Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Clinical features, gene mutation profile and prognosis analysis of diffuse large B-cell lymphoma complicated with follicular lymphoma / 白血病·淋巴瘤

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.

Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.

Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population / 中国医学科学院学报

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

Predictive Effects of Different Insulin Resistance Indexes on Diabetes Risk in Hypertensive Population / 中国医学科学院学报

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.

Clinicopathological characteristics and prognostic analysis of patients with female genital tract diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathological characteristics, gene mutation profile, and prognostic factors of diffuse large B-cell lymphoma (DLBCL) in female genital tract.Methods:A retrospective analysis was performed on the clinicopathological data of 30 patients with female genital tract DLBCL who were admitted to Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2003 to October 2021. Targeted sequencing was used to detect 55 lymphoma-related genes, and the gene mutation status of patients was evaluated. Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed by Cox proportional hazards model.Results:The median age of 30 female genital tract DLBCL patients at diagnosis was 58 years old (23-77 years old). The initial symptoms mainly included abdominal pain, distension, and masses (8 cases, 32%). Tumors most commonly located in the adnexal region (including ovaries and fallopian tubes) (13 cases, 45%), of which 9 cases were unilateral. Twenty-one cases (70%) had multiple extra-nodal involvements, 22 cases (73%) had Ann Arbor stage Ⅲ-Ⅳ, 8 cases (27%) had Eastern Cooperative Oncology Group (ECOG) score of ≥2, and 22 cases (73%) had elevated lactate dehydrogenase (LDH), 21 cases (70%) had International Prognostic Index (IPI) score of 3-5. Within 30 patients, 11 patients (37%) received surgery, and all patients received R-CHOP regimen-based chemotherapy. All 30 cases were evaluated for efficacy, the complete remission rate was 83% (25/30), the 5-year progression-free survival (PFS) rate was 69.7%, and the 5-year overall survival (OS) rate was 79.6%. Univariate analysis showed that ECOG score ≥2 was associated with worse OS ( P = 0.048). Among the 30 patients, 7 patients (23%) were primary and 23 patients (77%) were secondary. The proportions of patients with Ann Arbor stage Ⅲ-Ⅳ, IPI score 3-5 and elevated LDH in secondary patients were higher than those in primary patients (all P < 0.001), but there were no significant differences in PFS and OS between the two ( P values were 0.261 and 0.671). The targeted sequencing results of 16 patients showed that the mutation rates of PIM1, MYD88, KMT2D, TP53, CARD11, CCND3 and GNA13 were all > 20%, and TP53 mutation was associated with poorer PFS and OS ( P values 0.012 and 0.002). Conclusions:Female genital tract DLBCL is a rare invasive extranodal DLBCL with similar survival prognosis in primary and secondary patients. High-frequency mutations of PIM1, MYD88 and TP53 genes may provide new directions for treatment.

Gadoxetate-Enhanced MRI as a Diagnostic Tool in the Management of Hepatocellular Carcinoma:Report from a 2020 Asia-Pacific Multidisciplinary Expert Meeting

Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.

Independent and joint association of physical activity and sedentary behavior on all-cause mortality / 中华医学杂志(英文版)

BACKGROUNDS@#Physical activity (PA) and sedentary behavior (SB) have been associated with mortality, while the joint association with mortality is rarely reported among Chinese population. We aimed to examine the independent and joint association of PA and SB with all-cause mortality in southern China.@*METHODS@#A cohort of 12,608 China Hypertension Survey participants aged ≥35 years were enrolled in 2013 to 2014, with a follow-up period of 5.4 years. Baseline self-reported PA and SB were collected via the questionnaire. Kaplan-Meier curves (log-rank test) and Cox proportional hazards regression were performed to evaluate the associations of PA and SB on all-cause mortality.@*RESULTS@#A total of 11,744 eligible participants were included in the analysis. Over an average of 5.4 years of follow-up, 796 deaths occurred. The risk of all-cause mortality was lower among participants with high PA than those with low to moderate level (5.2% vs. 8.9%; hazards ratio [HR]: 0.75, 95% confidence interval [CI]: 0.61-0.87). Participants with SB ≥ 6 h had a higher risk of all-cause mortality than those with SB <6 h (7.8% vs. 6.0%; HR: 1.37, 95% CI: 1.17-1.61). Participants with prolonged SB (≥6 h) and inadequate PA (low to moderate) had a higher risk of all-cause mortality compared to those with SB < 6 h and high PA (11.2% vs. 4.9%; HR: 1.67, 95% CI: 1.35-2.06). Even in the participants with high PA, prolonged SB (≥6 h) was still associated with the higher risk of all-cause mortality compared with SB < 6 h (7.0% vs. 4.9%; HR: 1.33, 95% CI: 1.12-1.56).@*CONCLUSIONS@#Among Chinese population, PA and SB have a joint association with the risk of all-cause mortality. Participants with inadequate PA and prolonged SB had the highest risk of all-cause mortality compared with others.

