The impact of LDL-C/HDL-C ratio on severity of coronary artery disease and 2-year outcome in patients with premature coronary heart disease: results of a prospective, multicenter, observational cohort study / 中华心血管病杂志

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.

Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma / 中国医学科学杂志(英文版)

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project / 老年心脏病学杂志（英文版）

BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Prolonging dual antiplatelet therapy improves the long-term prognosis in patients with diabetes mellitus undergoing complex percutaneous coronary intervention / 老年心脏病学杂志（英文版）

OBJECTIVE@#To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI).@*METHODS@#A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581).@*RESULTS@#Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371).@*CONCLUSIONS@#For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

Association between Fruit and Vegetable Intake and Arterial Stiffness: The China-PAR Project / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness.@*METHODS@#We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges.@*RESULTS@#Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83).@*CONCLUSION@#Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.

Clinical Analysis of Pediatric Acute Myeloid Leukemia with CCLG-AML 2015 Regimen / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical effects of CCLG-AML-2015 protocol on newly diagnosed children with acute myeloid leukemia (AML).@*METHODS@#The clinical data of 60 newly diagnosed AML children in the Department of Hematology and Oncology, Wuhan Children's Hospital from August 2015 to September 2019 were summarized, the effect of chemotherapy using the CCLG-AML-2015 regimen (hereinafter referred to as the 2015 regimen) were retrospectively analyzed. 42 children with AML treated by the AML-2006 regimen (hereinafter referred to as the 2006 regimen) from February 2010 to July 2015 were used as control group.@*RESULTS@#There were no statistical differences between the 2015 regimen group and the 2006 regimen group in sex, age at first diagnosis, and risk stratification (P>0.05). The complete remission rate of bone marrow cytology after induction of 1 course of chemotherapy (84.7% vs 73.1%, P=0.155), and minimal residual disease detection (MRD) negative (42.3% vs 41.4%, P=0.928) in the 2015 regimen group were not statistically different than those in the 2006 regimen group. The bone marrow cytology CR (98.1% vs 80.6%, P=0.004) and MRD negative (83.3% vs 52.8%, P=0.002) in the 2015 regimen group after 2 courses of induction were higher than those in the 2006 regimen group. The 5-year overall survival (OS) rate in the 2015 regimen group (62.3%±6.4% vs 20.6%±6.4%, P=0.001), the 5-year disease-free survival (EFS) rate (61.0%±6.4% vs 21.0% ±6.4% , P=0.001) were better than those in the 2006 regimen group. The 5-year OS and EFS of high-risk transplant patients in the 2015 regimen group were significantly better than those of high-risk non-transplant patients (OS: 86.6%±9.0% vs 26.7%±11.4%, P=0.000; EFS: 86.6%±9% vs 26.7%±11.4%, P=0.000).@*CONCLUSION@#The 2015 regimen can increase the CR rate after 2 courses of induction compared with the 2006 regimen. High-risk children receiving hematopoietic stem cell transplantation can significantly improve the prognosis.

Impact of prolonging dual antiplatelet therapy on long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus undergoing drug-eluting stent implantation / 中华心血管病杂志

