Causal effects of circulating vitamin levels on the risk of heart failure:a Mendelian randomization study

BACKGROUND Observational studies suggest inverse associations between serum vitamin levels and the risk of heart failure(HF). However, the causal effects of vitamins on HF have not been fully elucidated. Here, we conducted a Mendelian randomization(MR) study to investigate the causal associations between genetically determined vitamin levels and HF.METHODS Genetic instrumental variables for circulating vitamin levels, including vitamins A, B, C, D, and E, which were assessed as either absolute or metabolite levels were obtained from public genome-wide association studies. Summary statistics for single-nucleotide-polymorphisms and HF associations were retrieved from the HERMES Consortium(47,309 cases and 930,014controls) and FinnGen Study(30,098 cases and 229,612 controls). Two-sample MR analyses were implemented to assess the causality between vitamin levels and HF per outcome database, and the results were subsequently combined by meta-analysis.RESULTS Our MR study did not find significant associations between genetically determined circulating vitamin levels and HF risk. For absolute vitamin levels, the odds ratio for HF ranged from 0.97(95% confidence interval [CI]: 0.85–1.09, P = 0.41) for vitamin C to 1.05(95% CI: 0.61–1.82, P = 0.85) for vitamin A. For vitamin metabolites, the odds ratio ranged between 0.94(95% CI:0.75–1.19, P = 0.62) for α-tocopherol and 1.11(95% CI: 0.98–1.26, P = 0.09) for γ-tocopherol.CONCLUSION Evidence from our study does not support the causal effects of circulating vitamin levels on HF. Therefore,there may be no direct beneficial effects of vitamin intake on the prevention of primary HF.

Cholesterol paradox in the community-living old adults:is higher better?

OBJECTIVE To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.METHODS A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 com-munity older adults.After the baseline survey,the last follow-up was March 31,2021 with an average 8.13 years of follow-up.Cox proportional hazard model was used to estimate the hazard ratios(HR)with 95%CI for cardiovascular disease(CVD)death and all-cause death in associations with baseline lipid indicators.RESULTS A total of 4499 participants were recruited,and the mean levels of uric acid,body mass index,systolic blood pres-sure,diastolic blood pressure,fasting plasma glucose,total cholesterol(TC),triglyceride,and low-density lipoprotein cholesterol(LDL-C)showed an upward trend with the increasing remnant cholesterol(RC)quarters(Ptrend<0.05),while the downward tr-end was found in high-density lipoprotein cholesterol(HDL-C).During the total 36,596 person-years follow-up,the CVD mortal-ity and all-cause mortality during an average 8.13 years of follow-up was 3.87%(95%CI:3.30%-4.43%)and 14.83%(95%CI:13.79%-15.86%)with 174 CVD death participants and 667 all-cause death participants.After adjusting for confounders,the higher level of TC(HR=0.854,95%CI:0.730-0.997),LDL-C(HR=0.817,95%CI:0.680-0.982)and HDL-C(HR=0.443,95%CI:0.271-0.724)were associated with lower risk of CVD death,and the higher level of HDL-C(HR=0.637,95%CI:0.501-0.810)were associated with lower risk of all-cause death.The higher level of RC(HR=1.276,95%CI:1.010-1.613)increase the risk of CVD death.Com-pared with the normal lipid group,TC≥6.20 mmol/L group and LDL-C≥4.10 mmol/L group were no longer associated with lower risk of CVD death,while RC≥0.80 mmol/L group was still associated with higher risk of CVD death.In normal lipid gr-oup,the higher levels of TC,LDL-C and HDL-C were related with lower CVD death.CONCLUSIONS In community older adults,higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range.Higher RC was associated with higher CVD mortality,which may be a better lipid indicator for es-timating the CVD death risk in older adults.