Exploring the causal relationship between hip circumference and type 2 diabetes based on mendelian randomization / 中华疾病控制杂志

Objective To investigate the causal association between hip circumference (HC) and type 2 diabetes mellitus (T2DM) based on Mendelian randomization. Methods The genetic variants data of the HC and T2DM from the Genetic Investigation of Anthropometric Traits (GIANT) and DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) database were matched according to the single nucleotide polymorphism (SNP) rsID. Genetic loci strongly related to the HC were used as instrumental variables; and the inverse-variance weighting, MR-Egger regression model and weighting median method were carried out to analyze the causal effect of HC on T2DM. Results Fifty-two, nine and fifteen SNPs were matched in the total cohort, female cohort and male cohort, respectively. Heterogeneity test suggested the SNPs were homogeneous. We found HC to be positively associated with T2DM risk (OR=1.065, 95% CI: 1.030-1.100, OR=1.103, 95% CI: 1.057-1.150 and OR=1.583, 95% CI: 1.273-1.968, respectively) in above three cohorts, respectively. Sensitivity analysis showed the results were robust. Conclusions There is a relationship between HC and T2DM of people, and HC may be the risk factor of T2DM.

Predictive value of four score systems on the bleeding risk in atrial fibrillation patients treated with dabigatran / 中华心血管病杂志

Objective: To compare the predictive value of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores on the bleeding risk in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran. Methods: Data of 942 NVAF patients participating a non-interventional prospective study of anticoagulant therapy with dabigatran, which was conducted in 12 centers from February 2015 to December 2017 in China, were analyzed. Complete HAS-BLED HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores data and follow-up data were available in the enrolled patients. The endpoint of the study was bleeding events occurred during a 6 months follow-up. Cox proportional hazards models were constructed to analyze the associations between HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores and risk of bleeding, and the area under the curve (AUC) of receiver operating characteristics curves (ROC) of each score was used to set the predictive value for bleeding risk. Results: Among the 942 patients, the mean age was (65.3±11.2) years old, 542 (57.5%) were males. A total of 93 (9.9%) bleeding events occurred during follow up, 89 (9.4%) events were minor bleeding, and 4 (0.4%) events were major bleeding. Patients with a high-risk HAS-BLED score had a 1.87-fold increased risk of bleeding compared with low-risk patients (HR = 2.87, 95% CI:1.26-6.51, P = 0.012). There was no statistically significant difference between low-medium-high-risk grading in other scoring systems and bleeding risk (all P>0.05). The AUC (95%CI) of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores were 0.558 (0.525-0.590), 0.520 (0.487-0.553), 0.513(0.480-0.545), 0.523(0.490-0.555), respectively. The AUC of all bleeding score systems were of ≤ 0.700. Conclusion: Among the NVAF patients taking dabigatran in China, the HAS-BLED bleeding risk score is superior to other 3 bleeding risk score on predicting the bleeding risk in these patients, but its predictive value is still relatively low.