Objective: To explore and compare the effect of standard or prolonged dual antiplatelet therapy (DAPT) on the long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus after drug-eluting stent (DES) implantation. Methods: Consecutive patients with diabetes mellitus, ≥65 years old, underwent DES implantation, and had no adverse events within 1 year after operation underwent percutaneous coronary intervention (PCI) from January to December 2013 in Fuwai Hospital were enrolled in this prospective cohort study. These patients were divided into three groups according to DAPT duration: standard DAPT duration group (11 ≤ DAPT duration≤ 13 months) and prolonged DAPT duration group (13<DAPT duration≤ 24 months; DAPT duration>24 months). All the patients were followed up at 1, 6 months, 1, 2 and 5 years in order to collect the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and type 2 to 5 bleeding events defined by the Federation of Bleeding Academic Research (BARC). MACCE were consisted of all cause death, myocardial infarction, target vessel revascularization or stroke. The incidence of clinical adverse events were compared among 3 different DAPT duration groups, and Cox regression model were used to analyze the effect of different DAPT duration on 5-year long-term prognosis. Results: A total of 1 562 patients were enrolled, aged (70.8±4.5) years, with 398 female (25.5%). There were 467 cases in standard DAPT duration group, 684 cases in 13<DAPT duration≤ 24 months group and 411 cases in DAPT duration>24 months group. The patients in standard DAPT duration group and the prolonged DAPT duration groups accounted for 29.9% (467/1 562) and 70.1% (1 095/1 562), respectively. The 5-year follow-up results showed that the incidence of all-cause death in 13<DAPT duration≤ 24 months group (4.8%(33/684) vs. 8.6%(40/467),P=0.011) and DAPT duration>24 month group(4.1%(17/411) vs. 8.6%(40/467),P=0.008) were significantly lower than in standard DAPT group. The incidence of myocardial infarction in 13<DAPT duration≤ 24 months group was lower than in standard DAPT duration group (1.9%(13/684) vs. 5.1%(24/467),P=0.002). The incidence of MACCE in 13<DAPT duration≤ 24 months group was the lowest (standard DAPT duration group, 13<DAPT duration≤ 24 months group and DAPT duration>24 month group were 19.3% (90/467), 12.3% (84/684), 20.2% (83/411), respectively, P<0.001). There was no significant difference in the incidence of stroke and bleeding events among the three groups (all P>0.05). Multivariate Cox analysis showed that compared with the standard DAPT group, prolonged DAPT to 13-24 months was negatively correlated with MACCE (HR=0.601, 95%CI 0.446-0.811, P=0.001), all-cause death (HR=0.568, 95%CI 0.357-0.903, P=0.017) and myocardial infarction (HR=0.353, 95%CI 0.179-0.695, P=0.003). DAPT>24 months was negatively correlated with all-cause death (HR=0.687, 95%CI 0.516-0.913, P=0.010) and positively correlated with revascularization (HR=1.404, 95%CI 1.116-1.765, P=0.004). There was no correlation between prolonged DAPT and bleeding events. Conclusions: For elderly patients with coronary heart disease complicated with diabetes mellitus underwent DES implantation, and had no MACCE and bleeding events within 1 year after operation, appropriately prolonging of the DAPT duration is related to the reduction of the risk of cardiovascular adverse events. Patients may benefit the most from the DAPT between 13 to 24 months. In addition, prolonging DAPT duration does not increase the incidence of bleeding events in this patient cohort.

Recurrent and Refractory Langerhans Cell Histiocytosis in Children Treated with the Combination of Cladribine and Cytarabine / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children.@*METHODS@#Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae.@*RESULTS@#Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus.@*CONCLUSION@#2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.

Infection in Children with Acute Myeloid Leukemia in the Intensive Chemotherapy Period / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics of infection in children with acute myeloid leukemia (AML) after high intensive chemotherapy， so as to provide reference for prevention and control of infection.@*METHODS@#56 children diagnosed as acute myeloid leukemia in our hospital from January 2016 to August 2019 were enrolled and retrospectively analyzed, the infection rate, pathogens of disease and common location of infection during the induction and consolidation period were analyzed.@*RESULTS@#The total infection rate of the patients was 93.4%－96.4%, the average of serious infection rate was 16.0%(11.3%－19.6%), and the infection related mortality was 10.7%. Fever of unknown cause was the main reason of infection, while blood flow infections were the most common in severe infection, which were mainly caused by Gramnegative bacteria. The rate of fungal infection was 35.7% during chemotherapy.@*CONCLUSION@#Children with AML shows a high incidence of infection in each stage of chemotherapy. The serious illness caused by blood flow infection and take antifungal drugs to reduce the occurrence of fungal infection in AML patients should be paid attention.

