1.Clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma
Boen WANG ; Siyuan CHEN ; Qing SHI ; Muchen ZHANG ; Hongmei YI ; Lei DONG ; Li WANG ; Shu CHENG ; Pengpeng XU ; Weili ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(9):1162-1168
Objective·To analyze the clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma(DLBCL),including clinical characteristics,pathological characteristics,gene mutation profiles,and prognostic factors.Methods·One hundred and forty-nine patients with kidney-involved DLBCL,admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from July 2005 to November 2021,were retrospectively analyzed for their clinicopathological data,survival and prognostic factors,which included therapeutic methods,clinical outcomes,staging,etc.Gene mutation profiles were evaluated by targeted sequencing of 54 lymphoma-related genes.Prognostic factors were also analyzed based on the information mentioned above.Results·A total of 149 kidney-involved DLBCL cases were included,of which 89 patients(58.4%)were aged over sixty,121 patients(81.2%)were staged Ann Arbor Ⅲ?Ⅳ,27 patients(18.1%)had an Eastern Cooperative Oncology Group(ECOG)performance status of two or more,121 patients(81.2%)had elevated serum lactate dehydrogenase(LDH)level,111 patients(74.5%)had extranodal invasion in at least two organs and 131 patients(87.9%)scored over 2 points on the international prognosis index(IPI).The estimated 5-year overall survival(OS)rate and progression-free survival(PFS)rate of kidney-involved DLBCL patients were 52.2%and 50.4%respectively.Univariate analysis revealed that elevated serum LDH levels were an adverse prognostic factor for both OS(P=0.048)and PFS(P=0.033).In pathological characteristics,145 patients(97.3%)belonged to DLBCL,not otherwise specified(NOS)and 39 patients(26.3%)belonged to germinal center B-cell(GCB)according to Hans classification.Among 144 patients who could be evaluated for clinical outcomes,87 patients(60.4%)got complete response(CR).Targeted sequencing data from 75 kidney-involved DLBCL patients showed high mutation frequency in PIM1(n=23,31%),MYD88(n=22,29%),CD79B(n=21,28%)and KMT2D(n=18,24%),with CD79B mutation indentified as an adverse prognostic factor for OS in patients with kidney-involved DLBCL(P=0.034).Conclusion·Elevated serum LDH level is an adverse prognostic factor in patients with kidney-involved DLBCL.The prognosis of patients with CD79B mutations is poor.
2.Analysis of clinicopathological features, therapeutic efficacy, prognosis and mutation in 11 patients with cardiac diffuse large B-cell lymphoma
Na ZHAO ; Qing SHI ; Shu CHENG ; Li WANG ; Pengpeng XU ; Weili ZHAO
Journal of Leukemia & Lymphoma 2024;33(2):97-103
Objective:To investigate the clinicopathological features, mutation, therapeutic efficacy and the factors influencing the prognosis of patients with cardiac diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 cardiac DLBCL patients in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to October 2020 were retrospectively analyzed. NovaSeq sequencing platform was used to detect gene mutations in 5 patients, and bioinformatics analysis of sequencing data was conducted through public database to identify the mutation sites of pathogenic genes. Kaplan-Meier method was used to analyze the progression-free survival (PFS) and the overall survival (OS). Univariate Cox proportional risk model was used to analyze the influencing factors of prognosis.Results:Among 11 patients with cardiac DLBCL, 5 were male and 6 were female. The age [ M ( Q1, Q3)] was 61 years (45 years, 70 years). All 11 patients were non-germinal center B-cell (non-GCB) type. There were 2 primary cases and 9 secondary cases; 9 cases with Ann Arbor stage of Ⅲ-Ⅳ, 10 cases with increased lactate dehydrogenase (LDH) and 9 cases with international prognostic index (IPI) score equal to or higher than 3 scores. Among 11 patients, 9 cases received a first-line treatment based on the R-CHOP (rituximab, cyclophosphamide, epirubicin/doxorubicin hydrochloride liposomes, vincristine and prednisone) regimen, of which 8 patients achieved complete remission (CR), and 1 patient achieved stable disease (SD); 1 patient received IR2 (ibrutinib + rituximab + lenalidomide) treatment regimen and achieved SD, and 1 patient received supportive treatment only and achieved progression of the disease. The follow-up time was 39.9 months (25.6 months, 57.3 months). The 3-year PFS rate and 3-year OS rate of 11 patients was 54.5%, 77.9 %, respectively. Univariate Cox regression analysis showed that gender, B symptoms, Ann Arbor stage, LDH level, number of extranodal lesions, IPI score were not correlated with PFS and OS of patients (all P > 0.05). Among 5 cases undergoing gene detection, KMT2D mutations and PIM1 mutations were detected in 2 cases,respectively. Interestingly, KMT2D mutations were only found in secondary cardiac DLBCL patients (2/3), while PIM1 mutations were only detected in primary cardiac DLBCL patients (2/2). Conclusions:Most cardiac DLBCL patients are non-GCB type and have advanced clinical stage, while may benefit from R-CHOP treatment regimen. PIM1 and KMT2D are the commonly mutated genes in cardiac DLBCL.
