Search

Abstract Objectives Our aim was to assess the trend in gynaecologic cancer (GC) mortality in the period from 2010 to 2022 in the United States, with focus on the impact of the pandemic on increased deaths. Methods GC mortality data were extracted from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform. We analysed mortality trends and evaluated observed vs. predicted mortality for the period from 2020 to 2022 with joinpoint regression and prediction modelling analyses. Results A total of 334,382 deaths among adults aged 25 years and older with gynaecologic cancer were documented from 2010 to 2022. The overall age-standardised mortality rate (ASMR, per 100,000 persons) for ovarian cancer-related death decreased gradually from 7.189 in 2010 to 5.517 in 2019, yielding an APC (annual percentage change) of -2.8%. However, the decrease in ovarian cancer-related mortality slowed down by more than 4-fold during the pandemic. Cervical cancer -related mortality decreased slightly prior to the pandemic and increased during the pandemic with an APC of 0.6%, resulting in excess mortality of 4.92%, 9.73% and 2.03% in 2020, 2021 and 2022, respectively. For uterine corpus cancer, the ASMR increased from 1.905 in 2010 to 2.787 in 2019, and increased sharply to 3.079 in 2021 and 3.211 in 2022. The ASMR rose steadily between 2013 and 2022, yielding an APC of 6.9%. Conclusions Overall, we found that GC-related mortality increased during the COVID-19 pandemic, and this increase was not specific to age, race, or ethnicity.

Abstract Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Abstract Background High fasting plasma glucose (FPG) has been listed as one of the risk factors for bladder cancer. We here estimated the global, regional, and national levels of bladder cancer burden attributable to high FPG from 1990 to 2019. Methods Bladder cancer data attributable to high FPG were extracted from the Global Burden of Disease Study 2019, and analyzed by age, sex, year, and location. Age‐standardized rates were utilized to evaluate the burden between different populations. The temporal trend of the burden was estimated through the Joinpoint analysis. Results In 2019, high FPG contributed to 22,823.33 (95% uncertainty interval [UI], 4694.88–48,962.26) deaths and 399,654.91 (95% UI, 81,609.35–865,890.95) disability‐adjusted life years (DALYs) of bladder cancer globally. Since 1990, the global age‐standardized death and DALY rates of bladder cancer attributable to high FPG increased apparently by 39.18% and 41.48%, respectively. During the last 30 years, high FPG‐related age‐standardized death and DALY rates of bladder cancer have increased in all countries. In 2019, Central Europe showed the greatest high FPG‐related age‐standardized death and DALY rates of bladder cancer, but Andean Latin America had the lowest rates. Nationally, Lebanon showed the greatest high FPG‐related age‐standardized death and DALY rates of bladder cancer in 2019. High FPG‐attributable deaths and DALYs of bladder cancer were more considerable among males and older people. Countries with high SDI showed higher levels of age‐standardized death and DALY rates of bladder cancer due to high FPG and presented remarkable upward trends in rates in the last 30 years. Conclusions Globally, the high FPG‐associated bladder cancer burden has remarkably increased in all countries, and showed a higher level among countries with higher SDI. Monitoring FPG levels among patients with bladder cancer is critical to lower the corresponding burden.

Abstract Echocardiography is the first-line diagnostic technique for heart diseases. Although artificial intelligence techniques have made great improvements in the analysis of echocardiography, the major limitations remain to be the built neural networks are normally adapted to a few diseases and specific equipment. Here, we present an end-to-end deep learning framework named AIEchoDx that differentiates four common cardiovascular diseases (Atrial Septal Defect, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, prior Myocardial Infarction) from normal subjects with performance comparable to that of consensus of three senior cardiologists in AUCs (99.50% vs 99.26%, 98.75% vs 92.75%, 99.57% vs 97.21%, 98.52% vs 84.20%, and 98.70% vs 89.41%), respectively. Meanwhile, AIEchoDx accurately recognizes critical lesion regions of interest along with each disease by visualizing the decision-making process. Furthermore, our analysis indicates that heterogeneous diseases, like dilated cardiomyopathy, could be classified into two phenogroups with distinct clinical characteristics. Finally, AIEchoDx performs efficiently as an anomaly detection tool when applying handheld device-produced videos. Together, AIEchoDx provides a potential diagnostic assistant tool in either cart-based echocardiography equipment or handheld echocardiography device for primary and point-of-care medical personnel with high diagnostic performance, and the application of lesion region identification and heterogeneous disease phenogrouping, which may broaden the application of artificial intelligence in echocardiography.

Abstract Background The current study investigated the relationship between behavioural and psychological symptoms of dementia (BPSD) knowledge and positive aspects of caregiving (PAC), in addition, how caregiving attitude and self-efficacy mediate or moderate this relationship. Methods Two hundred twenty-nine formal caregivers (51males and 178females) who has worked in nursing homes for more than a month were recruited.With a cross-sectional, face-to-face survey, structural questionnaires were implemented to evaluate formal caregiver’s BPSD knowledge, attitude, self-efficacy and PAC.A 13-item self-developed questionnaire was used to assess caregiver’s BPSD knowledge about disease characteristics, care and risks, and treatment needs. Dementia attitude, self-efficacy and positive aspects of caregiving were measured by dementia attitude scale, the General self-efficacy scale, and Chinese version of positive aspects of caregiving respectively. Model 5 in the PROCESS micro was employed in order to verify the mediating effect of attitude and the moderating effect of self-efficacy on the relationship between BPSD knowledge and PAC. Results The results showed that greater BPSD knowledge was associated with increased PAC, and this relationship was fully mediated by increased friendly attitude toward people with dementia. Moreover, direct effect was moderated by self-efficacy, and that only among those with high self-efficacy, the direct effect of BPSD knowledge was found on promoting PAC. Conclusions By elucidating the knowledge-attitude-practice pathway in handling patient’s BPSD, the current study extends existing literature and provides insights for developing psychoeducation programs among formal caregivers.

Introduction: Cancer is the leading cause of death among children. Objectives: We report on the latest estimates of the burden of cancer among children at the global, regional, and national levels from 1990 to 2019. Methods: Based on the Global Burden of Disease Study 2019, children’s cancer data were analyzed by sex, age, year, and location. Age-standardized rates were used to compare the burdens among regions and nations. Joinpoint analysis was applied to assess the temporal trend of the global childhood cancer burden. Results: In 2019, 291,319 (95% uncertainty interval [UI], 254,239 to 331,993) new cases and 98,834 (86,124 to 113,581) deaths from childhood cancer were documented globally. Further, 8,302,464 (7,230,447 to 9,555,118) DALYs and 1,806,630 (1,567,808 to 2,089,668) prevalent cases were recorded in the same year. Age-standardized incidence and prevalence rates of childhood cancer were greatest in higher SDI settings and increased most significantly in Australasia and Southern Latin America over the last 30 years. However, although age-standardized death and DALY rates of childhood cancer have remarkably decreased in all regions since 1990, countries with a lower SDI showed the highest rates in 2019, particularly in countries in Eastern Sub-Saharan Africa. Among all cancers, leukemia has shown the largest decrease in burden since 1990. Despite this, leukemia was still the most common cancer and the leading cause of death among children in 2019, followed by brain and central nervous system cancer. Conclusions: On a global scale, the childhood cancer burden has significantly fallen over the last 30 years, but is still higher in lower SDI countries. Effective interventions and collaborations among nations should be facilitated to improve healthcare among children with cancer in countries with lower SDI.

ObjectivesWe developed and tested a deep learning (DL) framework applicable to color Doppler echocardiography for automatic detection and quantification of atrial septal defects (ASDs).BackgroundColor Doppler echocardiography is the most commonly used non-invasive imaging tool for detection of ASDs. While prior studies have used DL to detect the presence of ASDs from standard 2D echocardiographic views, no study has yet reported automatic interpretation of color Doppler videos for detection and quantification of ASD.MethodsA total of 821 examinations from two tertiary care hospitals were collected as the training and external testing dataset. We developed DL models to automatically process color Doppler echocardiograms, including view selection, ASD detection and identification of the endpoints of the atrial septum and of the defect to quantify the size of defect and the residual rim.ResultsThe view selection model achieved an average accuracy of 99% in identifying four standard views required for evaluating ASD. In the external testing dataset, the ASD detection model achieved an area under the curve (AUC) of 0.92 with 88% sensitivity and 89% specificity. The final model automatically measured the size of defect and residual rim, with the mean biases of 1.9 mm and 2.2 mm, respectively.ConclusionWe demonstrated the feasibility of using a deep learning model for automated detection and quantification of ASD from color Doppler echocardiography. This model has the potential to improve the accuracy and efficiency of using color Doppler in clinical practice for screening and quantification of ASDs, that are required for clinical decision making.

