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A flat or concave lower midface profile is generally considered less attractive. Paranasal augmentation is usually performed to move paranasal deficiency to relative convexity. Herein, we present a viable and simplified modality with diced expanded polytetrafluoroethylene to correct paranasal deficiency. Between February of 2020 and April of 2021, 19 patients underwent procedures to correct paranasal deficiency. Paranasal augmentation was performed with diced expanded polytetrafluoroethylene. All procedures were performed via intranasal approach. Preoperative and postoperative photographs were taken. Of these 19 patients (18 women and 1 man), deficiency of 18 patients were caused by congenital factors and 1 by cleft deformities. All but 1 procedures were carried out bilaterally. Procedures were performed in conjunction with additional operations mainly including rhinoplasty and minimally invasive midface lift. Age of patients ranged from 19 to 57 years, with a mean of 37 years. Follow-up time ranged from 8 to 22 months, with a mean of 12.6 months. All patients were satisfied with esthetic improvement and facial holistic profile. No severe complications and reoperation arisen in any of the patients. Temporary discomfort involved foreign body sensation in 1 case and numbness in 2 cases. The present technique provides a viable and simplified method to give the face a more balanced appearance and achieves esthetically superior results.

BackgroundBreast cancer (BC) is the most common malignancy among women. Nicotinamide (NAM) metabolism regulates the development of multiple tumors. Herein, we sought to develop a NAM metabolism-related signature (NMRS) to make predictions of survival, tumor microenvironment (TME) and treatment efficacy in BC patients.MethodsTranscriptional profiles and clinical data from The Cancer Genome Atlas (TCGA) were analyzed. NAM metabolism-related genes (NMRGs) were retrieved from the Molecular Signatures Database. Consensus clustering was performed on the NMRGs and the differentially expressed genes between different clusters were identified. Univariate Cox, Lasso, and multivariate Cox regression analyses were sequentially conducted to develop the NAM metabolism-related signature (NMRS), which was then validated in the International Cancer Genome Consortium (ICGC) database and Gene Expression Omnibus (GEO) single-cell RNA-seq data. Further studies, such as gene set enrichment analysis (GSEA), ESTIMATE, CIBERSORT, SubMap, and Immunophenoscore (IPS) algorithm, cancer-immunity cycle (CIC), tumor mutation burden (TMB), and drug sensitivity were performed to assess the TME and treatment response.ResultsWe identified a 6-gene NMRS that was significantly associated with BC prognosis as an independent indicator. We performed risk stratification according to the NMRS and the low-risk group showed preferable clinical outcomes (P < 0.001). A comprehensive nomogram was developed and showed excellent predictive value for prognosis. GSEA demonstrated that the low-risk group was predominantly enriched in immune-associated pathways, whereas the high-risk group was enriched in cancer-related pathways. The ESTIMATE and CIBERSORT algorithms revealed that the low-risk group had a higher abundance of anti-tumor immunocyte infiltration (P < 0.05). Results of Submap, IPS, CIC, TMB, and external immunotherapy cohort (iMvigor210) analyses showed that the low-risk group were indicative of better immunotherapy response (P < 0.05).ConclusionsThe novel signature offers a promising way to evaluate the prognosis and treatment efficacy in BC patients, which may facilitate clinical practice and management.

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS–CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS–CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS–CRC patients with postoperative recurrence or metastasis.

A high-rate aqueous zinc-ion battery is assembled by β-MnO2 electrode with residual NH4+. The NH4+ could stabilize the chemical structure of the distorted Mn3+O6 by forming Mn–O⋯H bond and serve as a “retractable spring” to avoid tunnel collapse.

Subclinical necrotic enteritis (SNE) is a severe intestinal disease in broilers which brings huge economic losses to poultry industry. Herein, the effects of Bacillus amyloliquefaciens BLCC1-0238 (B. amyloliquefaciens BLCC1-0238) alone or in combination with mannan-oligosaccharides (MOS) on the SNE challenge model in broilers were comprehensively explored. A total of 360 broilers were randomly divided into 4 groups, including an SNE infection control (IC), an antibiotic pretreatment control (AC), a B. amyloliquefaciens BLCC1-0238 pretreatment (BP), and a B. amyloliquefaciens BLCC1-0238 + MOS pretreatment (BMP). The results showed that compared with the IC, three pretreatment groups significantly improved the growth performance, lowered the overall mortality, and reduced intestinal mucosal lesions in broilers. Additionally, the expression levels of claudin-3 and peroxisome proliferator-activated receptor-gamma coactivator-1α in the BP and BMP groups and the levels of mucin-2 and mechanistic target of rapamycin in the BMP group were significantly upregulated compared with the IC. By contrast, the expression levels of interferon-γ, interleukin-10, and secretory immunoglobulin A in the BP and BMP groups were significantly downregulated. In conclusion, these findings show that B. amyloliquefaciens BLCC1-0238 in combination with MOS can exert synergetic effects by the interplay between them on improving growth performance and combating the SNE infection in broilers.

China has enacted the "Clean Heating" (CH) policy in north China. The domain-specific impacts on PM

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.