3.Clinicopathologic characteristics,gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma
Zhishan DU ; Yue WANG ; Ziyang SHI ; Qing SHI ; Hongmei YI ; Lei DONG ; Li WANG ; Shu CHENG ; Pengpeng XU ; Weili ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(1):64-71
Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.
4.Synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein and its methylated derivatives
Pengpeng ZHANG ; Jie ZHANG ; Yiting TIAN ; Zhiqun SHI ; Huiping MA ; Linlin JING
Journal of Central South University(Medical Sciences) 2024;49(2):236-246
Objective:Hypoxia is a common pathological phenomenon,usually caused by insufficient oxygen supply or inability to use oxygen effectively.Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity.This study aims to explore the synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein(6-OHG)and its methoxylated derivatives. Methods:The 6-OHG and its methoxylated derivatives,including 4',6,7-trimethoxy-5-hydroxyisoflavone(compound 3),4',5,6,7-tetramethoxyisoflavone(compound 4),4',6-imethoxy-5,7-dihydroxyisoflavone(compound 6),and 4'-methoxy-5,6,7-trihydroxyisoflavone(compound 7),were synthesized by methylation,bromination,methoxylation,and demethylation using biochanin A as raw material.The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy(1H-NMR)and mass spectrometry(MS).The purity of these compounds was detected by high pressure chromatography(HPLC).The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical(DPPH)free radical scavenging assay.PC12 cells were divided into a normal group,a hypoxia model group,rutin(1×10-9-1×10-5 mol/L)groups,and target compounds(1×10-9-1×10-5 mol/L)groups under normal and hypoxic conditions.Cell viability was detected by cell counting kit-8(CCK-8)assay,the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened.PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity,and the cell morphology was observed under light microscope.The apoptotic rate was determined by flow cytometry,and the expressions of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by Western blotting. Results:The structure of 6-OHG and its 4 methylated derivatives were correct,and the purity was all more than 97%.When the concentration was 4 mmol/L,the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16%and 86.94%,respectively,which were higher than those of rutin,the positive control.The removal rates of chemical compounds 3,4,and 6 were all lower than 20%.Compared with the normal group,the cell viability of the hypoxia model group was significantly decreased(P<0.01).Compared with the hypoxia model group,compounds 3,4,and 6 had no significant effect on cell viability under hypoxic conditions.At all experimental concentrations,the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group(all P<0.05).The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group(both P<0.05).The anti-hypoxia activity of 6-OHG and compound 7 was excellent,and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L.After PC12 cells was treated with 6-OHG(1×10-6 mol/L)and compound 7(1×10-7 mol/L),the cell damage was reduced,the apoptotic rate was significantly decreased(P<0.01),and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group(both P<0.01). Conclusion:The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation.6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities,which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.
