Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer.

BACKGROUND: 5-Hydroxymethylcytosine-enriched gene profiles and regions show tissue-specific and tumor specific. There is a potential value to explore cell-free DNA 5-hydroxymethylcytosine feature biomarkers for early gastric cancer detection. METHODS: A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the different 5-hydroxymethylcytosine modification features of cell free DNA. Significantly differential 5-hydroxymethylcytosine modification genes were identified to construct a gastric cancer diagnostic model. Data set from GEO was used as an external testing set to test the robustness of the diagnostic model. RESULTS: Accounting for more than 90% of 5-hydroxymethylcytosine peaks were distributed in the gene body in both the gastric cancer and control groups. The diagnostic model was developed based on five different 5-hydroxymethylcytosine modification genes, FBXL7, PDE3A, TPO, SNTG2 and STXBP5. The model could effectively distinguish gastric cancer patients from controls in the training (AUC = 0.95, sensitivity = 88.6%, specificity = 94.3%), validation (AUC = 0.87, sensitivity = 73.3%, specificity = 93.3%) and testing (AUC = 0.90, sensitivity = 81.9%, specificity = 90.2%) sets. The risk scores of the controls from the model were significantly lower than those of gastric cancer patients in both our own data (P < 0.001) and GEO external testing data (P < 0.001), and no significant difference between different TNM stage patients (P = 0.09 and 0.66). Furthermore, there was no significant difference between the healthy control and benign gastric disease patients in the testing set from GEO (P = 0.10). CONCLUSIONS: The characteristics of 5-hydroxymethylcytosine in cell free DNA are specific to gastric cancer patients, and the diagnostic model constructed by five genes' 5-hydroxymethylcytosine features could effectively identify gastric cancer patients.

Risk-stratified approach by aMAP score for community population infected with hepatitis B and C to guide subsequent liver cancer screening practice: A cohort study with 10-year follow-up.

The aim of this study was to determine whether the age-Male-ALBI-Platelet (aMAP) score is applicable in community settings and how to maximise its role in risk stratification. A total of thousand five hundred and three participants had an aMAP score calculated at baseline and were followed up for about 10 years to obtain information on liver cancer incidence and death. After assessing the ability of aMAP to predict liver cancer incidence and death in terms of differentiation and calibration, the optimal risk stratification threshold of the aMAP score was explored, based on absolute and relative risks. The aMAP score achieved higher area under curves (AUCs) (almost all above 0.8) within 10 years and exhibited a better calibration within 5 years. Regarding absolute risk, the risk of incidence of and death from liver cancer showed a rapid increase after an aMAP score of 55. The cumulative incidence (5-year: 8.3% vs. 1.3% and 10-year: 20.9% vs. 3.6%) and mortality (5-year: 6.7% vs. 1.1% and 10-year: 17.5% vs. 3.1%) of liver cancer in individuals with an aMAP score of ≥55 were significantly higher than in those with a score of <55 (Grey's test p < .001). In terms of relative risk, the risk of death from liver cancer surpassed that from other causes after an aMAP score of ≥55 [HR = 1.38(1.02-1.87)]. Notably, the two types of death risk had opposite trends between the subpopulation with an aMAP score of ≥55 and < 55. To conclude, this study showed the value of the aMAP score in community settings and recommends using 55 as a new risk stratification threshold to guide subsequent liver cancer screening.

Efficacy and safety of systemic treatments for patients with recurrent/metastatic head and neck squamous cell carcinoma: A systematic review and network meta-analysis.

A variety of systemic chemotherapy regimens have been used for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, most guidelines have been derived from a single clinical trial, and no studies have comprehensively compared their efficacy and safety. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases. Eligible studies reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and ≥ 3 adverse events rate (AEs). Eighteen eligible trials involving 4930 patients and 15 treatment regimens were included. The results suggest that patients with R/M HNSCC exhibit better tumor response with the cetuximab/platinum/5-FU, pembrolizumab/platinum/5-FU or pembrolizumab alone, accompanied by a low AE rate. Nivolumab also showed better efficacy than other single agents. Immunotherapy has achieved better efficacy.

