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 evaluate the efficacy and safety of the pegaspargase, etoposide, methotrexate, and dexamethasone (PEMD) regimen in patients with early-stage nonupper respiratory digestive tract or advanced extranodal natural killer/T-cell lymphoma (ENKTL) .Methods:This retrospective analysis included 38 patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL who received PEMD regimen for induction chemotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2022. Survival outcomes and prognostic factors were examined by Kaplan-Meier, and the Log-rank test was used to compare survival.Results:The study population had a median age of 48 years (range, 26-72 years) and included 30 males (78.9%) and 8 females (21.1%). 7 patients’ age >60 years (18.4%). The Eastern Cooperative Oncology Group (ECOG) performance score was >1 in 7 patients (18.4%) ; 20 patients (52.6%) had elevated lactate dehydrogenase levels; and 37 patients (97.4%) exhibited extranodal involvement. Using the Ann Arbor staging system, 37 patients (97.4%) were classified as stage Ⅲ-Ⅳ. The median number of treatment cycles was 5 (1-6), and the median follow-up duration was 60 months (24 - 101 months). Interim efficacy assessment revealed an overall response rate of 52.7%. At 2 and 4 years, the progression-free survival (PFS) rates were 34.2% (95% CI 22.0%-53.2%) and 25.5% (95% CI 14.7%-44.4%), respectively, and the overall survival rates were 50.0% (95% CI 36.4%-68.7%) and 45.5% (95% CI 31.4%-65.7%), respectively. The risk factors for worse PFS were ECOG performance score >1 [ HR=3.711 (95% CI 1.494-9.218), P=0.005]; bone marrow infiltration [ HR=2.251 (95% CI 1.026 - 4.938), P=0.043]; and Prognostic Index for Natural Killer/T-Cell Lymphoma score of 3 - 5 [ HR=2.350 (95% CI 1.009 - 5.476), P=0.048]. Multivariate analysis identified ECOG performance score >1 as an independent risk factor for PFS [ HR=7.971 (95% CI 2.222 - 28.591), P=0.001]. The main adverse effect was anemia in 31 patients (81.6%) . Conclusion:The PEMD regimen was safe and effective for patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL.

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.

Intravascular large B-cell lymphoma (IVLBCL) is a rare large B-cell lymphoma subtype. We report a patient who presented with "recurrent fever and pancytopenia." A 64-year-old female patient had previously been diagnosed with Waldenstrom’s macroglobulinemia and had received zanubrutinib treatment. In February 2023, the patient revisited due to "recurrent fever and pancytopenia." A positron emission tomography/computed tomography scan demonstrated significant enlargement of the bilateral adrenal glands. After an adrenal biopsy, she was diagnosed with diffuse large B-cell lymphoma, not otherwise specified. The patient received chemotherapy with the R-CHOP regimen (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone). After three treatment courses, a cranial magnetic resonance imaging examination indicated central nervous system infiltration of the lymphoma. After reviewing the pathology of the adrenal biopsy, the final diagnosis was revised as IVLBCL. Despite aggressive treatment, the disease continued to progress, and the patient died two months later. According to a multidisciplinary level, this article discusses the case from the perspective of a multidisciplinary team collaboration, involving imaging, pathology, dermatology, and lymphoma, to provide reference opinions for the clinical diagnosis and treatment of IVLBCL.

Intravascular large B cell lymphoma (IVLBCL) is a rare, aggressive subtype of diffuse large B cell lymphoma, with nasal turbinate involvement being uncommon. We report a 51-year-old woman with a 1-month history of fever of unknown origin. Laboratory findings showed cytopenia, hypertriglyceridemia, elevated ferritin, increased soluble CD25, and bone marrow hemophagocytosis. No infectious cause was identified. PET-CT revealed abnormal 18F-fluorodeoxyglucose (FDG) uptake in the nasal turbinates. Turbinate biopsy revealed tumor cells localized predominantly within vascular lumens, positive for CD20, BCL6, PAX5, and MUM1, with a Ki-67 index >60%, confirming a diagnosis of IVLBCL with hemophagocytic lymphohistiocytosis (HLH). The patient received one cycle of the DEP regimen (liposomal doxorubicin, etoposide, and methylprednisolone) for HLH, followed by five cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and consolidation with auto-HSCT, achieving sustained complete remission. IVLBCL outcomes are heterogeneous; early diagnosis and prompt treatment improve survival, and R-CHOP plus auto-HSCT may be an effective strategy.

Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

ObjectiveTo investigate the seroprevalence of Japanese encephalitis virus (JEV) IgG antibodies among the healthy individuals in Huzhou City, Zhejiang Province, so as to provide a scientific basis for the development of prevention and control strategies for Japanese B encephalitis (JE). MethodsA cross-sectional study was conducted from 2023 to 2024. Serum samples were collected from healthy individuals across 12 age groups (<8 months, 8 months‒<2 years, 2‒<4 years, 4‒<6 years, 6‒<8 years, 8‒<10 years, 10‒<15 years, 15‒<20 years, 20‒<30 years, 30‒<40 years, 40‒<50 years, 50‒ years) and tested for JEV IgG antibody to determine positivity rates. ResultsThe overall JEV IgG antibody seroprevalence rate was 57.75 % among the healthy individuals in Huzhou City. The positivity rates for the age groups of <8 months, 8 months‒<2 years, 2‒<4 years, 4‒<6 years, 6‒<8 years, 8‒<10 years, 10‒<15 years, 15‒<20 years, 20‒<30 years, 30‒<40 years, 40‒<50 years, and 50‒ years were 10.14%, 23.76%, 77.31%, 66.88%, 73.87%, 58.33%, 41.67%, 55.06%, 47.00%, 61.00%, 62.00%, and 92.00%, respectively, with a statistically significant difference observed in different age groups (χ²=243.996, P<0.001). Seroprevalence rates also differed significantly between males and females (χ²=9.999, P=0.002). Among subjects vaccinated with 0,1 or 2 doses of live attenuated Japanese encephalitis virus vaccine (JEV-L), the IgG antibody seroprevalence rate was 4.76%, 27.27% and 72.33%, respectively (χ²=108.568, P<0.001). Within the 2 doses group, the IgG antibody seroprevalence rate at <1 year, 1 year, 2 years and 3‒5 years after immunization were 80.85%, 77.36%, 66.67% and 65.45%, respectively, indicating a declining trend with time increased since vaccination (Z=-2.024, P=0.043). ConclusionAdults aged 50‒ years maintain high antibody levels, whereas levels are lower among the age groups of <2 years and 8‒<30 years and wane with time since vaccination in Huzhou City. It is recommended to maintain the routine JE vaccination schedule while exploring booster vaccination strategies for the age groups of 8‒<30 years, in order to enhance population immunity against JEV.

Cantharidin(CTD),a natural compound used to treat multiple tumors in the clinic setting,has been limited due to acute kidney injury(AKI).However,the major cause of AKI and its underlying mechanism remain to be elucidated.Serum creatinine(SCr)and blood urea nitrogen(BUN)were detected through pathological evaluation after CTD(1.5 mg/kg)oral gavage in mice in 3 days.Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was used to investigate lipids disorder after CTD exposure in mice.Then,spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI)was used to detect the kidney spatial distribution of lipids.Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro.The results showed that the levels of SCr and BUN were increased,and tubular necrosis was observed in mouse kidneys,resulting in acute tubular necrosis(ATN)in CTD-induced AKI.Then,lipidomics results revealed that after CTD exposure,232 differential lipid metabolites and 11 pathways including glycerophospholipid(GP)and sphingolipid(SL)metabolism were disrupted.Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed.Subsequently,integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla,whereas SL metabolism was inhibited in the renal cortex.Up-regulated lysophosphatidylcholine(LysoPC)(18∶2(9Z,12Z)),LysoPC(16∶0/0∶0),glycerophosphocholine,and down-regulated sphingomyelin(SM)(d18∶0/16:0),SM(d 18∶1/24:0),and SM(d42∶1)were key differential lipids.Among them,LysoPC(16∶0/0∶0)was increased in the CTD group at 1.1196 μg/mL,which aggravated CTD-induced ATN in human kidney-2(HK-2)cells.LysoPC acyltransferase was inhibited and choline phos-photransferase 1(CEPT1)was activated after CTD intervention in mice and in HK-2 cells.CTD induces ATN,resulting in AKI,by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla,LysoPC(16:0/0:0),LysoPC acyltransferase,and CEPT1 may be the therapeutic targets.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Objective To analyze the clinical significance of subjective visual vertical (SVV) tests at different head deflection angles in assessing utricle function in patients with benign paroxysmal positional vertigo (BPPV). Methods A total of 61 BPPV patients who were treated at the Hearing Impairment and Vertigo Diagnosis and Treatment Center of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2022 to May 2023 were retrospectively included, and 29 healthy adults were selected as controls. SVV tests were performed on all research subjects at different head deflection angles: upright head (0°), left head 45° (L45°), right head 45° (R45°). The test results between the two groups were compared. Results SVV absolute value at R45° in BPPV group was lower than that in the control group (P＝0.003); there was no significant difference in SVV values at 0° and L45° between the two groups. There was no statistical difference in SVV values at different head deflection angles between the control group and the left BPPV group. SVV absolute value at R45° in right BPPV group was lower than that in the control group (P＜0.001); there was no statistical difference in SVV values at 0° and L45° between the two groups. Conclusions SVV test can provide subjective information about the utricle, and SVV tests at different head deflection angles can fine-tune evaluate the function of the utricle in BPPV patients.