The Relationship between Plasma sST2/Reg3α Levels and Acute Graft-Versus-Host Disease in Children After Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between plasma sST2/Reg3α levels and acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 29 pediatric patients received allo-HSCT treatment in Department of Hematology and Oncology of Wuhan Children's Hospital from January 2019 to January 2020 were collected. Peripheral blood samples were collected at 14 and 28 day after allo-HSCT. The plasma concentrations of sST2 and Reg3α were detected by Luminex assay.@*RESULTS@#Among 29 patients there were 15 males and 14 females with a median age of 53 (29-117) months. After allo-HSCT, 18 patients developed grade 0-I aGVHD; while 11 patients developed grade II-IV aGVHD. These included skin aGVHD in 6 cases, gastrointestinal aGVHD (GI-aGVHD) in 3 cases and gastrointestinal/skin aGVHD in 5 cases. Plasma sST2 level in II-IV aGVHD group showed significantly higher than that in 0-I aGVHD group at 28 days after allo-HSCT [101.81 (73.94-150.77) ng/ml vs 48.97 (28.82-56.69) ng/ml, P=0.021]. Also, the plasma sST2 level was significantly higher in GI-aGVHD group than that in no-aGVHD group at 28 days after allo-HSCT [118.74 (87.00-243.36) ng/ml vs 48.97 (23.55-61.40) ng/ml, P=0.004]. Plasma sST2 level ≥65.34 ng/ml at 28 days after allo-HSCT showed a sensitivity of 85.7% and a specificity of 87.5% in predicting II-IV aGVHD. And the patients with a plasma sST2 level ≥65.34 ng/ml showed a significantly higher incidence of II-IV aGVHD than those with plasma sST2 level of < 65.34 ng/ml after allo-HSCT (P=0.021). There was no significant difference in plasma Reg3α level between the patients with II-IV aGVHD and the non-aGVHD ones.@*CONCLUSION@#The increasing plasma sST2 level after allo-HSCT in children indicates the development of II-IV aGVHD, so sST2 is promising as a biomarker for predicting II-IV aGVHD.

Analysis of the Outcome and Prognostic Factors of Cyclosporine A in Children with Non-severe Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To summarize the long-term efficacy of cyclosporine (CsA) in the treatment of non-severe aplastic anemia (NSAA) in children, and explore the early significant indicators.@*METHODS@#Data of 36 NSAA children in Department of Hematological Oncology, Wuhan Children's Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2013 to December 2017 were analyzed retrospectively. All the children received oral CsA immunosuppressive therapy, and CsA trough concentration was checked to maintain at the rage of 200-250 μg/L after 2 weeks. The evaluation time points were at 3, 6, 12, 18 and 24 months, and assessment items were peripheral white blood cell differential count and reticulocyte's percentage and count.@*RESULTS@#The 36 NSAA cases were composed of 16 males and 20 females, whose median age was 5.46 (2.92-7.99) years old, and median follow-up time was 28.00 (10.00-38.25) months. After taking oral CsA for 24 months, the number of cumulative effective cases was 21. There were 4 cases of complete remission (CR), 17 cases of partial remission (PR), and 15 cases of non-remission (NR). The total effective rate was 58.33%, and median effect-acting time of CsA was 3.0 (0.5-10.0) months. Compared with ineffective group, neutrophil (NEU) and red blood cell (RBC) of effective group (CR+PR) began to increase significantly at the 3rd month, and hemoglobin (Hb), platelet (PLT) and white blood cell (WBC) increase significantly at the 6th month after oral CsA administration (P<0.05). Except for 2 cases who received component transfusion within 3-12 months after taking oral CsA for 3 months in effective group, the others did not need.@*CONCLUSION@#The overall effective rate of oral CsA in children with NSAA was 58.33%. Stopping blood transfusion after the 3 months of treatment may be considered as a turning point for disease outcomes, and levels of NEU, RBC at the 3rd month and Hb, PLT, WBC at the 6th month as indicators for predicting disease prognosis.