Circulating circRNA expression profile and its potential role in late recurrence of paroxysmal atrial fibrillation post catheter ablation

BACKGROUND Catheter-based pulmonary vein isolation(PVI) is an effective and well-established intervention for symptomatic paroxysmal atrial fibrillation(PAF). Nevertheless, late recurrences of atrial fibrillation(LRAF) occurring during 3 to 12months are common, and the underlying mechanisms remain elusive. Circular RNAs(circ RNAs) in atrial tissue have been linked to the pathophysiological mechanisms and progression of PAF in a few studies. However, their expression patterns in peripheral blood and regulatory function in LRAF are not clear.METHODS In the present study, the expression profile of circulating circ RNAs in three paired nonvalvular PAF patients with or without LRAF was investigated by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction(q RT-PCR). Bioinformatics analyses, including Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis, and circ RNA/mi RNA regulatory network, were performed to predict the functions and potential regulatory roles of differentially expressed(DE) circ RNAs.RESULTS A total of 12,834 circ RNAs, comprising 5,491 down-regulated and 7,343 up-regulated circ RNAs, were found to be DE in blood smaples from the two groups in peripheral blood between LRAF and non-recurrence control individuals. The most enriched GO categories in terms of molecular function, biological process, and cellular component features were catalytic activity,cellular metabolic process, and intracellular part, respectively. The KEGG enrichment study revealed that the most important metabolic process controlled by DE circ RNAs is endocytosis. In the circ RNA/micro RNAs interaction network, four up-regulated circ RNAs(hsa_circ_0002665, hsa_circ_0001953, hsa_circ_0003831, and hsa_circ_0040533) and one down-regulated circ RNA(hsa_circ_0041103) were predicted to play potential regulatory roles in the pathogenesis of LRAF.CONCLUSIONS This investigation discovered the expression pattern of circulating circ RNAs that is indicative of PAF late recurrence, which may serve as risk markers or therapeutic targets for LRAF after PVI.

SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis

Objective:SOX11 is expressed in numerous malignancies,including hepatocellular carcinomas(HCC),but its oncogenic function has not been elucidated.Here,we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma(LIHC)dataset to investigate the function of SOX11 in tumorgenesis.Methods:SOX11 expression data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)were validated by immunohistochemistry(IHC).Co-expression,differential expression,and functional analyses utilized TCGA-LIHC,Timer 2.0,Metascape,GTEx,and LinkedOmics databases.Associations with immune infiltration,ferroptosis,and immune checkpoint genes were assessed.Genetic changes were explored via CBioPortal.Logistic regression,receiver operating characteristic curve(ROC),Kaplan-Meier analysis,and nomogram modeling evaluated associations with HCC clinicopathological features.SOX11’s impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.Results:SOX11 was significantly elevated in HCC tumors compared to controls.SOX11-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels.Significant associations were found between SOX11 levels,immune infiltration,ferroptosis,and immune checkpoint genes in HCC tissue.SOX11 levels correlated with HCC stage,histologic grade,and tumor status,and independently predicted overall and disease-specific survival.SOX11 expression effectively distinguished between tumor and normal liver tissue.Spearman correlations highlighted a significant relationship between SOX11 and ferroptosis-associated genes.Decreased SOX11 levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.Conclusions:SOX11 was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.

Plasma metabolites and risk of myocardial infarction:a bidirectional Mendelian randomization study

BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several genetic and environmental factors.It is essential to understand the function of plasma metabolites in the development of MI and unravel its complex pathogenesis.METHODS This study employed a bidirectional Mendelian randomization(MR)approach to investigate the causal relationships between plasma metabolites and MI risk.We used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice versa.In addition,the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite(1400 metabolites)and MI(20,917 individuals with MI and 440,906 individuals without MI)susceptibility.Inverse variance weighted was the primary method for estimating causal effects.MR estimates are expressed as beta coefficients or odds ratio(OR)with 95%CI.RESULTS We identified 14 plasma metabolites associated with the occurrence of MI(P<0.05),among which 8 plasma metabolites[propionylglycine levels(OR=0.922,95%CI:0.881–0.965,P<0.001),gamma-glutamylglycine levels(OR=0.903,95%CI:0.861–0.948,P<0.001),hexadecanedioate(C16-DC)levels(OR=0.941,95%CI:0.911–0.973,P<0.001),pentose acid levels(OR=0.923,95%CI:0.877–0.972,P=0.002),X-24546 levels(OR=0.936,95%CI:0.902–0.971,P<0.001),glycine levels(OR=0.936,95%CI:0.909–0.964,P<0.001),glycine to serine ratio(OR=0.930,95%CI:0.888–0.974,P=0.002),and mannose to trans-4-hydroxyproline ratio(OR=0.912,95%CI:0.869–0.958,P<0.001)]were correlated with a decreased risk of MI,whereas the remaining 6 plasma metabolites[1-palmitoyl-2-arachidonoyl-GPE(16:0/20:4)levels(OR=1.051,95%CI:1.018–1.084,P=0.002),behenoyl dihydrosphingomyelin(d18:0/22:0)levels(OR=1.076,95%CI:1.027–1.128,P=0.002),1-stearoyl-2-docosahexaenoyl-GPE(18:0/22:6)levels(OR=1.067,95%CI:1.027–1.109,P=0.001),alpha-ketobutyrate levels(OR=1.108,95%CI:1.041–1.180,P=0.001),5-acetylamino-6-formylamino-3-methyluracil levels(OR=1.047,95%CI:1.019–1.076,P<0.001),and N-acetylputrescine to(N(1)+N(8))-acetylspermidine ratio(OR=1.045,95%CI:1.018–1.073,P<0.001)]were associated with an increased risk of MI.Furthermore,we also observed that the mentioned relationships were unaffected by horizontal pleiotropy(P>0.05).On the contrary,MI did not lead to significant alterations in the levels of the aforementioned 14 plasma metabolites(P>0.05 for each comparison).CONCLUSIONS Our bidirectional MR study identified 14 plasma metabolites associated with the occurrence of MI,among which 13 plasma metabolites have not been reported previously.These findings provide valuable insights for the early diagnosis of MI and potential therapeutic targets.

The characteristic and dynamic electrocardiogram changes on hyperkalemia in a hemodialysis patient with heart failure:a case report

Hyperkalemia,usually associated with predisposing chronic diseases as heart failure(HF),severe kidney disease or diabetes mellitus(DM),[1]is defined as an elevation of potassium concentration more than 5.5 mmol/L,[2].

Establishment of an Assessment System for the Prediction of Severe Post-operative Complications after Hepatectomy Based on Preoperative Parameters

Objective At present,there is no appropriate system to evaluate the severe complications of liver surgery through the preoperative factors.This study aimed to design and verify a risk assessment system for the prediction of severe post-operative complications after a hepatectomy based on the preoperative parameters.Methods A retrospective analysis was performed on 1732 patients who had undergone liver surgery.The severity of the complications was graded by Accordion Severity Grading of post-operative complications.The variables were screened by multivariate analysis,and graded scores were assigned to the selected variables.A logistic regression equation was used to form the liver operation risk formula(LORF)for the prediction of severe post-operative complications.The LORF was verified by the receiver operating characteristic(ROC)curve.Results The multivariate correlation analysis revealed the independent influencing factors of the severe post-operative complications of liver surgery were Child-Pugh grade(OR=4.127;P<0.001),medical diseases requiring drug treatment(OR=3.092;P<0.001),the number of liver segments to be removed(OR=2.209;P=0.006),organ invasion(OR=4.538;P=0.024),and pathological type(OR=4.023;P=0.002).The binomial logistic regression model was established to obtain the calculation formula(LORF)of the severe complication risk.The area under the ROC curve(AUC)of the LORF was 0.815.The cut-off value of the expected probability of severe complications was 0.3225(32.25%).Furthermore,in the validation data set,the corresponding AUC of the LORF was 0.829.Conclusion As a novel and simplified assessment system,the LORF could effectively predict the severe post-operative complications of liver surgery through the preoperative factors,and therefore it could be used to evaluate the risk of severe liver surgical complications before surgery.

