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Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular processes, including development and stress response. Many lincRNAs have been bioinformatically identified in plants, but their evolutionary dynamics and expression characteristics are still elusive. Here, we systematically identified thousands of lincRNAs in 26 plant species, including 6 non-flowering plants, investigated the conservation of the identified lincRNAs in different levels of plant lineages based on sequence and/or synteny homology and explored characteristics of the conserved lincRNAs during plant evolution and their co-expression relationship with protein-coding genes (PCGs). In addition to confirmation of the features well documented in literature for lincRNAs, such as species-specific, fewer exons, tissue-specific expression patterns and less abundantly expressed, we revealed that histone modification signals and/or binding sites of transcription factors were enriched in the conserved lincRNAs, implying their biological functionalities, as demonstrated by identifying conserved lincRNAs related to flower development in both the Brassicaceae and grass families and ancient lincRNAs potentially functioning in meristem development of non-flowering plants. Compared to PCGs, lincRNAs are more likely to be associated with transposable elements (TEs), but with different characteristics in different evolutionary lineages, for instance, the types of TEs and the variable level of association in lincRNAs with different conservativeness. Together, these results provide a comprehensive view on the evolutionary landscape of plant lincRNAs and shed new insights on the conservation and functionality of plant lincRNAs.

Post-operative bleeding after total knee arthroplasty (TKA) is a frequent cause of post-operative complications. This study compared blood loss and indicators of coagulation and fibrinolysis between TKA patients living at low or high altitudes.We retrospectively analyzed 120 patients at our institution who underwent primary TKA from May 2019 to March 2020, and we divided them into those living in areas about 500 m or 3000 m above sea level. We compared the primary outcome of total blood loss between them. We also compared them in terms of several secondary outcomes: coagulation and fibrinolysis parameters, platelet count, reduction in hemoglobin, hidden blood loss, intra-operative blood loss, transfusion rate, and incidence of thromboembolic events and other complications.Total blood loss was significantly higher in the high-altitude group than in the low-altitude group (mean, 748.2 mL [95% CI, 658.5-837.9] vs 556.6 mL [95% CI, 496.0-617.1]; p = 0.001). The high-altitude group also showed significantly longer activated partial thromboplastin time, prothrombin time, and thrombin time before surgery and on post-operative day one, as well as increased levels of fibrinogen/fibrin degradation product on post-operative days one and three. Ecchymosis was significantly more frequent in the high-altitude group (41.7 vs 21.7%; relative risk (RR) = 1.923 [95% CI, 1.091-3.389]; p = 0.019). The two groups showed similar transfusion rates, and none of the patients experienced venous thromboembolism, pulmonary embolism, or infection.High altitude may alter coagulation and fibrinolysis parameters in a way that increases risk of blood loss after TKA. Such patients may benefit from special management to avoid bleeding events.

Antibodies are important immune molecules that are elicited by B cells to protect our bodies during viral infections or vaccinations. In humans, the antibody repertoire is diversified by programmed DNA lesion processes to ensure specific and high affinity binding to various antigens. Broadly neutralizing antibodies (bnAbs) are antibodies that have strong neutralizing activities against different variants of a virus. bnAbs such as anti-HIV bnAbs often have special characteristics including insertions and deletions, long complementarity determining region 3 (CDR3), and high frequencies of mutations, often at improbable sites of the variable regions. These unique features are rare mutational outcomes that are acquired during antibody diversification processes. In this review, we will discuss possible mechanisms that generate these rare antibody mutational outcomes. The understanding of the mechanisms that generate these rare mutational outcomes during antibody diversification will have implications in vaccine design strategies to elicit bnAbs.

The phosphatidylinositol 3-kinase-Akt signaling pathway plays an essential role in regulating cell proliferation and apoptosis. Akt kinase is at the center of this signaling pathway and interacts with a variety of proteins. Akt is overexpressed in almost 80% of tumors. However, inhibiting Akt has serious clinical side effects so is not a suitable treatment for cancer. During recent years, Akt scaffold proteins have received increasing attention for their ability to regulate Akt signaling and have emerged as potential targets for cancer therapy. In this paper, we categorize Akt kinase scaffold proteins into four groups based on their cellular location: membrane-bound activator and inhibitor, cytoplasm, and endosome. We describe how these scaffolds interact with Akt kinase, how they affect Akt activity, and how they regulate the specificity of Akt signaling. We also discuss the clinical application of Akt scaffold proteins as targets for cancer therapy.

Considered as an autoimmune disease, rheumatoid arthritis (RA) is an chronic inflammatory disorder that causes inflammation of the joints. This study is performed with the aim to clarify the expression of phospholipase D1 (PLD1) in RA and its specific regulation role of RA as well as the underlying mechanisms. In this study, synovial tissue samples were collected from RA patients, and RA-fibroblast-like synoviocytes (FLSs) were subsequently isolated. The expression levels of PLD1 and pathway-related proteins were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting or immunohistochemistry (IHC). Upon shPLD1 treatment, cell viability, proliferation, migration, invasion, and the level of inflammation-related factors were measured by Cell Counting Kit-8 (CCK-8), Edu, wound healing, Transwell and enzyme-linked immunosorbent assay (ELISA). Furthermore, C-reactive protein (CRP), rheumatoid factor (RF), arthritis score and synovial tissue lesions were assessed by collecting the blood or tissues from collagen induced arthritis (CIA) model rats. Our results showed that PLD1 level was increased in RA synovial tissues. Cell viability, proliferation, migration, invasion, and the level of inflammatory factors were reduced upon PLD1 knockdown in RA-FLSs. Moreover, p-IκBα/IκBα, β-catenin, p-IKKβ/IKKβ and TCF-4 were inhibited under PLD1 knockdown treatment. PLD1 knockdown alleviated the collagen-induced addition of arthritis score, CRP and RF, as well as the filling of inflammatory cells and proliferation of synovium in CIA model rat. To sum up, knockdown of PLD1 could reduce RA-FLSs metastasis as well as inflammatory response by modulating the activity of NF-κB and Wnt/β-catenin pathways.