5.Correlation between geriatric nutritional risk index and adverse events in elderly hemodialysis patients
Zhihua SHI ; Yidan GUO ; Pengpeng YE ; Chunxia ZHANG ; Xiaoling ZHOU ; Meng JIA ; Xiyou ZHANG ; Yang LUO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(1):42-45
Objective To explore the relationship between geriatric nutritional risk index(GNRI)and adverse outcomes in elderly patients undergoing maintenance hemodialysis(MHD).Methods A prospective cohort trial was conducted on 337 MHD patients aged ≥60 years in hemodialysis centers of 11 hospitals in Beijing from April to June 2017.Their baseline data were collected,and they were divided into non-malnutrition(GNRI≥98,226 cases),mild malnutrition(92≤GNRI<98,81 cases),and major malnutrition groups(GNRI<92,30 cases).All of them were followed up until June 2018.The endpoint events were all-cause mortality and cardiovascular disease(CVD)mortality.Kaplan-Meier survival analysis was used to compare the cumulative survival rate among the 3 groups.Multivariate Cox regression model was employed to analyze the relationship of GNRI with all-cause and CVD mortality.Results The mild and major malnutrition groups had significantly lower BMI,serum albumin level and GNRI(P<0.01).During the median follow-up of 52(4.4-52.0)weeks,56(16.6%)patients died of all-cause death and 25(44.6%)of CVD death.Kaplan-Meier survival curve showed significant differences in all-cause mortality(x2=30.484,P<0.01)and CVD mortality(x2=22.398,P<0.01)in the 3 groups.Multivariate Cox regression analysis indicated that,as a continuous variable,elevated GNRI was a protective factor for all-cause mortality(HR=0.910,95%CI:0.870-0.952,P=0.000)and CVD mortality(HR=0.895,95%CI:0.852-0.940,P=0.000),and as a categorical variable,mild and major malnutri-tion were independently correlated with all-cause and CVD mortality(P<0.05).Conclusion GNRI is an independent risk factor for all-cause and CVD mortality in elderly MHD patients.Mo-nitoring the nutritional status using GNRI can predict the risk of adverse prognosis.
6.Analysis of changes in cerebral blood flow during maintenance hemodialysis in middle-aged and elderly patients
Yidan GUO ; Wei CUI ; Pengpeng YE ; Zhihua SHI ; Meng JIA ; Xiaoling ZHOU ; Yang LUO
Chinese Journal of Nephrology 2024;40(10):792-797
Objective:To investigate the changes and associated factors of cerebral blood flow in middle-aged and elderly patients undergoing maintenance hemodialysis (MHD).Methods:This was a prospective observational study. End-stage renal disease (ESRD) patients undergoing MHD aged over 50 years at Beijing Shijitan Hospital, Capital Medical University from January 2023 to June 2023 were included. General clinical data of the selected individuals were collected, and dialysis related indicators were recorded and calculated. Mean flow velocity (MFV) of the middle cerebral arterial was measured by transcranial Doppler sonography (TCD) to represent cerebral blood flow throughout dialysis. Hemodialysis-related variables were collected. The MFV values of bilateral middle cerebral artery were measured through temporal windows at 7 time points: 15 minutes before dialysis (T1), 15 minutes (T2), 30 minutes (T3), 60 minutes (T4), 120 minutes (T5), 180 minutes (T6) during dialysis, and the endpoint of dialysis (T7), and the average values were recorded. The ΔMFV was calculated as pre-minus endpoint values of MFV. The Spearman rank correlation method was used to analyze the correlations between ΔMFV and dialysis-related variables, and multiple linear regression method was used to analyze the related factors of the changes in MFV.Results:This study included a total of 123 patients undergoing MHD, aged (63.63±8.44) years (range 50-85 years), including 99 males (80.5%). TCD examination demonstrated a decline trend in MFV throughout dialysis. The MFV at T7 was significantly lower than that at T1 ( Z=-7.650, P<0.001). The Spearman correlation analysis showed that the decline in MFV was correlated with ultrafiltration volume ( r=0.356), ultrafiltration rate ( r=0.371), the difference in systolic pressure (pre-analysis minus post-dialysis, r=0.251), the difference in mean arterial pressure (pre-dialysis minus post-dialysis, r=0.194), combined diabetes ( r=0.293), dialysis vintage ( r=0.220), Kt/V ( r=0.287), and serum albumin ( r=-0.295). Multiple linear regression analysis showed that combined with diabetes ( B=3.889, 95% CI 1.373-6.405, P=0.003), decreased serum albumin ( B=-0.456, 95% CI -0.877--0.036, P=0.034), increased ultrafiltration rate ( B=11.099, 95% CI 6.402-15.797, P<0.001) and the decline in systolic pressure ( B=0.062, 95% CI 0.008-0.116, P=0.026) were significantly associated with the decline in MFV throughout dialysis. Conclusions:In middle and elderly patients with ESRD undergoing hemodialysis, there is a decline trend in cerebral blood flow during hemodialysis. The combination of diabetes, lower serum albumin, higher ultrafiltration rate, and intradialytic systolic pressure decline are the risk factors influencing the intradialytic decline of cerebral blood flow.