Effect of prophylactic closure on adverse events after colorectal endoscopic submucosal dissection: A meta-analysis.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) has a high en bloc resection rate and is widely performed for large colorectal lesions. However, colorectal ESD is associated with a high frequency of adverse events (AEs), and the efficacy of prophylactic endoscopic closure after ESD for preventing AEs is still controversial. This meta-analysis was conducted to assess the efficacy of closure on AEs following colorectal ESD. METHODS: We searched PubMed, Embase, and the Cochrane Library for eligible studies. The chi-square-based Q statistics and the I2 test were used to test for heterogeneity. Pooling was conducted using a fixed or random effects model. RESULTS: We identified eight eligible studies that compared the effects of closure vs non-closure with respect to delayed bleeding, delayed perforation, and post-ESD coagulation syndrome. Compared with non-closure (5.2%), closure was associated with a lower incidence (0.9%) of delayed bleeding (pooled odd ratios [ORs]:0.19, 95% CI: 0.08-0.49) following ESD. The pooled ORs showed no significant differences in incidence of delayed perforation (pooled OR: 0.22; 95% CI: 0.05-1.03) or post-ESD coagulation syndrome (pooled OR:0.75; 95% CI: 0.26-2.18) between the closure and non-closure groups. CONCLUSION: Prophylactic endoscopic closure may reduce the incidence of delayed bleeding following ESD of colorectal lesions. Future studies are needed to further illuminate risk factors and stratify high risk subjects for a cost-effective preventive strategy.

18ß-glycyrrhetinic acid inhibited mitochondrial energy metabolism and gastric carcinogenesis through methylation-regulated TLR2 signaling pathway.

The natural phenolic substance, 18ß-glycyrrhetinic acid (GRA), has shown enormous potential in the chemoprevention of cancers with rich resources and biological safety, but the GRA-regulated genetic and epigenetic profiles are unclear. Deregulated mitochondrial cellular energetics supporting higher adenosine triphosphate provisions relative to the uncontrolled proliferation of cancer cells is a cancer hallmark. The Toll-like receptor 2 (TLR2) signaling pathway has emerged as a key molecular component in gastric cancer (GC) cell proliferation and epithelial homeostasis. However, whether TLR2 influenced GC cell energy metabolism and whether the inhibition effects of GRA on GC relied on TLR2 signaling were not illustrated. In the present study, TLR2 mRNA and protein expression levels were elevated in gastric tumors in the K19-Wnt1/C2mE (Gan) mice model, GC cell lines and human GCs, and the overexpression of TLR2 was correlated with the high histological grade and was a poor prognostic factor in GC patients. Further gain and loss of function showed that TLR2 activation induced GC cell proliferation and promoted reactive oxygen species (ROS) generation, Ca2+ accumulation, oxidative phosphorylation and the electron transport chain, while blocking TLR2 inhibited mitochondrial function and energy metabolism. Furthermore, GRA pretreatment inhibited TLR2-activated GC cell proliferation, energy metabolism and carcinogenesis. In addition, expression of TLR2 was found to be downregulated by GRA through methylation regulation. Collectively, the results demonstrated that GRA inhibited gastric tumorigenesis through TLR2-accelerated energy metabolism, suggesting GRA as a promising therapeutic agency targeting TLR2 signaling in GC.

Differences in the treatment and control of hypertension in urban and rural residents of the northeastern region of the People's Republic of China: a cross-sectional study.

BACKGROUND: Hypertension is a significant global public health problem and an important risk factor for cardiovascular diseases. We aimed to determine treatment and control rates of hypertension and to explore related risk factors by urban and rural areas. METHODS: A cross-sectional survey of 14,956 participants (≥ 15 years) was conducted in Jilin Province, China from July 2014 to December 2015 using questionnaire forms and physical measurements. RESULTS: Total rates of hypertension treatment, control, and controlled blood pressure among treated subjects were 31.7%, 8.8%, and 27.9% in the Jilin Province. Rates of hypertension treatment, control, and controlled blood pressure among treated subjects were 35.9%, 13.7%, and 38.3% in urban areas and 28.4%, 5.0%, and 17.5% in rural areas, respectively. Higher treatment of hypertension was associated with older age, female sex, other races (except Han), and higher body fat percentage in both areas. Among urban residents, higher education was additionally associated with higher treatment of hypertension; among rural residents, a family history of coronary artery disease and unemployment were associated with higher treatment of hypertension. Higher control of hypertension was associated with unemployment, married status, higher education, healthy body mass index, lower abdominal waist circumference, non-smoking status, and lower visceral adiposity index in urban residents; higher control of hypertension was associated with younger age in rural residents. CONCLUSION: Treatment and control rates of hypertension in urban and rural areas were lower than the national average; blood pressure control in patients taking antihypertensive drugs needs further improvement.