The hepatitis B virus X (HBx) protein plays a critical role in the initiation and progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). In the early stage of the disease, HBx facilitates tumor onset by inactivating the tumor suppressor p53. The p53-encoding gene, however, is frequently mutated or deleted as the cancer progresses to the late stage and, under such circumstance, the p53 homolog TAp63 can harness HCC growth by transactivating several important p53-target genes.To determine whether HBx regulates TAp63, we performed co-immunoprecipitation assay, real-time quantitative polymerase chain reaction, immunoblotting, and flow cytometry analysis in p53-null cancer cell lines, Hep3B and H1299.HBx interacts with the transactivation domain of TAp63, as HBx was co-immunoprecipitated with TAp63 but not with ΔNp63. The interaction between HBx and TAp63 abolished transcriptional activity of TAp63, as evidenced by the reduction of the levels of its target genes p21 and PUMA , consequently leading to restricted apoptosis and augmented proliferation of HCC cells.HBV induces progression of HCC that harbors defective p53 by inhibiting the tumor suppressor TAp63.

Glaucoma is characterized by the progressive loss of retinal ganglion cells (RGCs), although the pathogenic mechanism remains largely unknown. To study the mechanism and assess RGC degradation, mouse models are often used to simulate human glaucoma and specific markers are used to label and quantify RGCs. However, manually counting RGCs is time-consuming and prone to distortion due to subjective bias. Furthermore, semi-automated counting methods can produce significant differences due to different parameters, thereby failing objective evaluation. Here, to improve counting accuracy and efficiency, we developed an automated algorithm based on the improved YOLOv5 model, which uses five channels instead of one, with a squeeze-and-excitation block added. The complete number of RGCs in an intact mouse retina was obtained by dividing the retina into small overlapping areas and counting, and then merging the divided areas using a non-maximum suppression algorithm. The automated quantification results showed very strong correlation (mean Pearson correlation coefficient of 0.993) with manual counting. Importantly, the model achieved an average precision of 0.981. Furthermore, the graphics processing unit (GPU) calculation time for each retina was less than 1 min. The developed software has been uploaded online as a free and convenient tool for studies using mouse models of glaucoma, which should help elucidate disease pathogenesis and potential therapeutics.青光眼是一种特征为视网膜神经节细胞（RGC）持续性丢失的疾病，其发病机制尚不明确。为了研究青光眼的发病机制并评估RGC的减少过程，通常使用小鼠模型来模拟人类青光眼，并使用特定标记物标记量化RGC的数量。人工手动计算RGC数量的方式非常耗时，并且很容易收到主观偏见的影响。半自动计数的方式会因为参数设置不同而导致结果存在较大的差异，这不符合客观计算的要求。为了提高计数的准确性和效率，该文提出了一种基于改进YOLOv5的全自动计数算法，该算法使用五通道代替单个通道，并添加注意力机制提高计数精度。在整个小鼠视网膜RGC数量的计算过程中，先通过将视网膜分割成小的部分重叠区域并单独计数，然后使用非最大抑制算法将所有分割区域计算结果汇总在一起得到最终个数。自动计数结果显示，该文的算法与手动计数结果有很强的相关性（平均皮尔逊相关系数约等于0.993），而且模型的平均精准度AP达到了0.981。此外，每个小鼠视网膜在GPU下的计算时间少于一分钟，全自动计数的软件已经在网上开源供大家免费使用，它将为使用小鼠模型进行青光眼研究的研究人员提供一个方便的工具，以了解青光眼的发病机制并开发潜在的治疗药物。.

Approximately 80% of human pancreatic ductal adenocarcinomas (PDAC) harbor TP53 mutations, among which, R273H is the most frequent. Although p53-R273H is known to possess gain-of-function properties, how it is regulated in PDAC has not been extensively explored. Here we identify valosin-containing protein (VCP) as a regulator of p53-R273H by conducting immunoprecipitation-tandem mass spectrometry analysis. VCP bound p53-R273H at its DNA binding domain. Ectopic or endogenous VCP stabilized p53-R273H by binding to MDM2 and disrupting its association with mutant p53. Inhibition of VCP either by genetic depletion or the pharmacologic inhibitor CB-5083 increased ubiquitination and degradation of p53-R273H, leading to cell death. Consistently, ablation of VCP markedly retarded growth of cultured PDAC cells and xenograft PDAC tumors. Together, these results unveil VCP as a novel partner of p53-R273H in promoting PDAC growth and as a potential target for developing anti-PDAC therapy. Significance: These findings identify valosin-containing protein (VCP) as a novel regulator of p53-R273H stability and suggest VCP as a potential target for development of pancreatic cancer therapy.

Purpose To compare the changes in subfoveal choroidal thickness (SFChT) in myopic children treated with 0.01% atropine, orthokeratology (OK), or their combination in myopic children, and to study the connection between increase in SFChT and axial length (AL) elongation. Methods This is a prospective, randomized, controlled study. A total of 67 children were included; 22 patients were randomly assigned to the SA group (patients with spectacles and 0.01% atropine), 24 patients were randomly assigned to the OK group (OK), and 21 patients were randomly assigned to the OKA group (OK and 0.01% atropine). Comprehensive ophthalmologic examinations were performed at baseline, 1 month, 6 months, and 12 months. Results After 1 month, SFChT increased by 5.41 ± 1.65 μm in the SA group, 17.46 ± 2.79 μm in the OK group, and 20.19 ± 2.18 μm in the OKA group (P = 0.00), whereas AL was not significantly increased. After 12 months, the changes of SFChT were not increased significantly compared with that at 1 month; AL increased by 0.20 ± 0.03 mm in the SA group, 0.28 ± 0.03 mm in the OK group, and 0.14 ± 0.03 mm in the OKA group (P = 0.00). The change in SFChT at 12 month was negatively correlated with the change in AL at 12 months. Conclusion The control of AL elongation was better in SA group than OK group. The increase in SFChT was best in OKA group, followed by OK group, and the changes were significant after only 1 month. In addition, the increase in SFChT may influence AL elongation and myopia progression.

