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BackgroundLeft ventricular ejection fraction (LVEF) is often used to classify heart failure (HF) . Some HF patients were observed to have improved ejection fraction after treatment, thus giving rise to the concept of HF with improved EF (HFimpEF) . However, most relevant studies have focused on European countries and the US, and there are few reports on the clinical characteristics and diagnosis of this population in China.ObjectiveTo analyze the clinical characteristics, prognosis and prognostic predictors in Chinese HFimpEF patients.MethodsParticipants included in this case-control study were chronic HF inpatients who were recruited from Department of Heart Center, Hebei General Hospital from June 1, 2018, to May 1, 2020. Demographic data and baseline clinical information were obtained from the electronic medical record, in particular, clinical phenotypes of HF classified by baseline and follow-up LVEF included four: HF with preserved EF (HFpEF) , HF with mid-range EF (HFmrEF) , HF with reduced EF (HFrEF) and HFimpEF. Follow-up was conducted via electronic medical record review, outpatient department and telephone since the last reexamination with echocardiography. The follow-up continued through 2021-06-01, with all-cause death and all-cause readmission as endpoint events. Predictors of HFimpEF were explored by binary Logistic regression. Kaplan-Meier estimator was used to describe the survival of patients with all-cause death and all-cause readmission. Cox regression model was used to identify risk factors for all-cause death and all-cause readmission.ResultsA total of 530 cases were included, including 245 (46.2%) with HFpEF, 55 (10.4%) with HFmrEF, 133 (25.1%) with HFrEF, and 97 (18.3%) with HFimpEF. HFimpEF patients had lower mortality than did HFpEF patients (P=0.014) and HFmrEF patients (P

Although changes in the mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) have been linked to increased susceptibility to several cancers, the relationship between the mtDNA copy number in PBLs and the risk of cancer precursors has not been investigated. In this study, we measured the relative mtDNA copy number in PBLs of 143 patients with histologically confirmed oral premalignant lesions (OPLs) and of 357 healthy controls that were frequency-matched to patients according to age, sex and race. OPL patients had a significantly higher mtDNA copy number than the controls (1.36 ± 0.74 versus 1.11 ± 0.32; P < 0.001). In analyses stratified by sex, race, alcohol consumption and smoking status, the mtDNA copy number was higher in the OPL patients than in the controls in all the strata. Using the median mtDNA copy number in the control group as a cutoff, we found that individuals with a high mtDNA copy number had significantly higher risk of having OPLs than individuals with a low mtDNA copy number (adjusted odds ratio, 1.93; 95% confidence interval, 1.23-3.05, P = 0.004). Analysis of the joint effect of alcohol consumption and smoking revealed even greater risk for OPLs. Our results suggest that high mtDNA copy number in PBLs is significantly associated with having OPLs. To our knowledge, this is the first epidemiologic study to show that the mtDNA copy number may indicate the risk of cancer precursors.

Introduction: The aim of this study is to explore the potential factors in hearing outcomes and verify the role of oxidant‐antioxidant equilibrium on the prognosis of sudden sensorineural hearing loss (SSNHL) treated with hyperbaric oxygen therapy (HBOT). Methods: Ninety‐two patients who were diagnosed with SSNHL between January 2018 and December 2019 in our hearing clinic center were included in this study. All patients were treated with intravenous dexamethasone, and 72 cases were treated with additional HBOT for 10 consecutive days. Peripheral blood was collected prior to any treatment to determine the blood cell count and hemoglobin (HGB), hematocrit (HCT), and superoxide dismutase (SOD) levels. Pure tone audiometry was measured before and after treatment. Complete and overall recovery rate was evaluated. Multivariate logistic analysis was used to identify prognostic factors. Results: The rate of overall recovery was significantly higher in the patient with combined therapy compared to patients treated with steroids only (51.4% vs 25.0%, p =.036). The levels of HGB, HCT, and SOD were much higher in the patients with better hearing outcomes (p =.027,.033, and.011, respectively). Multivariate logistic analysis demonstrated that patients with higher initial hearing thresholds, or hearing loss at overall frequency, were more prone to have poor hearing gains after HBOT. Conclusion: HBOT is effective as an early adjuvant therapy for SSNHL. Hearing loss at low frequency, low initial hearing thresholds, as well as high HBG, HCT, and SOD levels are positive prognostic factors for SSNHL patients treated with HBOT. [ABSTRACT FROM AUTHOR]

Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-associated deaths worldwide. Despite great progress in early diagnosis and multidisciplinary tumor management, the long-term prognosis of HCC remains poor. Currently, metabolic reprogramming during tumor development is widely observed to support rapid growth and proliferation of cancer cells, and several metabolic targets that could be used as cancer biomarkers have been identified. The liver and mitochondria are the two centers of human metabolism at the whole organism and cellular levels, respectively. Thus, identification of prognostic biomarkers based on mitochondrial-related genes (Mito-RGs)—the coding-genes of proteins located in the mitochondria—that reflect metabolic changes associated with HCC could lead to better interventions for HCC patients. In the present study, we used HCC data from The Cancer Genome Atlas (TCGA) database to construct a classifier containing 10 Mito-RGs (ACOT7, ADPRHL2, ATAD3A, BSG, FAM72A, PDK3, PDSS1, RAD51C, TOMM34, and TRMU) for predicting the prognosis of HCC by using 10-fold Least Absolute Shrinkage and Selection Operation (LASSO) cross-validation Cox regression. Based on the risk score calculated by the classifier, the samples were divided into high- and low-risk groups. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), t-distributed stochastic neighbor embedding (t-SNE), and consensus clusterPlus algorithms were used to identify metabolic pathways that were significantly different between the high- and low-risk groups. We further investigated the relationship between metabolic status and infiltration of immune cells into HCC tumor samples by using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm combined with the Tumor Immune Estimation Resource (TIMER) database. Our results showed that the classifier based on Mito-RGs could act as an independent biomarker for predicting survival of HCC patients. Repression of primary bile acid biosynthesis plays a vital role in the development and poor prognosis of HCC, which provides a potential approach to treatment. Our study revealed cross-talk between bile acid and infiltration of tumors by immune cells, which may provide novel insight into immunotherapy of HCC. Furthermore, our research may provide a novel method for HCC metabolic therapy based on modulation of mitochondrial function. [ABSTRACT FROM AUTHOR]

Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8+ cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20-2.70]; matched cohort [2.24, 1.36-3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4+ cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis. [ABSTRACT FROM AUTHOR]

UHRF1 promotes melanoma progression by inducing cell proliferation, and is correlated with poor prognosis of melanoma patients. However, the regulation mechanism has not been fully elaborated. Here, we detected hsa-let-7b expression and its role in melanoma. Through Targetscan and miRanda predication, 30 overlapped miRNAs were found; further survival analysis revealed that hsa-let-7b was the only miRNA that affected the overall survival. Overexpressed hsa-let-7b could significantly inhibit the proliferation ability of A375 and A2058 cells, and this phenomenon was reversed after co-transfection with pLenti-UHRF1. In conclusion, hsa-let-7b regulates melanoma cells proliferation in vitro by targeting UHRF1. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most malignant types of skin cancer. However, the efficacy and utility of available drug therapies for melanoma are limited. The objective of the present study was to identify potential genes associated with melanoma progression and to explore approved therapeutic drugs that target these genes. Weighted gene co-expression network analysis was used to construct a gene co-expression network, explore the associations between genes and clinical characteristics and identify potential biomarkers. Gene expression profiles of the GSE65904 dataset were obtained from the Gene Expression Omnibus database. RNA-sequencing data and clinical information associated with melanoma obtained from The Cancer Genome Atlas were used for biomarker validation. A total of 15 modules were identified through average linkage hierarchical clustering. In the two significant modules, three network hub genes associated with melanoma prognosis were identified: C-X-C motif chemokine receptor 4 (CXCR4), interleukin 7 receptor (IL7R) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG). The receiver operating characteristic curve indicated that the mRNA levels of these genes exhibited excellent prognostic efficiency for primary and metastatic tumor tissues. In addition, the proximity between candidate genes associated with melanoma progression and drug targets obtained from DrugBank was calculated in the protein interaction network, and the top 15 drugs that may be suitable for treating melanoma were identified. In summary, co-expression network analysis led to the selection of CXCR4, IL7R and PIK3CG for further basic and clinical research on melanoma. Utilizing a network-based method, 15 drugs that exhibited potential for the treatment of melanoma were identified. [ABSTRACT FROM AUTHOR]

