Continuous cropping system altered soil microbial communities and nutrient cycles.

Understanding the response of microbial communities and their potential functions is essential for sustainability of agroecosystems under long-term continuous cropping. However, limited research has focused on investigating the interaction between soil physicochemical factors and microbial community dynamics in agroecosystems under long-term continuous cropping. This study probed into the physicochemical properties, metabolites, and microbial diversity of tobacco rhizosphere soils cropped continuously for 0, 5, and 20 years. The relative abundance of bacterial genera associated with nutrient cycling (e.g., Sphingomonas) increased while potential plant pathogenic fungi and beneficial microorganisms showed synergistic increases with the duration of continuous cropping. Variations in soil pH, alkeline nitrogen (AN) content, and soil organic carbon (SOC) content drove the shifts in soil microbial composition. Metabolites such as palmitic acid, 3-hydroxypropionic acid, stearic acid, and hippuric acid may play a key role in soil acidification. Those results enhance our ability to predict shifts in soil microbial community structure associated with anthropogenic continuous cropping, which can have long-term implications for crop production.

Evaluating the efficacy of balloon pulmonary angioplasty using quantitative analysis of SPECT pulmonary ventilation/perfusion scintigraphy in patients with chronic thromboembolic pulmonary hypertension.

Background: Single-photon emission computed tomography (SPECT) ventilation perfusion imaging is the main imaging method for the diagnosis of pulmonary embolism, and its application in the diagnosis and efficacy evaluation of chronic thromboembolic pulmonary hypertension (CTEPH) has been paid more and more attention. In recent years, with the development of computer software technology, ventilation/perfusion (V/Q) imaging quantitative analysis technology has become more and more mature. The objective of this study was to investigate the utility of quantitative analysis of pulmonary V/Q scintigraphy in evaluating the efficacy of balloon pulmonary angioplasty (BPA) in patients with CTEPH. Methods: In this retrospective analysis, we collected data of patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital from April 2018 to September 2020. The sample consisted of 23 males and 28 females, with an average age of 55.1±12.7 years. All patients underwent V/Q scintigraphy within one week before surgery, and we reviewed the pulmonary angiography within 1-3 months following the last BPA procedure. We repeated V/Q scintigraphy within 1 week before or after the pulmonary angiography, at the time of collecting clinical and hemodynamic parameters of these patients. We divided the patients into two groups based on the presence of residual pulmonary hypertension post-surgery and compared the pre- and post-operative quantitative pulmonary perfusion defect percentage scores (PPDs%) using the t-test. Results: In all, 102 V/Q scintigraphy scans were performed in 51 patients. The quantitative PPDs% were positively correlated with the hemodynamic indexes mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and mean right ventricular pressure (RVP) (r=0.605, 0.391, and 0.464, respectively, all P<0.001) and negatively correlated with the 6-minute walking distance (6MWD) (r=-0.254, P=0.010). The average preoperative quantitative PPDs% were (49.0±15.6)% which significantly decreased to (33.5±13.9)% after surgery (t=11.249, P<0.001). The preoperative quantitative PPDs% were (54.7±15.7)% and (44.0±13.8)% in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=2.599, P=0.012). The postoperative quantitative PPDs% were (41.5±12.5)% and (26.3±11.0)%, in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=4.647, P<0.001). Conclusions: In this study, we found that quantitative analysis of SPECT pulmonary V/Q scintigraphy adequately reflected the pulmonary artery pressure and clinical status in patients with CTEPH. Our results demonstrate its definite utility in predicting residual pulmonary hypertension and in evaluating the postoperative efficacy of BPA in patients with CTEPH.

Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.

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

From genomic spectrum of NTRK genes to adverse effects of its inhibitors, a comprehensive genome-based and real-world pharmacovigilance analysis.