Osteoclast-like giant cell tumor (OGCT) is a common bone tumor, occasionally observed in some extraosseous organs, but rarely involving the digestive system, especially the liver. Previously reported osteoclast-like giant cell carcinoma of the liver often coexists with sarcomatoid or hepatocellular carcinoma. Undifferentiated liver tumors with osteoclast-like giant cells (OGCs) are extremely rare. Due to its rarity, there is no consensus for diagnosis and treatment of undifferentiated liver tumors with OGCs. Definitive diagnosis comes from surgery, so there is often a long delay in diagnosis following the occurrence of symptoms. This case describes an extremely rare case of an undifferentiated liver tumor with OGCs in detail. It also summarizes the previously published cases based on liver tumors with OGCs from August 1980 to June 2021, providing extensive evidence to improve preoperative diagnosis and management options.

Abstract Background Ovarian cancer (OV) is deemed the most lethal gynecological cancer in women. The aim of this study was to construct an effective gene prognostic model for predicting overall survival (OS) in patients with OV. Methods The expression profiles of glycolysis‐related genes (GRGs) and clinical data of patients with OV were extracted from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analyses were conducted, and a prognostic signature based on GRGs was constructed. The predictive ability of the signature was analyzed using training and test sets. Results A gene risk signature based on nine GRGs (ISG20, CITED2, PYGB, IRS2, ANGPTL4, TGFBI, LHX9, PC, and DDIT4) was identified to predict the survival outcome of patients with OV. The signature showed a good prognostic ability for OV, particularly high‐grade OV, in the TCGA dataset, with areas under the curve (AUC) of 0.709 and 0.762 for 3‐ and 5‐year survival, respectively. Similar results were found in the test sets, and the AUCs of 3‐, 5‐year OS were 0.714 and 0.772 in the combined test set. And our signature was an independent prognostic factor. Moreover, a nomogram combining the prediction model and clinical factors was developed. Conclusion Our study established a nine‐GRG risk model and nomogram to better predict OS in patients with OV. The risk model represents a promising and independent prognostic predictor for patients with OV. Moreover, our study on GRGs could offer guidance for the elucidation of underlying mechanisms in future studies.

The roles of ubiquitin-related genes in hepatocellular carcinoma (HCC) have not been thoroughly investigated. This study aimed to systematically examine ubiquitin-related genes and identify subtypes and stratify prognosis of HCC by using ubiquitin-related signatures. Survival, biological processes, tumor microenvironment (TME), and genomic alterations of the HCC subtypes were investigated. Patients with HCC were classified into two subtypes (clusters 1 and 2) with distinct survival outcomes, pathways, and genomic alterations. Cluster 2 had better prognosis than did cluster 1. Hepatitis B, hepatitis C, Janus tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, and natural killer cell-mediated cytotoxicity were enriched in cluster 1. Moreover, cluster 2 had a higher immune score and immune cell infiltrations, whereas cluster 1 had a lower immune score and immune infiltrations. Additionally, mutations, amplifications, and deletions among the phosphatidylinositol 3-kinase (PI3K)-AKT, p53, and receptor tyrosine kinase (RTK)-RAS pathways more frequently occurred in cluster 1, while those among the Hippo, MYC, and Notch signaling pathways were found in cluster 2. Finally, a prognostic signature, consisting of eight ubiquitin-related genes, was established and validated. In brief, our study established a new classification and developed a prognostic signature for HCC.

IntroductionThis study aimed to describe the latest epidemiology of female breast cancer globally, analyze the change pattern of the incidence rates and the disease’s association with age, period, and birth cohort, and subsequently present a forecast of breast cancer incidence.MethodsData for analysis were obtained from Global Burden of Disease (GBD) Study 2019 and World Population Prospects 2019 revision by the United Nations (UN). We described the age-standardized incidence rates (ASIRs) from 1990 to 2019 and then calculated the relative risks of period and cohort using an age-period-cohort model, and predicted the trends of ASIRs to 2035.ResultsIn 2019, the global incidence of breast cancer in women increased to 1,977,212 (95% uncertainty interval = 1 807 615 to 2 145 215), with an ASIR of 45.86 (41.91 to 49.76) per 100 000 person-year. Among the six selected countries facing burdensome ASIRs, only the USA showed a downward trend from 1990 to 2019, whereas the others showed an increasing or stable trend. The overall net drift was similar in Japan (1.78%), India (1.66%), and Russia (1.27%), reflecting increasing morbidity from 1990 to 2019. The increase in morbidity was particularly striking in China (2.60%) and not significant in Germany (0.42%). The ASIRs were predicted to continue to increase globally, from 45.26 in 2010 to 47.36 in 2035. In most countries and regions, the age specific incidence rate is the highest in those aged over 70 years and will increase in all age groups until 2035. In high-income regions, the age specific incidence rates are expected to decline in women aged over 50 years.ConclusionsThe global burden of female breast cancer is becoming more serious, especially in developing countries. Raising awareness of the risk factors and prevention strategies for female breast cancer is necessary to reduce future burden.

Abstract Circular RNAs (circRNAs) are a new class of endogenous regulatory RNAs characterized by covalently closed cyclic structure lacking poly-adenylated tails, and are capable of regulating gene expression at transcription or post-transcription levels. Recently, plentiful circRNAs have been discovered in breast cancer and some circRNAs expression profiles are specifically involved in the triple-negative breast cancer (TNBC). TNBC is a type of malignant tumor defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. Considering its clinical characteristics of high invasion, metastasis, poor prognosis, and lack of effective response to conventional chemotherapies or targeted therapies, it could be a promosing option to discover specific circRNAs as new targets for TNBC treatment. Meanwhile, accumulating evidence has demonstrated that circRNAs are dysregulated in TNBC tissues and are correlated with clinicopathological features and prognosis of TNBC patients. Furthermore, looking for circRNAs with high specificity and sensitivity will provide a new opportunity for the early diagnosis, clinical treatment, and prognosis monitoring of TNBC. Herein, we reviewed the biogenesis, regulatory mechanisms, and biological functions of circRNAs in TNBC and summarized the relationship between circRNAs expression and the clinicopathology, diagnosis, and prognosis of patients with TNBC.

Previous studies of correlations of microRNA (miR)-499 rs3746444 and miR-196a-2 rs11614913 polymorphisms with glioma risk have yielded inconsistent results. In this study, relationships between these two polymorphisms and glioma risk and survival were evaluated. In total, 605 patients and 1,300 controls were genotyped. rs3746444 increased glioma risk in five genetic models (GA versus AA, odds ratio [OR], 95% confidence interval [CI] = 1.31 [1.05–1.66], p = 0.02; GG versus AA, OR [95% CI] = 10.70 [6.13–18.69], p < 0.0001; GA + GG versus AA, OR [95% CI] = 1.82 [1.47–2.24], p < 0.0001; GG versus AA + GA, OR [95% CI] = 9.99 [5.74–17.40], p < 0.0001; G versus A, OR [95% CI] = 2.18 [1.82–2.60], p < 0.0001). rs11614913 decreased glioma risk in a recessive model (OR [95% CI] = 0.79 [0.64–0.97], p = 0.03). No relationships between either SNP and survival were found. rs3746444 in the miR-499 seed region could affect target recognition. Bioinformatics analyses indicated that miR-499 rs3746444 is involved in various biological processes and pathways, including “cell adhesion molecule binding,” “positive regulation of catabolic process,” “NF-kappa B pathway,” and “PI3K-Akt pathway,” by targeting mRNAs. Our results suggested that miR-499 rs3746444 and miR-196a-2 rs11614913 have crucial roles in glioma susceptibility.