The metabolic side effects of 12 antipsychotic drugs used for the treatment of schizophrenia on glucose: a network meta-analysis.

BACKGROUND: Antipsychotics have serious metabolic side effects on blood glucose. However, the comparative influence of these drugs on blood glucose levels has not been comprehensively evaluated. We conducted a network meta-analysis to create a hierarchy of the side effects of 12 antipsychotic drugs on changes in blood glucose levels. METHODS: A systematic search of the PubMed, EMBASE and Cochrane databases (last search June 2016) was conducted to identify studies that reported randomized controlled trials (RCTs) comparing changes in blood glucose levels between patients receiving one of 12 antipsychotic drugs or a placebo for the treatment of schizophrenia or related disorders. The studies we searched were limited to those published in English. Two reviewers independently extracted data. The primary outcome of interest was changes in fasting glucose levels. RESULTS: We included 47 studies with 114 relevant arms. Of the antipsychotic drugs, only olanzapine was associated with significantly increased glucose levels compared to a placebo (mean difference (MD) = 3.95, 95% confidence interval (CI) = 0.14 to 7.76). Moreover, olanzapine was associated with a significantly greater change in the glucose levels than ziprasidone (MD = 5.51, 95% CI = 1.62 to 9.39), lurasidone (MD = 5.58, 95% CI = 0.53 to 10.64) or risperidone (MD = 3.05, 95% CI = 0.87 to 5.22). Ziprasidone and lurasidone were associated with minimal glucose changes compared to the other antipsychotics. CONCLUSIONS: Olanzapine was associated with a significantly greater change in blood glucose levels than ziprasidone, lurasidone, risperidone or placebo treatment. The application of a hierarchy of glucose metabolism-related side effects may help clinicians tailor the choice of antipsychotic drug to meet the needs of individual patients.

Association Study between Ghrelin Gene Polymorphism and Metabolic Syndrome in a Han Chinese Population.

BACKGROUND: Ghrelin, in humans, is a hormone secreted from the stomach with an orexigenic effect, which is good for digestion and absorption, as well as regulating physical growth, metabolism, and energy balance. It is also involved in the development of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). This study assessed the association between single nucleotide variants of the GHRL gene and the risk of metabolic syndrome in a Han Chinese population. METHODS: A case-control study was performed on 3780 Han Chinese comprising 1813 MetS cases and 1967 controls. Three missense polymorphisms in GHRL (rs26802, rs10490816, and rs696217) were selected, and the association between these polymorphisms and the risk of MetS was investigated. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation (IDF). RESULTS: Using Pearson's 2 test, we found that there were no significant differences in genotype distributions and allele frequencies between cases and controls (all p > 0.05). There were also no significant differences in haplotype distributions between MetS cases and healthy controls. Furthermore, we confirmed that rs26802 of the GHRL gene is associated with body mass index (BMI), waist circumference, systolic blood pressure (SBP), and fasting glucose; rs10490816 is associated with triglycerides (TG) and total cholesterol (TC); while rs696217 is associated with hip circumference and fasting glucose. CONCLUSIONS: We concluded that mutations in the GHRL gene did not confer risk for MetS in our study population. Therefore, functional analysis and replication studies in other populations are needed to further investigate the exact role of the GHRL gene in MetS.

Association of BUD13 polymorphisms with metabolic syndrome in Chinese population: a case-control study.