7.Protective effect and mechanism of baicalein on hypoxia-induced cortical neuron injury in rats
Dongmei ZHANG ; Jie ZHANG ; Zhiqun SHI ; Pengpeng ZHANG ; Hongqiang TAN ; Huiping MA
China Pharmacy 2023;34(12):1431-1436
OBJECTIVE To explore the protective effect and possible mechanism of baicalein on hypoxia-induced cortical neuron injury in rats. METHODS The cortical neurons of rats (RN-C cells) were studied and cultured under hypoxic conditions (5%CO2, 94% N2, 1%O2) for 24 hours; the effects of different concentrations of baicalein (0.01, 0.1, 1, 10, 100 μmol/L) on the survival rate of hypoxic RN-C cells were investigated; the effects of baicalein (0.1 μmol/L) on the activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), migration rate, apoptotic rate, cell cycle and the expressions of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2 X protein (Bax) were all detected. RESULTS Compared with control group, the survival rate of cells in the hypoxia group was significantly reduced (P<0.01); 0.01, 0.1 and 1 μmol/L baicalein could reverse survival rate of hypoxia-induced cortical neurons (P<0.05 or P<0.01). Scratch experiments showed that baicalein significantly increased the migration rate of hypoxic RN-C cells (P<0.01). Compared with control group, the activity of LDH in the supernatant and the content of MDA in the cells, apoptotic rate and the proportion of cells in G1 phase, were significantly increased in the hypoxia group, while SOD activity and the proportion of cells in G2+S phase was decreased significantly (P<0.01). The protein expressions of cleaved caspase-3 were increased significantly, while the ratio of Bcl-2/Bax in cells was significantly reduced (P<0.05 or P<0.01). Compared with hypoxia group, the above indexes were all reversed significantly in baicalein group (P<0.01). CONCLUSIONS Baicalein can promote the proliferation and migration of cortical neurons, improve hypoxia-induced cell apoptosis and cell cycle distribution, decrease the activity of LDH in supernatant and the level of cellular lipid peroxidation, and improve antioxidant levels. Its mechanism may be related to regulating the caspase- 3/Bax/Bcl-2 pathway.
8.Clinical evaluation of combined geriatric nutritional risk index and modified creatinine index predicting all-cause mortality in middle-aged and older patients undergoing maintenance hemodialysis
Zhihua SHI ; Yidan GUO ; Chunxia ZHANG ; Xiaoling ZHOU ; Pengpeng YE ; Meng JIA ; Yang LUO
Chinese Journal of Nephrology 2023;39(9):680-687
Objective:To explore the relationship between geriatric nutritional risk index (GNRI) and modified creatinine index (mCI) and all-cause mortality in maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. The MHD patients aged≥50 years old at hemodialysis centers of eleven hospitals in Beijing from April to June 2017 were selected as subjects. Baseline clinical data of the patients were collected. The patients were divided into high GNRI group (≥98) and low GNRI group (<98), and high mCI group (≥20.16 mg·kg -1·d -1) and low mCI group (<20.16 mg·kg -1·d -1), and further divided into 4 groups: G1 group (high GNRI and high mCI), G2 group (high GNRI and low mCI), G3 group (low GNRI and high mCI) and G4 group (low GNRI and low mCI). The differences of clinical characteristics among the four groups were compared. The patients were followed-up until June 2018 or death or loss, and the endpoint event was all-cause mortality. Kaplan-Meier survival analysis was used to compare the differences of the cumulative survival rates among the four groups. A multivariate Cox regression model was used to analyze the relationship between GNRI and mCI and all-cause mortality. Results:A total of 613 patients were included in the study, aged (63.65±7.78) years old (ranged from 50 to 81 years old), with 355 males (57.91%). The GNRI and mCI were (99.35±5.75) and (20.16±2.79) mg·kg -1·d -1, respectively. There were 232 patients (37.85%) in the G1 group, 177 patients (28.87%) in the G2 group, 95 patients (15.50%) in the G3 group, and 109 patients (17.78%) in the G4 group. There were statistically significant differences in age, sex, proportion of diabetes, proportion of coronary heart disease, body mass index, serum albumin and serum creatinine among the four groups (all P<0.05). A total of 69 patients (11.26%) died during a median follow-up time of 52(4, 52) weeks. Kaplan-Meier survival curve results showed that the mortality of patients with low GNRI was higher than that of patients with high GNRI (log-rank χ 2=26.956, P<0.001), and the mortality of patients with low mCI was higher than that of patients with high mCI (log-rank χ 2=25.842, P<0.001). The mortality was 3.45% in group G1, 10.73% in group G2, 9.47% in group G3, and 30.28% in group G4, and the differences among the four groups were statistically significant (log-rank χ 2=57.153, P<0.001). Multivariate Cox regression analysis results showed that as continuous variables, GNRI ( HR=0.911, 95% CI 0.882-0.941, P<0.001) and mCI ( HR=0.873, 95% CI 0.797-0.956, P=0.003) were correlated with all-cause death. As categorical variables, compared with high GNRI group and high mCI group, patients with low GNRI ( HR=3.469, 95% CI 2.125-5.665, P<0.001) and low mCI ( HR=3.255, 95% CI 1.879-5.640, P<0.001) had higher risks of death. Compared with G1 group, patients in G2 group ( HR=2.488, 95% CI 1.079-5.738, P=0.033) and G4 group ( HR=9.449, 95% CI 4.362-20.470, P<0.001) had higher risks of death. Conclusions:GNRI and mCI are independent predictive factors of all-cause mortality in MHD patients. The combination of GNRI and MCI can more accurately predict the risk of all-cause death in middle-aged and elderly MHD patients.