Prognostic study of 229 follicular lymphoma patients treated with rituximab combined with chemotherapy / 中华血液学杂志

Objective@#To explore the clinical characteristics of follicular lymphoma (FL) in the era of rituximab combined with chemotherapy and the prognostic significance of the follicular lymphoma international prognostic index (FLIPI), follicular lymphoma international prognostic index 2 (FLIPI2), international prognostic index (IPI), revised international prognostic index (R-IPI), National Comprehensive Cancer Network international prognostic index (NCCN-IPI) among Chinese patients.@*Methods@#229 FL patients who were treated initially with rituximab combined with CHOP-like (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy from November 2008 to April 2018 were analyzed retrospectively and all were scored by the above clinical index. Univariate and multivariate survival analysis were performed on 201 patients who completed the treatment and were followed regularly.@*Results@#In the univariate survival analysis, age>60 years, hemoglobin<120 g/L, elevated serumβ2- macroglobulin, involvement of bone marrow and elevated CRP were the risk prognostic factors for overall survival (OS) and progression free survival (PFS). Moreover, the analysis of the OS and PFS between rituximab (R) maintenance (RM) group and non-maintenance (non-RM) group showed that the OS and PFS of RM group were better than those of non-RM. In the multivariate analysis of OS, hemoglobin<120 g/L, involvement of bone marrow, elevated CRP and non-RM were independent prognostic factors. In the multivariate analysis of PFS, hemoglobin<120 g/L, CRP and non-RM were independent prognostic factors. When FLIPI2 was included in the multivariate analysis, CRP and FLIPI2 were independent prognostic factors in both OS and PFS, and non-RM was independent prognostic factors in PFS.@*Conclusion@#FLIPI2 is the better risk stratification in FL patients in the era of rituximab.

Effects of prenatal maternal cold stress on spontaneous, exploratory and anxious behaviors in offspring / 中国应用生理学杂志

OBJECTIVE@#To study the effects of prenatal cold stress on the behavior and mood of offspring in pregnant rats.@*METHODS@#Six SPF-class Wister pregnant rats were randomly divided into normal temperature control group and cold stress group with 3 rats in each group. The pregnant female rats in the normal temperature control group were kept in the environment of (22 ±2)℃, and the pregnant female rats in the cold stress group were placed in the artificial intelligence climate chamber at(4 ±0.1)℃ for 7 days before the birth, and the young rats were divided into normal temperature after the young rats were born. After the young rats were born, they were divided into normal temperature control group of male rats (MR, 22), normal temperature control group of mother rats (FR, 15), cold stress group of male rats (MC, 15), and cold stress group of female rats (FC, 15) .In the fourth generation of the offspring, the open field experiment and the elevated cross maze test were carried out.@*RESULTS@#In the open field experiment, there was no significant difference in spontaneous activity and exploration behavior between the normal temperature control group and the cold stress group (P＞0.05). In the elevated plus maze experiment, the retention time of the open arms, the number of open arms and the distance of the male and female rats in the cold stress group were significantly higher than those in the normal temperature control group (P＜0.05).@*CONCLUSION@#Prenatal maternal cold stress has no significant effect on spontaneous activity, exploration behavior and activity level of offspring, but the offspring have obvious abnormal behaviors with reduced anxiety behavior.

Presence of multiple abnormal immunologic markers is an independent prognostic factor of diffuse large B-cell lymphoma / 医学前沿

Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan-Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple ( ⩾ 3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P 60 years for OS (P = 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.

Peripheral leukocyte count and risk of bleeding in patients with non-valvular atrial fibrillation taking dabigatran: a real-world study / 中华医学杂志(英文版)

Background@#The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran.@*Methods@#A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed.@*Results@#During 6-month follow-up, 87 participants occurred bleeding events. For every 1 × 109/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99–1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75 × 109/L. For leukocyte counts < 6.75 × 109/L, the HR (95% CI) was 0.88 (0.69–1.13), and for leukocyte counts ≥ 6.75 × 109/L, the HR (95% CI) was 1.28 (1.09–1.51).@*Conclusion@#This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran.@*Clinical trial registration@#NCT02414035, https://clinicaltrials.gov.