BACKGROUND: BUD13 homolog (BUD13), one of submits of the retention and splicing complex, was identified in yeast as a splicing factor that affected nuclear pre-mRNA retention. While more and more studies demonstrated that BUD13 played a potential role in the pathogenesis of metabolic syndrome (MetS). This objective was to reassess whether novel locus of BUD13 were linked to MetS and individual complements in the northeast of China. METHODS: A total of 3850 individuals were recruited in this case-control study, including 1813 MetS cases and 2037 healthy controls. The diagnostic criteria was according to the International Diabetes Federation (IDF). Metabolic complements such as waist circumference (WC), triglyceride, high-density lipoprotein cholesterol (HDL-C), systolic and diastolic blood pressure (SBP and DBP), and fasting glucose were measured. We explored the association between two novel single nucleotide polymorphism (SNPs) of BUD13 (rs7118999 and rs10488698) and MetS and its complements. RESULTS: Using binary logistic regression analysis we found that there were no significant associations between SNPs and MetS in different heritance models (all P > 0.05). However, novel locus of BUD13 were linked to individual complements in MetS cases. Rs7118999 conferred to risk of WC (P = 0.016) and the carrier of TT might have higher susceptibility to MetS. While rs10488698 was associated with HDL-C (P = 0.001) and the carrier of TT was significantly associated with higher level of HDL-C. CONCLUSIONS: We concluded that novel mutations in BUD13 did not confer risk for MetS in our study population, but these mutations changed the level of metabolic complements.

The Efficacy and Safety of Dendritic Cells Co-Cultured with Cytokine-Induced Killer Cell Therapy in Combination with TACE-Predominant Minimally-Invasive Treatment for Hepatocellular Carcinoma: a Meta-Analysis.

BACKGROUND: To evaluate the efficacy and safety of dendritic cells (DCs) co-cultured with cytokine-induced killer cell (CIK) immunotherapy combined with transcatheter arterial chemoembolization (TACE) or TACE plus local ablation therapy for hepatocellular carcinoma (HCC). METHODS: Our meta-analysis included a comprehensive search for relevant studies published through December 12, 2014. We used Cochrane Library, PubMed, CBM, VIP, CNKI, and Wanfang data. Depending on the heterogeneity among the included studies, we calculated the pooled odds ratio (OR) and mean difference (MD) using fixed- or random-effects models. Publication biases were assessed using funnel plots and Begg's tests. Sensitivity analyses were also performed. RESULTS: Seven randomized controlled trials (RCTs) and one controlled clinical trial (CCT) that included 693 patients and met the inclusion criteria were analyzed. Pooled results showed that DC-CIK immunotherapy combined with TACE or TACE plus local ablation therapy significantly improved 1-year (OR = 2.00, p = 0.02) and 2-year overall survival (OR = 1.77, p = 0.04). A favored overall response rate (ORR) (OR = 1.51, p = 0.03), disease control rate (DCR) (OR = 1.81, p = 0.01), and better quality of life (OR = 3.30, p < 0.01) were observed in the DC-CIK group. Additionally, when tumor-associated T lymphocyte subsets were compared, our analyses demonstrated that the percentage of CD3+ T cells (MD(CD3+) = 21.37, p = 0.005) and the ratio of CD4+/CD8+ (MD(CD4+/CD8+) = 2.83, p = 0.02) were significantly increased in the DC-CIK therapy group. CONCLUSIONS: The combination of DC-CIK immunotherapy and TACE or TACE plus local ablation therapy improves 1- and 2-year overall survival, ORR, DCR, and provides a better quality of life for patients with HCC.

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy.