Comprehensive characterization of CRC with germline mutations reveals a distinct somatic mutational landscape and elevated cancer risk in the Chinese population

Objective:Hereditary colorectal cancer(CRC)accounts for approximately 5%–10%of all CRC cases.The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population.Methods:We performed the first population study investigating the germline mutation status in more than 1,000(n=1,923)Chinese patients with CRC and examined their relationship with the somatic mutational landscape.Germline alterations were examined with a 58-gene next-generation sequencing panel,and somatic alterations were examined with a 605-gene panel.Results:A total of 92 pathogenic(P)mutations were identified in 85 patients,and 81 likely pathogenic(LP)germline mutations were identified in 62 patients,accounting for 7.6%(147/1,923)of all patients.MSH2 and APC was the most mutated gene in the Lynch syndrome and non-Lynch syndrome groups,respectively.Patients with P/LP mutations had a significantly higher ratio of microsatellite instability,highly deficient mismatch repair,family history of CRC,and lower age.The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-P group.The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the nonLynch syndrome group.Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Population risk analysis indicated that the overall odds ratio was 11.13(95%CI:8.289–15.44)for the P group and 20.68(95%CI:12.89–33.18)for the LP group.Conclusions:Distinct features were revealed in Chinese patients with CRC with germline mutations.The Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Patients with P/LP germline mutations exhibited higher CRC risk.

Comparison of Obesity Prevalence among Middle and High School Graduates before and after the COVID-19 Lockdown

The world has been engulfed in a COVID-19 pandemic that has significantly affected the health and economics of the population.The Chinese authorities imposed lockdown measures to limit the spread of COVID-19 and stopped school programs for children and adolescents.Such measures have been associated with increased sedentary time and reduced physical activity[1-3].An online questionnaire study of youth in China compared activity patterns before and after the COVID-19 lockdown.

Detection rates of adenomas,advanced adenomas,and colorectal cancers among the opportunistic colonoscopy screening population:a single-center,retrospective study

Background: Colorectal cancer (CRC) screening is effective in reducing CRC incidence and mortality. The aim of this study was to retrospectively determine and compare the detection rate of adenomas, advanced adenomas (AAs) and CRCs, and the number needed to screen (NNS) of individuals in an average-risk Chinese population of different ages and genders. Methods: This was a retrospective study performed at the Institute of Health Management, Chinese People’s Liberation Army General Hospital. Colonoscopy results were analyzed for 53,152 individuals finally enrolled from January 2013 to December 2019. The detection rate of adenomas, AAs, or CRCs was computed and the characteristics between men and women were compared using chi-squared test. Results: The average age was 48.8 years (standard deviation [SD], 8.5 years) for men and 50.0 years (SD, 9.0 years) for women, and the gender rate was 66.27% (35,226) vs . 33.73% (17,926). The detection rates of adenomas, AAs, serrated adenomas, and CRCs were 14.58% (7750), 3.09% (1641), 1.23% (653), and 0.59% (313), respectively. Men were statistically significantly associated with higher detection rates than women in adenomas (17.20% [6058/35,226], 95% confidence interval [CI] 16.74-17.53% vs . 9.44% [1692/17,926], 95% CI 8.94-9.79%, P < 0.001), AAs (3.72% [1309], 95% CI 3.47-3.87% vs . 1.85% [332], 95% CI 1.61-2.00%, P < 0.001), and serrated adenomas (1.56% [548], 95% CI 1.43-1.69% vs . 0.59% [105], 95% CI 0.47-0.70%, P < 0.001). The detection rate of AAs in individuals aged 45 to 49 years was 3.17% (270/8510, 95% CI 2.80-3.55%) in men and 1.69% (69/4091, 95% CI 1.12-1.86%) in women, and their NNS was 31.55 (95% CI 28.17-35.71) in men and 67.11 (95% CI 53.76-89.29) in women. The NNS for AAs in men aged 45 to 49 years was close to that in women aged 65 to 69 years (29.07 [95% CI 21.05-46.73]). Conclusions: The detection rates of adenomas, AAs, and serrated adenomas are high in the asymptomatic population undergoing a physical examination and are associated with gender and age. Our findings will provide important references for effective population-based CRC screening strategies in the future.