RNA-binding proteins (RBPs) play crucial roles in multiple cancers. However, very few RBPs and their association with immune genes have been systematically studied in liver cancer (LC). We aimed to identify an immune-related RBP signature to predict the survival of LC patients. Bioinformatics methods were used to identify differentially expressed, immune-related, and prognostic RBPs and to develop an immune-related RBP signature based on data from the Cancer Genome Atlas (TCGA) cohort. We obtained eight differentially expressed, immune-related, and prognostic RBPs to construct a risk signature. The signature could effectively distinguish between high- and low-risk patients, and its predictive capacity was validated in the International Cancer Genomics Consortium (ICGC) cohort. We speculated that the high-risk group was more sensitive to targeted therapy. The immune-related RBP signature is an independent prognostic biomarker for LC patients and can expand the application of targeted therapy through patient stratification.

Background Platelet-rich fibrin (PRF) can promote fat graft survival, but the reported mixing ratio of PRF to fat ranges from 1:25 to 1:2, lacking a clear standard for clinical application. Objectives The authors sought to explore the long-term effects of PRF on grafted fat and their optimal mixing ratio. Methods Nude mice were randomly divided into a control group (receiving subcutaneous injection of fat granules) and 4 PRF groups (receiving subcutaneous injection of PRF and fat granules at volume ratios of 1:5, 1:10, 1:15, and 1:20, respectively). The graft samples (n = 12) were obtained in weeks 4, 8, and 12 to (1) calculate retention rates; (2) evaluate gene and protein expression of vascular endothelial growth factor A (VEGF-A), peroxisome proliferator-activated receptor-γ (PPAR-γ), type I collagen A1 (COL1-A1), and B-cell lymphoma-2 associated X protein (BAX); (3) perform hematoxylin and eosin, Masson’s trichrome, α-smooth muscle action, and periplipin-1 stainings; and (4) count the microvessels and viable adipocytes. Results Compared with the control group, PRF groups had higher retention rates, a higher gene/protein expression of VEGF-A, a lower gene/protein expression of COL1-A1 and BAX, less fibrosis, and more microvessels and viable adipocytes. Group 1:10 was superior to other groups in terms of retention rates and other evaluation indexes. The expression of PPAR-γ did not significantly differ among groups. Conclusions PRF may not play a long-term effect on adipogenesis, but it can still promote fat graft survival through facilitating vascularization, regulating collagen production, and inhibiting apoptosis. PRF can achieve the best promoting effect when the mixing ratio of PRF to fat is 1:10, which is recommended as the optimal ratio for clinical application.

Three-dimensional (3D) bioprinting has emerged as a promising scaffold fabrication strategy for tissue engineering with excellent control over scaffold geometry and microstructure. Nanobiomaterials as bioinks play a key role in manipulating the cellular microenvironment to alter its growth and development. This review first introduces the commonly used nanomaterials in tissue engineering scaffolds, including natural polymers, synthetic polymers, and polymer derivatives, and reveals the improvement of nanomaterials on scaffold performance. Second, the 3D bioprinting technologies of inkjet-based bioprinting, extrusion-based bioprinting, laser-assisted bioprinting, and stereolithography bioprinting are comprehensively itemized, and the advantages and underlying mechanisms are revealed. Then the convergence of 3D bioprinting and nanotechnology applications in tissue engineering scaffolds, such as bone, nerve, blood vessel, tendon, and internal organs, are discussed. Finally, the challenges and perspectives of convergence of 3D bioprinting and nanotechnology are proposed. This review will provide scientific guidance to develop 3D bioprinting tissue engineering scaffolds by nanotechnology.

This study aimed to explore the roles of ERCC1/XPF gene polymorphisms in the occurrence of breast cancer in the Uygur and Han ethnic groups in Xinjiang, China. Single nucleotide polymorphisms (SNPs) were detected by TaqMan real‐time PCR. The rs11615 G>A and rs2276466 C>G variant frequencies were higher in Uygur patients with breast cancer than in Han patients, while the frequency of rs2298881 C>A was higher in Han patients. We found that rs2298881 C>A (CA vs. CC: OR = 0.35, 95% CI = 0.20‐0.60; AA vs. CC: OR = 0.13, 95% CI = 0.04‐0.34; CA + AA vs. CC: OR = 0.33, 95% CI = 0.18‐0.51; AA vs. CA + CC: OR = 0.24, 95% CI = 0.08‐0.62; CA vs. AA + CC: OR = 0.49, 95% CI = 0.29‐0.82) was associated with a reduced breast cancer risk and rs3212986 C>A (AA vs. CC: OR = 4.80, 95% CI = 1.79‐15.29,; CA+AA vs. CC: OR = 1.71, 95% CI = 1.06‐2.77; AA vs. CA+CC: OR = 4.12, 95% CI =1.58‐12.89) and rs11615 G > A (AA vs. GG: OR = 3.49, 95% CI =1.54‐8.55; GA + AA vs. GG: OR = 1.98, 95% CI = 1.21‐3.27; AA vs. GA+GG: OR = 2.87, 95% CI = 1.30‐6.85) were associated with an elevated breast cancer risk among Uygur individuals. In addition, Uygur patients with breast cancer with 2‐3 combined risk genotypes of ERCC1 had a higher risk than patients with 0‐1 risk genotypes (OR = 2.91; 95% CI = 1.54‐5.71, p = 0.001). However, we failed to detect a statistically significant association between ERCC1/XPF polymorphisms and breast cancer risk in five genetic models among Han individuals. Our results showed that ERCC1/XPF gene polymorphisms predispose Uygur individuals to breast cancer; this finding should be verified by further large‐scale analyses., Distribution of ERCC1/XPF gene polymorphisms in Han and Uygur women with breast cancer was different. ERCC1/XPF gene polymorphisms predispose Uygur individuals to breast cancer.