ObjectiveExposure to high altitudes represents physiological stress that leads to significant changes in cardiovascular properties. However, long-term cardiovascular adaptions to high altitude migration of lowlanders have not been described. Accordingly, we measured changes in cardiovascular properties following prolonged hypoxic exposure in acclimatized Han migrants and Tibetans.MethodsEchocardiographic features of recently adapted Han migrant (3–12 months, n = 64) and highly adapted Han migrant (5–10 years, n = 71) residence in Tibet (4,300 m) using speckle tracking echocardiography were compared to those of age-matched native Tibetans (n = 75) and Han lowlanders living at 1,400 m (n = 60).ResultsShort-term acclimatized migrants showed increased estimated pulmonary artery systolic pressure (PASP) (32.6 ± 5.1 mmHg vs. 21.1 ± 4.2 mmHg, p < 0.05), enlarged right ventricles (RVs), and decreased fractional area change (FAC) with decreased RV longitudinal strain (−20 ± 2.8% vs. −25.5 ± 3.9%, p < 0.05). While left ventricular ejection fraction (LVEF) was preserved, LV diameter (41.7 ± 3.1 mm vs. 49.7 ± 4.8 mm, p < 0.05) and LV longitudinal strain (−18.8 ± 3.2% vs. −22.9 ± 3.3%, p < 0.05) decreased. Compared with recent migrants, longer-term migrants had recovered RV structure and functions with slightly improved RV and LV longitudinal strain, though still lower than lowlander controls; LV size remained small with increased mass index (68.3 ± 12.7 vs. 59.3 ± 9.6, p < 0.05). In contrast, native Tibetans had slightly increased PASP (26.1 ± 3.4 mmHg vs. 21.1 ± 4.2 mmHg, p < 0.05) with minimally altered cardiac deformation compared to lowlanders.ConclusionRight ventricular systolic function is impaired in recent (5 years) but without impairment of LV systolic or diastolic function. In contrast, cardiac size, structure, and function of native Tibetans are more similar to those of lowland dwelling Hans.

Abstract Background The epidemiology of esophageal cancer (EC) can elucidate its causes and risk factors and help develop prevention strategies. We aimed to provide an overview of the burden, trends, and risk factors of EC in China from 1990 to 2017. We also investigated the differences between China, Japan, and South Korea and discussed the possible causes of the disparities. Methods We used the Global Burden of Disease Study 2017 to obtain data on incident cases, deaths, disability-adjusted life-year (DALY) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALY rate of EC in China, Japan, and South Korea from 1990 to 2017. Trend analysis was performed using joinpoint analysis. We measured the associations between ASIR, ASDR, and age-standardized DALY rate and the socio-demographic index (SDI) for 1990–2017. We also analyzed the risk factors associated with EC deaths and DALYs. Results China recorded 234,624 (95% uncertainty intervals: 223,240–246,036) incident cases of and 212,586 (202,673–222,654) deaths from EC in 2017. The ASIR and ASDR declined from 1990 to 2017. Until 2017, the ASIR was 12.23, and ASDR was 11.25 per 100,000 persons. The DALYs were 4,464,980 (4,247,816–4,690,846) with an age-standardized rate of 222.58 per 100,000 persons in 2017. The ASIR, ASDR, and age-standardized DALY rate in China were twice those of Japan and South Korea. These three indicators showed a decreasing trend, whereas SDI increased, in all three countries from 1990 to 2017. Tobacco and alcohol use remained the major risk factors for EC death and DALYs, especially for men in China and women in Japan and South Korea. High body mass index (BMI) and low-fruit diet were the main risk factors for women in China. Conclusions The incident cases and deaths of EC in China, Japan, and South Korea increased from 1990 to 2017, whereas the ASIR, ASDR, and age-standardized DALY rate declined. China had the greatest burden of EC among three countries. SDI and aging along with tobacco use, alcohol use, high BMI, and low-fruit diet were the main risk factors of death and DALYs and should be paid more attention.

Human papillomavirus (HPV) is a clear etiology of cervical cancer (CC). However, the associations between HPV infection and DNA methylation have not been thoroughly investigated. Additionally, it remains unknown whether HPV‐related methylation signatures can identify subtypes of CC and stratify the prognosis of CC patients. DNA methylation profiles were obtained from The Cancer Genome Atlas to identify HPV‐related methylation sites. Unsupervised clustering analysis of HPV‐related methylation sites was performed to determine the different CC subtypes. CC patients were categorized into cluster 1 (Methylation‐H), cluster 2 (Methylation‐M), and cluster 3 (Methylation‐L). Compared to Methylation‐M and Methylation‐L, Methylation‐H exhibited a significantly improved overall survival (OS). Gene set enrichment analysis (GSEA) was conducted to investigate the functions that correlated with different CC subtypes. GSEA indicated that the hallmarks of tumors, including KRAS signaling, TNFα signaling via NF‐κB, inflammatory response, epithelial–mesenchymal transition, and interferon‐gamma response, were enriched in Methylation‐M and Methylation‐L. Based on mutation and copy number variation analyses, we found that aberrant mutations, amplifications, and deletions among the MYC, Notch, PI3K‐AKT, and RTK‐RAS pathways were most frequently detected in Methylation‐H. Additionally, mutations, amplifications, and deletions within the Hippo, PI3K‐AKT, and TGF‐β pathways were presented in Methylation‐M. Genes within the cell cycle, Notch, and Hippo pathways possessed aberrant mutations, amplifications, and deletions in Methylation‐L. Moreover, the analysis of tumor microenvironments revealed that Methylation‐H was characterized by a relatively low degree of immune cell infiltration. Finally, a prognostic signature based on six HPV‐related methylation sites was developed and validated. Our study revealed that CC patients could be classified into three heterogeneous clusters based on HPV‐related methylation signatures. Additionally, we derived a prognostic signature using six HPV‐related methylation sites that stratified the OS of patients with CC into high‐ and low‐risk groups.

Abstract Background LncRNA MEG3 expressed abnormally in various cancers including breast cancer, but no studies reported the correlation between MEG3 SNPs and breast cancer susceptibility among Chinese women. Methods This study is aimed to explore the association between three SNPs of MEG3 (rs3087918, rs7158663, rs11160608) and breast cancer. The study is a population-based case-control study including 434 breast cancer patients and 700 healthy controls. Genotyping was performed using Sequenom MassArray technique. Function prediction of rs3087918 were based on RNAfold and lncRNASNP2 databases. Results Pooled analysis indicated that rs3087918 was related to a decreased risk of breast cancer [GG vs. TT: OR (95%) = 0.67(0.45–0.99), P = 0.042; GG vs. TT + TG: OR (95%) = 0.69(0.48–0.99), P = 0.046], especially for women aged

Abstract Background Investigations of disease incidence, mortality, and disability-adjusted life years (DALYs) are valuable for facilitating preventive measures and health resource planning. We examined the tracheal, bronchus, and lung (TBL) cancer burdens worldwide according to sex, age, and social development index (SDI) at the global, regional, and national levels. Methods We assessed the TBL cancer burden using data from the Global Burden of Disease (GBD) database, including 21 regions, 195 countries, and territories in the diagnostic period 1990–2017. The data of TBL cancer-related mortality and DALYs attributable to all known risk factors were also analyzed. Age-standardized rates (ASRs) and their estimated annual percentage changes (EAPCs) were calculated. Results Incident cases, deaths, and DALYs of TBL cancer increased worldwide (100.44%, 82.30%, and 61.27%, respectively). The age-standardized incidence rate (ASIR) was stable (EAPC = 0.02, 95% confidence interval [CI] − 0.03 to 0.08), but the age-standardized death (EAPC = − 0.34, 95%CI − 0.38 to − 0.3) and DALY rate decreased generally (EAPC = − 0.74, 95%CI − 0.8 to − 0.68). However, the change trend of ASIR and ASDR among sexes was on the contrary. China and the USA always had the highest incidence, mortality, and DALYs of TBL cancer. Significant positive correlations between ASRs and SDI were observed, especially among females. High (36.86%), high-middle (28.78%), and middle SDI quintiles (24.91%) carried the majority burden of TBL cancer. Tobacco remained the top cause of TBL cancer death and DALYs, followed by air pollution, the leading cause in the low-middle and low-SDI quintiles. Metabolic risk-related TBL cancer mortality and DALYs among females increased but was stable among males. The main ages of TBL cancer onset and death were > 50 years, and the DALYs concentrated in 50 − 69 years. Conclusions To significantly reduce the growing burden of TBL cancer, treatment resources need to be skewed according to factors such as risks and geography, especially for high-risk groups and high-burden areas. Asia had the greatest TBL cancer burden, followed by high-income North America. Tobacco remains the leading cause of death and DALYs, followed by air pollution. Effective prevention measures against tobacco and air pollution should be strengthened.