Association of cardiovascular diseases with milk intake among general Chinese adults / 中华医学杂志(英文版)

BACKGROUND@#The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults.@*METHODS@#A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations.@*RESULTS@#Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake.@*CONCLUSIONS@#Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.

Cardiovascular disease risk in diabetes patients aged 40 years old and above in China / 中华心血管病杂志

Objective: To evaluate the incidence of cardiovascular disease (CVD), ischemic and hemorrhagic cardiovascular events among Chinese diabetic patients aged 40 years and above with different CVD risk levels. Methods: This study enrolled participants aged 40 years and above in 15 provinces from a prospective cohort study, the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). Participants were categorized into two groups according to the presence or absence of diabetes at baseline. Individuals were further classified into low (0-4.9%), moderate (5%-9.9%) and high risk groups (≥10%), based on predicted ten-year CVD risk using the China-PAR equations. Two followed-up surveys were conducted between 2007 and 2015 to identify CVD events, which were defined as nonfatal acute myocardial infarction, or death due to coronary heart disease, or stroke. Ischemic cardiovascular events included nonfatal acute myocardial infarction, or death due to coronary heart disease, or ischemic stroke. Hemorrhagic cardiovascular events included subarachnoid hemorrhage and intracerebral hemorrhage. The incidences of CVD, ischemic and hemorrhagic cardiovascular events were compared in diabetes and non-diabetes population with different CVD risk levels. Results: This study included 89 209 participants aged 40 years and above, the average follow-up period was 8.5 years. The age was (54.8±9.4) years, and 36 794 (41.2%) were men, and 5 730 (6.4%) were diabetic patients. In diabetes patients aged 40 years and above, 53.7% (3 075/5 730) were at high risk of CVD. Age-and sex-adjusted incidence of CVD, ischemic and hemorrhagic cardiovascular events (1 066.93/100 000 person-years, 824.23/100 000 person-years, and 211.56/100 000 person-years) were significantly lower in diabetes patients than those in non-diabetes population with high CVD risk (1 773.73/100 000 person-years, 1 228.18/100 000 person-years, and 446.49/100 000 person-years) (all P<0.001). Among high CVD risk populations, incidence of ischemic events was significantly higher in diabetic patients than in non-diabetes population (1 638.47/100 000 person-years vs. 1 228.18/100 000 person-years, P<0.001), but incidence of hemorrhagic events tended to be lower in diabetic patients than in non-diabetes population (415.70/100 000 person-years vs. 446.49/100 000 person-years, P=0.635). Incidence of ischemic and hemorrhagic events were similar between diabetes patients and non-diabetes population at low or moderate CVD risk groups (all P>0.05). Conclusions: More than half of diabetes patients aged 40 years and above in China have high CVD risk. The incidence of CVD, ischemic and hemorrhagic cardiovascular events are different in diabetic patients with different CVD risk levels.

Effect of the Risk Factors for Treatment-Related Death in Children with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the possible risk factors of death in children with acute lymphoblastic leukemia (ALL) after treatment.@*METHODS@#The clinical data of 31 children with newly diagnosed acute lymphoblastic leukemia and dead after treatment in the Hematology Oncology Department of Wuhan children's Hospital from January 1, 2016 to December 31, 2019 were retrospectively analyzed. Univariate factor analysis and multivariate Cox regression analysis were used to analyze the each indexes of ALL children, and the possible risk factors causes of death in ALL children after treatment were analyzed.@*RESULTS@#Among 230 newly diagnosed ALL children, 31 (13.4%) cases were dead. Among them, there were 12 male and 19 female. The mortality rates were 9%(12/133) for male and 19.5%(19/97) for female, which showed a significantly difference（P=0.02）； among the dead ALL children, 6 were less than 1 year old, 23 were 1-10 years old, and 2 was more than 10 years old. The mortality rates in different age groups were 46.1 % (6/13), 11.7%(23/195) and 9%(2/22), respectively, which showed a significantly difference（P=0.00）； the mortality rates of the ALL children in standard risk group, medium risk group and high risk group were 6.7% (4/59), 11.9% (13/10@*CONCLUSION@#The female, less than 1 year old at initial diagnosis, high risk ALL, WBC>50×10