Manganese dioxide (MnO

The association between vitamin C intake and breast cancer is unclear. This meta-analysis aimed to precisely assess the association of vitamin C intake with breast cancer risk and mortality. We searched the PubMed, Embase, and Web of Science databases up to June 2020 and found 69 studies relevant to breast cancer risk (54 studies) and survival (15 studies). Relative risks and 95% confidence intervals were calculated using the random-effects models. Pooled results suggested that the highest versus lowest vitamin C intake was significantly associated with a lower risk of breast cancer incidence (Relative Risk = 0.86; 95% confidence interval, 0.81-0.92). Dietary vitamin C but not supplements was found to reduce breast cancer risk (Relative Risk = 0.89; 95% confidence interval, 0.82-0.96). For the highest versus lowest vitamin C intake, the pooled hazard risk for breast cancer-specific mortality was 0.78 (95% confidence interval, 0.69-0.88), totality mortality was 0.82 (95% confidence interval, 0.74-0.91), and recurrence was 0.81 (95% confidence interval, 0.67-0.99). Our analysis suggests that higher vitamin C intake is significantly associated with reduced breast cancer incidence and mortality. However, the intake of vitamin C supplements has no significant effect on breast cancer prevention.

Introduction Sonodynamic Therapy (SDT) has good targeting and non-invasive advantages in solid cancers, but its antitumor effect is not sufficient to replace traditional treatments. Some studies that combined SDT with chemotherapy or nanoparticles have managed to enhance its efficiency and overcome the side effects of chemotherapy. Materials and methods In this study, we synthesized and characterized mesoporous silica nanoparticles (MSN-DOX-Ce6) loaded with doxorubicin (DOX) and sonosensitizer, chlorin e6 (Ce6). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of MSN-DOX-Ce6 under ultrasound (US) treatment. Results The characterization tests showed that the nanoparticles are uniformly sized spheres with mesoporous structure, resulting in a high drug-loading efficiency. In the in vitro experiments, MSN-DOX-Ce6 could effectively inhibit cell proliferation under US but not more than other treatment groups. However, the in vivo studies showed that MSN-DOX-Ce6+US has better antitumor effect than DOX+Ce6+US or DOX alone on xenograft tumor-bearing mice. Conclusion In summary, MSNs showed a great potential for DOX and Ce6 delivery. We concluded that under US, MSN-DOX-Ce6 nanocomposites increase the antitumor effect of DOX and SDT and thereby are a potential treatment for solid tumors.

Background Platelet-rich fibrin (PRF) can promote fat graft survival, but limited data are currently available, and the underlying mechanism of this effect has not yet been explained. Objectives The aim of this study was to explore the mechanism by which PRF promotes fat graft survival, from the aspects of angiogenesis, adipogenesis, cellular apoptosis, and collagen production. Methods Nude mice were randomly assigned to a PRF group (subcutaneously injected with PRF and fat in the ratio of 1:5 by volume) and a control group (subcutaneously injected with normal saline and fat in the ratio of 1:5 by volume). On days 0, 3, 7, 14, 21, and 28 after transplantation, graft samples (n = 12) were obtained for quantification of target growth factors. In weeks 1, 2, 3, and 4 after transplantation, graft samples (n = 12) were obtained for the following evaluations. The volume and weight retention rates were calculated; gene and protein expression of vascular endothelial growth factor A (VEGF-A), peroxisome proliferator–activated receptor γ (PPAR-γ), COL1-A1, and BAX were evaluated; hematoxylin & eosin staining, Masson’s trichrome staining, α smooth muscle actin staining, and perilipin-1 staining were performed to evaluate graft survival. Results After transplantation, the concentrations of growth factors produced by the fat increased to varying degrees, and the addition of PRF made these concentration changes ever greater. Compared with the control group, the PRF group had a higher volume and weight retention rate, a higher expression level of VEGF-A and PPAR-γ, a lower expression level of COL1-A1 and BAX, a higher vessel density, less fibrosis, and more viable adipocytes. Conclusions PRF can promote autocrine function of the grafted fat to produce more growth factors. It greatly increased fat retention rate, possibly by promoting vascularization and adipogenic differentiation, inhibiting cellular apoptosis, and regulating collagen production.

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.

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.