Introduction: The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has facilitated the development of precision oncology. Two first-generation NTRK inhibitors (larotrectinib and entrectinib) are currently approved for the treatment of patients with solid tumors harboring NTRK gene fusions. Nevertheless, comprehensive NTRK profiling at the pan-cancer genomic level and real-world studies pertaining to the adverse events of NTRK inhibitors are lacking. Methods: We characterize the genome of NTRK at the pan-cancer level through multi-omics databases such as The Cancer Genome Atlas (TCGA). Through the FDA Adverse Event Reporting System (FAERS) database, we collect reports of entrectinib and larotrectinib-induced adverse events and perform a pharmacovigilance analysis using various disproportionality methods. Results: NTRK1/2/3 expression is lower in most tumor tissues, while they have higher methylation levels. NTRK gene expression has prognostic value in some cancer types, such as breast invasive carcinoma (BRCA). The cancer type with highest NTRK alteration frequency is skin cutaneous melanoma (SKCM) (31.98%). Thyroid carcinoma (THCA) has the largest number of NTRK fusion cases, and the most common fusion pair is ETV6-NTRK3. Adverse drug events (ADEs) obtained from the FAERS database for larotrectinib and entrectinib are 524 and 563, respectively. At the System Organ Class (SOC) level, both drugs have positive signal value for "nervous system disorder". Other positive signals for entrectinib include "cardiac disorders", "metabolism and nutrition disorders", while for larotrectinib, it is "hepatobiliary disorders". The unexpected signals are also listed in detail. ADEs of the two NTRK inhibitors mainly occur in the first month. The median onset time of ADEs for entrectinib and larotrectinib was 16 days (interquartile range [IQR] 6-86.5) and 44 days ([IQR] 7-136), respectively. Conclusion: Our analysis provides a broad molecular view of the NTRK family. The real-world adverse drug event analysis of entrectinib and larotrectinib contributes to more refined medication management.

Effect of T Stages on the Choice of Axillary Evaluation Modality in Breast Cancer Patients With 1-2 Sentinel Lymph Node Metastases.

INTRODUCTION: The survival benefit of axillary lymph node dissection (ALND), sentinel lymph node biopsy (SLNB) combined with radiation, and ALND combined with radiation remains unclear in breast cancer (BC) patients with 1-2 metastatic sentinel lymph nodes (SLNs). This study aims to rigorously evaluate the prognostic impact of these axillary evaluation modalities on BC patients with varying T-stages and to construct a survival prediction nomogram. METHODS: Following screening for inclusion and exclusion criteria, data pertaining to BC patients were extracted from the SEER database. Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Kaplan-Meier curves and Cox proportional hazards model among patients with different stages who underwent various axillary evaluation modalities. A nomogram was constructed to predict the probability of OS and BCSS. RESULTS: A total of 20,283 patients were included, comprising 9626 who underwent breast-conserving surgery (BCS) and 10,657 who underwent mastectomy. In the T4 stage stratified analysis, both BCS and mastectomy groups exhibited superior OS and BCSS with ALND compared to SLNB combined with radiation. Further, ALND combined with radiation improved OS. However, for T1-3 stages, patients treated with ALND experienced similar or worse survival compared to those treated with SLNB combined with radiation. The calibration curve and C-index (0.746-0.794) of the nomogram demonstrated the efficacy of the survival prediction model. CONCLUSION: In T1-3 BC patients with 1-2 metastatic SLNs, SLNB combined with radiation is a safe alternative to ALND. Conversely, for T4 patients, ALND combined with radiation may offer a preferable choice.

Stachydrine represses the proliferation and enhances cell cycle arrest and apoptosis of breast cancer cells via PLA2G2A/DCN axis.

Considering the therapeutic efficacy of Stachydrine on breast cancer (BC), this study aims to decipher the relevant mechanism. The effects of Stachydrine on BC cell viability, proliferation and apoptosis were firstly investigated. Then, Bioinformatics was applied to sort out the candidate interacting with Stachydrine as well as its expression and downstream target in BC. Relative expressions of genes of interest as well as proliferation- and apoptosis-related factors in BC cells were quantified through quantitative reverse-transcription PCR and western blot as appropriate. As a result, Stachydrine inhibited the proliferation, down-regulated the expressions of proliferating cell nuclear antigen and CyclinD1, enhanced cell cycle arrest and apoptosis, and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9 in BC cells. Phospholipase A2 Group IIA (PLA2G2A) was predicted as the candidate interacting with Stachydrine and to be lowly expressed in BC. PLA2G2A silencing reversed while PLA2G2A overexpression reinforced the effects of Stachydrine. Decorin (DCN) was the downstream target of PLA2G2A and also lowly expressed in BC. PLA2G2A silencing counteracted yet overexpressed PLA2G2A strengthened the promoting effects of Stachydrine on DCN level. Collectively, Stachydrine inhibits the growth of BC cells to promote cell cycle arrest and apoptosis via PLA2G2A/DCN axis.

Characteristics of soil microbial communities in farmland with different comprehensive fertility levels in the Panxi area, Sichuan, China.