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence and mortality, deprives countless patients of health and even life. According to global cancer statistics, there were an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths in 2020, with the age-standardized incidence and mortality rates of 201.0 and 100.7 per 100,000, respectively. Although remarkable advancements have been made in therapeutic strategies recently, the overall prognosis of cancer patients remains not optimistic. Consequently, there are still many severe challenges to be faced and difficult problems to be solved in cancer therapy today. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from tea leaves, has received much attention for its antitumor effects. Accumulating investigations have confirmed that EGCG can inhibit tumorigenesis and progression by triggering apoptosis, suppressing proliferation, invasion, and migration, altering tumor epigenetic modification, and overcoming chemotherapy resistance. Nevertheless, its regulatory roles and biomolecular mechanisms in the immune microenvironment, metabolic microenvironment, and immunotherapy remain obscure. In this article, we summarized the most recent updates about the effects of EGCG on tumor microenvironment (TME), metabolic reprogramming, and anti-cancer immunotherapy. The results demonstrated EGCG can promote the anti-cancer immune response of cytotoxic lymphocytes and dendritic cells (DCs), attenuate the immunosuppression of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), and inhibit the tumor-promoting functions of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and various stromal cells including cancer-associated fibroblasts (CAFs), endothelial cells (ECs), stellate cells, and mesenchymal stem/stromal cells (MSCs). Additionally, EGCG can suppress multiple metabolic reprogramming pathways, including glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, and nucleotide synthesis. Finally, EGCG, as an immunomodulator and immune checkpoint blockade, can enhance immunotherapeutic efficacy and may be a promising candidate for antitumor immunotherapy. In conclusion, EGCG plays versatile regulatory roles in TME and metabolic reprogramming, which provides novel insights and combined therapeutic strategies for cancer immunotherapy.

Predictive value of hepatitis B serological indicators for mortality among cancer survivors and validation in a gastric cancer cohort.

Hepatitis B virus (HBV) infection has gradually been considered to associate with cancer development and progression. This study aimed to explore the associations of serological indicators of HBV infection with mortality risk among cancer survivors and further validated using a gastric cancer (GC) cohort from China, where HBV infection is endemic. National Center for Health Statistics' National Health and Nutrition Examination Survey (NHANES) data were used in this study. Individuals with positive results of hepatitis B core antigen (anti-HBc) were considered to have current or past HBV infection. Serological indicators were positive only for hepatitis B surface antibodies (anti-HBs), indicating vaccine-induced immunity, whereas negativity for all serologic indicators was considered to indicate the absence of HBV infection and immunity to HBV. The GC cohort included patients from the First Hospital of Jilin University, China. The median follow-up time of the NHANES was 10 years; during the follow-up, 1505 deaths occurred. The results revealed that anti-HBs-positive cancer survivors had a 39% reduced risk of mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.44-0.85). Men and individuals aged <65 years old with past exposure to HBV had higher mortality risk (HR 1.52, 95% CI 1.09-2.13; HR 2.07, 95% CI 1.13-3.83). In this GC cohort, individuals who were only anti-HBs-positive showed a reduced risk of mortality (HR 0.77, 95% CI 0.62-0.95). Thus, anti-HBs positivity was a significant factor of decreased mortality among cancer survivors. More rigorous surveillance is necessary for cancer survivors with anti-HBc positivity, particularly men, and younger individuals.

Locally advanced head and neck squamous cell carcinoma treatment efficacy and safety: a systematic review and network meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced (LA) at diagnosis. The combination of radiotherapy (RT), chemotherapy, targeted therapy, and immunotherapy are the primary LA-HNSCC treatment options. Nevertheless, the choice of optimal LA-HNSCC treatment remains controversial. We systematically searched public databases for LA-HNSCC-related studies and assess treatment effectiveness and safety by assessing the objective response rate (ORR), ≥3 adverse events (AEs), overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), local-region control (LRC), and disease-specific survival (DSS). 126 randomized controlled clinical trials (RCTs) were included in this study. We show that concurrent RT with nimotuzumab or conventional concurrent chemo-radiotherapy (CCRT) had significantly better efficacy and long-term survival without increasing AEs than RT alone. Accelerated fractionated radiotherapy (AFRT) showed better efficiency than conventional fractionated RT, although it had higher AEs. In addition, concurrent cetuximab combined with RT failed to show a significant advantage over RT alone. Trial registration: PROSPERO CRD42022352127.

The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.