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

Background Thymidylate synthase (TYMS) polymorphisms are reported to be related to susceptibility to some cancers. However, no study exists on TYMS polymorphisms and glioma risk. This study aimed to evaluate the relationship between two common TYMS gene variants (rs1059394 C>T, rs2847153 G>A) and glioma susceptibility. Methods This case-control study included 605 patients and 1300 cancer-free individuals. Genotyping was performed using Sequenom Mass-ARRAY. We determined odds ratios (ORs) and their 95% confidence intervals (CIs) to estimate the correlations. Results The analysis revealed that rs1059394 TT and CT+TT genotype had significantly low glioma risk (TT to CC: OR = 0.71, 95% CI = 0.52-0.97, P = 0.03; CT+TT to CC: OR = 0.74, 95% CI = 0.55-0.99, P = 0.04). However, no significant difference was found between rs2847153 and glioma risk in any genetic model (P﹥0.05). In high-grade gliomas, the GA and GA+AA genotypes of rs2847153 made the majority of genotypes, compared with GG genotype (GA to GG: OR = 2.01, 95% CI = 1.39-2.91, P < 0.001; GA+AA to GG: OR = 1.78, 95% CI =1.25-2.54, P < 0.001). Moreover, online expression quantitative trait locus (eQTL) analysis indicated that these two polymorphisms may alter TYMS gene expression in transformed fibroblast cells. Conclusion Our study provides evidence of the effect of TYMS rs1059394 on the susceptibility of glioma. In high-grade gliomas, compared with GG genotype, the GA and GA+AA genotypes of rs2847153 comprise a larger proportion.

Ferroptosis is a newly discovered type of cell death mediated by iron-dependent lipid peroxide. The disturbance of iron metabolism, imbalance of the amino acid antioxidant system, and lipid peroxide accumulation are considered distinct fingerprints of ferroptosis. The dysregulation of ferroptosis has been intensively studied in recent years due to its participation in various diseases, including cancer, kidney injury, and neurodegenerative diseases. Notably, increasing evidence indicates that ferroptosis plays different roles in a wide spectrum of liver diseases. On the one hand, inhibiting ferroptosis may counteract the pathophysiological progression of several liver diseases, such as alcoholic liver injury, nonalcoholic steatosis hepatitis and fibrosis. On the other hand, inducing ferroptosis may restrict the emergence of secondary resistance to current medicines, such as sorafenib, for hepatocellular carcinoma (HCC) therapy. Here, we summarize the biological characteristics and regulatory signalling pathways of ferroptosis involved in liver disease. The current available medical agents targeting ferroptosis, including inducers or inhibitors applied in liver diseases, are also reviewed. This work aims to provide new insight into the emerging role of pathogenesis and therapeutic approaches for liver diseases.

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.

Bone morphogenetic proteins receptor type 1B (BMPR1B) was a multifunctional signaling molecule and its abnormal expression associated with poorer prognosis. We aimed to explore the relationship between BMPR1B polymorphisms and breast cancer susceptibility among northwest population.A total of 450 healthy controls and 434 patients with breast cancers were recruited in this study. Two candidate polymorphisms, rs1434536 and rs1970801 were genotyping using Sequenom MassArray technique. Expression quantitative trait loci analysis in the GTEx portal was adopted to determine the correlation between the rs1434536 and rs1970801 polymorphism and level of BMPR1B expression.We found that the T allele of rs1434536 was associated with an increased susceptibility of breast cancer [CT+TT vs. CC: adjusted OR (95% CI) = 1.35(1.02-1.78), PBMPR1B polymorphisms (rs1434536 and rs1970801) may increase susceptibility to breast cancer in Chinese Han women.

A new family of modified polar codes and a new permutation selection scheme for belief propagation list (BPL) decoding are presented. We first propose a new code construction methodology to interpolate between Reed-Muller (RM) codes and polar codes. By taking advantage of an existing partial order on bit-channels whose corresponding indices share the same Hamming weight, we analyze the complexity of the new construction method. It is shown that we need to compute the reliability of roughly a fraction 1/log3/2N of all the bit-channels contained in the subset. Then, we explore a special family of factor-graph layer permutations called stable permutations (SPs) that preserve a specified information set when the corresponding bit permutations are applied to message bit indices. Simulation results show that the error-rate performance of the new family of codes is better than that of 5G polar codes under successive cancellation list (SCL) decoding. In addition, the SP selection scheme stands out as a preferred one for BPL decoding in terms of error-rate performance, while the average number of iterations per belief propagation (BP) decoder on the permuted factor graph is close to that of the original BP decoder when an early stopping condition is applied.

Cancer is the leading cause of death among children.We report on the latest estimates of the burden of cancer among children at the global, regional, and national levels from 1990 to 2019.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.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.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.