Glioma is the most common tumor of the central nervous system; variation in susceptibility and prognosis worldwide suggests that there are molecular and genetic differences among individuals. The H19 gene plays a dual role in carcinogenesis. In this study, associations between H19 polymorphisms and susceptibility as well as prognosis in glioma were evaluated. In total, 605 patients with glioma and 1,300 cancer-free subjects were enrolled in the study. Individuals with the rs3741219 A>G allele were less likely to develop glioma (relative risk [RR] = 0.54, 95% confidence interval [95% CI] = 0.45–0.63, p < 0.001), whereas rs217727 G>A and rs2839698 G>A genotypes were not associated with glioma risk. The associations between H19 polymorphisms and prognosis were assessed, including overall survival and progression-free survival. Three focused H19 polymorphisms did not show a significant effect on survival. Further analysis based on false-positive report probability validated these significant results. In the haplotype analysis, individuals with the Grs217727Ars2839698Grs3741219 haplotype were less likely to develop glioma (odds ratio [OR] = 0.33, 95% CI = 0.23–0.46, p = 0.02). Overall, carriers of the rs3741219 AG or GG genotype of H19 have a decreased susceptibility to glioma, but polymorphisms in this gene are not related to prognosis.

Background: Antihypertensive drugs might play a key role in the risk and poor prognosis of colorectal cancer. However, current epidemiologic evidence remains inconsistent. The aim of this study is to quantify the association between antihypertensive drugs and colorectal cancer.Methods: To identify available studies, we systematically searched electronic databases: PubMed, Web of Science, Embase, Cochrane Library. The risk estimates and their corresponding 95% confidence intervals (CIs) were collected and analyzed by using random-effects models. Heterogeneity test and sensitivity analysis were also performed.Results: Overall, 37 observational studies were included in this analysis (26 studies with cohort design, three studies with nested case-control design, and 8 studies with case-control design). Antihypertensive drugs did not present a significant effect on the risk or overall survival of patients with colorectal cancer [Risk ratio (RR) = 1.00, 95% CI: 0.95–1.04; Hazard ratio (HR) = 0.93, 95% CI: 0.84–1.02]. In the subgroup analysis, diuretics use was significantly associated with a worse overall survival of patients with colorectal cancer (HR = 1.27; 95% CI: 1.14–1.40). However, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was associated with improved progression-free survival of patients who suffered from colorectal cancer (HR = 0.83; 95% CI: 0.72–0.95).Conclusion: Antihypertensive drug usage did not influence the risk and overall survival of patients with colorectal cancer in general. Further investigation reminded us that diuretics use might reduce the overall survival time in colorectal cancer patients, whereas those who took Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers had a longer progression-free survival.

Mutations in the human O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase gene (SEPSECS) are associated with progressive cerebello-cerebral atrophy (PCCA), also known as pontocerebellar hypoplasia type 2D (PCH2D). Early-onset profound developmental delay, progressive microcephaly, and hypotonia that develops toward severe spasticity have been previously reported with SEPSECS mutations. Herein we report a case with severe global developmental delay, myogenic changes in the lower limbs, and insomnia, but without progressive microcephaly and brain atrophy during infancy and toddlerhood in a child harboring the SEPSECS missense variant c.194A>G (p. Asn65Ser) and a novel splicing mutation c.701+1G>A. With these findings we communicate the first Chinese SEPSECS mutant case, and our report indicates that SEPSECS mutations can give rise to a milder phenotype.

Abstract Background Statistical data on the incidence, mortality, and burden of breast cancer and the relevant risk factors are valuable for policy-making. We aimed to estimate breast cancer incidence, deaths, and disability-adjusted life years (DALYs) by country, gender, age group, and social-demographic status between 1990 and 2017. Methods We extracted breast cancer data from the 2017 Global Burden of Disease (GBD) study from 1990 through 2017 in 195 countries and territories. Data about the number of breast cancer incident cases, deaths, DALYs, and the age-standardized rates were collected. We also estimated the risk factors attributable to breast cancer deaths and DALYs using the comparative risk assessment framework of the GBD study. Results In 2017, the global incidence of breast cancer increased to 1,960,681 cases. The high social-development index (SDI) quintile included the highest number of breast cancer death cases. Between 2007 and 2017, the ASDR of breast cancer declined globally, especially in high SDI and high middle SDI countries. The related DALYs were 17,708,600 in 2017 with high middle SDI quintile as the highest contributor. Of the deaths and DALYs, alcohol use was the greatest contributor in most GBD regions and other contributors included high body mass index (BMI) and high fasting plasma glucose. Conclusion The increasing global breast cancer burden is mainly observed in lower SDI countries; in higher SDI countries, the breast cancer burden tends to be relieving. Therefore, steps against attributable risk factors should be taken to reduce breast cancer burden in lower SDI countries.

MicroRNAs bind to the 3′ untranslated regions of mRNAs, affecting translation, tumorigenesis, and apoptosis. This study evaluated the role of TYMS (rs1059394, C > T, and rs2847153, G > A), RYR3 (rs1044129, G > A), KIAA0423 (rs1053667, T > C), and GOLGA7 (rs11337, G > T) polymorphisms for assessment of glioma risk and prognosis among the Chinese Han population. Five single-nucleotide polymorphisms were assessed in 605 glioma patients and 1,300 controls. We found a significant correlation between rs1059394 and glioma susceptibility in the homozygote and dominant genetic models (TT versus CC, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.52–0.97, p = 0.03; CT+TT versus CC, OR = 0.74, 95% CI = 0.55–0.99, p = 0.04). The results of the Kaplan-Meier and log rank tests revealed that the rs11337 GG genotype correlated with better overall survival of glioma patients (p = 0.017) than the GT genotype. Multivariate Cox regression analysis results also showed that the rs11337 GT genotype correlated with worse overall survival (p = 0.017, hazard ratio [HR] = 1.25, 95% CI = 1.04–1.5) than the GG genotype. These results suggest that GOLGA7 (rs11337) polymorphism may play a role in the prognosis of glioma patients and that TYMS (rs1059394) is associated with glioma risk. Keywords: GOLGA7, rs11337, polymorphism, cancer risk, prognosis, microRNA-binding site

Abstract DNA polymerase kappa (POLK), one of the specialized Y family DNA polymerases, functions in translesion synthesis and is suggested to be related with cancers. Single nucleotide polymorphisms (SNPs) in specialized DNA polymerases have been demonstrated to be associated with cancer risk. To evaluate the association of two common POLK variants (rs3213801 C>T and rs5744533 C>T) with glioma, we conducted a case‐control study and genotyped these two POLK variants in 605 patients and 1300 healthy controls. The association analysis revealed no significant correlations were observed between these two POLK SNPs and glioma risk. However, the POLK rs3213801 CT genotype was found to be higher in older glioma patients (≥40) than in younger patients (P = .026). Compared with patients harboring the CC genotype, the frequencies of POLK rs5744533 CT and CT+TT genotypes were increased in patients with lower World Health Organization (WHO) grade glioma (P = .028, 0.044, respectively). According to Kaplan‐Meier analysis and log‐rank tests, POLK SNPs were not correlated with either the overall survival or progression‐free survival. Nevertheless, multivariate analysis revealed that the age (≥40) could increase the risk of death in glioma patients (P