Low deceleration capacity is associated with higher stroke risk in patients with paroxysmal atrial fibrillation / 中华医学杂志(英文版)

Background@#Deceleration capacity (DC) is a non-invasive marker for cardiac autonomic dysfunction; however, few studies have shown that the influence factors of cardiac autonomic dysfunction and the correlations between DC and stroke risk in paroxysmal atrial fibrillation (AF). We aimed to explore the influencing factors of abnormal DC and the relationships between DC and stroke risk in patients with paroxysmal AF.@*Methods@#The study included hospitalized paroxysmal AF patients with DC measurements derived from 24-h Holter electrocardiography recordings taken between August 2015 and June 2016. Multivariable regression analysis was performed to evaluate the associations between correlated variables and abnormal DC values. The relationship between DC and ischemic stroke risk scores in patients with paroxysmal AF was analyzed.@*Results@#We studied 259 hospitalized patients with paroxysmal AF (143 [55.2%] male, mean age 66.4 ± 12.0 years); 38 patients of them showed abnormal DC values. In the univariate analysis, age, hypertension, heart failure, and previous stroke/transient ischemic attack (TIA) were significantly associated with abnormal DC values. Among these factors, a history of previous stroke/TIA (odds ratio = 2.861, 95% confidence interval: 1.356–6.039) were independently associated with abnormal DC values in patients with paroxysmal AF. The abnormal DC group showed a higher stroke risk with the score of congestive heart failure, hypertension, age >75 years, diabetes mellitus, previous stroke and TIA (CHADS2) (2.25 ± 1.48 vs. 1.40 ± 1.34, t = -4.907, P = 0.001) and CHA2DS2-vascular disease, age 65–74 years and female category (VASc) (3.76 ± 1.95 vs. 2.71 ± 1.87, t = -4.847, P = 0.001) scores. Correlation analysis showed that DC was negatively correlated with CHADS2 scores (r = -0.290, P < 0.001) and CHA2DS2-VASc scores (r = -0.263, P > 0.001).@*Conclusions@#Lower DC is closely associated with previous stroke/TIA, and is also correlated negatively with higher stroke risk scores in patients with paroxysmal AF. It could be a potential indicator of stroke risk in paroxysmal AF patients.

Interstitial pneumonia in patients with diffuse large B-cell lymphoma receiving RCHOP and RCDOP regimens / 中华血液学杂志

Objective@#To identify the risk factors and clinical features associated with the interstitial pneumonia in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) or rituximab, cyclophosphamide, liposomal doxorubicin, vincristine and prednisone (RCDOP) regimens.@*Methods@#A retrospective study was conducted in 836 patients with DLBCL admitted to the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 114 patients were treated with RCDOP regimen. Using the method of propensity score matching according to age, gender, IPI score of patients, 114 patients treated with RCHOP regimen were selected as controls. Clinical data, including comorbidities, gender, age, B symptoms, international prognostic index (IPI) score, disease stage, serum lactic dehydrogenase (LDH) and β2 microglobulin (β2-MG) level were collected and the risk factors of interstitial pneumonia were further analyzed.@*Results@#The interstitial pneumonia developed more frequently in RCDOP group than RCHOP group (28.95% vs 2.60%, P<0.01) . As the dose of liposomal doxorubicin elevated from 25-30 mg/m2 to 35-40 mg/m2, the incidence of interstitial pneumonia accordingly increased from 17.30% to 38.71% (P<0.05) . By multivariate analysis, disease stage was an independent factor of interstitial pneumonitis.@*Conclusions@#Front line regimens containing liposomal doxorubicin in DLBCL patients link to a higher incidence of dose-dependent interstitial pneumonia. Prevention and surveillance should be emphasized in future studies.

Low deceleration capacity is associated with higher stroke risk in patients with paroxysmal atrial fibrillation / 中华医学杂志(英文版)