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease

BACKGROUND Growth differentiation factor 15(GDF-15)has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events.This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality,considering traditional risk factors and other biomarkers.METHODS A prospective study was conducted and 3699 patients with stable coronary artery disease(CAD)were enrolled into the research.Baseline GDF-15 levels were measured.Median follow-up was 3.1 years during the study.We analyzed clinical variables and several biomarkers.Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction(MI),heart failure,stroke,cardiovascular death,and non-cardiovascular death.RESULTS Baseline GDF-15 levels for 3699 patients were grouped by quartile(≤1153,1153-1888,1888-3043,>3043 ng/L).Higher GDF-15 levels were associated with older age,male gender,history of hypertension,and elevated levels of N-terminal pro Btype natriuretic peptide(NT-pro BNP),soluble suppression of tumorigenesis-2(sST2),and creatine(each with P<0.001).Adjusting for established risk factors and biomarkers in Cox proportional hazards models,a 1 standard deviation(SD)increase in GDF-15 was associated with elevated risk of clinical events[hazard ratio(HR)=2.18,95%confidence interval(CI):(1.52-3.11)],including:MI[HR=2.8395%CI:(1.03-7.74)],heart failure[HR=2.7195%CI:(1.18-6.23)],cardiovascular and non-cardiovascular death[HR=2.48,95%CI(1.49-4.11)]during the median follow up of 3.1 years.CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death,independent of clinical risk factors and other biomarkers.GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Effect of Home Blood Pressure Telemonitoring Plus Additional Support on Blood Pressure Control:A Randomized Clinical Trial

Objective Current clinical evidence on the effects of home blood pressure telemonitoring(HBPT)on improving blood pressure control comes entirely from developed countries.Thus,we performed this randomized controlled trial to evaluate whether HBPT plus support(patient education and clinician remote hypertension management)improves blood pressure control more than usual care(UC)in the Chinese population.Methods This single-center,randomized controlled study was conducted in Beijing,China.Patients aged 30-75 years were eligible for enrolment if they had blood pressure[systolic(SBP)≥140 mmHg and/or diastolic(DBP)≥90 mmHg;or SBP≥130 mmHg and/or DBP≥80 mmHg with diabetes].We recruited 190 patients randomized to either the HBPT or the UC groups for 12 weeks.The primary endpoints were blood pressure reduction and the proportion of patients achieving the target blood pressure.Results Totally,172 patients completed the study,the HBPT plus support group(n=84),and the UC group(n=88).Patients in the plus support group showed a greater reduction in mean ambulatory blood pressure than those in the UC group.The plus support group had a significantly higher proportion of patients who achieved the target blood pressure and maintained a dipper blood pressure pattern at the12th week of follow-up.Additionally,the patients in the plus support group showed lower blood pressure variability and higher drug adherence than those in the UC group.Conclusion HBPT plus additional support results in greater blood pressure reduction,better blood pressure control,a higher proportion of dipper blood pressure patterns,lower blood pressure variability,and higher drug adherence than UC.The development of telemedicine may be the cornerstone of hypertension management in primary care.

Prevalence and influencing factors of cognitive frailty in elderly with diabetes mellitus in China:A meta-analysis

