AcornHRD: an HRD algorithm highly associated with anthracycline-based neoadjuvant chemotherapy in breast cancer in China.

PURPOSE: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. METHODS AND MATERIALS: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. RESULTS: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005]). CONCLUSION: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.

HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis.

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation's effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers (p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64-1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61-1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

Targeting Molecular Mechanisms of Obesity- and Type 2 Diabetes Mellitus-Induced Skeletal Muscle Atrophy with Nerve Growth Factor.

Skeletal muscle plays a critical role in metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). Muscle atrophy, characterized by a decrease in muscle mass and function, occurs due to an imbalance between the rates of muscle protein synthesis and degradation. This study aimed to investigate the molecular mechanisms that lead to muscle atrophy in obese and T2DM mouse models. Additionally, the effect of nerve growth factor (NGF) on the protein synthesis and degradation pathways was examined. Male mice were divided into three groups: a control group that was fed a standard chow diet, and two experimental groups that were fed a Western diet. After 8 weeks, the diabetic group was injected with streptozotocin to induce T2DM. Each group was then further divided into NGF-treated or non-treated control group. In the gastrocnemius muscles of the Western diet group, increased expressions of myostatin, autophagy markers, and ubiquitin ligases were observed. Skeletal muscle tissue morphology indicated signs of muscle atrophy in both obese and diabetic mice. The NGF-treated group showed a prominent decrease in the protein levels of myostatin and autophagy markers. Furthermore, the NGF-treated group showed an increased Cyclin D1 level. Western diet-induced obesity and T2DM may be linked to muscle atrophy through upregulation of myostatin and subsequent increase in the ubiquitin and autophagy systems. Moreover, NGF treatment may improve muscle protein synthesis and cell cycling.

Prediction of heavy metal lead contamination accident in Three Gorges Reservoir Area.

Water contamination incidents have become a significant ecological and environmental threat, particularly concerning the security of drinking water source areas (DWSAs). This research aimed to address this issue by integrating Geographic Information System (GIS) into bidimensional hydrodynamic water quality mathematical model developed using C + + and FORTRAN programming languages. The focus was on the Heshangshan drinking water source area (HDWSA), and the TECPLOT360 software was utilized for visualizing pollutant migration and dispersion processes. The study specifically considered a hypothetical lead (Pb) contamination accident, which is situated in the Three Gorges Reservoir Area (TGRA). The spatio-temporal variations in Pb concentration throughout the entire DWSA were analyzed, along with a comparison of Pb concentration changes during different water seasons. The results indicate that, during the accident, the Pb concentration at the water intake in the drought season, decline season, flood season, and impounding season reached the standard limits at 76, 58, 44, and 48 min, respectively. Moreover, the entire DWSA achieved standard levels of Pb concentration at 124, 89, 71, and 74 min during the respective seasons. The study also observed an expansion and subsequent contraction of the Pb contamination area in the DWSA, with the transfer rate of Pb concentration ranked as flood season > impounding season > decline season > drought season.

The Associations between Exposure to Multiple Heavy Metals and Total Immunoglobulin E in U.S. Adults.

