minister (Chen), adjunctive (Zuo), and guide (Shi)", confirming that XAJDD may serve as a promising natural therapeutic agent against DLBCL.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

Background: High-dose methotrexate (HD-MTX)-based chemotherapy followed by whole-brain radiotherapy is the most commonly used approach for patients with newly diagnosed Primary central nervous system lymphoma (PCNSL). However, HD-MTX is a hospital-based drug requiring adequate fluid management and may not be well tolerated in elderly patients with an increased prevalence of comorbid illness. Fotemustine is a third-generation nitrosourea, which is easily penetrated through the blood-brain barrier (BBB) due to its high fat-soluble and low molecular weight, and is indicated for primary brain tumors and disseminated malignant melanoma. Our Center has innovatively conducted three prospective clinical trials using fotemustine-based regimens for the treatment of newly diagnosed PCNSL patients (Wu J et al, J Neurooncol 2018, Wu J et al, Cancer Biol Med 2021, Zhang X et al, ASH 2022), the results of the above studies suggest that the fotemustine-containing regimen has efficacy in the treatment of newly diagnosed PCNSL and has few toxic side effects. Therefore, this study increased the sample size, extended the follow-up time and set up a control group to analyze the efficacy and safety of fotemustine-containing regimens compared with HD-MTX-containing regimens in the treatment of newly diagnosed PCNSL patients. Methods: From April 2011 to December 2021, 114 patients with newly diagnosed PCNSL who received HD-MTX-containing regimens (HD-MTX plus cytarabine [HD-MA], rituximab, HD-MTX plus temozolomide [R-MT]) or fotemustine-containing regimens (fotemustine, teniposide plus dexamethasone [FTD], fotemustine, temozolomide plus dexamethasone [FVD], rituximab, fotemustine, pemetrexed plus dexamethasone [RFPD]) were retrospectively analyzed in this study. Among them, 27 and 15 patients received the HD-MA and R-MT protocol, respectively; 15, 12, and 45 patients received the FTD, FVD and R-FPD protocol, respectively. Results: Of the 114 patients, the objective response rate (ORR) did not differ significantly between the HD-MTX-containing group and the fotemustine-containing group (67% vs 68%, P=0.879). The median follow-up time for 114 patients was 28.5 months (range 2-122 months). Neither the progression free survival (PFS) (P=0.783) nor the overall survival (OS) (P=0.918) exhibited remarkably difference between HD-MTX-containing group and fotemustine-containing group. Notably, we noted that patients treated with HD-MTX-containing regimens experienced more serious adverse events, including leukopenia, anemia, thrombocytopenia, digestive tract toxicity, and mucosis (all P < 0.05) than those undergoing fotemustine-containing therapeutics. Conclusion: Fotemustine-based chemotherapeutics conferred a safer effect on newly-diagnosed PCNSL patients compared with HD-MTX-containing regimens together with comparable efficiency.

6515 Background: Patients with relapsed/refractory T-lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) are clinically manifested by rapid disease progression, poor prognosis and lack of therapeutic options. There is an urgent need to develop other effective modalities. Apart from its expression in normal T and NK cells and no expression in other tissue cells, CD7 is highly expressed in T-ALL/LBL cells. Therefore, CD7 is considered a potential target for the development of CAR-T therapy for T-ALL/LBL. The challenge, however, is to avoid fratricide caused by the expression of CD7 in T cells. We developed a CAR-T cell injection based on CD7 nano antibodies, named PA3-17 injection, by blocking the expression of CD7 molecule on the surface of T cells through anti-CD7 protein expression blocker (PEBL) and evaluate the safety, efficacy and Recommended Phase II Dose (RP2D) of PA3-17 Injection in patients with r/r T-ALL/LBL in a phase I clinical study. Methods: The clinical study (NCT05170568) adopted a "3+3" dose escalation schema and proceed cohort expansion. T-ALL/LBL patients who met the inclusion/exclusion criteria were deployed by entering three dose groups (DL: 0.5×106, 2×106, 4×106 CAR-T/kg) to evaluate the initial safety, efficacy and dose-limited toxicities (DLTs). All patients were treated with lymphodepleting chemotherapy pre-treatment before CAR-T cell infusion. The primary endpoints were DLTs and maximum tolerable dose (MTD). Results: As of Nov 28th, 2023, a total of 12 patients were enrolled (3 patients in dose 1, 2, 3 group, 3 patients in RP2D group), all of whom received a single infusion of PA3-17 injection and completed a 28- day DLTs assessment. The median age of enrolled patients was 33.5 years (range 20-64), and 25.0% (3/12) of patients had previously received hematopoietic stem cell transplantation. No DLTs occurred. The RP2D was 2×106 CAR-T/kg. The safety analysis showed that 83.3% (10/12) of patients developed cytokine release syndrome (CRS), of which 25% (3/12) had grade 3, and no grade 4 CRS occurred, 16.7% (2/12) of patients experienced 1-2 grade of immune effector cell-associated neurotoxicity syndrome (ICANS), and no grade 3 or higher ICANS occurred. The efficacy data showed that the best ORR was 83.3% (10/12) and the CR rate was 75% (9/12). The median follow-up time was 213.5 days. Five patients (Pt 1/5/6/7/9) maintained CR for more than 6 months. One patient (Pt6) had a tumor mass with a diameter greater than 7cm at baseline prior CAR-T infusion but achieved CR 28 days after infusion, then she underwent transplantation at sixth month but died at eighth month because of heart problems, which is unrelated with PA3-17 infusion. Conclusions: PA3-17 injection has shown a good safety profile and encouraging efficacy in r/r T-ALL/LBL patients. RP2D has been determined and the key Phase II clinical study is about to begin. Clinical trial information: NCT05170568 .

