Objective:To investigate the impact of peripheral blood prolymphocyte percentage on the prognosis of patients with chronic lymphocytic leukemia (CLL) .Methods:This study included 300 patients diagnosed with CLL at the Department of Hematology of Jiangsu Provincial People’s Hospital from October 2011 to December 2020. The association between prolymphocyte percentage and other parameters was analyzed, and the optimal cutoff prolymphocyte percentage was determined by X-tile analysis. Further survival analysis and prognostic model construction were used to validate the predictive value of prolymphocyte percentage.Results:Of the 300 eligible patients with CLL who were enrolled, 50 received Bruton tyrosine kinase inhibitors (BTKi) as first-line treatment. The group with higher prolymphocyte percentage comprised more patients in the advanced stages ( P=0.010) and had higher β 2-microglobulin ( P<0.001), unmutated immunoglobulin heavy-chain variable region gene ( P<0.001), and TP53 aberration ( P=0.004). The optimal cutoff percentage of prolymphocytes was 1%. Patients with a prolymphocyte percentage >1% had significantly shorter treatment-free survival (TFS) ( P<0.001) and overall survival time ( P=0.007) than patients with a prolymphocyte percentage ≤1%. On multivariate analysis, prolymphocyte percentage >1% tended to have an independent prognostic value for TFS [ HR=1.405 (95% CI 0.971~2.032), P=0.071]. Compared with the nomogram of CLL international prognostic index (CLL-IPI) alone, the nomogram of CLL-IPI combined with prolymphocyte percentage showed better discrimination (area under the curve: 0.778 vs. 0.637; P=0.006). In addition, patients with a prolymphocyte percentage >1% were more likely to progress after BTKi treatment ( P=0.038) . Conclusion:Peripheral blood prolymphocyte percentage was associated with various clinical and biological parameters and prognosis among patients with treatment-naive CLL.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Objective:To investigate the impact of peripheral blood prolymphocyte percentage on the prognosis of patients with chronic lymphocytic leukemia (CLL) .Methods:This study included 300 patients diagnosed with CLL at the Department of Hematology of Jiangsu Provincial People’s Hospital from October 2011 to December 2020. The association between prolymphocyte percentage and other parameters was analyzed, and the optimal cutoff prolymphocyte percentage was determined by X-tile analysis. Further survival analysis and prognostic model construction were used to validate the predictive value of prolymphocyte percentage.Results:Of the 300 eligible patients with CLL who were enrolled, 50 received Bruton tyrosine kinase inhibitors (BTKi) as first-line treatment. The group with higher prolymphocyte percentage comprised more patients in the advanced stages ( P=0.010) and had higher β 2-microglobulin ( P<0.001), unmutated immunoglobulin heavy-chain variable region gene ( P<0.001), and TP53 aberration ( P=0.004). The optimal cutoff percentage of prolymphocytes was 1%. Patients with a prolymphocyte percentage >1% had significantly shorter treatment-free survival (TFS) ( P<0.001) and overall survival time ( P=0.007) than patients with a prolymphocyte percentage ≤1%. On multivariate analysis, prolymphocyte percentage >1% tended to have an independent prognostic value for TFS [ HR=1.405 (95% CI 0.971~2.032), P=0.071]. Compared with the nomogram of CLL international prognostic index (CLL-IPI) alone, the nomogram of CLL-IPI combined with prolymphocyte percentage showed better discrimination (area under the curve: 0.778 vs. 0.637; P=0.006). In addition, patients with a prolymphocyte percentage >1% were more likely to progress after BTKi treatment ( P=0.038) . Conclusion:Peripheral blood prolymphocyte percentage was associated with various clinical and biological parameters and prognosis among patients with treatment-naive CLL.