Soil bacterial communities are intricately linked to ecosystem functioning, and understanding how communities assemble in response to environmental change is ecologically significant. Little is known about the assembly processes of bacteria communities across agro-ecosystems, particularly with regard to their environmental adaptation. To gain further insights into the microbial community characteristics of agro-ecosystems soil in the Panxi area of Sichuan Province and explore the key environmental factors driving the assembly process of the microbial community, this study conducted field sampling in major farmland areas of Panxi area and used Illumina MiSeq high-throughput sequencing technology to conduct bacterial sequencing. Soil organic matter (SOM), alkali-hydrolyzed nitrogen (AN), available phosphorus (AP), available potassium (AK) and other environmental factors were determined. The membership function method and principal component analysis method were used to evaluate the fertility of the soil. The results revealed minimal differences in alpha diversity index among samples with different comprehensive fertility indices, while NMDS analysis showed that community differences between species were mainly reflected in high fertility and low fertility (R: 0.068, p: 0.011). Proteobacteria, Acidobacteria and Actinobacteria were the main types of microbial communities, accounting for more than 60% of the relative abundance. Proteobacteria accounted for a higher proportion in the high fertility samples, while Acidobacteria and Actinobacteria accounted for a higher proportion in the middle and low fertility samples. Both the neutral theoretical model and zero model analysis showed that the microbial communities in tobacco-planting soil with different comprehensive fertility indices presented a random assembly process. With the increase in environmental distance difference, the diversity of the microbial community in medium and low-fertility soil also increased, but there was no significant change in high-fertility soil. Redundancy analysis showed that pH and SOM were the key factors affecting microbial community composition. The results of this study can provide a theoretical reference for the study of environmental factors and microbial communities in tobacco-growing soil.

Comprehensive analysis of nicotinamide metabolism-related signature for predicting prognosis and immunotherapy response in breast cancer.

Background: Breast 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. Methods: Transcriptional 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. Results: We 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). Conclusions: The novel signature offers a promising way to evaluate the prognosis and treatment efficacy in BC patients, which may facilitate clinical practice and management.

Convergence of 3D Bioprinting and Nanotechnology in Tissue Engineering Scaffolds.

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.

Heterogeneous changes of chemical compositions, sources and health risks of PM2.5 with the "Clean Heating" policy at urban/suburban/industrial sites.

China has enacted the "Clean Heating" (CH) policy in north China. The domain-specific impacts on PM2.5 constituents and sources in small cities are still lacking, which obstruct the further policy optimization. Here, we performed an intensive observation covering the heating period (HP) and pre-heating period (PHP) in winter of 2017 at urban (UR), industrial (IS), and suburban (SUR) sites in one of the "2 + 26" cities. The mean PM2.5 concentrations at UR and IS decreased by 15.2 % and 4.6 %, while increased by 9.8 % at SUR in the HP compared with the PHP, indicating the heterogeneous responses. The lowest contribution percentages of coal combustion (14.6 %) and industrial emissions (17.1 %) to PM2.5 at UR in the HP implied the CH policy played more effective role. The most increase in NO3-/SO42- ratio by 26.8 % and the highest NO3- concentration at UR in the HP were linked mainly with the thermal-NOx emitted from natural gas (NG) burning in view of NOx emission reductions from other sources. The highest concentrations of OC, SO42-, K+, and Cl-, and contribution percentages of biomass burning (20.0 %) and coal combustion (24.8 %) to PM2.5 at SUR in the HP evidenced the enhanced usage of biomass/coal. Coal banning in the HP at IS and UR led to the obvious decreases in OC, SO42-, As, and Sb. Secondary nitrate became the largest PM2.5 source at IS and UR in the HP. Coal banning, emission control on large-size enterprises and ignored control on small-size enterprises efficiently modified the concentrations and health risks of heavy metals. The lowest carcinogenic risks moved from SUR in the PHP to UR in the HP. The policies on de-NOx of NG-burning related enterprises, reduction of biomass/coal usage in suburban area, and strict regulation of small-size enterprises were urgently need to further improve the air quality.

Effects of alfalfa saponins on the production performance, serum biochemical factors, and immune factors in Small-Tailed Han sheep.