Background Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. Results: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73-0.81), the specificity was 0.81 (95% CI 0.73-0.86), the PLR was 3.99 (95% CI 2.81-5.65), the NLR was 0.28 (95% CI 0.23-0.35), the DOR was 14.18 (95% CI 8.47-23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81-0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68-0.86), the specificity was 0.85 (95% CI 0.78-0.90), and the AUC was 0.89 (95% CI 0.86-0.91). Conclusion: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.

Qiling Baitouweng Tang (QLBTWT) is a traditional clinical formula for treating diffuse large B-cell lymphoma (DLBCL), but its molecular action is not fully understood. This research is utilized in silico analysis and liquid chromatography tandem mass spectrometry (LC‒MS/MS) to identify the active constituents of QLBTWT with anti-DLBCL properties and their targets. The study identified 14 compounds, including quercetin, naringenin, and astilbin, as potentially effective against DLBCL. Molecular modeling highlighted the favorable interaction of quercetin with the JAK2 protein. In vitro studies confirmed the ability of quercetin to inhibit DLBCL cell growth and migration while inducing apoptosis and causing G2/M phase cell cycle arrest. Molecular dynamics simulations revealed that quercetin binds to JAK2 as a type II inhibitor. In vivo studies in U2932 xenograft models demonstrated that QLBTWT inhibited tumor growth in a dose-dependent manner, which was associated with the JAK2/STAT3 signaling pathway. Overall, this study elucidates the therapeutic effect of QLBTWT on DLBCL through quercetin-mediated suppression of the JAK2/STAT3 pathway, offering novel therapeutic insights for DLBCL.

OBJECTIVE:The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.METHODS:Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.RESULTS:On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.CONCLUSION:Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

目的:采用数据挖掘方法,探讨癌毒理论指导下的老年弥漫大B细胞淋巴瘤的辨治规律.方法:通过回顾性研究方法,收集倪海雯主任课题组2016年6月—2021年7月治疗老年弥漫大B细胞淋巴瘤的有效病例147例,通过MedcaseV5.2仓公诊籍国医脉案数据记录挖掘系统,运用频数分析与关联规则分析,基于癌毒病机理论从症状、病机、处方用药等多方面对于医案进行数据挖掘分析.结果:通过数据挖掘及症状、病机、药物关联分析得出,临床表现中常见症状为颈部肿块、腹痛、神疲乏力、发热,其次是纳差、寐差等,舌象中频数较高的是苔白,质红,质淡,脉象频数较高的是细、弦脉,症状病机集外高关联病机要素为"虚、毒、痰、热、瘀",气虚、癌毒为病机关键,夹杂痰、热、瘀.临床用药以扶正解毒为治则,扶正强调培补中焦,如太子参、黄芪等;消癌解毒当注意夹杂之热、痰、瘀之不同,分别采用清热解毒、化痰解毒,化瘀解毒,如半枝莲、蛇舌草、夏枯草、莪术、姜黄、浙贝母、茯苓等.结论:老年弥漫大B细胞淋巴瘤病位在脾肾,属本虚标实,本虚以脾气亏虚多见,癌毒贯穿始终,夹杂痰、瘀、热为患.临床以健脾益气,消癌解毒为主,佐以化痰、清热、消瘀.