The occurrence and progression of tumors are inseparable from glucose metabolism. With the development of tumors, the volume increases gradually and the nutritional supply of tumors cannot be fully guaranteed. The tumor microenvironment changes and glucose deficiency becomes the common stress environment of tumors. Here, we discuss the mutual influences between glucose deprivation and other features of the tumor microenvironment, such as hypoxia, immune escape, low pH, and oxidative stress. In the face of a series of stress responses brought by glucose deficiency, different types of tumors have different coping mechanisms. We summarize the tumor studies on glucose deficiency in the last decade and review the genes and pathways that determine the fate of tumors under harsh conditions. It turns out that most of these genes help tumor cells survive in glucose-deprivation conditions. The development of related inhibitors may bring new opportunities for the treatment of tumors.

Elder and booster vaccination associates with decreased risk of serious clinical outcomes in comparison of Omicron and Delta variant: A meta-analysis of SARS-CoV-2 infection.

Background: The COVID-19 pandemic brings great pressure to the public health systems. This meta-analysis aimed to compare the clinical outcomes among different virus variants, to clarify their impact on medical resources and to provide evidence for the formulation of epidemic prevention policies. Methods: A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases using the key words "Omicron" and "Delta." The adjusted Risk ratios (RRs), Odds ratios (ORs) and Hazard ratios (HRs) were extracted, and RRs and Rate difference % (RD%) were used to interpret the risk estimates of the outcomes ultimately. Results: Forty-three studies were included, with 3,812,681 and 14,926,841 individuals infected with SARS-CoV-2 Delta and Omicron variant, respectively. The relative risks of hospitalization, death, ICU admission, and mechanical ventilation use after infection with the Omicron variant were all significantly reduced compared those after infection with the Delta variant (RRhospitalization = 0.45, 95%CI: 0.40-0.52; RRdeath = 0.37, 95%CI: 0.30-0.45; RRICU = 0.35, 95%CI: 0.29-0.42; RRmechanical ventilation = 0.33, 95%CI: 0.25-0.44). The change of both absolute and relative risks for hospitalization was more evident (RR = 0.47, 95%CI: 0.42-0.53；RD% =10.61, 95%CI: 8.64-12.59) and a significant increase was observed for the absolute differences in death in the elderly (RD% = 5.60, 95CI%: 4.65-6.55); the change of the absolute differences in the risk of hospitalization and death were most markedly observed in the patients with booster vaccination (RD%hospitalization = 8.60, 95CI%: 5.95-11.24; RD%death = 3.70, 95CI%: 0.34-7.06). Conclusion: The ability of the Omicron variant to cause severe clinical events has decreased significantly, as compared with the Delta variant, but vulnerable populations still need to be vigilant. There was no interaction between the vaccination doses and different variants.

The prognostic significance of bromodomain protein 4 expression in solid tumor patients: A meta-analysis.

BACKGROUND: Cancer is a leading cause of death worldwide. At present, several inhibitors of bromodomain protein 4 have shown promising anti-tumor responses in clinical trials. Numerous studies have reported the value of bromodomain protein 4 expression in predicting the prognosis of patients with cancers, but their conclusions remain controversial. Therefore, we conducted a meta-analysis to explore the association between bromodomain protein 4 and patient prognosis with the aim to provide new directions for the development of strategies for targeted cancer therapy. METHODS: The meta-analysis was registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/; Registration No. CRD42020184948) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. PubMed Central, PubMed, Cochrane Library and Embase were thoroughly searched to identify eligible studies published through March 31, 2021. Odds ratios with 95% confidence intervals were calculated to demonstrate the relationship between bromodomain protein 4 expression and clinicopathological features. We computed pooled estimated hazard ratios with 95% confidence intervals using Stata 12.0 software to clarify the relationship between bromodomain protein 4 expression and overall survival of various cancers. A quality assessment of the eligible articles was performed based on the Newcastle-Ottawa scale. RESULTS: A total of 974 patients from 10 studies were enrolled in the meta-analysis. Our results revealed that compared to low bromodomain protein 4 expression, high bromodomain protein 4 expression in cancer tissues was significantly associated with lymph node metastasis (Odds ratio = 3.59, 95% confidence interval: 2.62-4.91), distant metastasis (Odds ratio = 4.22, 95% confidence interval: 2.40-7.45), advanced TNM stage (III+IV vs. I+II: Odds ratio = 3.23, 95% confidence interval: 1.29-8.08), and poorly differentiated tumors (Odds ratio = 1.87, 95% confidence interval: 1.33-2.63). In addition, an elevated expression of bromodomain protein 4 tended to shorten survival time (Hazard ratio = 2.23, 95% confidence interval: 1.62-3.07). The subgroup analysis results showed that bromodomain protein 4 upregulation was related to poor prognosis in patients with digestive system cancers (Hazard ratio = 2.54, 95% confidence interval: 1.85-3.50). CONCLUSION: This meta-analysis indicated that bromodomain protein 4 may serve as a promising prognostic biomarker for cancers and a direct effective cancer treatment target.