This integrative multistage study was aimed to identify circulating microRNAs (miRNAs) as prognostic biomarkers and investigate the treatment target for early‐stage non‐small cell lung cancer (NSCLC) patients. In stage I–II NSCLC patients, we screened and validated the miRNA ratio signatures predictive of prognosis in serum. In tumor, we found that the expression of miR‐150 in identified miRNA signatures was also associated with survival. Increased miR‐150 expression promoted NSCLC cell proliferation and migration and vice versa. Specific mRNA cleavage sites targeted by endogenous miR‐150 in 3′ untranslated region (UTR) of SRCIN1 was identified by utilizing our recently developed novel Stem‐Loop‐Array reverse‐transcription polymerase chain reaction (SLA‐RT‐PCR) assay. The blocking action of miR‐150 resulted in repressed NSCLC cell growth in vitro and knockdown of miR‐150 caused substantial tumor volume reduction in vivo. Our findings suggest that miR‐150 binding on specific recognition sites in 3′ UTR of tumor suppressor gene SRCIN1 present a potential therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

BACKGROUND Greater than 40% of renal cell carcinoma (RCC) cases in the United States are attributed to excessive body weight. Moreover, obesity also may be linked to RCC prognosis. However, the molecular mechanisms underlying these associations are unclear. In the current study, the authors evaluated the role of promoter methylation in obesity-related genes in RCC tumorigenesis and disease recurrence. METHODS Paired tumors (TU) and normal adjacent (N-Adj) tissues from 240 newly diagnosed and previously untreated white patients with RCC were examined. For the discovery phase, 63 RCC pairs were analyzed. An additional 177 RCC pairs were evaluated for validation. Pyrosequencing was used to determine CpG methylation in 20 candidate obesity-related genes. An independent data set from The Cancer Genome Atlas also was analyzed for functional validation. The association between methylation and disease recurrence was analyzed using multivariate Cox proportional hazards models and Kaplan-Meier survival analysis. RESULTS Methylation in neuropeptide Y ( NPY), leptin ( LEP), and leptin receptor ( LEPR) was significantly higher in TU compared with N-Adj tissues ( P<.0001) in both the discovery and validation groups. High methylation in LEPR was associated with an increased risk of disease recurrence (hazard ratio, 3.15; 95% confidence interval, 1.23-8.07 [ P = .02]). Patients with high methylation in LEPR had a shorter recurrence-free survival compared with patients in the low-methylation group (log-rank P = 2.25 × 10−3). In addition, high LEPR methylation in TU was associated with more advanced features ( P≤.05). Consistent with the findings of the current study, lower LEPR expression in TU compared with N-Adj tissues ( P = 1.00 × 10−3) was found in data from The Cancer Genome Atlas. CONCLUSIONS Somatic alterations of promoter methylation in the NPY, LEP, and LEPR genes are involved in RCC tumorigenesis. Furthermore, LEPR methylation appears to be associated with RCC recurrence. Future research to elucidate the biology underlying this association is warranted. Cancer 2017;123:3617-27. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma, mitochondria, prognosis, bile acid, tumor microenvironment Keywords: hepatocellular carcinoma; mitochondria; prognosis; bile acid; tumor microenvironment EN hepatocellular carcinoma mitochondria prognosis bile acid tumor microenvironment 1 1 1 01/20/22 20220117 NES 220117 There is an error in the Funding statement. [Extracted from the article]

Aim It has been reported that BMI-1, a gene transcription promoter overexpressed in various human cancers, is associated with poor survival. We investigated whether BMI-1 is a marker for cervical cancer by detecting the expression of BMI-1 in cervical cancer. Methods An immunohistochemistry (IHC) streptavidin-peroxidase technique was used to identify BMI-1 protein expression in 302 cervical cancer specimens. Reverse transcription polymerase chain reaction and Western blot were employed to measure BMI-1 mRNA and protein level. The correlation between BMI-1 expression and clinicopathological factors was analyzed. Results Both BMI-1 mRNA and protein expression were evident in cervical carcinoma tissues. An intense positive rate of 55.3% (167/302) was observed by IHC. High BMI-1 expression was correlated with clinical stage, lymph node metastasis, vascular invasion and human papillomavirus (HPV) infection ( P < 0.05), but there is insufficient evidence to confirm its value in tumor size, age, estrogen or progesterone receptor ( P > 0.05). The BMI-1 protein level was positively correlated with the clinical stages of cervical carcinoma and a high BMI-1 expression was associated with poor prognosis ( P < 0.05). Conclusion The high expression of BMI-1 in cervical cancer is related to tumor progression, lymph node metastasis and HPV infection, suggesting that cervical cancer with excessive BMI-1 expression possesses high metastases potential and that BMI-1 may be a promising biomarker for predicting metastasis in cervical cancer. [ABSTRACT FROM AUTHOR]