Background Liver cancer has caused a serious disease burden worldwide wherein prognostic risk factors may have had a significant role. However, previous studies have focused on liver cancer distributions and trend variations without analyzing the role of risk factors. Methods We assessed liver cancer burden attributable to five recognized risk factors as well as temporal trends from 1990 to 2019 based on the 2019 Global Burden of Disease Study. The risk exposure levels and their contributed burden were estimated by cause, sex, age, and location. Furthermore, the relationship between the risks and social-demographic index (SDI) was investigated. Results The total liver cancer burden attributable to risk factors is still increasing year by year in terms of death and disability-adjusted life years. However, the burden attributable to alcohol use and smoking has shown a downward trend in recent years. Risk-related burden in males was more than three times as that in females, the burden among the middle-aged and elderly was the most serious, and Central Asia, high-income Asia Pacific and East Asia exhibited the highest burden worldwide. The exposure levels of the five recognized risk factors were generally positively correlated with SDI value. However, the risk-related liver cancer burden first increased and then decreased with the SDI value. Conclusion These findings could help in understanding the role of prognostic risk factors in liver cancer burden, in promoting the development of relevant studies, and in proposing better prevention and control policies tailored to local conditions.

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.

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.

INTRODUCTION Auricular cartilage has been largely reported as an available substitute of defected tarsus to restore lower eyelid stability. However, undesirable results such as displacement, detachment, warping, down-gaze disturbance, and surface irregularity of the cartilage graft have been reported in previous reports, some of which require reoperations. In this study, the authors present a new technique to use strips of auricular cartilage with a local flap to restore the lower eyelid stability for a reliable eyelid support. METHODS From 2013 to 2018, the technique was carried out on 13 patients who suffered inadequate lower eyelid support with cicatricial retraction or ectropion and incomplete eyeball coverage, which was caused by soft tissue deletion secondary to different etiologies. Two kinds of local flaps were used to reconstruct the anterior soft tissue layer, whereas the posterior layer was supported with a π-shaped auricular cartilage. The preoperative and postoperative photographs were taken. Three indexes, including the vertical distance between inferior corneal margin and inferior palpebral margin, the maximal breadth of palpebral conjunctiva caused by ectropion, and the maximal palpebral fissure breadth when eyelid is closed, were measured before and 6 months after the operation to evaluate the operative effect. RESULTS The average follow-up was 32 months (range, 6-62 months). The local flap survived in all patients. No complications were seen in any of the patients. Postoperative average of the aforementioned first 2 indexes measured at 6 months was 0 mm, whereas the preoperative one was 2.69 and 1.08 mm, respectively. Postoperative average of the third index was also far more lower than the preoperative one (0.08 vs 2.77 mm). The difference between the preoperative and postoperative evaluation of the 3 indexes was statistically significant (paired t test, P < 0.001). No further intervention was required. CONCLUSIONS The present technique using a combination of π-shaped auricular cartilage and a local flap provides a satisfying horizontal and vertical support to maintain the lower eyelid in a normal position without compromising the mobility of the lower eyelid. This technique can be used as an effective and safe method for lower eyelid support.

Plough pan can affect crop growth, nutrient uptake and the fates of substances in the environment. To determine the effects of plough pan thickness on crop and environment, a field survey and a field experiment were conducted on a typical calcareous fluvo-aquic soil in a winter wheat-summer maize rotation system in Northern China Plain from 2014 to 2016. Specifically, the thickness of plough pans was surveyed in 108 field plots in 2014, and then based on the survey results a field experiment was established to study the effects of different plough pan thicknesses (PP15: 15 cm of plough pan; PP10: 10 cm of plough pan; PP5: 5 cm of plough pan; PP0: 0 cm of plough pan) on crop growth, nitrogen (N) utilization and the environment. The survey showed that the thickness of topsoil averaged at 14.7 cm, and the plough pan was approximately 15 cm deep. The plough pan was found at 76% of the survey locations, and it was distributed commonly from 15 to 30 cm beneath the soil surface. Breaking the original plough pan partially or completely could promote the net photosynthesis rate, leaf water use efficiency, crop yield, and N use efficiency, decrease N2O emission, but increase CO2 emission. Among all treatments, breaking plough pans completely (PP0) and by 2/3 (PP5) resulted in best crop performance, whose photosynthetic parameters (especially net photosynthetic rate and leaf water use efficiency) were significantly higher than PP10 and PP15. For both wheat and maize, PP5 resulted in greater yield (7 130 kg ha−1 for wheat and 8 240 kg ha−1 for maize) than other treatments. Although it did not differ with PP0 significantly, PP5 had significantly higher N uptake (410 kg ha−1) and N use efficiency (40.1%) than PP10 and PP15. The magnitude of N2O emission peak decreased with an increasing degree of plough pan breakage. The cumulative N2O emission and intensity in PP5 was obviously lower than that in PP10 and PP15. Annual cumulative CO2 emission did not differ significantly among PP5, PP10 and PP15. Net ecosystem productivity (NEP) of the rotation system increased as the thickness of plough pan decreased, so PP5 had relative higher NEP (9 740 kg C ha−1) than PP10 and PP15. Thus, considering better crop growth, higher yield, optimized N utilization, lower N2O and CO2 emissions, as well as higher NEP and less mechanical costs, breaking the original plough pan partially is a good choice to ameliorating the plough pan restrictions in the Northern China Plain.