Relationship of PTEN/PI3K/AKT Signaling Pathway Protein Expression with Apoptosis and Drug-resistance of Children's ALL Primary Cells Treated with Daunorubicin / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship of PTEN/PI3K/AKT signaling pathway protein expression with apoptosis and drug-resistance of children's ALL primary cells treated with daunorubicin (DNR).@*METHODS@#The bone marrow mononuclear cells in newly diagnosed and untreated B-ALL children were collected and cultured. After the treatment of primary-cultured cells with DNR of final concentration 0.5 mg/L for 24 h, the cell apoptosis rate was detected by using cell apoptosis assay kit; the samples were collected at the on test of culture and after drug treatment, then expression levels of PTEN, PI3K and AKT proteins were detected by Western blot, moreover the interindex correlation was analyzed.@*RESULTS@#After DNR treatment, the apoptosis rate in PTEN low expression group was lower than that in PTEN high expression group (P＜0.05), showing high positive correlation of the cell apoptosis rate with the expression of PTEN before DNR treatment; the cell apoptosis rate in PI3K and AKT low expression group was higher than that in PI3K and AKT high expression group (P＜0.01); however, the expression of PI3K and AKT proteins was down-regulated after treatment with DNR (P＜0.01).@*CONCLUSION@#The difference of PTEN expression is present in primary cells of B-ALL children, however the change of PTEN expression is not significant after DNR treatment, suggesting that the PTEN expression correlates with DNR-resistance. The DNR can induce the apoptosis of childrens B-ALL primary cells by down-regulating the expression of PI3K and AKT signaling pathway proteins.

Effect of long-chain non-coding RNA AP000344. 3 on the proliferation and invasion of human bladder cancer cells and its mechanism / 临床与实验病理学杂志

Purpose To investigate the effect of specific long-chain non-coding RNA AP000344. 3 on the proliferation and invasion of bladder cancer cells and its mechanism. Methods qRT-PCR was used to detect the expression of AP000344. 3 in bladder cancer cells and normal bladder epithelial cells. The cancer cells with the lowest expression rate were selected for subsequent experiments. The AP000344. 3 plasmid or the negative control plasmid was transferred into bladder cancer cells by Lipofectamine 2000, and the transfection efficiency of AP000344. 3 was detected by qRT-PCR. Cell proliferation activity was measured by MTT method,and cell invasion ability was detected by Transwell assay. Bioinformatics was used to predict downstream miRNA and downstream genes of AP000344. 3. qRT-PCR and Western blot were used to detect the expression of downstream genes. Results The expression of AP000344. 3 in bladder cancer cells was significantly lower than that in normal bladder epithelial cells (P < 0. 01) ,and the expression of AP000344. 3 was the lowest in BIU87 cells (P < 0. 01) . The expression of AP000344. 3 in BIU87 cells was up-regulated at 48 h after transfection with AP000344. 3 (P < 0. 01) . The proliferation activity of BIU87 cells was decreased (P < 0. 05) ,and the cell invasion ability was decreased (P < 0. 05) . AP000344. 3 can target and bind to miR-135a-5p,and miR-135a-5p to human chemokine-like factor superfamily member 3 (CMTM3) . After up-regulation of AP000344. 3,miR-135a-5p expression was down-regulated (P < 0. 01) ,and CMTM3 was up-regulated in mRNA and protein expression (P < 0. 01) . Conclusion AP000344. 3 is significantly down-regulated in bladder cancer cells,and up-regulation of AP000344. 3 can inhibit the proliferation and invasion of bladder cancer cells. The mechanism may be to inhibit the expression of miR-135a-5p and up-regulate the expression of CMTM3 protein,providing a theoretical basis for finding new therapeutic targets for bladder cancer.