By retrospective study of the epidemiological characteristics of sports-related sudden death (SrSD), the risk factors associated with SrSD were analyzed and explored to provide a scientific basis for comprehensive prevention and treatment of SrSD.The personal information (sex, age, occupation, etc.), case information (time, place, type of sports, relative time between SrSD occurrence and exercise, etc.), death related information (sign or prodrome, medical history and surgical history, etc.), rescue situation (witnesses, on-site assistance, the availability of paramedics, etc.) of 374 SrSD cases in Guangdong Province from 2017 to 2021 were collected. Statistical analysis was conducted aiming at the key factors.In the 374 cases, there were significantly more males than females (19.78:1); the number of people aged between39 and 59 was the largest (151, 40.37%); non-manual workers (68.98%) were more than manual workers; the top three sports with the highest number cases were basketball (34.49%), running (19.52%) and badminton (12.03%); from 3 pm to 9 pm (63.10%) was the time period with the highest incidence of events; sudden death mainly occurred during exercise (75.27%) and within 1 h after exercise (20.05%); the on-site rescue rate was very low (6.15%); the rate of autopsies was extremely low (1.07%); sudden cardiac death was the most common cause (67.11%).SrSD is most common in males aged39 to 59 years old, mostly in non-manual workers, and usually occurs in basketball and running. Sudden death is more likely to occur during exercise and within 1 h after exercise. Therefore, the above potential risk factors should be focused on and studied in daily comprehensive prevention and treatment to provide scientific basis for accurate prevention and first aid of such sudden death.

To study the phenomenon of pulmonary hypostasis in corpses of various causes of death, and to explore the potential value of this phenomenon in assisting forensic pathological diagnosis of drowning.A total of 235 cases with clear cause of death through systematic autopsy were collected from January 2011 to June 2021 in Guangzhou. According to the location of body discovery, the cases were divided into the water body group (97 cases) and the nonThe detection rate of pulmonary hypostasis in the water drowning group (90 cases) was 0, and the negative rate was 100%. The detection rate of pulmonary hypostasis in the water nonThe disappearance of pulmonary hypostasis can be used as a specific cadaveric sign to assist in the forensic pathological diagnosis of drowning.

Antibiotic resistance is the most important factor leading to failed Helicobacter pylori eradication therapy, and personalized treatment based on antibiotic susceptibility is becoming increasingly important. To strengthen the understanding of antibiotic genotypic resistance of H. pylori and identify new antibiotic resistance loci, in this study, we identified phenotypic resistance information for 60 clinical isolates and compared the concordance of phenotypic and genotypic resistance using whole-genome sequencing (WGS). Clarithromycin and levofloxacin genotypic resistance was in almost perfect concordance with phenotypic resistance, with kappa coefficients of 0.867 and 0.833, respectively. All strains with the R16H/C mutation and truncation in

The C-terminal of G protein-coupled receptors is now recognized as being important for G protein activation and signaling function. To detect the role of C-terminal tail in receptor activation, we used the α1b-AR, which has a long C-terminal of 164 amino acids. We constructed the intramolecular FRET sensors, in which the C-terminal was truncated to 10 (∆C-10), 20 (∆C-20), 30 (∆C-30), 50 (∆C-50), 70 (∆C-70), or 90 (∆C-90). The truncated mutants of ∆C-10, ∆C-20, or ∆C-30 cannot induce FRET signal changes and downstream ERK1/2 phosphorylation. However, the truncated mutants of ∆C-50, ∆C-70, or ∆C-90 induce significant FRET signal changes and downstream ERK1/2 phosphorylation, especially ∆C-90. This is particularly true in the case of the ∆C-90, ∆C-70, or ∆C-50 which retained the potential phosphorylation sites (Ser401, Ser404, Ser408, or Ser410). The ∆C-90 showed an increase in agonist-induced FRET signal changes and ERK1/2 phosphorylation in PKC- or endocytosis-dependent and EGFR-, src-, or β-arrestin2-independent.

Purpose: To compare the clinical efficacies of 0.01% atropine and orthokeratology (OK) in slowing the development of myopia, and to evaluate their effects on basal tear secretion and tear film stab...

B-cell CLL/lymphoma 7 protein family member C (BCL7C) located at chromosome 16p11.2 shares partial sequence homology with the other two family members, BCL7A and BCL7B. Its role in cancer remains completely unknown. Here, we report our finding of its tumor-suppressive role in ovarian cancer. Supporting this is that BCL7C is downregulated in human ovarian carcinomas, and its underexpression is associated with unfavorable prognosis of ovarian cancer as well as some other types of human cancers. Also, ectopic BCL7C restrains cell proliferation and invasion of ovarian cancer cells. Consistently, depletion of BCL7C reduces apoptosis and promotes cell proliferation and invasion of these cancer cells. Mechanistically, BCL7C suppresses mutant p53-mediated gene transcription by binding to mutant p53, while knockdown of BCL7C enhances the expression of mutant p53 target genes in ovarian cancer cells. Primary ovarian carcinomas that sustain low levels of BCL7C often show the elevated expression of mutant p53 target genes. In line with these results, BCL7C abrogates mutant p53-induced cell proliferation and invasion, but had no impact on proliferation and invasion of cancer cells with depleted p53 or harboring wild-type p53. Altogether, our results demonstrate that BCL7C can act as a tumor suppressor to prevent ovarian tumorigenesis and progression by counteracting mutant p53 activity.