9.Association of body mass index and waist circumference with risk of all-cause mortality in middle-aged and elderly patients receiving maintenance hemodialysis
Zhihua SHI ; Yidan GUO ; Chunxia ZHANG ; Xiaoling ZHOU ; Pengpeng YE ; Yang LUO
Chinese Journal of Nephrology 2023;39(11):809-814
Objective:To investigate the association between body mass index (BMI) and waist circumference (WC) with all-cause mortality in middle-aged and elderly patients receiving maintenance hemodialysis (MHD).Methods:It was a prospective cohort study. The clinical data of MHD patients aged ≥50 years old from eleven hemodialysis centers from April to June 2017 in Beijing were analyzed. The patients were divided into low BMI group [body mass index (BMI)<18.5 kg/m 2], normal BMI group (18.5 kg/m 2≤BMI <24.0 kg/m 2), overweight group (24.0 kg/m 2≤BMI<28.0 kg/m 2) and obesity group (BMI≥28.0 kg/m 2) by BMI, and central obesity group (male ≥85 cm, female ≥80 cm) and normal WC group (male <85 cm, female <80 cm) by WC. Kaplan-Meier survival analysis method was used to compare the difference of all-cause mortality between those groups. Multivariate Cox regression model was used to analyze the association of BMI and WC with all-cause mortality. Results:A total of 613 MHD patients were enrolled, with age of (63.82±7.14) years old and 258 (42.09%) females. There were 46 (7.50%) patients in the low BMI group, 303 (49.43%) patients in the normal BMI group, 227 (37.03%) patients in the overweight group and 37 (6.04%) patients in the obesity group. In addition, 346 (56.44%) patients were categorized as central obesity. Kaplan-Meier survival analysis results showed that the all-cause mortality rates of low BMI group (log-rank χ2=13.571, P<0.001) and obesity group (log-rank χ2=6.664 P=0.010) were higher than that of normal BMI group, and the all-cause mortality rate of central obesity group was higher than that of normal WC group (log-rank χ2=5.698, P=0.017). Multivariate Cox regression analysis results showed that,besides the low BMI group and obesity group (with normal BMI group as a reference, HR=5.289, 95% CI 2.318-12.067, P<0.001; HR=5.360, 95% CI 2.088-13.760, P<0.001, respectively), normal BMI and overweight combined with central obesity were also independently correlated with all-cause mortality (with normal WC group as a reference, HR=2.605, 95% CI 1.199-5.663, P=0.016; HR=1.787, 95% CI 1.026-3.732, P=0.031, respectively). Conclusions:Lower and higher BMI or combined central obesity are independently associated with all-cause mortality in the middle-aged and elderly patients receiving MHD.
10.Clinical features, gene mutation profile and prognosis analysis of diffuse large B-cell lymphoma complicated with follicular lymphoma
Weiying BAO ; Pengpeng XU ; Qing SHI ; Muchen ZHANG ; Rong SHEN ; Yang HE ; Huiling QIU ; Hongmei YI ; Lei DONG ; Li WANG ; Shu CHENG ; Ying QIAN ; Weili ZHAO
Journal of Leukemia & Lymphoma 2023;32(2):92-96
Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.

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