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Objective:To analysis the risk factors for major adverse cardiovascular event (MACE) in pregnant women with valvular heart disease (VHD) and to construct a risk prediction model.Methods:The clinical data of 245 pregnant women with VHD who were hospitalized in Beijing Anzhen Hospital from January 1, 2012, to June 1, 2023 were retrospectively analyzed, including general information, pre-pregnancy and pregnancy-associated cardiac conditions, and MACE. Univariate analysis and logistic regression models were employed to identify risk factors for MACE during pregnancy among pregnant women with VHD. Furthermore, a predictive model was constructed and internal validation was conducted using bootstrap techniques.Results:(1) Among 245 pregnant women with VHD, the incidence of MACE was 18.0% (44/245), and the most common MACE was heart failure (61.4%, 27/44). The mitral valve was the most frequently affected valve (64.9%, 159/245). Prior to pregnancy, the most common type of valve surgery undertaken was mechanical valve replacement, representing 31.4% (77/245) of surgeries. In contrast, among those pregnant women who did not undergo valve surgery before pregnancy, the most common lesion type was mitral regurgitation (17.6%, 43/245). (2) Comparing the maternal and infant outcomes of warfarin, low molecular weight heparin (LMWH) and LMWH sequential with warfarin, the fetal loss rate (36%, 15/42) and malformation rate (7%, 3/42) were the highest, but the MACE rate (12%, 5/42) was the lowest in warfarin group. The fetal loss rate (1/19), malformation rate (1/19) and artificial valve thrombosis rate (0) of LMWH sequential with warfarin were the lowest, and the fetal loss rate and artificial valve thrombosis rate of the three anticoagulation methods were statistically significant (all P<0.05). (3) There were no significant differences in gestational age, age of diagnosis of heart disease, weight at delivery, pre-pregnancy body mass index, proportion of multiparous women and chronic medical history between women with MACE and those without MACE (all P>0.05). (4) Binary logistic regression analysis identified the following as risk factors for MACE during the second trimester of pregnancy among pregnant women with VHD: pre-pregnancy cardiac symptoms, history of corrective surgery for congenital heart disease, pregnancy risk grade Ⅴ, anticoagulation with LMWH during pregnancy, and arrhythmia (all P<0.05). Based on the results of multivariate analysis, a receiver operating characteristic curve was constructed, with an area under the curve of 0.837, indicating good discriminative ability. The calibration plot demonstrated a close alignment between the standard curve and the calibration prediction curve, suggesting excellent calibration of the model. Conclusions:Pregnant women with VHD are at a high risk of experiencing MACE during gestation. Five risk factors, including pre-pregnancy cardiac symptoms, history of corrective surgery for congenital heart disease, pregnancy risk grade Ⅴ, anticoagulation with LMWH, and arrhythmia, could aid in identifying high-risk pregnant women.

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Objective The aim of this study was to use bioinformatics methods to integrate gene expression profiles and spli-cing profiles,and identify potential biomarkers that play a role in endocrine therapy resistance.Methods The gene datasets of endo-crine therapy sensitive and resistant cells from the Gene expression omnibus(GEO)database were downloaded to screen for differenti-ally expressed genes and differential splicing genes related to endocrine therapy resistance,and perform Hallmark enrichment analysis and Gene set enrichment analysis(GSEA)on these genes.The cancer genome atlas(TCGA)and the breast cancer data in the Molecu-lar taxonomy of breast cancer international consortium(METABRIC)were downloaded,and compared the expression of differential genes in tumor and adjacent tissues,as well as the differences between different tumor stages and grades.The relationship between dif-ferential expressed genes and overall survival(OS),alternative splicing,and immune infiltration were explored in patients receiving endocrine therapy.Results GEO data analysis showed that differentially expressed genes were mainly enriched in breast cancer treat-ment response related to pathways and immune-related pathways,and differentially spliced genes were mainly enriched in breast canc-er treatment response related to pathways.The genes that undergo differential expression and splicing simultaneously included CAMK2B,EVL,MZB1and PTPRG.Among them,the expression of MZB1 was associated with OS and immune cell infiltration in pa-tients receiving endocrine therapy,and the precursor mRNA of MZB1 underwent more alternative 3'splicing in drug-resistant cells.Conclusion The expression of MZB1 is related to the effect on endocrine therapy in breast cancer,and its mechanism may be the change of immune related function caused by alternative splicing.MZB1 can serve as a potential biomarker for endocrine therapy to improve prognosis.