Dietary inflammatory index, and depression and mortality risk associations in U.S. adults, with a special focus on cancer survivors.

Introduction: A higher risk for depression and mortality is associated with the inflammatory potential of diet measured through the Dietary Inflammatory Index (DII). The roles of DII in the risk of depression and death in cancer survivors were unclear. We aimed to examine the association between energy-adjusted DII (E-DII) score and risk of depression, and mortality using data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES), with a special focus on cancer survivors. Methods: The 24-h dietary recall interview was used as a basis to calculate the E-DII score and the Patient Health Questionnaire-9 (PHQ-9) was used to measure the depressive outcomes. Logistic regression analyses were performed to determine the association between quartiles of E-DII score and depression. Cox proportional hazard regression and competing risk analyses were used to estimate the risks of quartiles of E-DII score or depression on mortality. Results: A total of 27,447 participants were included; including 24,694 subjects without cancer and 2,753 cancer survivors. The E-DII score and depression were not distributed differently between the two groups. However, the E-DII scores were positively associated with within each group's depression (all P trend < 0.001) and participants with higher E-DII scores had a higher risk of depression (subjects without cancer: ORQ4 vs Q1: 2.17, 95% CI: 1.75-2.70; cancer survivors: ORQ4 vsQ1: 1.78, 95% CI: 1.09-2.92). The median follow-up time were 87 person-months, a total of 1,701 (4.8%) and 570 (15.2%) all-cause deaths in subjects without cancer and cancer survivors were identified by the end of 2019. The highest E-DII scores quartile was associated with the highest risk of all-cause (HRQ4 vsQ1: 1.90, 95% CI: 1.54-2.35) and cardiovascular disease (CVD) cause death (HRQ4 vsQ1: 2.50, 95% CI: 1.69-2.3.7) in the subjects without cancer. Moreover, participants with depressive symptoms had higher all-cause mortality (HR: 1.29, 95% CI: 1.04-1.59). No significant correlation was found for E-DII scores or depression with all-cause, cancer-cause or CVD-cause mortality in cancer survivors. Conclusion: Our findings demonstrate that E-DII score was positively associated with depression risk. A higher E-DII score or depressive symptom may increase the risks of all-cause and CVD-cause mortality only among general subjects.

Association of Helicobacter pylori infection with estimated glomerular filtration rate in a Chinese population.

BACKGROUND: Helicobacter pylori (H. Pylori) infection is reported to be associated with extragastric disorders which include kidney diseases. But the association between H. pylori infection and estimated glomerular filtration rate (eGFR) is unclear as far. Thus, we performed the study to investigate the prevalence of H. pylori infection and its association with eGFR in a Chinese population. MATERIALS AND METHODS: We conducted a cross-sectional study in adults who took health examination at the First Hospital of Jilin University in 2019. All the subjects received 14C-labled urea breath test to determine the H. pylori infection, and we analyzed the relationship between prevalence of H. pylori infection and eGFR. RESULTS: Among 3593 participants in the health checkup, the positive rate of H. pylori infection was 37.3%. H. pylori-positive participants had a lower level of eGFR than H. pylori-negative participants. In univariate analysis, we observed that the positive rate of H. pylori infection and RR (relative risk) became larger with eGFR decreased, however, the association was not significant after adjustment for other factors. Further multivariable analysis showed age and sex were the main confounders between eGFR and H. pylori infection. CONCLUSIONS: The correlation between eGFR and positive rate of H. pylori infection was confounded by age and sex.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) as a prognostic biomarker in gastrointestinal cancer: a meta-analysis.

BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) has recently been shown to be dependent on or independent of Matrix metalloproteinases (MMPs) in its roles in tumorigenesis and progression. This appreciation has prompted various studies assessing the prognostic value of TIMP-1 in patients with gastrointestinal cancer, however, the conclusions were still inconsistent. The aim of this study was to assess the prognostic value of TIMP-1-immunohistochemistry (IHC) staining and pretreatment serum/plasma TIMP-1 level in gastrointestinal cancer survival as well as the association between TIMP-1 and clinicopathologic features. METHODS: The meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration NO. CRD42020185407) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A highly sensitive literature search was performed in electronic databases including PubMed, EMBASE and the Cochrane Library. Heterogeneity analysis was conducted using both chi-square-based Q statistics and the I2 test. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the prognostic value of TIMP-1 using the fixed-effects model. Odds ratios (ORs) with 95% CIs were calculated to evaluate the associations between TIMP-1 and clinicopathological characteristics. The meta-analysis was conducted using STATA 12.0 software. RESULTS: A total of 3,958 patients from twenty-two studies were included in the meta-analysis. Elevated TIMP-1 levels were significantly associated with poor survival in gastrointestinal cancer (TIMP-1-IHC staining: HR = 2.04, 95% CI [1.59-2.61], I 2 = 35.7%, P Q = 0.156; pretreatment serum/plasma TIMP-1 levels: HR = 2.02, 95% CI [1.80-2.28], I 2 = 0%, P Q = 0.630). Moreover, clinicopathological parameter data analysis showed that elevated TIMP-1 levels were significantly associated with lymph node metastasis (N1/N2/N3 vs N0: OR = 2.92, 95% CI [1.95-4.38]) and higher TNM stages (III/IV vs I/II: OR = 2.73, 95% CI [1.23-6.04]). CONCLUSION: Both TIMP-1-positive IHC staining and high serum/plasma TIMP-1 levels are poor prognostic factors for the survival of gastrointestinal cancer. In addition, TIMP-1 overexpression was correlated with more advanced clinicopathological features.

A Practical Model is Equivalent to the BALAD or BALAD-2 Score in Predicting Long-term Survival after Hepatectomy in Chinese Patients with Hepatocellular Carcinoma.

Aim: To evaluate the predictive value of the BALAD and BALAD-2 scores on long-term survival after hepatectomy in Chinese hepatocellular carcinoma (HCC) patients and to attempt to establish a more practical or effective model. Methods: A total of 251 HCC patients underwent hepatectomy were recruited. The BALAD and BALAD-2 scores were calculated with total bilirubin, albumin, alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxyprothrombin. The associations of the two scores and their components with the overall survival were analyzed. Finally, three prediction models were explored and constructed. Results: We observed that HCC patients had 5-year survival rates that worsened with increasement of BALAD and BALAD-2 scores. The BALAD and BALAD-2 scores demonstrated fine value in predicting overall survival with Harrell-C statistics of 0.665 (0.618-0.712) and 0.603 (0.554-0.636). After two variables, largest tumor size and BMI, were included in BALAD [0.720 (0.671-0.769)] or BALAD-2 [0.701 (0.649-0.751)] multivariate models, the Harrell-C statistic increased significantly than BALAD (P=0.048) or BALAD-2 (P<0.001) alone. Taking into account availability and expense, an equivalent BAA-BS model was established based on total bilirubin, albumin, AFP, BMI and largest tumor size. The Harrell-C statistic of BAA-BS model [0.723(0.674-0.772)] was similar to that of BALAD (P=0.820) or BALAD-2 (P=0.209) multivariate model. And, the continuous net reclassification index and integrated discriminatory improvement were not statistically different. Finally, a nomogram of the equivalent BAA-BS model was constructed to assist surgeons and patients in predicting 5-year survival rates. Conclusion: Both BALAD and BALAD-2 scores were highly suitable for predicting long-term survival after hepatectomy in Chinese HCC patients. A significant increase in predictive efficacy was observed after the addition of largest tumor size and BMI to BALAD or BALAD-2 score. Even if AFP-L3 and DCP are not detected, an equivalent BAA-BS model also obtained an excellent discriminatory performance.