Background: Exposure to ambient particulate matter pollution (APMP) is a global health issue that directly affects the human respiratory system. Thus, we estimated the spatiotemporal trends in the burden of APMP-related respiratory diseases from 1990 to 2019.Methods: Based on the Global Burden of Disease Study 2019, data on the burden of APMP-related respiratory diseases were analyzed by age, sex, cause, and location. Joinpoint regression analysis was used to analyze the temporal trends in the burden of different respiratory diseases over the 30 years.Results: Globally, in 2019, APMP contributed the most to chronic obstructive pulmonary disease (COPD), with 695.1 thousand deaths and 15.4 million disability-adjusted life years (DALYs); however, the corresponding age-standardized death and DALY rates declined from 1990 to 2019. Similarly, although age-standardized death and DALY rates since 1990 decreased by 24% and 40%, respectively, lower respiratory infections (LRIs) still had the second highest number of deaths and DALYs attributable to APMP. This was followed by tracheal, bronchus, and lung (TBL) cancer, which showed increased age-standardized death and DALY rates during the past 30 years and reached 3.78 deaths per 100,000 persons and 84.22 DALYs per 100,000 persons in 2019. Among children aged < 5 years, LRIs had a huge burden attributable to APMP, whereas for older people, COPD was the leading cause of death and DALYs attributable to APMP. The APMP-related burdens of LRIs and COPD were relatively higher among countries with low and low-middle socio-demographic index (SDI), while countries with high-middle SDI showed the highest burden of TBL cancer attributable to APMP.Conclusions: APMP contributed substantially to the global burden of respiratory diseases, posing a significant threat to human health. Effective actions aimed at air pollution can potentially avoid an increase in the PM2.5-associated disease burden, especially in highly polluted areas.

BackgroundThe treatment for locally advanced breast cancer (LABC) is a severe clinical problem. The postoperative radiotherapy is a conventional treatment method for patients with LABC, whereas the effect of preoperative radiotherapy on outcome of LABC remains controversial. This study aimed to examine and compare the overall survival (OS) in patients with LABC who underwent preoperative radiotherapy or postoperative radiotherapy.MethodsThis retrospective cohort study included 41,618 patients with LABC from the National Cancer Database (NCDB) between 2010 and 2014. We collected patients’ demographic, clinicopathologic, treatment and survival information. Propensity score was used to match patients underwent pre-operative radiotherapy with those who underwent post-operative radiotherapy. Cox proportional hazard regression model was performed to access the association between variables and OS. Log-rank test was conducted to evaluate the difference in OS between groups.ResultsThe estimated median follow-up of all included participants was 69.6 months (IQR: 42.84-60.22); 70.1 months (IQR: 46.85-79.97) for postoperative radiotherapy, 68.5 (IQR: 41.13-78.23) for preoperative radiotherapy, and 67.5 (IQR: 25.92-70.99) for no radiotherapy. The 5-year survival rate was 80.01% (79.56-80.47) for LABC patients who received postoperative radiotherapy, 64.08% (57.55-71.34) for preoperative radiotherapy, and 59.67% (58.60-60.77) for no radiotherapy. Compared with no radiation, patients receiving postoperative radiotherapy had a 38% lower risk of mortality (HR=0.62, 95%CI: 0.60-0.65, p

BackgroundEpidemiological trends of type 2 diabetes mellitus attributable to fine particulate matter (PM2.5) pollution remain unclear. Here, we estimated spatiotemporal trends of type 2 diabetes mellitus burden attributable to PM2.5 pollution, including ambient particulate matter pollution (APMP) and household air pollution (HAP), from 1990–2019.MethodsData were obtained from the Global Burden of Disease Study 2019 and were analyzed by age, sex, year, and location. Joinpoint regression analysis was applied in the analysis of temporal trends in type 2 diabetes mellitus burden over the 30 years.ResultsGlobally, PM2.5 pollution contributed to 292.5 thousand deaths and 13 million disability-adjusted life-years (DALYs) in 2019. APMP ranked third among all risk factors, causing an increase in type 2 diabetes mellitus burden from 1990, whereas the impact of HAP significantly fell during the same period. Both APMP and HAP contributed the most to deaths and DALYs of type 2 diabetes mellitus among older people. However, the age-standardized death and DALY rates of type 2 diabetes mellitus attributable to APMP were greater among males and people in the middle socio-demographic index countries, especially in Southern Sub-Saharan Africa. For HAP, type 2 diabetes mellitus burden was modestly higher in females and was highest in Oceania, which was the only region with an increase from 1990.ConclusionsPM2.5 pollution resulted in substantial and increasing type 2 diabetes mellitus burden worldwide. Hence, governments and health systems should take steps to reduce air pollution to mitigate this increasing burden.

Background: Colorectal cancer remains a public health problem worldwide. Dietary risk factors play a key role in the carcinogenesis and progression of colorectal cancer. This study aimed to explore the geographical and temporal trends in various dietary factor-related colorectal cancers.Methods: Data were extracted from the Global Burden of Disease (GBD) 2019 study, including the deaths, disability-adjusted life-years (DALYs), age-standardized rate (ASR), and summary exposure value (SEV) among 4 world regions, 11 age groups, 21 regions, and 204 countries and territories between 1990 and 2019. The estimated annual percentage changes (EAPCs) were calculated to evaluate the variation trend of ASR.Results: Dietary factors were the leading cause of colorectal cancer death and DALY rate, regardless of age. Dietary factor-related deaths and DALYs accounted for 32 and 34% of global colorectal cancer, respectively. Further analysis showed that low whole grain intake remained the leading cause of cancer death and DALY rate, followed by milk and calcium. Diets that were low in whole grains, milk, and calcium accounted for 81.61% of deaths and 81.64% of DALYs. Deaths and DALYs of dietary factors related to colorectal cancer grew by half from 1990 to 2019. All ASRs remained higher for men than women. Asia carried the highest colorectal cancer burden attributed to dietary risks, especially for East Asia [age-standardized death rate (ASDR): EAPC = 1.15, 95% CI:0.88–1.42; DALY: EAPC = 1.08, 95% CI:0.82–1.34]. The heavy burden also existed in high-middle and middle socio-demographic index (SDI) quintiles. China has always had the highest deaths and DALYs of colorectal cancer attributable to dietary risks, followed by the USA, India, and Japan.Conclusions: Large variations existed in the dietary risk-related colorectal cancer burdens among sexes, regions, and countries. More targeted interventions to address modifiable dietary risk factors would save 32% of deaths and 34% of DALYs for colorectal cancer.

BackgroundChronic kidney disease (CKD) is a public health problem largely caused by diabetes. The epidemiology of diabetes mellitus–related CKD (CKD-DM) could provide specific support to lessen global, regional, and national CKD burden.MethodsData were derived from the GBD 2019 study, including four measures and age-standardized rates (ASRs). Estimated annual percentage changes and 95% CIs were calculated to evaluate the variation trend of ASRs.ResultsDiabetes caused the majority of new cases and patients with CKD in all regions. All ASRs for type 2 diabetes–related CKD increased over 30 years. Asia and Middle socio-demographic index (SDI) quintile always carried the heaviest burden of CKD-DM. Diabetes type 2 became the second leading cause of CKD and CKD-related death and the third leading cause of CKD-related DALYs in 2019. Type 2 diabetes–related CKD accounted for most of the CKD-DM disease burden. There were 2.62 million incident cases, 134.58 million patients, 405.99 thousand deaths, and 13.09 million disability-adjusted life-years (DALYs) of CKD-DM worldwide in 2019. Age-standardized incidence (ASIR) and prevalence rate (ASPR) of type 1 diabetes–related CKD increased, whereas age-standardized death rate (ASDR) and DALY rate decreased for females and increased for males. In high SDI quintile, ASIR and ASPR of type 1 diabetes–related CKD remained the highest, with the slowest increase, whereas the ASDR and age-standardized DALY rate remained the lowest there. In high SDI quintile, ASIR of type 2 diabetes–related CKD was the highest, with the lowest increasing rate. In addition, type 2 diabetes–related CKD occurred most in people aged 80-plus years worldwide. The main age of type 2 diabetes–related CKD patients was 55–64 years in Asia and Africa. The prevalence, mortality, and DALY rate of type 2 diabetes–related CKD increased with age. As for incidence, there was a peak at 80 years, and after age of 80, the incidence declined. CKD-DM-related anemia was mainly in mild to moderate grade.ConclusionsIncreasing burden of CKD-DM varied among regions and countries. Prevention and treatment measures should be strengthened according to CKD-DM epidemiology, especially in middle SDI quintile and Asia.