Purpose To investigate the clinical efficacy of 0.01% atropine in slowing the progression of myopia in children and to evaluate the influence of 0.01% atropine on secretion of basal tear and stability of tear film. Methods Eighty children aged 5–14 years with myopia, 40 were randomly divided into two groups consisting of those who received spectacles in addition to 0.01% atropine (SA group) and those who received only spectacles (S group). The remaining 40 children who were wearing orthokeratology (OK) lenses for 3 months were randomly divided into two groups comprising those who received OK lenses in addition to 0.01% atropine (OKA group) and those who received only OK lenses (OK group). Comprehensive ophthalmologic examinations, including slit-lamp examination, visual acuity testing, autorefraction, intraocular pressure, axial length (AL), corneal topography, Schirmer’s test, and tear film break-up time (TBuT), were performed before treatment and after every 3 months treatment. Results During the follow-up visits, evidently better spherical equivalent (SE) control over 3, 6 and 12 months was observed in the SA and OKA groups compared with the S and OK groups. The AL over 3, 6, and 12 months was evidently inhibited in the SA and OKA groups compared with the S and OK groups. No statistically significant differences in Schirmer’s test and TBuT results were observed between the S and SA groups and between the OK and OKA groups. However, statistically significant differences were found in TBuT results between before treatment and after 3 months treatment in the OK group (P t test) and the OKA group (P t test). Conclusions 0.01% atropine can effectively control myopia progression and axial elongation regardless of combined treatment with spectacles or OK lenses. And 0.01% atropine has no evident effect on Schirmer’s test and TBuT results; however, researchers also found that Schirmer’s test and TBuT results showed a tendency to reduce after treatment with 0.01% atropine.

Colorectal cancer (CRC) is the third most common malignant tumor. DNA damage played a crucial role on tumorigenesis, and abnormal DNA repair pathways affected the occurrence and progress of CRC. In current study, we aimed to construct a DNA repair-related genes (DRG) signature to predict the overall survival (OS) of CRC patients. Differentially expressed DRGs (DE-DRGs) were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic gene signature was identified by univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the model was evaluated by utilizing Kaplan-Meier curves and Time-dependent receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA) was performed to explore the underlying biological processes and signaling pathways. Single sample gene set enrichment analysis (ssGSEA) was implemented to estimate the immune status between the different risk group. A total of 118 DE-DRGs were identified between 42 normal samples and 488 CRC samples in TCGA cohort, and 36 DE-DRGs were associated with OS in the univariate Cox regression. A 9 DE-DRGs (ESCO2, AXIN2, PLK1, CDC25C, IGF1, TREX2, ALKBH2, ESR1 and MC1R) signature was constructed to classify patients into high-risk and low-risk group. The risk score was an independent prognostic indicator for OS (HR>1, P

To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.初治多发性骨髓瘤患者的基因突变及表达异常.分析初治多发性骨髓瘤（NDMM）患者常见基因的突变及表达异常.取208例NDMM患者的骨髓细胞，用DNA测序法检测6种基因的表达水平及28种基因的突变状态。应用FISH法检测多发性骨髓瘤常见的细胞遗传学异常.61例（29.33%）NDMM患者检测到基因突变，≥5例患者发生突变的基因包括NRAS、PRDM1、FAM46C、MYC、CCND1、LTB、DIS3、KRAS和CRBN。83例（39.90%）患者检测到6种基因的过表达，以细胞周期调节基因的过表达为主，分别是CCND1、CCND3、BCL-2、CCND2 FGFR3和MYC。169例（81.25%）患者检测到基因单核苷酸多态性改变，主要为TP53基因P72R多态性 (70.17%)。染色体结构异常与基因表达异常有一定相关性，与染色体结构正常者相比较，14q32缺失患者中CCND1基因过表达比例更高，13q14缺失患者中FGFR3过表达比例更高，而1q21扩增患者中CCND2、BCL-2、FGFR3基因过表达比例更高.NDMM患者存在多种基因突变和表达异常，但是缺乏主要的单个基因突变或表达异常。累及RAS/MAPK通路的基因突变及细胞周期蛋白CCND的过表达是常见的基因异常.

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP), in which exon open reading frame 15 (ORF15) of RPGR has been implicated to play a substantial role. We identified a novel hemizygous missense mutation E585K of RPGR from whole-exome sequencing of RP. RNA-Seq analysis and functional study were conducted to investigate the underlying pathogenic mechanism of the mutation. Our results showed that the mutation actually affected RPGR ORF15 splicing. RNA-Seq analysis of the human retina followed by validation in cells revealed a complex splicing pattern near the 3′ boundary of RPGR exon 14 in the ORF15 region, resulting from a variety of alternative splicing events (ASEs). The wildtype RPGR mini-gene expressed in human 293T cells confirmed these ASEs in vitro. In contrast, without new RNA species detected, the mutant mini-gene disrupted the splicing pattern of the ORF15 region, and caused loss of RPGR transcript heterogeneity. The RNA species derived from the mutant mini-gene were predominated by a minor out-of-frame transcript that was also observed in wildtype RPGR, resulting from an upstream alternative 5′ splice site in exon 14. Our findings therefore provide insights into the influence of RPGR exonic mutations on alternative splicing of the ORF15 region, and the underlying molecular mechanism of RP.

The mutational spectrum and prognostic factors of NRAS-mutated (NRASmut) acute myeloid leukemia (AML) are largely unknown. We performed next-generation sequencing (NGS) in 1,149 cases of de novo AML and discovered 152 NRASmut AML (13%). Of the 152 NRASmut AML, 89% had at least one companion mutated gene. DNA methylation-related genes confer up to 62% incidence. TET2 had the highest mutation frequency (51%), followed by ASXL1 (17%), NPM1 (14%), CEBPA (13%), DNMT3A (13%), FLT3-ITD (11%), KIT (11%), IDH2 (9%), RUNX1 (8%), U2AF1 (7%) and SF3B1(5%). Multivariate analysis suggested that age ≥ 60 years and mutations in U2AF1 were independent factors related to failure to achieve complete remission after induction therapy. Age ≥ 60 years, non-M3 types and U2AF1 mutations were independent prognostic factors for poor overall survival. Age ≥ 60 years, non-M3 types and higher risk group were independent prognostic factors for poor event-free survival (EFS) while allogenic hematopoietic stem cell transplantation was an independent prognostic factor for good EFS. Our study provided new insights into the mutational spectrum and prognostic factors of NRASmut AML.

