Development a survival prediction model for patients with Paget disease of the breast based on the SEER database

Background:We explored the risk factors that affect the prognosis of patients with Paget disease of the breast(PD)and constructed a survival prediction model.Methods:The data of PD patients from 2004 to 2014 were collected through the SEER database.The factors affecting the prognosis of PD patients were analysed by a single factor,and the prediction model of the independent risk factor transformation model diagram that affected their 1-,3-,and 5-year survival rates was screened by multivariate Cox proportional hazard regression analysis coefficients.The consistency index was used to evaluate its predictive value,and its predictive performance was tested by the 1000 bootstrap method.Then,the calibration curve was used to verify the predictive performance of the model,and the receiver operating characteristic curve and decision curve analysis were used to assess the sensitivity and practicability of the model compared to the American Cancer Commission staging(AJCC)staging system.Results:The consistency index of the model was 0.795(95%confidence interval 0.773–0.818).The calibration curve shows good consistency,while the receiver operating characteristic curve shows the sensitivity of the model to predict the survival rate of PD at 1,3,and 5 years.Decision curve analysis confirmed that the nomogram can predict the survival rate of PD patients at 1,3,and 5 years instead of the traditional AJCC system.Conclusion:Regarding the independent prognostic factors of age,marital status,AJCC classification,surgery,radiotherapy,chemotherapy and marital status conversion in PD patients,the nomogram established in sequence has higher accuracy and clinical value than the traditional AJCC system.

Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

基于一种距离相关的超高维生存数据Model-Free特征筛选

随着大数据时代的来临,数据维度爆炸式增长,超高维数据的降维问题逐渐成为众多研究领域的热点话题。由于响应变量通常存在右删失,处理超高维完全数据的降维方法在右删失数据中将不再适用。本研究提出一种新的基于距离相关能有效处理超高维右删失数据的特征筛选方法。首先利用距离相关系数计算每个协变量对响应变量的边际效应,建立与该系数有关的筛选指标,然后再根据事先确立的筛选准则进行特征筛选。提出的特征筛选方法不依赖任何模型结构假定,因此可以有效避免模型指定错误带来的不良后果。此外,该方法采用的距离协方差估计量是总体距离协方差的一个无偏估计,统计准确性和计算精度高。模拟和实证研究表明,提出的方法能在保留所有重要变量的前提下快速剔除与响应变量相关程度较弱的协变量,从而达到降低参数维数的目的。

Long-term survival after liver transplantation for alcoholic liver disease

Currently,alcoholic cirrhosis is the second leading indication for liver transplantation in the United States and Europe.The quality of life and survival after a liver transplantation(LT)in patients with alcoholic liver disease(ALD)are similar to those in patients with other cirrhosis etiologies.The alcoholic relapse rate after a LT varies from 10%-50%,and these relapse patients are the ones who present a reduced long-term survival,mainly due to cardiovascular diseases and the onset of de novo neoplasms,including lung and upper aerodigestive tract.Nearly 40%of ALD recipients resume smoking and resume it early post-LT.Therefore,our pre-and post-LT follow-up efforts regarding ALD should be focused not only on alcoholic relapse but also on treating and avoiding other modifiable risk factors such as tobacco.The psychiatric and psychosocial pre-LT evaluation and the post-LT follow-up with physicians,psychiatrists and addiction specialists are important for reversing these problems because these professionals help to identify patients at risk for relapse as well as those patients who have relapsed,thus enabling responsive actions.

Correlation between serum free fatty acids levels and Gensini score in elderly patients with coronary heart disease