Objective: To explore the preferred test to screen for pulmonary arteriovenous malformations (PAVMs) and to predict the probability of interventional embolization.Methods: We performed a retrospective observational study evaluating patients with idiopathic PAVMs from 2009 to 2019. After clinical evaluation, a total of 105 patients were studied, including 71 patients with positive digital subtraction pulmonary angiography (DSPA) findings and 34 with negative DSPA findings. The following patient data were assessed: blood test, chest radiograph, transthoracic contrast echocardiography (TTCE), and DSPA findings.Results: The majority of patients with idiopathic PAVMs were female (66.2% with positive DSPA findings). We found a good κ-coefficient of 0.77 with strong consistency for inter observer agreement concerning the pulmonary right-to-left shunt (RLS) grade on TTCE, which was superior to conventional chest radiographs. The positive predictive value (PPV) of the radiographic features for PAVMs on DSPA was 0.83 (95% CI 0.64–1.0) and 0.44 for the possibility of embolization (95% CI 0.19–0.70). The PPV of the shunt grade of PAVMs on DSPA was 0.14 (95% CI 0.01–0.29) for grade 1, 0.74 (95% CI 0.60–0.88) for grade 2, and 0.97 (95% CI 0.92–1.0) for grade 3. The PPVs of pulmonary shunt grades 2 and 3 on TTCE for the possibility of embolization for PAVMs were 0.21 (95% CI, 0.05–0.36) and 0.87 (95% CI, 0.79–0.99), respectively.Conclusion: TTCE is the preferred screening test for PAVMs. The pulmonary RLS grade on TTCE not only identifies the likelihood of PAVMs but also predicts the probability for embolization.

The relationship between vitamin D and cardiovascular health in children remains unclear. Vitamin D deficiency (VDD) is supposed to be a potential risk factor associated with poorer outcomes after congenital heart disease (CHD) surgery. The maximum vasoactive-inotropic use after cardiac surgery is considered to be a good predictor of adverse outcomes. We aimed to assess the correlation between preoperative VDD and the maximum vasoactive-inotropic score (VISmax) at 24 h postoperatively. Nine hundred children with CHD were enrolled in this study, and preoperative total serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured by liquid chromatography-tandem mass spectrometry. Related demographic and clinical characteristics were collected. A total of 490 boys (54.4%) and 410 girls (45.6%) with a mean age of 1 year (range: 6 months-3 years) were enrolled. The median 25(OH)D level was 24.0 ng/mL, with 32.6% of patients having VDD [25(OH)D < 20 ng/mL]. The univariate analysis indicated that VDD [odds ratio (OR): 2.27; 95% confidence interval (CI): 1.48–3.50] is associated with a risk of increased VISmax at 24 h postoperation. Multivariate analysis revealed that VDD (OR: 1.85; 95% CI: 1.09–3.02), a Risk-adjusted Congenital Heart Surgery score of at least three points (OR: 1.55; 95% CI: 1.09–2.19), and cardiopulmonary bypass time (OR: 1.02; 95% CI: 1.01–1.02) were independently associated with an increased VISmax within 24 h after cardiac surgery. VDD in pediatric patients before cardiac surgery is associated with the need for increased postoperative inotropic support at 24 h postoperation.

Abstract Background Hodgkin lymphoma (HL) is an uncommon B cell lymphoma. We assessed the global, regional, and national burden of HL from 1990 to 2017, by gender, age, and social-demographic index (SDI). Methods Data on HL, including incidence, mortality, and disability adjusted life-years (DALY), from 1990 to 2017 were obtained from the 2017 Global Burden of Disease study. Estimated annual percentage changes (EAPCs) were calculated to assess incidence rate, mortality, and DALY trends. Results HL incidences increased by 38.66%, from 72,937 in 1990 to 101,133 in 2017, while the age-standardized incidence rate (ASIR) was relatively stable. ASIR decreased in the low SDI regions (EAPC = − 2.58; 95% CI, from − 2.66 to − 2.49) and was stable in the other four SDI regions. Incidence showed a bimodal distribution with peak values in patients aged 20–39 years and patients aged 60 years or higher. The number of death cases and DALYs were stable. The age-standardized death rate decreased by 2.36% (95% CI, from − 2.43% to − 2.30%) per year. The annual age-standardized DALY rate decreased by 2.29% (95% CI, from − 2.36% to − 2.21%). The incidence and mortality in male subjects was higher than that in female subjects. The incidence in male and female subjects aged 15–30 years old was close, whereas the biggest difference existed in patients aged

Abstract Introduction It remains unclear whether marital status could affect the breast cancer‐caused special survival (BCSS) of patients with breast cancer. Therefore, we sought to explore the influence of demographic and pathological factors on prognosis of patients with breast cancer. Materials and methods We selected patients meeting the eligibility criteria from the Surveillance, Epidemiology, and End Results (SEER) cancer registry program. We assessed the effect of marital status on overall survival (OS) and BCSS using Kaplan‐Meier curve and multivariate Cox proportional hazards regression. Results Compared with divorced/separated/widowed (DSW) patients, the married (AHR 0.7483, 95% CI: 0.729‐0.7682, P

Abstract Background MicroRNA-139-5p (miR-139) has been shown to play important roles in hepatocellular carcinoma (HCC) development. However, the exact mechanism of miR-139 in HCC remains largely unknown. Methods We investigated the function in human cell lines and patient tissue samples by experimental techniques in molecular biology including Co-IP assay, cell viability assay, quantitative real-time-PCR, et al. In addition, datasets were used to verify the results by database analysis. Statistical analysis was performed by using the GraphPad Prism 6 (GraphPad Software Inc., USA). A P value

Abstract Background It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC. Methods We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0). Results The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18–1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23–1.66) increased the risk of HCC. And GSTM1–GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22–2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22–1.71), GSTT1 null OR = 1.48, 95% CI = (1.25–1.77), GSTM1–GSTT1 null OR = 1.58, 95% CI = (1.19–2.09), while we didn’t obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1–GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null. Conclusions Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1–GSTM1 dual-null genotypes is more likely to develop HCC.

Sorafenib (SOR) is a multi-kinase inhibitor that was approved as the first-line systematic treatment agent of hepatocellular carcinoma (HCC). However, the anti-cancerous effect of SOR is dramatically impaired by the drug resistance, insufficient accumulation at tumor tissues, and limited tumor inner penetration. To combat the above issues, the PLA-based nanoparticles were first fabricated and co-loaded with SOR and plantamajoside (PMS), natural herbal medicines that possess excellent anti-cancerous effect on many types of drug resistant cancers. Then, the polypeptide CT, which is tumor-homing and cell membrane penetrable, was further decorated on the dual-agents loaded nanoparticles (CTNP-PMS/SOR) to enhance tumor accumulation of drugs. Importantly, the CT peptide is a conjugate derived from the covalent conjugation of CVNHPAFAC peptide, a tumor-homing peptide, on the fourth lysine of TAT, namely cell membrane penetrating peptide, through a pH-sensitive hydrazone bond. By this way, the cell penetrating ability of TAT was dramatically sealed under the normal condition and immediately recovered once the nanoparticles reached tumor sites. Both in vivo and in vitro experiments demonstrated that the anti-cancerous effect of SOR on malignant HCC was significantly enhanced after co-loaded with PMS. Mechanisms studies revealed that the PMS is capable of reprograming the tumor hypoxic microenvironment, which represents the main cause of drug-resistance of tumor cells. Besides, functionalization of the NP-PMS/SOR with CT peptides signally improved the accumulation of drugs at tumor sites and penetration of agents into tumor cells, which in turn resulted in stronger capacity of tumor growth inhibition.