Larynx cancer is one of the most common cancers in head and neck. This study aimed to investigate the health burden of larynx cancer at global, regional, and national levels. We collected data of larynx cancer between 1990 and 2017 from the Global Burden of Disease study, including incidence, mortality, and disability adjusted life-years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to assess the changes in age-standardized rate (ASR) of larynx cancer. From 1990 to 2017, LC incident cases increased by 58.67%; however, age-standardized incidence rate (ASIR) decreased, with an EAPC of -0.99. Additionally, the incident cases and ASIR of LC were 6-fold higher for male than those for female in 2017. Over the past 28 years, deaths and DALYs of larynx cancer increased by 33.84% and 25%. Contrarily, age-standardized death and DALY rate showed a downward trend. Incidence, death, and DALYs of larynx cancer were always the highest in people aged 50-69 years. Overall, all the ASRs showed downward trends globally. The majority of larynx cancer burden was observed in men, especially among male aged 50-69 years. South and East Asia carried the heaviest burden of larynx cancer worldwide.

Objectives: The prognostic role of WT1 in acute lymphoblastic leukemia (ALL) is still controversial. No study has focused on the prognostic role of WT1 expression in adult B-ALL patients receiving ...

Epidemiological studies have indicated that blood vitamin D levels are linked to cancer. Here we conducted a dose-response meta-analysis based on published observational studies to evaluate the association of vitamin D intake and blood vitamin D levels with breast cancer susceptibility. PubMed, EMBASE, and Web of Science databases were searched up to January 2019. The pooled odds ratio (OR) and 95% confidence intervals (CIs) were extracted to estimate the risk. We identified 70 relevant studies on blood vitamin D levels (50 studies) and vitamin D intake (20 studies), respectively. Linear and nonlinear trend analyses were performed and showed that an increase in blood vitamin D levels by 5 nmol/l was associated with a 6% decrease in breast cancer risk (OR = 0.94, 95% CI = 0.93-0.96). Similar results were obtained for premenopausal (OR = 0.96, 95% CI = 0.93-0.99) and postmenopausal women (OR = 0.96, 95% CI = 0.94-0.98). The pooled OR of breast cancer risk for a 400IU/day increase in vitamin D intake was 0.97 (95% CI = 0.92-1.02). In conclusion, we found that breast cancer risk was inversely related to blood vitamin D levels; however, no significant association was observed in vitamin D intake.

BackgroundStatistical 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.MethodsWe 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.ResultsIn 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.ConclusionThe 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.

Nanocarriers have great potential to enhance drug delivery efficiency and therapeutic effect for various cancers. However, premature drug leakage and non-specific targeting still limit the delivery efficiency. Here, we present a smart on-demand targeting nanotheranostic system (PO-PB@SPIOs) with stimuli-responsive releasing property to improve the delivery efficiency for ovarian cancer. This delivery system prevents premature drug leakage via boronate ester linkages and shields the targeting moieties (phenylboronic acid) from non-specific binding when circulating in the blood. The PO-PB@SPIOs would release the tumor-targeting payload (PB) in response to the tumor microenvironment. Then, PB was able to target the overexpressed sialic acids on tumor cells. The significant improvement of delivery efficiency was demonstrated in vivo by a significantly enhanced signal in near-infrared-fluorescence (NIRF)/magnetic-resonance (MR) imaging (5-fold higher) and a remarkable photo-thermal therapeutic effect (complete cure rate (CCR) up to 80%). Furthermore, due to the on-demand targeting and stimuli-responsive releasing strategy, this nanotheranostic system shows a greater delivery efficiency even than the active-targeting small molecules or control nanoformulations. We believe this delicate design has great potential to develop novel drug nanoformulation.

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

Recombination is a major force that shapes genetic diversity. Determination of recombination rate is important and can theoretically be improved by increasing the sample size. However, it is nearly impossible to estimate recombination rates using traditional population genetics methods when the sample size is large because these methods are highly computationally demanding. In this study, we used a refined machine learning approach to estimate the recombination rate of the human genome using the UK10K human genomic dataset with 7,562 genomic sequences and its three subsets with 200, 400 and 2,000 genomic sequences. The estimation was performed under the human Out-of-Africa demographic model. We not only obtained an accurate human genetic map, but also found that the fluctuation of estimated recombination rate is reduced along the human genome when the sample size increases. The estimated UK10K recombination rate heterogeneity is less than that estimated from its subsets. Our results demonstrate how the sample size affects the estimated recombination rate, and analyses of a larger number of genomes result in a more precise estimation of recombination rate. The accurate genetic map based on UK10K data set is also expected to benefit other human biology researches.

Background High‐grade serous ovarian carcinoma (HGSOC) is the most common and aggressive histotype of epithelial ovarian cancer. The heterogeneity and molecular basis of this disease remain incompletely understood. Methods To address this question, we have performed a single‐cell transcriptomics analysis of matched primary and metastatic HGSOC samples. Results A total of 13 571 cells are categorized into six distinct cell types, including epithelial cells, fibroblast cells, T cells, B cells, macrophages, and endothelial cells. A subset of aggressive epithelial cells with hyperproliferative and drug‐resistant potentials is identified. Several new markers that are highly expressed in epithelial cells are characterized, and their roles in ovarian cancer cell growth and migration are further confirmed. Dysregulation of multiple signaling pathways, including the translational machinery, is associated with ovarian cancer metastasis through the trajectory analysis. Moreover, single‐cell regulatory network inference and clustering (SCENIC) analysis reveals the gene regulatory networks and suggests the JUN signaling pathway as a potential therapeutic target for treatment of ovarian cancer, which is validated using the JUN/AP‐1 inhibitor T‐5224. Finally, our study depicts the epithelial‐fibroblast cell communication atlas and identifies several important receptor‐ligand complexes in ovarian cancer development. Conclusions This study uncovers new molecular features and the potential therapeutic target of HGSOC, which would advance the understanding and treatment of the disease., (1) Single‐cell transcriptomics analysis of HGSOC samples reveals six distinct cell types. (2) Characterization of epithelial cell subclusters identifies novel markers for HGSOC. (3) Subclustering fibroblast cells suggests their functional heterogeneity. (4) Our study also uncovers the JUN pathway and several ligand‐receptor signals as potential drivers for HGSOC.