Impact of Residual SYNTAX Score and Its Derived Indexes on Clinical Outcomes after Percutaneous Coronary Intervention: Data from a Large Single Center / 中华医学杂志(英文版)

<p><b>Background</b>Residual SYNTAX score (rSS) and its derived indexes including SYNTAX revascularization index (SRI) and clinical rSS had been developed to quantify and describe the extent of incomplete revascularization. This study was conducted to explore the utility of the three scores among real-world patients after percutaneous coronary intervention (PCI).</p><p><b>Methods</b>From January 2013 to December 2013, patients underwent PCI treatment at Fuwai Hospital were included. The primary endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events. The secondary endpoints were myocardial infarction, revascularization, stroke, and stent thrombosis. Kaplan-Meier methodology was used to determine the outcomes. Cox multivariable regression was to test the associations between scores and all-cause mortality.</p><p><b>Results</b>A total of 10,344 patients were finally analyzed in this study. Kaplan-Meier survival analysis indicated that greater residual coronary lesions quantified by rSS and its derived indexes were associated with increased risk of adverse cardiovascular events. However, after multivariate analysis, only clinical rSS was an independent predictor of 2-year all-cause death (hazard ratio: 1.02, 95% confidence interval: 1.01-1.03, P < 0.01). By receiver operating characteristic (ROC) curve analysis, clinical rSS had superior predictability of 2-year all-cause death than rSS and SRI (area under ROC curve [AUC]: 0.59 vs. 0.56 vs. 0.56, all P < 0.01), whereas rSS was superior in predicting repeat revascularization than clinical rSS and SRI (AUC: 0.62 vs. 0.61 vs. 0.61; all P < 0.01). When comparing the predictive capability of rSS ≥8 with SRI <70%, their predictabilities were not significantly different.</p><p><b>Conclusions</b>This study indicates that all three indexes (rSS, clinical rSS, and SRI) are able to risk-stratify patients and predict 2-year outcomes after PCI. However, their prognostic capabilities are different.</p>

Evaluation of the Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Bleeding Score for Predicting the Long-term Out-of-hospital Bleeding Risk in Chinese Patients after Percutaneous Coronary Intervention / 中华医学杂志(英文版)

<p><b>Background</b>The Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients (PARIS) bleeding score is a novel score for predicting the out-of-hospital bleeding risk after percutaneous coronary intervention (PCI). However, whether this score has the same value in non-European and American populations is unclear. This study aimed to assess the PARIS bleeding score's predictive value of bleeding in patients after PCI in the Chinese population.</p><p><b>Methods</b>We performed a prospective, observational study of 10,724 patients who underwent PCI from January to December 2013, in Fuwai Hospital, China. We defined the primary end point as major bleeding (MB) according to Bleeding Academic Research Consortium definition criteria including Type 2, 3, or 5. The predictive value of the PARIS bleeding score was assessed with the area under the receiver operating characteristic (AUROC) curve.</p><p><b>Results</b>Of 9782 patients, 245 (2.50%) MB events occurred during the 2 years of follow-up. The PARIS bleeding score was significantly higher in the MB group than that of non-MB group (4.00 [3.00, 5.00] vs. 3.00 [2.00, 5.00], Z = 3.71, P < 0.001). According to risk stratification of the PARIS bleeding score, the bleeding risk in the intermediate- and high-risk groups was 1.50 times (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.160-1.950; P = 0.002) and 2.27 times higher (HR: 2.27; 95% CI: 1.320-3.900; P = 0.003) than that in the low-risk group. The PARIS bleeding score showed a moderate predictive value for MB in the overall population (AUROC: 0.568, 95% CI: 0.532-0.605; P < 0.001) and acute coronary syndrome (ACS) subgroup (AUROC: 0.578, 95% CI: 0.530-0.626; P = 0.001) and tended to be predictive in the non-ACS subgroup (AUROC: 0.556, 95% CI: 0.501-0.611; P = 0.054).</p><p><b>Conclusion</b>The PARIS bleeding score shows good clinical value for risk stratification and has a significant, but relatively limited, prognostic value for out-of-hospital bleeding in the Chinese population after PCI.</p>