Objective:To systematically review the epidemiological characteristics and influencing factors of cognitive frailty in Chinese elderly with diabetes mellitus.Methods:PubMed,Embase,Web of Science,CINAHL,Cochrane Library,China National Knowledge Infrastructure(CNKI),Wanfang and Chinese biomedical literature database(CBM)were electronically searched to collect cross-sectional studies on the prevalence and influencing factors of cognitive frailty in Chinese elderly with diabetes mellitus from inception to November 1st,2022.After quality evaluation and data extraction of included studies,R4.2.2 software was used to perform metaanalysis.Results:A total of 7 Chinese and one English literatures involving 2208 participants were included.The results of meta-analysis showed that the prevalence rate of cognitive frailty in elderly diabetic patients was 17.1%(95%CI 8.7%to 30.9%).Subgroup analysis showed that the prevalence rate of cognitive frailty was 10.2%(95%CI 5.0%to 19.7%)in old diabetic adults in community,35.7%(95%CI 20.8%to 53.9%)in hospital,and the difference was statistically significant(P=0.01).The prevalence rate of cognitive frailty was 21.7%(95%CI 10.3%to 40.2%)in male diabetic old adults,24.2%(95%CI 13.3%to 40.1%)in female diabetic old adults,and the difference was not statistically significant(P=0.81).The rate was 12.6%(95%CI 6.6%to 22.5%)in 60~69 years old group,25.8%(95%CI 12.6%to 45.5%)in 70~79 years old group,53.0%(95%CI 23.9%to 80.2%)in diabetic old adults aged 80 years and above,and the difference was statistically significant(P=0.02).The influencing factors for cognitive frailty in diabetic old adults included educational level[OR=0.230,95%CI(0.117~0.454),P<0.0001],regular exercise[OR=0.357,95%CI(0.217~0.588),P<0.01],malnutrition[OR=2.372,95%CI(1.472~3.822),P=0.0004],depression[OR=3.207,95%CI(2.156~4.768),P<0.0001],and HbA1c≥7.0%[OR=3.112,95%CI(1.880~5.152),P<0.0001].Conclusion:The prevalence of cognitive frailty in Chinese elderly patients with diabetes is high,and there are differences in cognitive frailty prevalence among different sources and different ages.Educational level,exercise habits,nutritional status,depression and HbA1c are the factors affecting cognitive frailty in elderly patients with diabetes.Depression,malnutrition,HbA1c≥7.0%were risk factors,and high educational level,regular exercise were protective factors.Attention should be paid to early and accurate identification of cognitive frailty and intervention targeting influencing factors to delay or reverse its progression to adverse health outcomes.

Long-term adoptive immunotherapy achieves complete response and bone lesion repair in an elderly patient with macrofocal multiple myeloma

Managing Editor:Peng Lyu Macrofocal multiple myeloma(MFMM)is a distinct entity within multiple myeloma(MM)characterized by the presence of multiple lytic bone lesions,with clonal plasma cells in the bone marrow accounting for<10%.1,2 The revised 2022 Chinese guidelines for the diagnosis and treatment of MM state:in patients with<10%clonal plasma cells in multi-site bone marrow aspirates,attention should be given to MFMM,characterized by single or multiple bone destructive lesions,often accompanied by involvement of surrounding soft tissues or lymph nodes.3 Research is limited regarding the long-term use of adoptive immunotherapy for the treatment of MFMM;as such,we report herein the case of an elderly patient diagnosed with MFMM who experienced severe chemotherapy side effects and subsequently underwent adoptive immunotherapy.Remarkably,the patient benefited from 14 years of treatment[Figure 1A].

Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular outcomes in elderly patients with comorbid coronary heart disease and diabetes mellitus

OBJECTIVE To investigate the effects of sodium-glucose cotransporter 2 inhibitors(SGLT2i)on cardiovascular outcomes in elderly Chinese patients with comorbid coronary heart disease(CHD)and type 2 diabetes mellitus(T2DM).METHODS A retrospective cohort study was conducted on 501 elderly inpatients(≥60 years)with comorbid CHD/T2DM in Department of Cardiovascular Medicine and Endocrinology,Chinese PLA General Hospital from January 2018 to December 2019.These patients were divided into two groups according to the administration of SGLT2i.All the demographic characteristics and clinical data were collected.Cardiovascular outcomes,including all-cause mortality,major adverse cardiovascular events(MACE),and hospitalization for heart failure(HHF),were followed up.RESULTS In the cohort,there were 167 patients in the SGLT2i group and 334 patients in the control group.In the efficacy analyses,the incidence of MACE was lower in the SGLT2i group than in the control group:3.6%vs.9.3%(P=0.022).A lower risk of MACE was observed in the SGLT2i group[hazard ratio(HR)=0.40,95%CI:0.17-0.95].There was no significant difference in the incidence of all-cause mortality or HHF between the two groups.No significant difference of HR was observed for all-cause mortality(HR=0.41,95%CI:0.12-1.41)or HHF(HR=0.58,95%CI:0.12-2.81).CONCLUSIONS SGLT2i treatment exhibited benefits for elderly patients with comorbid CHD/T2DM with a lower risk for MACE.