Abstract: Urinary bladder cancer is a heterogeneous disease with diverse genetic and environmental risk factors that can influence disease risk or clinical course for recurrence, progression, and survival. Therefore, identification of these factors is paramount for disease prevention and optimal clinical management of bladder cancer patients. Of particular interest is the need to identify molecular biomarkers that can give accurate assessment of tumor biological potential and to predict treatment response. Recent advances in molecular biology, cytogenetic, and genomic research have spurred discovery efforts for novel genetic, epigenetic, and proteomic biomarkers that are prognostic for cancer. This review focuses on some of the important germ line polymorphisms found to be correlated with clinical outcomes in bladder cancer. So far, most of the identified candidate loci were based on prior knowledge of pathogenesis and had not been validated for clinical applications. The future challenges are to analyze the wealth of information from whole-genome studies, to understand the underlying biological mechanisms of these associations, the network of gene–gene and gene–environment interactions, and to apply these markers for the identification of high-risk population for targeted, personalized therapy. [Copyright &y& Elsevier]

Extracellular matrix metalloproteinase inducer (EMMPRIN), a member of the immunoglobulin superfamily, is present on the surface of tumor cells where it stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). We have analyzed the clinicopathological characteristics of EMMPRIN and MMP2 expression in normal brain tissue and pediatric gliomas and evaluated their prognostic value in diagnosing the latter. Immunochemistry analysis revealed EMMPRIN and MMP2 expression in cryo-sections of pediatric gliomas (45 samples) and normal brain tissue (20 samples). Both EMMPRIN and MMP2 were expressed in normal brain and glioma tissues with different levels of malignancy. The intensively positive expression rates of EMMPRIN (22/27) and MMP2 (21/27) in anaplastic astrocytoma and glioblastoma tissues were significantly higher than those in normal brain and low-grade astrocytoma tissues (2/28 and (1/2)8, respectively). Spearman analysis indicated that the expression level of EMMPRIN was significantly positively correlated with that of MMP2 (r = 0.86, p < 0.01). The positive expression of EMMPRIN and MMP2 was associated with higher grade gliomas. Patients with EMMPRIN+/MMP2+ expression had the lowest survival rate (p < 0.01). Based on these results, we conclude that EMMPRIN and MMP2 are expressed differently in normal brain and pediatric gliomas. The detection of their co-expression may facilitate the prediction of pediatric gliomas prognosis. [ABSTRACT FROM AUTHOR]

Background: The double-strand break (DSB) repair capacity has been implicated in the survival of patients in several cancer types. However, little is known about the prognostic importance of the key DSB repair genes-ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the Ku heterodimeric regulatory complex 86-kD subunit (Ku80)-in nonsmall cell lung cancer (NSCLC). To address this issue, the authors determined the messenger RNA (mRNA) expression of these genes in patients NSCLC and assessed their prognostic relevance.Methods: mRNA expression levels of ATM, DNA-PKcs, and Ku80 were measured in tumor and adjacent normal tissues from 140 patients with NSCLC by using quantitative real-time polymerase chain reaction analysis. Then, a Cox proportional hazards regression model and Kaplan-Meier plots were used to evaluate the association between the tumor:normal (T/N) expression ratios of the 3 genes and the overall survival rate and duration in patients with NSCLC.Results: mRNA expression of ATM and DNA-PKcs, but not of Ku80, was significantly higher in tumor tissues than in adjacent normal tissues (P=.003 and P<.001, respectively). The high T/N expression ratios of ATM and DNA-PKcs were associated significantly with a 1.82-fold increased risk of death (95% confidence interval, 1.05-2.70) and a 2.13-fold increased risk of death (95% confidence interval, 1.21-3.76), respectively. However, no significant association with risk was observed for Ku80. Kaplan-Meier analyses revealed that patients with high T/N expression ratios of ATM or DNA-PKcs had notably shorter median survival than patients with low ratios.Conclusions: The current findings suggested that the T/N expression ratios of ATM and DNA-PKcs may be useful for identifying NSCLC patients with a poor prognosis who may benefit from more aggressive therapy. [ABSTRACT FROM AUTHOR]