Abstract Background Estrogen exposure is a widely known risk factor for BC. And the interaction of estrogen with estrogen receptor (ER) plays an important role in breast cancer development. This case–control study aims to assess the association of genetic polymorphisms in the estrogen receptor genes with breast cancer (BC) susceptibility in Chinese Han women. Methods Four polymorphisms (rs2881766, rs9383951, rs9340799 in ESR1 and rs3020449 in ESR2) were genotyped in 459 patients and 549 healthy controls using the Sequenom MassARRAY method. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the associations. False-positive report probability (FPRP) was utilized to examine the noteworthiness of significant findings. Results We observed that rs2881766 was associated with a decreased BC risk (GG vs. TT: OR = 0.63, 95% CI = 0.44–0.91; GG vs. TT/GT: OR = 0.68, 95% CI = 0.49–0.95), while rs3020449 was associated with an increased risk of BC (CT vs. TT: OR = 1.58, 95% CI = 1.21–2.06; CT/CC vs. TT: OR = 1.54, 95% CI = 1.20–1.98; TT/CC vs. CT: OR = 1.48, 95% CI = 1.15–1.90). The other two polymorphisms have no relation with BC susceptibility. In addition, rs2881766 was correlated with lymph node metastasis and ER expression, and rs3020449 was related to tumor size, histological grade and ER expression. The values of false-positive report probability indicated that the significant associations of BC risk with both rs2881766 and rs3020449 were noteworthy. Conclusions Our study suggests that polymorphisms rs2881766 and rs3020449 in estrogen receptor genes were associated with BC susceptibility as well as clinical features in Chinese women. These findings need further validation in a large population.

Motor neuron and pancreas homeobox 1 (MNX1) is a key developmental gene. Previous studies found that it was upregulated in several tumors, but its role in breast cancer (BC) remains unclear. In order to have a better understanding of this gene in BC, we examined the expression of MNX1 in BC tissues and normal breast tissues by qRT-PCR and by analyzing data from The Cancer Genome Atlas (TCGA) database. We also assessed the association of MNX1 expression with BC clinicopathological features and investigated the impact of MNX1 on BC survival. Potential molecular function of MNX1 was predicted through protein-protein interactions and functional enrichment. The results showed that the expression of MNX1 was significantly increased in BC tissues, especially in the HER2-positive subtype, and MNX1 expression was associated with several clinical characteristics, including menopause status, receptor status, subtypes, tumor size, lymph node metastasis, and race. In addition, patients with higher MNX1 expression had poorer survival. Enrichment analysis suggested that MNX1 is probably involved in biological processes and pathways related to nuclear division, cell cycle, and p53 signaling. In conclusion, our study suggests that MNX1 may act as a tumor promoter in BC. We hope these findings will draw more attention to MNX1 in future cancer studies. Keywords: motor neuron and pancreas homeobox 1, MNX1, breast cancer, clinical, expression, prognosis

Background: The prevalence rate of hypertension and breast cancer increases with advancing age. Renin-angiotensin system inhibitors (RASIs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics are widely used to treat patients with hypertension. Although, the association between the use of antihypertensive medication and breast cancer has been highly debated, recent evidence supporting this association remains controversial.Objective: To evaluate the association between the use of antihypertensive medication and the risk of breast cancer and its prognosis.Methods: This study was conducted using data from the PubMed, Embase, and Cochrane Library databases retrieved for the period from January 2000 to April 2021. Articles and their references were checked and summary effects were calculated using random- and fixed-effects models. Heterogeneity test and sensitivity analysis were also performed.Results: This meta-analysis included 57 articles, which were all related to breast cancer risk or prognosis. Assessment of breast cancer risk using the pooled data showed that the use of BBs or CCBs or diuretics was associated with increased cancer risk [BB: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.09–1.32; CCBs: RR = 1.06, 95% CI 1.03–1.08; diuretics: RR = 1.06, 95% CI 1.01–1.11]. Long-term use of diuretic increased the risk of breast cancer (RR = 1.10, 95% CI 1.01–1.20), whereas long-term RASIs treatment reduced the risk (RR = 0.78, 95% CI 0.68–0.91). In addition, we found that diuretic users may be related to elevated breast cancer-specific mortality [hazard ratio (HR) = 1.18, 95% CI 1.04–1.33], whereas using other antihypertensive medications was not associated with this prognosis in patients with breast cancer.Conclusion: Using CCBs, BBs, and diuretics increased the risk of breast cancer. In addition, diuretics may elevate the risk of breast cancer-specific mortality. The long-term use of RASIs was associated with a significantly lower breast cancer risk, compared with non-users. Thus, this analysis provides evidence to support the benefits of the routine use of RASIs in patients with hypertension, which has important public health implications.

To identify a glycolysis-related gene signature for the evaluation of prognosis in patients with breast cancer, we analyzed the data of a training set from TCGA database and four validation cohorts from the GEO and ICGC databases which included 1,632 patients with breast cancer. We conducted GSEA, univariate Cox regression, LASSO, and multiple Cox regression analysis. Finally, an 11-gene signature related to glycolysis for predicting survival in patients with breast cancer was developed. And Kaplan–Meier analysis and ROC analyses suggested that the signature showed a good prognostic ability for BC in the TCGA, ICGC, and GEO datasets. The analyses of univariate Cox regression and multivariate Cox regression revealed that it’s an important prognostic factor independent of multiple clinical features. Moreover, a prognostic nomogram, combining the gene signature and clinical characteristics of patients, was constructed. These findings provide insights into the identification of breast cancer patients with a poor prognosis.

The content of soil water affects the physiological activities of vegetation, and the type of vegetation also affects the soil water balance. It is of great significance to study the response of vegetation to soil moisture change, which is helpful for understanding the vulnerability of vegetation for regional and environmental protections. The response of vegetation to soil moisture in Guangdong Province from mid-October 2015 to the end of March 2017 was studied by using cloudy region drought index (CRDI) as the drought index and volumetric soil water content (VSWC) as the soil moisture index to measure the level of water stress on vegetation. Taking the peak and valley positions of CRDI and VSWC as characteristic points, the lag time of vegetation to volumetric soil water content was obtained by judging the difference between the peak and valley positions of the two indexes. The results indicate that the response of vegetation to volumetric soil water content in Guangdong lagged 3.33 periods (9–35 days) on average. When VSWC is sufficient, there is no obvious difference in time-lag between different types of vegetation. However, when VSWC is relatively insufficient, grass shows the fastest response to the change of volumetric soil water content. Both longitude and soil moisture affect the lag time of vegetation. Under the same conditions, the higher the soil humidity is, the longer the lag time is, and the longer the delay time is with the greater longitude. CRDI can reflect the time-lag effect between vegetation and VSWC in Guangdong, indicating it is a sensitive and applicable index for characterizing the time-lag phenomena of vegetation to soil moisture.

Immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma and non-small cell lung cancer. However, many patients with breast cancer (BC) show low response to ICIs due to the paucity of infiltrating immune cells. Pseudogenes, as a particular kind of long-chain noncoding RNA, play vital roles in tumorigenesis, but their potential roles in tumor immunology remain unclear. In this study that used data from online databases, the novel pseudogene HLA-DPB2 and its parental gene HLA-DPB1 were overexpressed and correlated with better prognosis in BC. Mechanistically, our results revealed that HLA-DPB2 might serve as an endogenous RNA to increase HLA-DPB1 expression by competitively binding with has-miR-370-3p. Functionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the HLA-DPB2/HLA-DPB1 axis was strongly relevant to immune-related biological functions. Further analysis demonstrated that high expression levels of the HLA-DPB2 and HLA-DPB1 were significantly associated with high immune infiltration abundance of CD8+ T cells, CD4+ T cells, Tfh, Th1, and NK cells and with high expression of majority biomarkers of monocytes, NK cell, T cell, CD8+ T cell, and Th1 in BC and its subtype, indicating that HLA-DPB2 can increase the abundance of tumor-infiltrating lymphocytes in the BC microenvironment. Also, the HLA-DPB2 and HLA-DPB1 expression levels positively correlated with the expression levels of programmed cell death protein 1, programmed cell death ligand 1, and cytotoxic T-lymphocyte-associated antigen-4. Our findings suggest that pseudogene HLA-DPB2 can upregulate HLA-DPB1 through sponging has-miR-370-3p, thus exerting its antitumor effect by recruiting tumor-infiltrating immune cells into the breast tumor microenvironment, and that targeting the HLA-DPB2/HLA-DPB1 axis with ICIs may optimize the current immunotherapy for BC.