This study aimed to determine the potential effects of alfalfa saponins on the production performance, serum biochemical factors, and immune factors in sheep. Twenty Small-Tailed Han sheep were equally and randomly divided into Groups 1-4, fed with diets containing 0, 5, 10, and 20 g alfalfa saponins per kg, respectively, for 40 consecutive days. During the treatments, the body weight change was recorded for each sheep. Before, during, and after the treatments of alfalfa saponins, serum was collected from each group to compare the levels of biochemical and immune factors. All sheep were killed after the treatments, and the longissimus dorsi muscle was collected to compare the meat quality. The results validated the effects of alfalfa saponins on the growth performance and meat quality in Small-Tailed Han sheep, and the supplementation level of 10 g/kg was the best. Alfalfa saponins also had effects on the levels of biochemical factors in serum. However, both dose- and time-dependent effects were observed. After a shorter feeding period (14 days), the concentrations of cholesterol (CHOL) and low-density lipoprotein (LDL) in Groups 2, 3, and 4 were all lower than those in the control group; however, when alfalfa saponins were continuously fed, this effect was not apparent or even gone. Supplying alfalfa saponins increased serum concentrations of IgA, IgG, IgE, IgM, IL-1, IFN-α, and IFN-ß. And this effect was distinctly observed in Groups 3 and 4. Based on the current results, the alfalfa saponins concentration of 10 g/kg (for 14 consecutive days) could be suggested as the optimum ratio for good health conditions of Small-Tailed Han sheep.

Research on Positioning Method in Underground Complex Environments Based on Fusion of Binocular Vision and IMU.

Aiming at the failure of traditional visual slam localization caused by dynamic target interference and weak texture in underground complexes, an effective robot localization scheme was designed in this paper. Firstly, the Harris algorithm with stronger corner detection ability was used, which further improved the ORB (oriented FAST and rotated BRIEF) algorithm of traditional visual slam. Secondly, the non-uniform rational B-splines algorithm was used to transform the discrete data of inertial measurement unit (IMU) into second-order steerable continuous data, and the visual sensor data were fused with IMU data. Finally, the experimental results under the KITTI dataset, EUROC dataset, and a simulated real scene proved that the method used in this paper has the characteristics of stronger robustness, better localization accuracy, small size of hardware equipment, and low power consumption.

Paranasal Augmentation: A Viable and Simplified Modality With Diced Expanded Polytetrafluoroethylene.

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.

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

A simpler noninvasive method of predicting markedly elevated pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension.

Several echocardiographic methods to estimate pulmonary vascular resistance (PVR) have been proposed. So far, most studies have focused on relatively low PVR in patients with a nonspecific type of pulmonary hypertension. We aimed to clarify the clinical usefulness of a new echocardiographic index for evaluating markedly elevated PVR in chronic thromboembolic pulmonary hypertension (CTEPH). We studied 127 CTEPH patients. We estimated the systolic and mean pulmonary artery pressure using echocardiography (sPAPEcho, mPAPEcho) and measured the left ventricular internal diameter at end diastole (LVIDd). sPAPEcho/LVIDd and mPAPEcho/LVIDd were then correlated with invasive PVR. Using receiver operating characteristic curve analysis, a cutoff value for the index was generated to identify patients with PVR > 1000 dyn·s·cm-5. We analyzed pre- and postoperative hemodynamics and echocardiographic data in 49 patients who underwent pulmonary endarterectomy (PEA). In this study, mPAPEcho/LVIDd moderately correlated with PVR (r = 0.51, p < 0.0001). There was a better correlation between PVR and sPAPEcho/LVIDd (r = 0.61, p < 0.0001). sPAPEcho/LVIDd ≥ 1.94 had an 77.1% sensitivity and 75.4% specificity to determine PVR > 1000 dyn·s·cm-5 (area under curve = 0.804, p < 0.0001, 95% confidence interval [CI], 0.66-0.90). DeLong's method showed there was a statistically significant difference between sPAPEcho/LVIDd with tricuspid regurgitation velocity2/velocity-time integral of the right ventricular outflow tract (difference between areas 0.14, 95% CI, 0.00-0.27). The sPAPEcho/LVIDd and mPAPEcho/LVIDd significantly decreased after PEA (both p < 0.0001). The sPAPEcho/LVIDd and mPAPEcho/LVIDd reduction rate (ΔsPAPEcho/LVIDd and ΔmPAPEcho/LVIDd) was significantly correlated with PVR reduction rate (ΔPVR), respectively (r = 0.58, p < 0.01; r = 0.69, p < 0.05). In conclusion, the index of sPAPEcho/LVIDd could be a simpler and reliable method in estimating CTEPH with markedly elevated PVR and also be a convenient method of estimating PVR both before and after PEA.