Objective The aim of this study was to use bioinformatics methods to integrate gene expression profiles and spli-cing profiles,and identify potential biomarkers that play a role in endocrine therapy resistance.Methods The gene datasets of endo-crine therapy sensitive and resistant cells from the Gene expression omnibus(GEO)database were downloaded to screen for differenti-ally expressed genes and differential splicing genes related to endocrine therapy resistance,and perform Hallmark enrichment analysis and Gene set enrichment analysis(GSEA)on these genes.The cancer genome atlas(TCGA)and the breast cancer data in the Molecu-lar taxonomy of breast cancer international consortium(METABRIC)were downloaded,and compared the expression of differential genes in tumor and adjacent tissues,as well as the differences between different tumor stages and grades.The relationship between dif-ferential expressed genes and overall survival(OS),alternative splicing,and immune infiltration were explored in patients receiving endocrine therapy.Results GEO data analysis showed that differentially expressed genes were mainly enriched in breast cancer treat-ment response related to pathways and immune-related pathways,and differentially spliced genes were mainly enriched in breast canc-er treatment response related to pathways.The genes that undergo differential expression and splicing simultaneously included CAMK2B,EVL,MZB1and PTPRG.Among them,the expression of MZB1 was associated with OS and immune cell infiltration in pa-tients receiving endocrine therapy,and the precursor mRNA of MZB1 underwent more alternative 3'splicing in drug-resistant cells.Conclusion The expression of MZB1 is related to the effect on endocrine therapy in breast cancer,and its mechanism may be the change of immune related function caused by alternative splicing.MZB1 can serve as a potential biomarker for endocrine therapy to improve prognosis.

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX₃CR1⁺CCR2^-Ly6C^-MHCII^- (MP1), CX₃CR1^lowCCR2^lowLy6C^-MHCII^- (MP2), CX₃CR1^-CCR2⁺Ly6C⁺MHCII^- (MP3), and CX₃CR1⁺CCR2^-Ly6C^-MHCII⁺ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.

Objective:To investigate the clinical characteristics and pregnancy outcomes in pregnant women with left ventricular non-compaction (LVNC).Methods:The clinical data of seven pregnant women with LVNC from January 2011 to December 2021 in Beijing Anzhen Hospital,Capital Medical University were retrospectively analyzed, including age, gestational age of symptom first occured, LVNC history, clinical symptoms, New York Heart Association (NYHA) cardiac function class, echocardiography, blood brain natriuretic peptide (BNP), treatment and the maternal and fetal outcomes.Results:Five cases were diagnosed before pregnancy, of which there were three women with medication; one case diagnosed in the month of pregnancy; one case diagnosed at 36 weeks of gestation. NYHA cardiac function was grade Ⅰ in four cases and grade Ⅱ in three cases before or during the first trimester of pregnancy. Of the five pregnant women who underwent echocardiography, there were one case of left ventricular insufficiency, three cases of mild left ventricular dysfunction and one case of normal left ventricular function before or during the first trimester of pregnancy. Of the five pregnant women to the second and third trimester of pregnancy, there were one case of grade Ⅳ, one case of grade Ⅲ, two cases of grade Ⅱ-Ⅲ and one case of grade Ⅱ in NYHA class ; three cases of left ventricular insufficiency, two cases of normal left ventricular function by echocardiography four cases had cardiac symptoms at 15-24 weeks of gestation and were treated with medication. In four cases, blood BNP increased to 214-1 197 ng/L during pregnancy, and were 89-106 ng/L after termination of pregnancy. There were 4 cases with arrhythmia. Indications for termination of pregnancy: LVNC complicated with heart failure in two cases, LVNC complicated with decreased cardiac function and threatened preterm birth in one case, complicated with pregnancy at full term in two cases, LVNC complicated with severe pulmonary hypertension in one case, and left ventricular dysfunction in one case. Cesarean section in four cases in the third-trimester, in one case in the second-trimester, and forceps curettage in two cases were taken. Two full-term infants,two preterm infants were born without LVNC.Conclusions:Women diagnosed with LVNC and low left ventricular ejection fraction before pregnancy are more prone to decreased cardiac function during pregnancy. Carrying out pregnancy risk assessment and strengthening the multi-disciplinary team management of high risk factors in pregnancy are conducive to achieve good pregnancy outcomes.