Objectives To investigate the relationship between serum fxee fatty acids （FFAs） levels and the severity of coronary artery lesions in elderly patients with coronary heart disease （CAD）. Methods A total of 172 elderly patients who underwent coronary angiography were divided into CAD group （n = 128） and non-CAD group （n = 44） according to the results of coronary angiography. Serum FFAs and lipid levels were measured and the Gensini score were calculated. Results No matter the differences between age, gender and the usage of stat- ins or not, there was no statistical significance in FFAs levels （P 〉 0.05）. In terms of the Gensini score, it was higher in patients aged 70-79 years than in patients 60-69 years old [15.00 （5.00, 34.00） vs. 10.00 （2.00, 24.00）, P 〈 0.05], higher in men than women [14.00 （4.00, 34.00） vs. 7.00 （2.50, 19.75）, P 〈 0.05], and higher in patients on statins [13.50 （4.25, 33.50）vs. 6.50 （2.00, 18.00）, P 〈 0.05]. The serum FFAs lev- els [449.50 （299.00, 624.75） mEq/L vs. 388.00 （258.50, 495.25） mEq/L, P 〈 0.05J and Gensini score [17.50 （8.00, 41.75） vs. 1.00 （0, 5.00）, P 〈 0.05] were higher in the CAD group than in the non-CAD group. In the CAD group, there was no statistical significance in FFAs levels among patients with different numbers of diseased coronary vessels （P 〉 0.05）. Furthermore, the FFAs levels were positively correlated with the Gensini score （r = 0.394, P = 0.005）. Regression analysis showed that the FFAs levels were related to the Gensini score independently after adjusting for the other risk factors. Conclusions The serum FFAs levels were associated with the Gensini score in elderly patients with CAD. It might indicate FFAs as a biomarker predicting the severity of coronary artery lesions.

Survival outcomes of right-lobe living donor liver transplantation for patients with high Model for End-stage Liver Disease scores

BACKGROUND: Controversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a high MELD score would result in inferior outcomes of right-lobe LDLT. METHODS: Among 411 consecutive patients who received right-lobe LDLT at our center, 143 were included in this study. The patients were divided into two groups according to their MELD scores: a high-score group (MELD score ≥25; n=75) and a low-score group (MELD score 【25; n=68). Their demographic data and perioperative conditions were compared. Univariable and multivariable analyses were performed to identify risk factors affecting patient survival. RESULTS: In the high-score group, more patients required preoperative intensive care unit admission (49.3% vs 2.9%; P【0.001), mechanical ventilation (21.3% vs 0%; P【0.001), or hemodialysis (13.3% vs 0%; P=0.005); the waiting time before LDLT was shorter (4 vs 66 days; P【0.001); more blood was transfused during operation (7 vs 2 units; P【0.001); patients stayed longer in the intensive care unit (6 vs 3 days; P【0.001) and hospital (21 vs 15 days; P=0.015) after transplantation;more patients developed early postoperative complications (69.3% vs 50.0%; P=0.018); and values of postoperative peak blood parameters were higher. However, the two groups had comparable hospital mortality. Graft survival and patient overall survival at one year (94.7% vs 95.6%; 95.9% vs 96.9%), three years (91.9% vs 92.6%; 93.2% vs 95.3%), and five years (90.2% vs 90.2%; 93.2% vs 95.3%) were also similar between the groups. CONCLUSIONS: Although the high-score group had signifi-cantly more early postoperative complications, the two groups had comparable hospital mortality and similar satisfactory rates of graft survival and patient overall survival. Therefore, a high MELD score should not be a contraindication to right-lobe LDLT if donor risk and recipient benefit are taken into full account.

Emergency resection surgery for colorectal cancer: Patterns of recurrent disease and survival

AIM To evaluate prognostic pathological factors associated with early metachronous disease and adverse longterm survival in these patients.METHODS Clinical and histological features were analysed retrospectively over an eight-year period for prognostic impact on recurrent disease and overall survival in patients undergoing curative resection of a primary colorectal cancer. RESULTS A total of 266 patients underwent curative surgery during the study period. The median age of the study cohort was 68 year(range 26 to 91) with a followup of 7.9 years(range 4.6 to 12.6). Resection was undertaken electively in 225(84.6%) patients and emergency resection in 35(13.2%). Data on timing of surgery was missing in 6 patients. Recurrence was noted in 67(25.2%) during the study period and was predominantly early within 3 years(82.1%) and involved hepatic metastasis in 73.1%. Emergency resection(OR = 3.60, P = 0.001), T4 stage(OR = 4.33, P < 0.001) and lymphovascular invasion(LVI) (OR = 2.37, P = 0.032) were associated with higher risk of recurrent disease. Emergency resection, T4 disease and a high lymph node ratio(LNR) were strong independent predictors of adverse long-term survival. CONCLUSION Emergency surgery is associated with adverse disease free and long-term survival. T4 disease, LVI and LNR provide strong independent predictive value of longterm outcome and can inform surveillance strategies to improve outcomes.

Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry

AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.

Celiac disease: Alternatives to a gluten free diet

Celiac disease is a chronic inflammatory disorder of the small intestine caused by the ingestion of gluten or related rye and barley proteins. At present, the only available treatment is a strict gluten-exclusion diet. However, recent understanding of the molecular basis for this disorder has improved and enabled the identif ication of targets for new therapies. This article aims to critically summarize these recent studies.

Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease

AIM:To investigate the capability of a biochemical and clinical model,BioCliM,in predicting the survival of cirrhotic patients.METHODS:We prospectively evaluated the survival of 172 cirrhotic patients.The model was constructed using clinical(ascites,encephalopathy and variceal bleeding) and biochemical(serum creatinine and serum total bilirubin) variables that were selected from a Cox proportional hazards model.It was applied to estimate 12-,52-and 104-wk survival.The model's calibration using the Hosmer-Lemeshow statistic was computed at 104 wk in a validation dataset.Finally,the model's validity was tested among an independent set of 85 patients who were stratified into 2 risk groups(low risk≤8 and high risk>8).RESULTS:In the validation cohort,all measures of fi t,discrimination and calibration were improved when the biochemical and clinical model was used.The proposed model had better predictive values(c-statistic:0.90,0.91,0.91) than the Model for End-stage Liver Disease(MELD) and Child-Pugh(CP) scores for 12-,52-and 104-wk mortality,respectively.In addition,the Hosmer-Lemeshow(H-L) statistic revealed that the biochemical and clinical model(H-L,4.69) is better calibrated than MELD(H-L,17.06) and CP(H-L,14.23).There were no significant differences between the observed and expected survival curves in the stratified risk groups(low risk,P=0.61;high risk,P=0.77).CONCLUSION:Our data suggest that the proposed model is able to accurately predict survival in cirrhotic patients.

Immunophenotypic signature of primary glioblastoma multiforme: A case of extended progression free survival

Glioblastoma-multiforme(GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and progression-free survival(PFS) remains short. Glioblastomas display a variety of molecular alterations, which necessitates determining which of these have a prognostic significance. This is a case of a 45-yearold patient who presented with progressive slurring of speech and features of raised intracranial pressure. Computed tomography(CT) scan revealed a large heterogeneously enhancing lesion in the left front-temporalperisylvian region with solid, cystic areas, suggestive of malignant glioma. Partial tumor-excision was followed by concurrent chemo-radiotherapy. Histopathologically, the tumor was astrocytoma grade-IV. Patient had an extended PFS of 12 mo, with an overall survival of 26 mo. Primary-GBM was confirmed using molecular markers and the immunophenotypic signature was defined by evaluating systemic expression of human telomerase reverse transcriptase, interleukin-6, neutrophil-lymphocyte ratio, tissue inhibitor of metalloproteinases-1, human chitinase-3-like-protein-1(YKL-40) and high mobility group-A1. Current findings suggest that this signature can identify worst outcomes, independent of clinical criteria.

Association between Free Triiodothyronine Levels and Peripheral Arterial Disease in Euthyroid Participants

This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease （PAD） among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine （FT3）, free thyroxin （FT4）, thyroid-stimulating hormone （TSH）, and thyroid antibodies were measured.

Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases

Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated.In this observational study,we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases(LBDs)and Alzheimer disease(AD),shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration.We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival.Disease progression in LBDs correlated positively with poly(ADP-Ribose)and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts,indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes.Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxo-d G)and myeloperoxidase concentrations in the striatum,suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism ofβ-amyloid entering the mitochondria and subsequent free radicals generation.Patients with lower striatal 8-oxo-d G and myeloperoxidase levels had a survival advantage in AD.The age of onset also affected disease progression.Tissue requests for the postmortem biochemistry,genetics,and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center(ADRC)Biospecimens Committee(ethics approval reference number:T1705,approval date:August 6,2019).Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health&Safety Biological Safety Committee(approval code:3739,approval date:February 25,2020).Radioactive Material Authorization was approved by the Washington University Environmental Health&Safety Radiation Safety Committee(approval code:1056,approval date:September 18,2019).