Abstract Background Conventional echocardiography is not sensitive enough to assess left ventricular (LV) dysfunction in hypertrophic cardiomyopathy (HCM) patients. This research attempts to find a new ultrasonic technology to better assess LV diastolic function, systolic function, and myocardial longitudinal and circumferential systolic strain of segments with different thicknesses in HCM patients. Methods This study included 50 patients with HCM and 40 healthy subjects as controls. The peak early and late mitral annulus diastolic velocities at six loci (Ea′ and Aa′, respectively) and the Ea′/Aa′ ratio were measured using real-time tri-plane echocardiography and quantitative tissue velocity imaging (RT-3PE-QTVI). The mean value of Ea′ at six loci (Em′) was obtained for the calculation of E/Em′ ratio. The LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), and LV ejection fraction (LVEF) were measured using real-time three-dimensional echocardiography (RT-3DE). LV myocardial longitudinal peak systolic strain (LPSS) and circumferential peak systolic strain (CPSS) in the apical-middle-basal segments (LPSS-api, LPSS-mid, LPSS-bas; CPSS-api, CPSS-mid, and CPSS-bas, respectively) were obtained using a software for two-dimensional speckle tracking imaging (2D-STI). According to the different segmental thicknesses (STs) in each HCM patient, the values (LPSS and CPSS) of all the myocardial segments were categorized into three groups and the respective averages were computed. Results The Ea′, Aa′, and, Ea′/Aa’ ratio in HCM patients were lower than those in the controls (all p

Cervical cancer (CC) is a leading cause of cancer-related death in women. Limited studies have investigated whether immune-related genes (IRGs) or tumor immune microenvironment (TIME) could be indicators for CC prognoses. The aim of this study was to develop an improved prognostic signature for CC based on IRGs or TIME to predict survival and response to immune checkpoint inhibitors (ICIs). A prognostic signature was constructed using bioinformatics method and its predictive capability was validated. The mechanisms underlying the signature’s predictive capability were explored with CIBERSORT algorithm and mutation analysis. Immunophenoscore (IPS) is validated for ICIs response, and was therefore explored in relation to the signature. A prognostic signature based on 11 IRGs was developed. A multivariate analysis revealed that the 11-IRG signature was an independent prognostic factor for overall survival (OS) and progression-free interval in CC patients. In the 11-IRG signature high-risk group, CD8 T cells and resting mast cells, which are found to associate with better OS in our study, were lower; activated mast cells, associated with poorer OS, were higher, compared with the low-risk group. An IPS analysis suggested that the 11-IRG signature low-risk group, which possessed a higher IPS, represented a more immunogenic phenotype that was more inclined to respond to ICIs. In short, an 11-IRG prognostic signature for predicting CC patients’ survival and response to ICIs was firmly established. The predictive capability of this model in CC requires further testing with the goal of better prognostic stratification and treatment management.

Abstract Background Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and lack of targets for therapy. This study aimed to explore the expression profile and potential function of lncRNAs in TNBC through bioinformatic methods. Methods Two microarrays of TNBC were obtained from the Gene Expression Omnibus database. Differentially expressed lncRNAs and mRNAs were screened out and the expressions of top lncRNAs and overlapping lncRNAs were validated using data from The Cancer Genome Atlas database. The co-expression analysis of lncRNAs and mRNAs was conducted using R software and functional enrichment analysis for was performed by Metascape. Kaplan–Meier Plotter was used for survival analysis. Results A total of 1034 dysregulated lncRNAs were found in the two microarrays, and there were 8 overlapped lncRNAs. Among them, 537 lncRNAs were significantly correlated with 451 protein-coding genes (PCGs). The co-expressed PCGs were mainly enriched in terms including cell division, cell cycle, and protein/DNA binding, and were involved in pathways in cancer and other pathways such as PI3K-Akt, MAPK, ErbB and p53 signaling pathways. Hub-genes in the co-expression network were identified, and 7 of them were associated with relapse-free survival of TNBC (MAGI2-AS3: HR = 0.51; GGTA1P: HR = 0.54; NAP1L2: HR = 0.59; CRABP2: HR = 0.41; SYNPO2: HR = 0.50; MKI67: HR = 2.23; COL4A6: HR = 1.91; all P

Background: Hexavalent chromium [Cr(VI)] is an occupational carcinogen that can cause lung and nasal cancers, but its association with mortality and incidence in many other cancers is unclear.Objectives: In this meta-analysis, we aimed to evaluate the relationship between exposure to Cr(VI) and the mortality and incidence of human cancers.Methods: We performed a search of the literature and extracted the standardized mortality ratios (SMRs), standardized incidence ratios (SIRs), and their corresponding 95% confidence intervals (CIs), to estimate risk values. Subgroup analyses were conducted by sex, occupation, and types of cancer to identify groups that were at high-risk or predisposed to certain cancers.Results: A total of 47 cohort studies covering the period 1985–2016 were included (37 studies reporting SMRs and 16 studies reporting SIRs). The summary SMR for all studies combined was 1.07 (95% CI: 1.01–1.15). Summary SMRs were higher among chromate production workers, chrome platers, and masons, and especially male workers. In the subgroup analysis, Cr(VI) exposure was related to a higher risk of death owing to lung, larynx, bladder, kidney, testicular, bone, and thyroid cancer. The meta-SIR of all studies combined was 1.06 (95% CI: 1.04–1.09). Summary SIRs were elevated among cement industry workers and tanners. Cr(VI) exposure was related to an elevated risk of respiratory system, buccal cavity, pharynx, prostate, and stomach cancers.Conclusions: Cr(VI) might cause cancers of the respiratory system, buccal cavity and pharynx, prostate, and stomach in humans, and it is related to increased risk of overall mortality owing to lung, larynx, bladder, kidney, testicular, bone, and thyroid cancer. In addition, there was a strong association between incidence and mortality risk of cancers and concentration of Cr(VI) in the air and the exposure time.

Accurate spatial information about irrigation is crucial to a variety of applications, such as water resources management, water exchange between the land surface and atmosphere, climate change, hydrological cycle, food security, and agricultural planning. Our study proposes a new method for extracting cropland irrigation information using statistical data, mean annual precipitation and Moderate Resolution Imaging Spectroradiometer (MODIS) land cover type data and surface reflectance data. The approach is based on comparing the land surface water index (LSWI) of cropland pixels to that of adjacent forest pixels with similar normalized difference vegetation index (NDVI). In our study, we validated the approach over mainland China with 612 reference samples (231 irrigated and 381 non-irrigated) and found the accuracy of 62.09%. Validation with statistical data also showed that our method explained 86.67 and 58.87% of the spatial variation in irrigated area at the provincial and prefecture levels, respectively. We further compared our new map to existing datasets of FAO/UF, IWMI, Zhu and statistical data, and found a good agreement with the irrigated area distribution from Zhu’s dataset. Results show that our method is an effective method apply to mapping irrigated regions and monitoring their yearly changes. Because the method does not depend on training samples, it can be easily repeated to other regions.

Air pollution in the form of PM _2.5 decreases life expectancy considering its contribution to morbidity and mortality. Therefore, scientific and accurate PM _2.5 exposure risk assessment is essential. However, the considering daily/hourly mean PM _2.5 concentration and overlooking population mobility in exposure risk assessments result in underestimation of its adverse effects. Thus, using social media data and exceedance PM _2.5 concentration, two novel indicators named hourly exceedance PM _2.5 exposure (HEPE) and daily cumulative variation of exceedance PM _2.5 exposure (DCEPE) are developed in our study. Spatiotemporal variation analysis of HEPE showed that the first exceedance PM _2.5 exposure risk was observed at 10:00; this lasted till the end of the day. According to the standard deviation ellipse (SDE) method analysis results, at first, the major spatial tendency direction was northeast-southwest, with the average center (AE) located in the Yuangang Township. Then, the HEPE in the western study area increased dramatically. The major spatial tendency direction shifted from northeast-southwest to east-west. Consequently, the AE of HEPE shifted to central study area. The spatiotemporal variation characteristics led us to investigate the mechanisms. A bivariate LISA was applied to detect the spatial association between DCEPE and city functional zones (CFZs). Results showed that highly spatial associations were found between the DCEPE and CFZs in the southwest of the study area. Residential neighborhoods and transportation services showed a closer relationship with the spatial distribution of DCEPE. Based on these results, we found increasing public health threats posed by PM _2.5 . Thus, HEPE is an essential factor to assess air pollution exposure risk. Moreover, more attention should be paid to the spatial association between DCEPE and city functions, which is important for the development of air pollution mitigation strategies.