Global Burden of Female Breast Cancer: Age-Period-Cohort Analysis of Incidence Trends From 1990 to 2019 and Forecasts for 2035.

Introduction: This 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. Methods: Data 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. Results: In 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. Conclusions: The 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.

Global, regional, and national childhood cancer burden, 1990-2019: An analysis based on the Global Burden of Disease Study 2019.

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

BMPR1B Polymorphisms (rs1434536 and rs1970801) are Associated With Breast Cancer Susceptibility in Northwest Chinese Han Females: A Case-Control Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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), Padjusted= 0.034; CT vs. CC adjusted OR (95% CI) = 1.39(1.03-1.87), Padjusted= 0.029]. For rs1970801, carrying minor allele T was significantly associated with an increased risk of breast cancer [GT+TT vs. GG: adjusted OR (95% CI) = 1.52(1.14-2.01), Padjusted= 0.004; GT vs. GG adjusted OR (95% CI) = 1.56(1.15-2.09), Padjusted= 0.004]. Stratified analyses found statistical significance existing in women under 49 years of age, BMI less than 24 kg/m2, and premenopausal women for both rs1434536 and rs1970801. Expression quantitative trait loci analysis in the GTEx portal proved that the minor alleles of rs1434536 T and rs1970801 T was significantly associated with higher expression level of BMPR1B. CONCLUSION: BMPR1B polymorphisms (rs1434536 and rs1970801) may increase susceptibility to breast cancer in Chinese Han women.

The accuracy and influencing factors of Doppler echocardiography in estimating pulmonary artery systolic pressure: comparison with right heart catheterization: a retrospective cross-sectional study.

BACKGROUND: Noninvasive assessment of pulmonary artery systolic pressure by Doppler echocardiography (sPAPECHO) has been widely adopted to screen for pulmonary hypertension (PH), but there is still a high proportion of overestimation or underestimation of sPAPECHO. We therefore aimed to explore the accuracy and influencing factors of sPAPECHO with right heart catheterization (RHC) as a reference. METHODS: A total of 218 highly suspected PH patients who underwent RHC and echocardiography within 7 days were included. The correlation and consistency between tricuspid regurgitation (TR)-related methods and RHC results were tested by Pearson and Bland-Altman methods. TR-related methods included peak velocity of TR (TR Vmax), TR pressure gradient (TR-PG), TR mean pressure gradient (TR-mPG), estimated mean pulmonary artery pressure (mPAPECHO), and sPAPECHO. With mPAP ≥ 25 mm Hg measured by RHC as the standard diagnostic criterion of PH, the ROC curve was used to compare the diagnostic efficacy of sPAPECHO with other TR-derived parameters. The ratio (sPAPECHO-sPAPRHC)/sPAPRHC was calculated and divided into three groups as follows: patients with an estimation error between - 10% and + 10% were defined as the accurate group; patients with an estimated difference greater than + 10% were classified as the overestimated group; and patients with an estimation error greater than - 10% were classified as the underestimated group. The influencing factors of sPAPECHO were analyzed by ordinal regression analysis. RESULTS: sPAPECHO had the highest correlation coefficient (r = 0.781, P < 0.001), best diagnostic efficiency (AUC = 0.98), and lowest bias (mean bias = 0.07 mm Hg; 95% limits of agreement, - 32.08 to + 32.22 mm Hg) compared with other TR-related methods. Ordinal regression analysis showed that TR signal quality, sPAPRHC level, and pulmonary artery wedge pressure (PAWP) affected the accuracy of sPAPECHO (P < 0.05). Relative to the good signal quality, the OR values of medium and poor signal quality were 0.26 (95% CI: 0.14, 0.48) and 0.23 (95% CI: 0.07, 0.73), respectively. Compared with high sPAPRHC level, the OR values of low and medium sPAPRHC levels were 21.56 (95% CI: 9.57, 48.55) and 5.13 (95% CI: 2.55, 10.32), respectively. The OR value of PAWP was 0.94 (95% CI: 0.89, 0.99). TR severity and right ventricular systolic function had no significant effect on the accuracy of sPAPECHO. CONCLUSIONS: In this study, we found that all TR-related methods, including sPAPECHO, had comparable and good efficiency in PH screening. To make the assessment of sPAPECHO more accurate, attention should be paid to TR signal quality, sPAPRHC level, and PAWP.