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

Lymph node ratio and preoperative CA 19-9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma

AIM:Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level. RESULTS: Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS. CONCLUSION: The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer.

Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma

BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification.CONCLUSION We have constructed a six-lncRNA signature for prognosis prediction of HCC.This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival

BACKGROUND The lack of space,as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms,remains controversial.AIM To evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease.METHODS One hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without(kidney transplant alone(KTA)group)and 77 with associated ipsilateral nephrectomy(KTIN group),were retrospectively reviewed.Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival.RESULTS Creation of space for future graft positioning was the main reason(n=74,96.1%)for associated ipsilateral nephrectomy.No significant difference in surgical comorbidity(lymphocele,wound infection,incisional hernia,wound hematoma,urinary infection,need for blood transfusion,hospitalization stay,Dindo Clavien classification and readmission rate)was observed between the two study groups.The incidence of primary nonfunction and delayed graft function was comparable in both groups[0%and 2.6%(P=0.497)and 9.1%and 16.9%(P=0.230),respectively,in the KTA and KTIN group].The 1-and 5-year graft survival were 94.8%and 90.3%,and 100%and 93.8%,respectively,in the KTA and KTIN group(P=0.774).The 1-and 5-year patient survival were 96.1%and 92.9%,and 100%and 100%,respectively,in the KTA and KTIN group(P=0.168).CONCLUSION Simultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short-and long-term graft survival.

Cardiovascular disease risk factor profiles in children with celiac disease on gluten-free diets

AIM:To describe the cardiovascular disease(CVD)risk factors in a population of children with celiac disease(CD)on a gluten-free diet(GFD).METHODS:This cross-sectional multicenter study was performed at Schneider Children’s Medical Center of Israel(Petach Tiqva,Israel),and San Paolo Hospital(Milan,Italy).We enrolled 114 CD children in serologic remission,who were on a GFD for at least one year.At enrollment,anthropometric measurements,blood lipids and glucose were assessed,and compared to values at diagnosis.The homeostasis model assessment-estimated insulin resistance was calculated as a measure of insulin resistance.RESULTS:Three or more concomitant CVD risk factors[body mass index,waist circumference,low density lipoprotein(LDL)cholesterol,triglycerides,blood pressure and insulin resistance]were identified in 14%of CD subjects on a GFD.The most common CVD risk factors were high fasting triglycerides(34.8%),elevated blood pressure(29.4%),and high concentrations of calculated LDL cholesterol(24.1%).On a GFD,four children(3.5%)had insulin resistance.Fasting insulin and HOMA-IR were significantly higher in the Italian cohort compared to the Israeli cohort(P<0.001).Children on a GFD had an increased prevalence of borderline LDL cholesterol(24%)when compared to values(10%)at diagnosis(P=0.090).Trends towards increases in overweight(from 8.8%to 11.5%)and obesity(from 5.3%to 8.8%)were seen on a GFD.CONCLUSION:This report of insulin resistance and CVD risk factors in celiac children highlights the importance of CVD screening,and the need for dietary counseling targeting CVD prevention.

Current treatment paradigm and survival outcomes among patients with newly diagnosed multiple myeloma in China:a retrospective multicenter study

Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).

Humic acid and free radical in environment of Kaschin-Beck disease areas

The humic acid contents in drinking water and soil in Kaschin-Beck disease areas were found more than that of non-disease areas in this research. Changes of free radical concentration in drinking water were agreed with that of humic acid contents in drinking water of Kaschin-Beck disease areas. A positive correlation of free radical concentration and humic acid content in drinking water has been shown (r=0.913) . The structure of I. R. spectra of humic acid under ultraviolet light has been changed. Thus it indicated that free radical was resulted from benzoqiunonyl groups of humic acid in environment.