Improvement in ejection fraction (EF) was observed in a subset of patients with heart failure (HF) and reduced ejection fraction (HFrEF). We analyzed and compared these patients with other HF phenotypes. Based on left ventricular ejection fraction(LVEF) at baseline and follow-up, the 561 HF patients were divided into 4 groups: HF preserved EF (HFpEF, LVEF ≥ 50% on both occasions, n = 258), HF mid-range EF (HFmrEF, fluctuating between LVEF 40 and 49% on both occasions, n = 61), HFrEF (LVEF < 40% on both occasions, n = 141), and HF improved EF (HFimpEF, defined as LVEF < 40% at baseline and LVEF ≥ 40% at follow-up with ≥10% absolute improvement, n = 101). The composite of HF readmission and all-cause mortality was considered the primary endpoint, and the secondary endpoint was all-cause mortality. The characteristics of HFimpEF differed from other HF phenotypes. β-blockers and aldosterone receptor antagonists were associated with improved LVEF. Kaplan-Meier curves showed the lowest incidence of the composite endpoint (p < 0.001) and all-cause mortality (p < 0.001) in HFimpEF. The risk of cardiovascular death was lowest in HFimpEF after controlling for competing events (p < 0.001), as were competing events (p < 0.001). Valvular heart disease (VHD) (HR 8.555, 95 CI% 2.126–34.420, p = 0.003) increased the risk of all-cause death, and anemia increased the risk of all-cause death (HR 5.533, 95 CI% 1.592–19.530, p = 0.007) and cardiovascular death in HFimpEF patients (HR 5.840, 95 CI% 1.088–31.356, p = 0.040). HFimpEF is an independent HF phenotype with a prognosis similar to HFmrEF and superior to HFpEF and HFrEF. When HFimpEF patients had VHD and anemia, the endpoint event rate was increased. • This study complements data from HFimpEF patients in Asia. • PSM and competing risk-adjusted survival curves suggest that HFimpEF has a higher survival rate than HFpEF and HFrEF. • Valvular heart disease and anemia increased the risk of poor prognosis in HFimpEF patients. [ABSTRACT FROM AUTHOR]

Abstract Introduction Disseminated intravascular coagulation (DIC) is a severe complication of critical conditions. There are several scoring systems used for the diagnosis of DIC, including the International Society on Thrombosis and Hemostasis (ISTH) Overt-DIC criteria, the Japanese Ministry of Health and Welfare (JMHW) criteria and the Chinese Society of Thrombosis and Hemostasis scoring system for DIC (CDSS). The objective of this prospective study was to evaluate the accuracy and predictive value of the CDSS. Materials and methods 1318 patients, aged 18–70 years old and suspected of DIC were enrolled from 18 hospitals across China. Participants were divided into two groups for analysis (group 1, non-hematological diseases; group 2, hematological diseases). 242 patients were excluded because of incomplete data collection and failure to follow-up. Results and conclusions The rates of concordance of diagnosis of DIC between the CDSS and two other scoring systems were close to 80%. The area under ROC curves of CDSS had a slight advantage when using the ISTH, JMHW criteria or prognosis as gold standard, respectively. The CDSS DIC was an independent predictor of mortality, and its odds-ratio was superior or comparable to that of the ISTH and JMHW criteria in the two groups. The CDSS DIC score also had a significant correlation with the APACHE II and SOFA score (p < 0.05). In summary, as a quantification standard of the Chinese experts' consensus, the CDSS is conducive to the standardized diagnosis of DIC because of its favorable diagnostic and prognostic utility. Highlights • The diagnostic rates for DIC from the three scoring systems varied with different illnesses. • The rates of concordance in the diagnosis of DIC between the CDSS and other two scoring systems were close to 80%. • When the ISTH, JMHW and prognosis was used as the gold standard, the AUC for CDSS had a slight advantage over the two others. • The CDSS DIC was an independent predictor of mortality, and the CDSS score may reflect DIC severity. [ABSTRACT FROM AUTHOR]