Background: Currently, there is still some controversy regarding whether early breast cancer patients with a tumor size of ≤5 cm and 1-3 positive lymph nodes should undergo postoperative radiotherapy (PRT). Materials and Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Then, we conducted propensity score matching (PSM), according to the radiotherapy record. The Kaplan-Meier and Cox regression analysis were conducted to explore prognostic factors in breast cancer. Results: A total of 6,777 patients aged 75+ years old were eligible and 2,361 patients were included after PSM. We found PRT could improve patient overall survival (OS) (P = 0.01, hazard ratio [HR] = 0.88, 95% confidence interval [CI], 0.80-0.97). Subgroup analysis revealed PRT could improve OS in patients with hormone receptor positive (HR+) (P = 0.001, HR = 0.84, 95% CI, 0.76 - 0.94) or white patients (P =0.004, HR = 0.86, 95% CI, 0.77 - 0.95). Conclusions: PRT may benefit for elderly women with early breast cancer, especially in HR+ patients or white patients. These findings may inform future optimized options whether elderly female patients with early breast cancer should undergo postoperative radiotherapy.

Increasing antibiotic resistant genes (ARG) are being detected in animal manure-amended soil, causing public concerns. However, the effects of animal manure fertilization on the ARG of vegetable endophytes remain unknown. In this study, high-throughput quantitative PCR (HT-qPCR) was used to explore the effects of poultry manure fertilization on the bacterial community and resistome in the soil, root endophytes, and leaf endophytes from

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., Novel 9‐gene risk signature based on glycolysis‐related genes was developed to predict ovarian cancer survival. A nomogram combining the gene signature and patient characteristics provided superior estimation of overall survival. Our research provided a new prognostic tool and guidelines for future research.

Key Points Question Should patients with T1 N0 M0 triple-negative breast cancer (TNBC) receive routine adjuvant chemotherapy and radiotherapy after surgery? Findings In this cohort study of 7739 postoperative patients diagnosed as having T1 N0 M0 TNBC from the Surveillance, Epidemiology, and End Results cancer registry program, receipt of adjuvant therapies was associated with an overall survival benefit. Adjuvant radiotherapy after breast-conserving surgery was associated with better overall and breast cancer–specific survival in patients aged 70 years and older but not in those younger than 70 years. Meaning Administration of adjuvant therapies to patients with different ages and cancer stages should be discussed carefully, which necessitates guidance from updated guidelines., This cohort study evaluates the association of different adjuvant therapies with survival outcomes in patients with triple-negative breast cancer., Importance Adjuvant chemotherapy remains the only recommended treatment for patients with triple-negative breast cancer (TNBC). However, the existing evidence is not enough to recommend adjuvant therapies to patients with T1 N0 M0 TNBC. Objective To evaluate the association of different adjuvant therapies with survival outcome in patients with T1 N0 M0 TNBC stratified by cancer stage and age. Design, Setting, and Participants Postoperative patients diagnosed as having T1 N0 M0 TNBC between 2010 and 2015 who were enrolled in the Surveillance, Epidemiology, and End Results cancer registry program were included in this population-based cohort study. Data analysis was performed from March 27, 2019, to August 10, 2020. Exposures Chemotherapy and radiotherapy. Main Outcomes and Measures Kaplan-Meier curve and univariate and multivariable Cox proportional hazards regression analyses were performed to compare overall survival (OS) and breast cancer-specific survival (BCSS) between the different treatments. Results A cohort of 7739 eligible patients (mean [SD] age, 59.5 [12.4] years; all female) were included in the present study. The 5-year OS of the total patients was 91.7% (95% CI, 90.9%-92.5%), and median follow-up was 45 months (95% CI, 44-46 months). Patients aged 70 years and older or with T1a TNBC were more likely to receive adjuvant radiotherapy than chemotherapy. Although any adjuvant therapy could improve OS in T1 N0 M0 TNBC, only chemotherapy was associated with significantly better breast cancer–specific survival (BCSS adjusted hazard ratio: 0.657; 95% CI, 0.460-0.939; P = .02). Adjuvant radiotherapy after breast-conserving surgery was associated with better OS and BCSS in patients aged 70 years and older but not in those younger than 70 years. For patients with T1c BC, chemotherapy after breast-conserving surgery or other surgery was associated with improved OS, whereas only chemotherapy after other surgery was associated with better BCSS. Conclusions and Relevance The findings of this cohort study suggest that adjuvant therapies could improve OS in patients with T1 N0 M0 TNBC, whereas only chemotherapy was associated with better BCSS. Older patients with early-stage TNBC may benefit from adjuvant radiotherapy. Administration of adjuvant therapies to patients with different ages and cancer stages should be discussed carefully, which necessitates guidance from updated guidelines.