Immunoglobulin E (IgE) is a type of immunoglobulin, and elevated serum total IgE is often present in allergic diseases. Exposure to environmental heavy metals has been markedly linked to allergic diseases, leading to elevated total IgE levels. However, studies concerning the effects of multiple metal exposures on total IgE levels are limited. Therefore, the current study seeks to explore the correlation between heavy-metal co-exposure and total IgE levels based on the National Health and Nutrition Examination Survey (NHANES, 2005-2006). Participants possessed complete data on total IgE levels, 11 urinary metal concentrations and other covariates. The correlations between 11 metals and total IgE levels were analyzed using multiple linear regression, and total IgE levels were a continuous variable. Total IgE levels exceeding 150 kU/L were considered sensitized. Binary logistic regression analyses were employed to assess the correlation between metal exposure and the occurrence of an allergic state. Then, the association between co-exposure to the 11 metals and total IgE levels or the occurrence of sensitization status was further analyzed by Bayesian kernel machine regression (BKMR), a multi-contaminant model. There were 1429 adults with complete data included. Based on the median concentration, molybdenum (Mo) had the highest concentration (46.60 µg/L), followed by cesium (Cs), barium (Ba), lead (Pb), and mercury (Hg). And the median (interquartile range) for total IgE levels was 43.7 (17.3, 126.0) kU/L. Multiple linear regression results showed that Pb was significantly and positively associated with total IgE levels (ß = 0.165; 95% CI: 0.046, 0.284). Binary logistic regression showed a significant positive correlation between urinary Pb (OR: 1.258; 95% CI: 1.052, 1.510) and tungsten (W) (OR: 1.251; 95% CI: 1.082, 1.447). Importantly, the BKMR model found a positive correlation between combined-metal exposure and total IgE levels and the occurrence of sensitization status. The mixed heavy-metal exposure was associated with increased total IgE levels, and this association may be driven primarily by the exposure of Pb and W. This study provides new insights into the relationship between heavy-metal exposure and allergic diseases. More research is needed to confirm these findings.

Rice Seed Protrusion Quantitative Trait Loci Mapping through Genome-Wide Association Study.

The germination of seeds is a prerequisite for crop production. Protrusion is important for seed germination, and visible radicle protrusion through seed covering layers is the second phase of the process of seed germination. Analyzing the mechanism of protrusion is important for the cultivation of rice varieties. In this study, 302 microcore germplasm populations were used for the GWAS of the protrusion percentage (PP). The frequency distribution of the PP at 48 h and 72 h is continuous, and six PP-associated QTLs were identified, but only qPP2 was detected repeatedly two times. The candidate gene analysis showed that LOC_Os02g57530 (ETR3), LOC_Os01g57610 (GH3.1) and LOC_Os04g0425 (CTB2) were the candidate genes for qPP2, qPP1 and qPP4, respectively. The haplotype (Hap) analysis revealed that Hap1 of ETR3, Hap1 and 3 of GH3.1 and Hap2 and 5 of CTB2 are elite alleles for the PP. Further validation of the germination phenotype of these candidate genes showed that Hap1 of ETR3 is a favorable allele for the germination percentage; Hap3 of GH3.1 is an elite allele for seed germination; and Hap5 of CTB2 is an elite allele for the PP, the germination percentage and the vigor index. The results of this study identified three putative candidate genes that provide valuable information for understanding the genetic control of seed protrusion in rice.

A new assessment method for water environment safety and its application.

The Three Gorges Reservoir area is recognized by its vast size, dense population, bustling economic and social activities along its banks, and by the significant volume of waterway traffic. These factors make it with a high risk of water pollution accidents, posing a serious threat to water environmental safety. Therefore, it is imperative to conduct a water environmental safety assessment in this region to ensure the safety of the water environment. In the present work, the Driving-Pressure-State-Impact-Response-Risk Water Environmental Safety model was proposed, and a comprehensive water environmental safety assessment system was established. The Water Environment Safety Index was introduced to measure the degree of water environment safety. This model synthesized multiple factors and their interrelationships, enabling a more accurate assessment of water environment safety. By adopting scientifically rigorous evaluation criteria, this assessment method enhanced the reliability and credibility of the results obtained. The water environment safety in the 22 counties and districts of the Three Gorges Reservoir area of Chongqing region from 2017 to 2021 was assessed in terms of temporal changes and spatial differentiation. In general, the overall water environment safety situation in the Three Gorges Reservoir area of Chongqing region is relatively safe, but a few counties/districts (such as Wanzhou District, Jiangjin District, etc.) are still in Warning. Spatially, the water environmental safety condition was relatively better in the northeast compared to the southwest. The main factors threatening water environment safety include: 1) the consequence of the Three Gorges Project, 2) severe soil erosion, 3) industrial, agricultural, and domestic pollution, and 4) frequent water pollution accidents. The present work provided a new method for conducting water environment safety assessments, which is expected to positively contribute to further research in this field.