Establishment of a diagnostic model of coronary heart disease in elderly patients with diabetes mellitus based on machine learning algorithms

OBJECTIVE To establish a prediction model of coronary heart disease(CHD)in elderly patients with diabetes mellitus(DM)based on machine learning(ML)algorithms.METHODS Based on the Medical Big Data Research Centre of Chinese PLA General Hospital in Beijing,China,we identified a cohort of elderly inpatients(≥60 years),including 10,533 patients with DM complicated with CHD and 12,634 patients with DM without CHD,from January 2008 to December 2017.We collected demographic characteristics and clinical data.After selecting the important features,we established five ML models,including extreme gradient boosting(XGBoost),random forest(RF),decision tree(DT),adaptive boosting(Adaboost)and logistic regression(LR).We compared the receiver operating characteristic curves,area under the curve(AUC)and other relevant parameters of different models and determined the optimal classification model.The model was then applied to 7447 elderly patients with DM admitted from January 2018 to December 2019 to further validate the performance of the model.RESULTS Fifteen features were selected and included in the ML model.The classification precision in the test set of the XGBoost,RF,DT,Adaboost and LR models was 0.778,0.789,0.753,0.750 and 0.689,respectively;and the AUCs of the subjects were 0.851,0.845,0.823,0.833 and 0.731,respectively.Applying the XGBoost model with optimal performance to a newly recruited dataset for validation,the diagnostic sensitivity,specificity,precision,and AUC were 0.792,0.808,0.748 and 0.880,respectively.CONCLUSIONS The XGBoost model established in the present study had certain predictive value for elderly patients with DM complicated with CHD.

Late-chronic cardiotoxicity and heart failure caused by ibrutinib:a case report and literature review

Richter syndrome (RS) is a rare transformation of relatively low-grade malignant chronic lymphocytic leukemia (CLL) to more aggressive lymphoma. The most common form of RS is transformation to diffuse large B-cell lymphoma (> 95%) and much less frequently (<1%)to Hodgkin lymphoma (HL), plasma blast lymphoma, or other rare lymphomas.

Small molecules facilitate single factor-mediated sweat gland cell reprogramming

Background: Large skin defects severely disrupt the overall skin structure and can irreversibly damage sweat glands(SGs), thus impairing the skin’s physiological function. This study aims to develop a stepwise reprogramming strategy to convert fibroblasts into SG lineages, which may provide a promising method to obtain desirable cell types for the functional repair and regeneration of damaged skin.Methods: The expression of the SG markers cytokeratin 5(CK5), cytokeratin 10(CK10), cytokeratin 18(CK18), carcinoembryonic antigen(CEA), aquaporin 5(AQP5) and α-smooth muscle actin(α-SMA) was assessed with quantitative PCR(qPCR), immunofluorescence and flow cytometry. Calcium activity analysis was conducted to test the function of induced SG-like cells(iSGCs). Mouse xenograft models were also used to evaluate the in vivo regeneration of iSGCs.BALB/c nude mice were randomly divided into normal group, SGM treatment group and iSGC transplantation group.Immunocytochemical analyses and starch-iodine sweat tests were used to confirm the in vivo regeneration of iSGCs.Results: Ectodermal dysplasia antigen(EDA) overexpression drove human dermal fibroblast(HDF) conversion into i SGCs in SG culture medium(SGM). qPCR indicated significantly increased mRNA levels of the SG markers CK5, CK18and CEA in iSGCs, and flow cytometry data demonstrated(4.18±0.04)% of iSGCs were CK5 positive and(4.36±0.25)%of iSGCs were CK18 positive. The addition of chemical cocktails greatly accelerated the SG fate program. qPCR results revealed significantly increased mRNA expression of CK5, CK18 and CEA in iSGCs, as well as activation of the duct marker CK10 and luminal functional marker AQP5. Flow cytometry indicated, after the treatment of chemical cocktails,(23.05±2.49)% of iSGCs expressed CK5^(+) and(55.79±3.18)% of iSGCs expressed CK18^(+), respectively. Calcium activity analysis indicated that the reactivity of iSGCs to acetylcholine was close to that of primary SG cells [(60.79±7.71)% vs.(70.59±0.34)%, ns]. In vivo transplantation experiments showed approximately(5.2±1.1)% of the mice were sweat test positive, and the histological analysis results indicated that regenerated SG structures were present in iSGCs-treated mice.Conclusions: We developed a SG reprogramming strategy to generate functional iSGCs from HDFs by using the single factor EDA in combination with SGM and small molecules. The generation of iSGCs has important implications for future in situ skin regeneration with SG restoration.