Ovarian cancer is one of the three most common female reproductive system cancers and has been a hot topic in the field of gynecology and oncology. Currently, surgery with chemotherapy is the common strategy in treatment of ovarian cancer, while it is always accompanied by drug resistance and some adverse effects. Over the past few years, traditional Chinese medicine (TCM) has been embraced by a large population of clinicians and researchers due to its high efficiency, low toxicity and minor side effects. Guizhi-Fuling Wan as a classical TCM formula has manifested certain efficacy in treating ovarian cancer. This article intends to further study the role and mechanism of Guizhi-Fuling Wan in treatment of ovarian cancer and explore the effective chemical components contained in the herbs of the formula. To this end, we reviewed the previous clinical studies and experiments to analyze the molecular mechanisms, pharmacological effects, active chemical components and their targets of action in treatment of ovarian cancer, thereby providing a theoretic basis for future studies and practices.

p53 inactivation is highly associated with tumorigenesis and drug resistance. Here, we identify a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), as an inhibitor of p53. RMRP is overexpressed and associated with an unfavorable prognosis in colorectal cancer. Ectopic RMRP suppresses p53 activity by promoting MDM2-induced p53 ubiquitination and degradation, while depletion of RMRP activates the p53 pathway. RMRP also promotes colorectal cancer growth and proliferation in a p53-dependent fashion in vitro and in vivo. This anti-p53 action of RMRP is executed through an identified partner protein, SNRPA1. RMRP can interact with SNRPA1 and sequester it in the nucleus, consequently blocking its lysosomal proteolysis via chaperone-mediated autophagy. The nuclear SNRPA1 then interacts with p53 and enhances MDM2-induced proteasomal degradation of p53. Remarkably, ablation of SNRPA1 completely abrogates RMRP regulation of p53 and tumor cell growth, indicating that SNRPA1 is indispensable for the anti-p53 function of RMRP. Interestingly and significantly, poly (ADP-ribose) polymerase (PARP) inhibitors induce RMRP expression through the transcription factor C/EBPβ, and RMRP confers tumor resistance to PARP inhibition by preventing p53 activation. Altogether, our study demonstrates that RMRP plays an oncogenic role by inactivating p53 via SNRPA1 in colorectal cancer.

Background: As an important downstream factor in the Hippo pathway, yes-associated protein 1(YAP1) has been detected to be elevated in various cancers and demonstrated to play a role in tumor development. Therefore, we evaluated by a meta-analysis the prognostic value of YAP1 in cancer patients. Results: Sixty-eight studies with 8631 patients were identified. The results indicated that YAP1 overexpression predicted unfavorable patient prognosis in studies with overall survival (OS) (HR=1.76, 95%CI: 1.50-2.06, p

Long noncoding RNA (lncRNA) polymorphisms are reportedly in connection with tumor susceptibility and prognosis. Glioma is one of the most aggressive and common cancers of the central nervous system. This study aimed to investigate the relationship between four lncRNA variants and glioma susceptibility and prognosis in a Chinese Han population. Sequenom Mass-ARRAY was used to genotype 605 patients with glioma and 1300 cancer-free individuals. Odds ratios or hazard ratios and related 95% confidence intervals were calculated to estimate the correlations. Logistic and Cox regression models, log-rank tests, and Kaplan-Meier curves were used for the statistical analysis. Six inheritance models showed that ANRIL rs2151280 variant genotype (A>G) was related to the susceptibility of glioma, while the other three lncRNAs showed no association. Patients treated with temozolomide or nimustine had better progression-free survival (PFS) and overall survival (OS) than those treated with platinum. Besides, patients aged older than 40 years showed a poorer OS. The Cox multivariate analysis revealed that the rs1136410 GG genotype (A>G) was beneficial for OS and PFS. The Kaplan-Meier analyses indicated that rs1136410 A>G and the rs7763881 A>C were associated with longer OS. ANRIL rs2151280 variant genotype might increase susceptibility of glioma. In addition, PARP1 rs1136410 variant genotype could be beneficial for the overall survival of patients with glioma. More research data are needed to further validate our results.

Hotspot p53 mutants augment cancer cell proliferation, metastasis and metabolism through their gain-of-function (GOF). Ovarian cancer sustains the highest frequency of TP53 mutations, but the mechanisms underlying regulation of mutant p53s’ GOF in this type of cancer remain incompletely understood. Herein, we identified the E3-ubiquitin ligase TRIM71 as a novel mutant p53-binding protein. Ectopic TRIM71-induced ubiquitination and proteasomal degradation of mutant p53 by binding to its transactivation (TA) domain, and inhibited the expression of a broad spectrum of mutant p53 target genes. Ectopic TRIM71 also restrained, whereas ablation of TRIM71 endorsed, ovarian carcinoma cell growth in vitro and in vivo. Significantly, TRIM71 overexpression is highly associated with favorable prognosis, particularly, in TP53-mutated ovarian carcinomas. Altogether, our findings unveil the anti-tumor function of TRIM71 in ovarian cancer development and prognosis by downregulating mutant p53s.

Introduction: Asia-Pacific Colorectal Screening (APCS) score has been implemented for colorectal cancer screening in asymptomatic cohort in many regions. However, no study has validated its efficiency in Asian outpatients with mild-self-limited gastrointestinal symptoms yet. The purpose of this study was to validate its efficiency in asymptomatic subjects and outpatients in Ningxia. Methods: The records of 329 asymptomatic participants and 300 outpatients were collected and analyzed from database in the General Hospital of Ningxia Medical University from September 2017 to April 2018. These 2 main groups were divided into 3 tiers based on the scores calculated by the category of APCS score. The detection rates of advanced colorectal neoplasia (ACRN) were further compared according to histopathological classifications of tissues acquired during colonoscopy. Results: Among the 329 participants screened in the asymptomatic cohort, 78 subjects (23.7%) were in the low-risk (LR) tier, 187 subjects (56.8%) in the moderate-risk (MR) tier, and 64 subjects (19.5%) in the high-risk (HR) tier. The percentage of ACRN in the LR, MR, and HR groups was 1.3, 8.6, and 20.3%, respectively. In the 300 outpatient cohorts, 78 patients (26%) were in the LR tier, 140 patients (46.7%) in the MR tier, and 82 patients (27.3%) in the HR tier. The detection rates of ACRN in the LR, MR, and HR groups were 0, 10, and 39%, respectively. Conclusion: APCS score is an effective method for ACRN screening in asymptomatic and also the outpatient subjects. Individuals with HR scores should be given priority for colonoscopy.