BACKGROUND@#Deceleration capacity (DC) is a non-invasive marker for cardiac autonomic dysfunction; however, few studies have shown that the influence factors of cardiac autonomic dysfunction and the correlations between DC and stroke risk in paroxysmal atrial fibrillation (AF). We aimed to explore the influencing factors of abnormal DC and the relationships between DC and stroke risk in patients with paroxysmal AF.@*METHODS@#The study included hospitalized paroxysmal AF patients with DC measurements derived from 24-h Holter electrocardiography recordings taken between August 2015 and June 2016. Multivariable regression analysis was performed to evaluate the associations between correlated variables and abnormal DC values. The relationship between DC and ischemic stroke risk scores in patients with paroxysmal AF was analyzed.@*RESULTS@#We studied 259 hospitalized patients with paroxysmal AF (143 [55.2%] male, mean age 66.4 ± 12.0 years); 38 patients of them showed abnormal DC values. In the univariate analysis, age, hypertension, heart failure, and previous stroke/transient ischemic attack (TIA) were significantly associated with abnormal DC values. Among these factors, a history of previous stroke/TIA (odds ratio = 2.861, 95% confidence interval: 1.356-6.039) were independently associated with abnormal DC values in patients with paroxysmal AF. The abnormal DC group showed a higher stroke risk with the score of congestive heart failure, hypertension, age >75 years, diabetes mellitus, previous stroke and TIA (CHADS2) (2.25 ± 1.48 vs. 1.40 ± 1.34, t = -4.907, P = 0.001) and CHA2DS2-vascular disease, age 65-74 years and female category (VASc) (3.76 ± 1.95 vs. 2.71 ± 1.87, t = -4.847, P = 0.001) scores. Correlation analysis showed that DC was negatively correlated with CHADS2 scores (r = -0.290, P < 0.001) and CHA2DS2-VASc scores (r = -0.263, P < 0.001).@*CONCLUSIONS@#Lower DC is closely associated with previous stroke/TIA, and is also correlated negatively with higher stroke risk scores in patients with paroxysmal AF. It could be a potential indicator of stroke risk in paroxysmal AF patients.

Peripheral leukocyte count and risk of bleeding in patients with non-valvular atrial fibrillation taking dabigatran: a real-world study / 中华医学杂志(英文版)

BACKGROUND@#The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran.@*METHODS@#A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed.@*RESULTS@#During 6-month follow-up, 87 participants occurred bleeding events. For every 1 × 10/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99-1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75 × 10/L. For leukocyte counts < 6.75 × 10/L, the HR (95% CI) was 0.88 (0.69-1.13), and for leukocyte counts ≥ 6.75 × 10/L, the HR (95% CI) was 1.28 (1.09-1.51).@*CONCLUSION@#This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran.@*CLINICAL TRIAL REGISTRATION@#NCT02414035, https://clinicaltrials.gov.

Impact of solid tumor history on treatment response and survival of patients with diffuse large B-cell lymphoma / 中华血液学杂志

Objective@#To observe whether the history of solid tumors affects the treatment response and survival situation of patients with diffuse large B-cell lymphoma (DLBCL) .@*Methods@#A retrospective study was conducted in 836 patients with DLBCL who were treated in the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 34 DLBCL patients who had the history of solid tumors were classified into double cancer group. From 802 patients without history of solid tumors, 68 DLBCL patients were selected as control group, using 1∶2 matching on propensity scores for age, gender, IPI score and etc. All patients included in the study had follow-up interviews through medical record and telephone for mortality from any cause. Treatment response and 3-year overall survival (OS) and progression-free survival (PFS) of two groups were analyzed.@*Results@#The complete remission rates after RCHOP (Rituximab+Cyclophosphamide+Vincristine+Adriamycin 50 mg/m2 or Epirubicin or Liposome Adriamycin+Prednisone) regimen were 79.4% and 67.6% in the double cancer group and the control group, respectively (P=0.210) . Among the 102 patients, 6 patients died in the double cancer group while 24 patients died in the control group and the median survival time of both two groups were not reached. The 3-year OS were (74.7±9.5) % and (63.5±6.1) % (χ2=2.791, P=0.095) , while 3-year PFS were (72.1±8.8) % and (54.3±6.4) % (χ2=1.400, P=0.237) in the double cancer group and the control group, respectively.@*Conclusion@#The history of solid tumors didn’t affect DLBCL patients’ treatment response and short-term survival.

Mitochondrial fusion-fission and heart failure / 基础医学与临床

Mitochondrial fusion,fission and dynamic transformation between the two are commonly known as mito-chondrial dynamics. Mitochondrial fusion-fission is related to a variety of biological functions of mitochondria inclu-ding regulation of energy metabolism, production of reactive oxygen species, maintenance of Ca2+homeostasis and influence of cellular death. Cardiac development,energy metabolism and ion homeostasis are closely related to the balance of mitochondrial fusion-fission.Mitochondrial fusion-fission disorders may cause myocardial cell dysfunction, damage and even the death of myocardial cells,which result in heart failure ultimately. Developing medicines tar-getting to reconstruct the balance of mitochondrial fusion-fission may provide new ideas and strategies for the treat-ment of chronic heart failure.