Potential roles of vitamin D binding protein in attenuating liver injury in sepsis

Background:In sepsis,vitamin D binding protein(VDBP)has been shown to be low-expressed.The current study examined the relationship between serum VDBP level and liver injury in sepsis patients,as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide(LPS).Methods:The human study included 78 sepsis patients and 50 healthy volunteers.Sepsis patients were categorized into sepsis survivor group(n=43)and sepsis non-survivor group(n=35)based on 28-day mortality for data analysis.Adult male C57BL/6 mice were subjected to cecal ligation and puncture(CLP).Serum samples were collected on day 1,3,5 and 7 to determine the levels of VDBP,25-hydroxyvitamin D[25(OH)D_(3)],1,25-dihydroxyvitamin D[1,25(OH)_(2)D_(3)],interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α).Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells.Results:Serum levels of VDBP,25(OH)D_(3),and 1,25(OH)_(2)D_(3)were significantly lower in sepsis patients vs.the healthy control(P<0.001),as well as in the sepsis non-survivor group vs.the sepsis survivor group(P<0.001,P=0.0338,or P=0.0013,respectively).Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation(APACHE)II score(r=−0.2565,P=0.0234)and Sequential Organ Failure Assessment score(r=−0.3522,P=0.0016),but lower serum albumin(ALB,r=0.4628,P<0.001)and total protein(TP,r=0.263,P=0.02).In CLP mice,there was a 5-day period of serum VDBP reduction,followed by return towards the baseline on day 7.VDBP was also decreased in LPS-treated THLE2 cells(P<0.001).VDBP overexpression reduced LPS-induced THLE2 damage.Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway.Conclusion:VDBP may be protective against sepsis-induced liver injury.

Individualized risk estimation for postoperative pulmonary complications after hepatectomy based on perioperative variables

BACKGROUND At present,there is no perfect system to evaluate pulmonary complications of liver surgery using perioperative variables.AIM To design and verify a risk assessment system for predicting postoperative pulmonary complications(PPCs)after hepatectomy based on perioperative variables.METHODS A retrospective analysis was performed on 1633 patients who underwent liver surgery.The variables were screened using univariate and multivariate analyses,and graded scores were assigned to the selected variables.Logistic regression was used to develop the liver operation pulmonary complication scoring system(LOPCSS)for the prediction of PPCs.The LOPCSS was verified using the receiver operating characteristic curve.RESULTS According to the multivariate correlation analysis,the independent factors which influenced PPCs of liver surgery were age[≥65 years old/<65 years old,odds ratio(OR)=1.926,P=0.011],medical diseases requiring drug treatment(yes/no,OR=3.523,P<0.001),number of liver segments to be removed(≥3/≤2,OR=1.683,P=0.002),operation duration(≥180 min/<180 min,OR=1.896,P=0.004),and blood transfusion(yes/no,OR=1.836,P=0.003).The area under the curve(AUC)of the LOPCSS was 0.742.The cut-off value of the expected score for complications was 5.The incidence of complications in the group with≤4 points was significantly lower than that in the group with≥6 points(2.95%vs 33.40%,P<0.001).Furthermore,in the validation dataset,the corresponding AUC of LOPCSS was 0.767.CONCLUSION As a novel and simplified assessment system,the LOPCSS can effectively predict PPCs of liver surgery through perioperative variables.