Background: Extranodal Natural Killer/T Cell Lymphoma (ENKTL) is a highly aggressive form of non-Hodgkin lymphoma (NHL), primarily found in Asia and commonly linked to Epstein-Barr virus (EBV) infection. Despite the treatment efficacy for early stage ENKTL has been improved in recent years, there is no consistent approach for clinical treatment. Current guidelines includes radiotherapy (RT) alone, concurrent chemoradiation therapy (CCRT), sequential chemoradiation, and sandwich chemoradiation. Here we present the final results of the efficacy and safety of sequential therapies of DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen or VIPD (etoposide, ifosfamide, cisplatin and dexamethasone) regimen combined with RT, and RT alone. M ethods: We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of sequential chemotherapy (DDGP vs VIPD regimen) followed by RT, sequential RT followed by chemotherapy, and RT alone in eligible patients with newly diagnosed stage I/II ENKTL. Upon study entry, patients were randomized 1:1:1:1:1 to receive either DDGP regimen followed by RT (DDGP+RT), or VIPD regimen followed by RT (VIPD+RT), or RT followed by DDGP regimen (RT+DDGP), or RT followed by VIPD (RT+VIPD), or RT alone. Patients assigned to the DDGP group were administered cisplatin (20 mg/m 2, intravenous, days 1-4), dexamethasone (15 mg/m 2, intravenous, days 1-5), gemcitabine (800 mg/m 2, intravenous, on days 1 and 8), and pegaspargase (2500 IU/m 2, intramuscular, on day 1). Those in the VIPD group received etoposide (100 mg/m 2, intravenous, days 1-3), ifosfamide (1.2 g/m 2, intravenous, days 1-3), cisplatin (33 mg/m 2, intravenous, days 1-3), and dexamethasone (40mg, intravenous, days 1-4). Both the DDGP and VIPD regimens were repeated every 21 days. For the sequential chemotherapy followed by RT group, patients underwent 3 cycles of either DDGP or VIPD regimen, followed by 50 Gy (2 Gy * 25 times) of intensity modulated radiotherapy (IMRT). In the sequential RT followed by chemotherapy group, patients were first given 50 Gy (2 Gy * 25 times) of IMRT and then sequential either DDGP or VIPD regimen. Meanwhile, the RT alone group received 50 Gy (2 Gy * 25 times) of IMRT only. The primary end point of our study was progression free survival (PFS), with secondary end points including complete remission rate (CRR), objective response rate (ORR), overall survival (OS). R esults: Our study, spanning January 2011 to August 2020, involved 244 patients from 22 centers across China, with 200 randomly assigned to receive treatment (40 in each group). Both the demographic and disease characteristics of the patients at baseline were generally consistent across all treatment groups. During a median follow-up of 72.1 months, the median PFS (mPFS) was not reached in neither the DDGP + RT nor RT + DDGP groups, compared to 36.3 months in the VIPD + RT group, 78.3 months in the RT + VIPD group, and 89.6 months in the RT alone group. The 5-year PFS rates for the DDGP + RT, VIPD + RT, RT + DDGP, RT + VIPD, and RT alone groups were 81.5%, 46.1%, 79.8%, 53.1%, and 57.5% respectively. Similarly, the 10-year PFS rates were 81.5%, 42.8%, 74.1%, 45.9%, and 45.7% respectively. Compared with RT alone, PFS was improved in DDGP + RT group (p = 0.006) and RT + DDGP group (p = 0.024). Compared with VIPD + RT, PFS was improved in DDGP + RT group (p = 0.006) and RT + DDGP group (p = 0.026). Either between DDGP +RT and RT + DDGP group or between VIPD +RT and RT +VIPD group, PFS showed no differences. Median OS was not reached in 5 groups. OS showed no differences in 5 groups (p = 0.27). The patients who failed from either VIPD regimen or RT alone received DDGP regimen. This might be the reason why the OS showed no differences between 5 groups. The CRRs of 5 groups (DDGP + RT, VIPD +RT, RT + DDGP, RT +VIPD, RT alone) were 87.5%, 57.5%, 82.5%, 69.2%, and 67.5%, respectively. Similarly, the ORRs were 97.5%, 77.5%, 90.0%, 74.4%, and 87.5%, respectively. Conclusions: The DDGP regimen exhibited promising outcomes in this randomized clinical trial for newly diagnosed early-stage ENKTL patients. The sequential therapies with DDGP regimen could improve the efficacy compared with RT alone. Patients could also benefit more from therapies with DDGP regimen than those with VIPD regimen. The order in which chemotherapy and RT were applied has no fatal impact on the prognosis of early-stage ENKTL.