B-cell acute lymphoblastic leukemia (B-ALL) in adults remains a highly challenging disease. Identifying new prognostic biomarkers is necessary to help select the best therapeutic schedules and to improve prognosis. We performed bioinformatics analyses of transcriptomic data to identify aberrantly-expressed mRNA transcripts in B-ALL and focused on RASD1 (Ras-related dexamethasone-induced 1). To date, no information is available on the prognostic value of RASD1 in B-ALL. Fifty-three consecutive adults with de novo B-ALL were enrolled in this study. Our data suggested that RASD1 was abnormally overexpressed in B-ALL. High RASD1 transcript levels at diagnosis were associated with lower survival probabilities (44% [20%–61%] vs. 79% [60%–97%]; P = 0.037) and were also an independent prognostic factor in adult B-ALL (HR = 4.9 [1.5–15.9]; P = 0.008). Functional in vitro analyses and bioinformatic analyses indicated that RASD1 promoted cell proliferation, cell cycle progression and chemotherapy resistance and inhibited cell apoptosis. These data demonstrated that RASD1 might serve as a novel prognostic biomarker for adult B-ALL and as a potential therapeutic target in adult B-ALL patients.

The association between hyperuricemia or gout and cancer risk has been investigated in various published studies, but their results are conflicting. We conducted a meta-analysis to investigate whether hyperuricemia or gout was associated with the cancer incidence and mortality. Linear and nonlinear trend analyses were conducted to explore the dose-response association between them. The pooled relative risk (RR) and 95% confidence interval (CI) were used to evaluate cancer risk. A total of 24 articles (33 independent studies) were eligible for inclusion. When compared participants with the highest SUA (hyperuricemia) levels and those with the lowest SUA levels, the pooled RR was 1.08 (95% CI, 1.04-1.12), it was significantly associated among males but not among females (males, RR = 1.07; 95% CI, 1.03-1.11; females, RR = 1.06; 95% CI, 0.96-1.17). Hyperuricemia increased total cancer mortality (RR = 1.15; 95% CI, 1.05-1.26), but a significant association was observed in females rather than in males (females: RR = 1.26; 95% CI, 1.09-1.45; males, RR = 1.02; 95% CI, 0.80-1.30). Linear relationships of SUA levels with overall cancer incidence (p for nonlinearity = 0.238) and overall cancer mortality (p for nonlinearity = 0.263) were identified. However, 1 mg/dL increment in SUA levels was weakly significant in overall cancer incidence (RR = 1.01; 95% CI, 1.01-1.01) but not associated with overall cancer mortality (RR = 1.01; 95% CI, 0.99-1.03). Gout was significantly associated with increased cancer incidence (RR = 1.19; 95% CI, 1.12-1.25). In conclusion, Hyperuricemia or gout was associated with higher cancer incidence and mortality. Though a potential linear relationship between them was found, we'd better treat this result with caution.

Since wild-type p53 is central for maintaining genomic stability and preventing oncogenesis, its coding gene TP53 is highly mutated in ~50% of human cancers, and its activity is almost abrogated in the rest of cancers. Approximately 80% of p53 mutations are single point mutations with several hotspot mutations. Besides loss of function and dominant-negative effect on the wild-type p53 activity, the hotspot p53 mutants also acquire new oncogenic functions, so-called ‘gain-of-functions’ (GOF). Because the GOF of mutant p53 is highly associated with late-stage malignance and drug resistance, these p53 mutants have become hot targets for developing novel cancer therapies. In this essay, we review some recent progresses in better understanding of the role of mutant p53 GOF in chemoresistance and the underlying mechanisms, and discuss the pros and cons of targeting mutant p53 for the development of anti-cancer therapies.

Apoptosis related protein in TGF-β signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-β, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, γ-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene. Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress- or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis.

OBJECTIVE The objective of this study was to measure the anatomical distance from the cervicovaginal junction to the uterovesical peritoneal reflection (CJ-PR). METHODS A total of 120 hysterectomy patients were selected as study subjects. The uterus was removed, and the CJ-PR distance was immediately measured. For total vaginal hysterectomy, measurement was performed intraoperatively. The cervical length was also measured postoperatively. RESULTS The median (interquartile) CJ-PR distance for all subjects was 3.3 (2.9-3.7) cm. Comparison of premenopausal and postmenopausal women without prolapse revealed median CJ-PR distances of 3.3 (3.0-3.6) cm and 3.0 (2.6-3.4) cm, respectively. The CJ-PR distance was longer in women with prolapse (4.6 [3.7-5.6] cm) than in those without prolapse (3.2 [2.8-3.6] cm). The median cervical lengths were 3.1 (2.7-3.6) cm for postmenopausal patients without prolapse and 4.4 (3.6-5.8) cm for postmenopausal patients with prolapse. CONCLUSIONS Knowledge of the CJ-PR distance may help gynecologists predict how far the uterovesical PR is from the anterior vaginal incision.