Validation of Predictive Value of Patterns of Nonadherence to Antiplatelet Regimen in Stented Patients Thrombotic Risk Score in Chinese Population Undergoing Percutaneous Coronary Intervention: A Prospective Observational Study / 中华医学杂志(英文版)

Background@#The patterns of nonadherence to antiplatelet regimen in stented patients (PARIS) thrombotic risk score are a novel score for predicting the risk of coronary thrombotic events (CTEs) after percutaneous coronary intervention (PCI) with drug-eluting stents. However, the prognostic value of this score has not been fully evaluated in non-Euro-American PCI populations.@*Methods@#We performed a prospective, observational study of 10,724 patients who underwent PCI in Fuwai hospital, China and evaluated the PARIS thrombotic risk score's predictive value of CTEs in the PCI population. The area under the receiver operating characteristic curve (AUROC) was used to assess the predictive value of the PARIS score for CTE.@*Results@#Among 9782 patients without in-hospital events, a total of 95 CTEs occurred during the 2-year follow-up. The PARIS score was significantly higher in patients with CTEs (3.38 ± 2.04) compared with patients without events (2.53 ± 1.70, P < 0.001). According to the risk stratification of the PARIS thrombotic score, the risk of CTEs in the high-risk group was 3.14 times higher than that in the low-risk group (hazard ratio [HR], 3.14; 95% confidence interval [CI], 1.92-5.13; P < 0.001). However, the risk of CTEs in the intermediate-risk and low-risk groups was not significant (HR, 1.39; 95% CI, [0.86-2.24]; P = 0.184). The PARIS score showed prognostic value in evaluating CTEs in the overall population (AUROC, 0.621; 95% CI, 0.561-0.681), the acute coronary syndrome (ACS) population (AUROC, 0.617; 95% CI, 0.534-0.700; P = 0.003), and the non-ACS population (AUROC, 0.647; 95% CI, 0.558-0.736; P = 0.001).@*Conclusions@#In a real-world Chinese population, the PARIS thrombotic risk score shows a modest prognostic value for CTEs in patients after PCI. This score also has a predictive value for CTEs in the ACS and non-ACS subgroup populations.

Prognostic Value of NT-proBNP in Stable Coronary Artery Disease in Chinese Patients after Percutaneous Coronary Intervention in the Drug-eluting Stent Era / 生物医学与环境科学（英文）

OBJECTIVE@#The predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable coronary artery disease (SCAD) in the drug-eluting stent era is not yet clear. We aimed to evaluate the prognostic value of NT-proBNP in SCAD patients after percutaneous coronary intervention (PCI).@*METHODS@#We examined 4,293 consecutive SCAD patients who underwent PCI between January 2013 and December 2013 in Fuwai Hospital, China. The primary endpoint was all-cause death. NT-proBNP levels were measured before PCI using Elisa kits (Biomedica, Austria). The indication for PCI was based on the degree of coronary stenosis and evidence of ischemia.@*RESULTS@#Among 3,187 SCAD patients with NT-proBNP data, after a 2-year follow-up, NT-proBNP levels were predictive for all-cause death in the SCAD population [area under the receiver operating characteristic curve, 0.768; 95% confidence interval (CI), 0.687-0.849; P < 0.001]. At the optimum cutoff point of 732 pg/mL, the sensitivity and specificity of death was 75.0% and 72.3%, respectively. In a multivariable Cox regression model, the death hazard ratio was 6.43 (95% CI, 2.99-13.82; P < 0.001) for patients with NT-proBNP levels ⪖ 732 pg/mL, compared with < 732 pg/mL.@*CONCLUSION@#NT-proBNP is a strong predictor of 2-year death with SCAD after PCI in the drug-eluting stent era.