Key Points Question Can a better prognosis model based on DNA repair–related genes be developed for the comprehensive evaluation of breast cancer? Findings In this prognostic study based on samples from 1096 women, a novel signature for breast cancer constructed using 8 DNA repair–related genes showed satisfactory performance for predicting survival in the training cohort from The Cancer Genome Atlas and the validation cohort from the Gene Expression Omnibus database. The DNA repair–related gene signature was an independent predictor of survival after adjustment for clinical characteristics. Meaning A prognostic signature based on 8 DNA repair–related genes predicted overall survival among female patients with breast cancer, thereby providing a new modality for the accurate diagnosis and targeted treatment of breast cancer., Importance Breast cancer (BC), a common malignant tumor, ranks first among cancers in terms of morbidity and mortality among female patients. Currently, identifying effective prognostic models has a significant association with the prediction of the overall survival of patients with BC and guidance of clinicians in early diagnosis and treatment. Objectives To identify a potential DNA repair–related prognostic signature through a comprehensive evaluation and to further improve the accuracy of prediction of the overall survival of patients with BC. Design, Setting, and Participants In this prognostic study, conducted from October 9, 2019, to February 3, 2020, the gene expression profiles and clinical data of patients with BC were collected from The Cancer Genome Atlas database. This study consisted of a training set from The Cancer Genome Atlas database and 2 validation cohorts from the Gene Expression Omnibus, which included 1096 patients with BC. A prognostic signature based on 8 DNA repair–related genes (DRGs) was developed to predict overall survival among female patients with BC. Main Outcomes and Measures Primary screening prognostic biomarkers were analyzed using univariate Cox proportional hazards regression analysis and the least absolute shrinkage and selection operator Cox proportional hazards regression. A risk model was completely established through multivariate Cox proportional hazards regression analysis. Finally, a prognostic nomogram, combining the DRG signature and clinical characteristics of patients, was constructed. To examine the potential mechanisms of the DRGs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Results In this prognostic study based on samples from 1096 women with BC (mean [SD] age, 59.6 [13.1] years), 8 DRGs (MDC1, RPA3, MED17, DDB2, SFPQ, XRCC4, CYP19A1, and PARP3) were identified as prognostic biomarkers. The time-dependent receiver operating characteristic curve analysis suggested that the 8-gene signature had a good predictive accuracy. In the training cohort, the areas under the curve were 0.708 for 3-year survival and 0.704 for 5-year survival. In the validation cohort, the areas under the curve were 0.717 for 3-year survival and 0.772 for 5-year survival in the GSE9893 data set and 0.691 for 3-year survival and 0.718 for 5-year survival in the GSE42568 data set. This DRG signature mainly involved some regulation pathways of vascular endothelial cell proliferation. Conclusions and Relevance In this study, a prognostic signature using 8 DRGs was developed that successfully predicted overall survival among female patients with BC. This risk model provides new clinical evidence for the diagnostic accuracy and targeted treatment of BC., This prognostic study evaluates a potential DNA repair–related prognostic signature to improve the accuracy of prediction of the overall survival of patients with breast cancer.

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.

Autophagy dysregulation is implicated in cadmium (Cd)-induced nephrotoxicity. The mammalian target of rapamycin complex 1 (mTORC1) is a negative regulator of autophagy, but its role in Cd-induced autophagy inhibition and possible regulatory mechanisms remains poorly understood. In the present study, Cd exposure activated mTORC1 in primary rat proximal tubular (rPT) cells, and two mTORC1 inhibitors (rapamycin and torin 1) were separately utilized to inhibit Cd-induced mTORC1 activation. Data showed that Cd-inhibited autophagic flux was markedly restored by two mTORC1 inhibitors, respectively, as evidenced by immunoblot analysis of autophagy marker proteins and tandem red fluorescent protein-green fluorescent protein-microtubule associated protein light chain 3 (RFP-GFP-LC3) fluorescence microscopy assay. Importantly, Cd exposure triggered the recruitment of mTORC1 onto lysosome membrane assessed by immunofluorescence co-localization analysis, which was obviously inhibited by rapamycin or torin 1. Moreover, Cd-induced lysosomal alkalization, suppressed vacuolar ATPases (V-ATPases) protein levels and impaired lysosomal degradation capacity were markedly reversed by rapamycin or torin 1. In summary, these findings demonstrate that Cd recruits mTORC1 to lysosome membrane to induce its activation, which results in lysosomal dysfunction and resultant autophagy inhibition in rPT cells.

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.

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.

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 P = 0.02]. Comparison between case groups showed genotype GG and TG/GG of rs3087918 were associated with her-2 receptor expression [GG vs. TT: OR (95%) = 2.37(1.24–4.63), P = 0.010; TG + GG vs. TT: OR (95%) = 1.50(1.01–2.24), P = 0.045]. We didn’t find statistical significance for rs11160608, rs7158663 and breast cancer. Structure prediction based on RNAfold found rs3087918 may influence the secondary structure of MEG3. The results based on lncRNASNP2 indicated that rs3087918 may gain the targets of hsa-miR-1203 to MEG3, while loss the target of hsa-miR-139-3p and hsa-miR-5091 to MEG3. Conclusions MEG3 rs3087918 was associated with a decreased risk of breast cancer. MEG3 haplotype TCG may increase the risk of breast cancer.