A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C

c-Met hyperactivity has been observed in numerous neoplasms. Several researchers have shown that the abnormal activation of c-Met is mainly caused by transcriptional activation. However, the molecular mechanism behind this transcriptional regulation is poorly understood. Here, we suggest that Smad3 negatively regulates the expression and activation of c-Met via a transcriptional mechanism. We explore the molecular mechanisms that underlie Smad3-induced c-Met transcription inhibition. We found in contrast to the high expression of c-Met, Smad3 showed low protein and mRNA levels. Smad3 and c-Met expressions were inconsistent between lung cancer tissues and cell lines. We also found that Smad3 overexpression suppresses whereas Smad3 knockdown significantly promotes Epithelial-Mesenchymal Transition and production of the angiogenic factors VEGF, CTGF and COX-2 through the ERK1/2 pathway. In addition, Smad3 overexpression decreases whereas Smad3 knockdown significantly increases protein and mRNA levels of invasion-related β-catenin and FAK through the PI3K/Akt pathway. Furthermore, using the chromatin immunoprecipitation analysis method, we demonstrate that a transcriptional regulatory complex consisting of HDAC1, Smad3 and mSin3A binds to the promoter of the c-Met gene. By either silencing endogenous mSin3A expression with siRNA or by pretreating cells with a specific HDAC1 inhibitor (MS-275), Smad3-induced transcriptional suppression of c-Met could be effectively attenuated. These results demonstrate that Smad3-induced inhibition of c-Met transcription depends on of a functional transcriptional regulatory complex that includes Smad3, mSin3A and HDAC1 at the c-Met promoter. Collectively, our findings reveal a new regulatory mechanism of c-Met signaling, and suggest a potential molecular target for the development of anticancer drugs.

The tumor suppressor p53 prevents tumorigenesis and cancer progression by maintaining genomic stability and inducing cell growth arrest and apoptosis. Because of the extremely detrimental nature of wild-type p53, cancer cells usually mutate the TP53 gene in favor of their survival and propagation. Some of the mutant p53 proteins not only lose the wild-type activity, but also acquire oncogenic function, namely “gain-of-function”, to promote cancer development. Growing evidence has revealed that various E3 ubiquitin ligases are able to target both wild-type and mutant p53 for degradation or inactivation, and thus play divergent roles leading to cancer cell survival or death in the context of different p53 status. In this essay, we reviewed the recent progress in our understanding of the p53-targeting E3 ubiquitin ligases, and discussed the potential clinical implications of these E3 ubiquitin ligases in cancer therapy.

Key Points Question What were the epidemiologic patterns and variation in the trends of thyroid cancer worldwide from 1990 to 2017? Findings In this cross-sectional study covering data on incidence, deaths, and disability-adjusted life-years and their temporal trends from 195 countries and 21 regions, increasing trends of thyroid cancer burden were observed, with significant differences by sex, region, country, age, and sociodemographic index. Almost half of the thyroid cancer burden was noted in Southern and Eastern Asia, and a third of patients with thyroid cancer resided in countries with a high sociodemographic index. Meaning This study suggests an increasing global burden of thyroid cancer; the geographic disparities may provide support for cancer health care planning and resource allocation., Importance Thyroid cancer is the most pervasive endocrine cancer worldwide. Studies examining the association between thyroid cancer and country, sex, age, sociodemographic index (SDI), and other factors are lacking. Objective To examine the thyroid cancer burden and variation trends at the global, regional, and national levels using data on sex, age, and SDI. Design, Setting, and Participants In this cross-sectional study, epidemiologic data were gathered using the Global Health Data Exchange query tool, covering persons of all ages with thyroid cancer in 195 countries and 21 regions from January 1, 1990, to December 31, 2017; data analysis was completed on October 1, 2019. All participants met the Global Burden of Disease Study inclusion criteria. Main Outcomes and Measures Outcomes included incidence, deaths, and disability-adjusted life-years (DALYs) of thyroid cancer. Measures were stratified by sex, region, country, age, and SDI. The estimated annual percentage changes (EAPCs) and age-standardized rates were calculated to evaluate the temporal trends. Results Increases of thyroid cancer were noted in incident cases (169%), deaths (87%), and DALYs (75%). Age-standardized incidence rate (ASIR) showed an upward trend over time, with an EAPC of 1.59 (95% CI, 1.51-1.67); decreases were noted in EAPCs of age-standardized death rate (−0.15; 95% CI, −0.19 to −0.12) and age-standardized DALY rate (−0.11; 95% CI, −0.15 to −0.08). Almost half (41.73% for incidence, 50.92% for deaths, and 54.39% for DALYs) of the thyroid cancer burden was noted in Southern and Eastern Asia. In addition, females accounted for most of the thyroid cancer burden (70.22% for incidence, 58.39% for deaths, and 58.68% for DALYs) and increased by years in this population, although the ASIR of males with thyroid cancer (EAPC, 2.18; 95% CI, 2.07-2.28) increased faster than that of females (EAPC, 1.38; 95% CI, 1.30-1.46). A third (34%) of patients with thyroid cancer resided in countries with a high SDI, and most patients were aged 50 to 69 years, which was older than the age in other quintiles (high SDI quintile compared with all other quintiles, P, This cross-sectional study examines the worldwide temporal trends of thyroid cancer according to geographic location, sex, age, and socioeconomic index.

Epidemiological studies showing the correlation between folate and the breast cancer risk have revealed inconsistent results. Hence, we conducted a dose-response meta-analysis of observational studies to obtain more reliable conclusions. We searched PubMed and Embase for studies published before April 2019 and identified 39 studies on folate intake and 12 studies on plasma folate level. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were extracted to estimate the breast cancer risk. Folate intake was inversely correlated with the breast cancer risk when the highest and lowest categories (OR = 0.85, 95% CI = 0.79-0.92) were compared, and the dose-response result showed that folate intake had a linear correlation with the breast cancer risk. Moreover, a higher folate intake correlated with a lower breast cancer risk in premenopausal women (OR = 0.80, 95% CI = 0.66-0.97), but not in postmenopausal women (OR = 0.94, 95% CI = 0.83-1.06). However, plasma folate levels were not correlated with the breast cancer risk (OR = 0.98, 95% CI = 0.82-1.17). Folate intake was negatively correlated with the breast cancer risk; however, its practical clinical significance requires further study. Furthermore, additional folate supplements should be considered carefully.