Studies have suggested that thymidylate (TYMS) polymorphisms are associated with breast cancer. However, inconsistent results were obtained and data from Asian populations are largely lacking. In this study, the relationships between two common TYMS polymorphisms (rs2790 and rs1059394) and the breast cancer risk were evaluated. We also studied the TYMS expression between tumor and para-carcinoma tissues, and the association between TYMS levels and prognosis of breast cancer. This hospital-based study included 434 patients and 450 cancer-free individuals. Genotying was performed using Sequenom Mass-ARRAY. The microarray dataset GSE115144 was downloaded to compare the differences in TYMS expression between tumor and para-carcinoma tissues. The microarray dataset GSE20685 was used to analysis the metastasis free survival (MFS) and overall survival (OS) of patients. The rs2790 polymorphism was related to a higher risk of breast cancer (recessive model: OR=1.50, 95%CI=1.02-2.21, P=0.038) and the C allele of rs1059394 was overrepresented in patients with tumor stage III-IV (heterozygote model: OR=0.60, 95%CI=0.39-0.94, P=0.025; dominant model: OR=0.59, 95%CI=0.39-0.89, P=0.013). The tumor tissues had a higher TYMS expression levels and patients with higher TYMS expression levels had worse OS. Overall, TYMS polymorphism may increase susceptibility to breast cancer in Chinese Han women and TYMS expression levels may be a predictive factor for breast cancer patients.

Introduction Sonodynamic Therapy (SDT) has good targeting and non-invasive advantages in solid cancers, but its antitumor effect is not sufficient to replace traditional treatments. Some studies that combined SDT with chemotherapy or nanoparticles have managed to enhance its efficiency and overcome the side effects of chemotherapy. Materials and Methods In this study, we synthesized and characterized mesoporous silica nanoparticles (MSN-DOX-Ce6) loaded with doxorubicin (DOX) and sonosensitizer, chlorin e6 (Ce6). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of MSN-DOX-Ce6 under ultrasound (US) treatment. Results The characterization tests showed that the nanoparticles are uniformly sized spheres with mesoporous structure, resulting in a high drug-loading efficiency. In the in vitro experiments, MSN-DOX-Ce6 could effectively inhibit cell proliferation under US but not more than other treatment groups. However, the in vivo studies showed that MSN-DOX-Ce6+US has better antitumor effect than DOX+Ce6+US or DOX alone on xenograft tumor-bearing mice. Conclusion In summary, MSNs showed a great potential for DOX and Ce6 delivery. We concluded that under US, MSN-DOX-Ce6 nanocomposites increase the antitumor effect of DOX and SDT and thereby are a potential treatment for solid tumors.

Previous studies have indicated a correlation between nut intake and cancer risk in humans. This meta-analysis aimed to determine the relationship between nut consumption and the risks of cancer incidence and mortality. The PubMed, Embase, and Web of Science databases were searched up to August 2019. Relative risks and 95% confidence intervals were calculated using random-effects and fixed-effects models. We included 38 studies on nut consumption and cancer risk and 9 studies on cancer-specific mortality. Compared with no nut intake, nut intake was associated with a lower cancer risk (Relative Risk=0.90; 95% confidence interval, 0.86-0.94). Inverse associations were observed with colorectal cancer, gastric cancer, pancreatic cancer, and lung cancer in subgroup analyses. Tree nut consumption was found to reduce cancer risk (Relative Risk=0.88; 95% confidence interval, 0.79-0.99). Dose-response curves suggested that protective benefits against cancer increased with increased nut intake (P=0.005, P-nonlinearity=0.0414). An inverse correlation with cancer-specific mortality (Odd Ratio=0.90; 95% confidence interval, 0.88-0.92) was observed. In conclusion, nut consumption is inversely associated with the risks of cancer incidence and mortality; a higher intake is significantly associated with a lower cancer risk.

Several studies have indicated that the use of antihypertensive medications may influence the incidence of bladder/kidney cancer, with some scholars refuting any such association. Hence, a systematic review is needed to verify this linkage. we comprehensively searched PubMed, Embase, Web of Science, and the Cochrane Library for original studies reporting a relationship between antihypertensive medications and risk of bladder/kidney cancer. We included 31 articles comprising 3,352,264 participants. We found a significant association between the risk of kidney cancer and any antihypertensive medications use (relative risk (RR) = 1.45, 95% CI 1.20-1.75), as well as angiotensin-converting enzyme inhibitors (RR = 1.24, 95% CI 1.04-1.48), angiotensin II receptor blockers (ARB) (RR = 1.29, 95% CI:1.22-1.37), beta-blockers (RR = 1.36, 95% CI 1.11-1.66), calcium-channel blockers (RR = 1.65, 95% CI 1.54-1.78) and diuretics (RR = 1.34, 95% CI 1.19-1.51). In case of bladder cancer, a statistical significance was observed with the use of ARB (RR = 1.07, 95% CI 1.03-1.11) but not with the other antihypertensive medications. There was a linear association between the duration of antihypertensive medications and the risk of kidney cancer (P = 0.061 for a non-linear trend) and the pooled RR for the per year increase in antihypertensive medications duration of use was 1.02 (95% CI: 1.01-1.02). Our results indicate that there is a significant association between each class of antihypertensive medications and the risk of kidney cancer, and this trend presented as a positive linear association. Furthermore, the use of ARB has been linked to the risk of bladder cancer.