Prediction and countermeasures of heavy metal copper pollution accident in the Three Gorges Reservoir Area.

In order to mitigate the hazards of water pollution in drinking water source areas (DWSAs), developing applicable models and proposing effective solutions is of paramount significance. The study developed the Heshangshan Drinking Water Source Area (HDWSA) Hydrodynamic Model, integrating Geographic Information System (GIS) into a two-dimensional hydrodynamic water quality model using FORTRAN. TECPLOT360 software (Software Tools for Numerical Simulation with Visualization) visualized contamination transportation and diffusion. The model's relative error is less than 6%, indicating its strong stability and high reliability. The HDWSA in the Three Gorges Reservoir Area (TGRA) was used as a case study, focusing on copper (Cu) as a pollutant. By regulating the flow downstream from the Xiangjiaba Reservoir, Scheduling Group 1 and Scheduling Group 2 respectively increased the flow by 4000 m3/s and 8000 m3/s. The study analyzed the spatio-temporal variations of Cu concentration following pollution accident and flow scheduling. Under accident conditions, it took 71, 61, 49, and 56 min for the Cu concentration in the study area to decrease to below the standard value (1 mg/L) during dry, falling, flood, and storage periods. Scheduling Groups 1 and 2 reduced the pollutant exceedance duration by 19-26 min and 12-18 min across the four water periods.

Can carbon emission trading improve carbon emission performance? Evidence from a quasi-natural experiment in China.

Carbon emission trading policies play a key role in reducing carbon emissions through market-based mechanisms. In the context of China's carbon neutrality goals and carbon peaking targets, it is important to predict and evaluate the effectiveness of such policies. The combined impact of carbon trading policies on carbon emission reduction and economic output has not been well investigated in previous studies. In this study, the impact of carbon emission trading policies on regional carbon emission performance was assessed through mechanism analysis and empirical tests. The mechanism analysis showed that carbon emission intensity reduction relied on three mediating effects: technological innovation incentives, industrial structure optimization, and energy substitution. For the empirical test, the multi-time difference-in-differences (DID) method was adopted to study the impact using panel data from 30 provinces in China between 2005 and 2019. Moreover, the specific impact mechanism was further tested using mediating effects. The results showed that China's carbon trading policy has significantly affected the carbon emission performance of the pilot regions, and factors such as GDP per capita, urbanization level, and capital-labor ratio have notably contributed to the reduction of carbon emission intensity. The proportions of the three mediating effects in the total effect were estimated to be 60.98%, 23.17%, and 10.14%, respectively. This study provides an empirical approach to the study of the impact of carbon trading policy on carbon emission reduction and economic output and can serve as a reference for addressing climate change and alleviating conflicts between the environment and economic growth in similar regions.

LncRNA TDRKH-AS1 promotes breast cancer progression via the miR-134-5p/CREB1 axis.

BACKGROUND: Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear. METHODS: We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis. RESULTS: TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC. CONCLUSIONS: Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.

Associations of allergy-related outcomes with depression in the US adults.

Evidences showed the link between allergy and depression, while the relationships of depression with allergy-related outcomes is insufficient. The objective of this study is to evaluate and compare the relationship of depression with allergy-related outcomes assessed using two different outcome indicators, in a population-based study. A cross-sectional study was performed of 1094 participants in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). The self-reported allergic symptoms of allergic rhinitis (AR) status and immunoglobulin E (IgE) were used to evaluate the allergy-related outcomes. The depression disorder was defined as the ≥ 10 points on the Patient Health Questionnaire-9. Logistic and linear regression models were performed to illustrate the associations of depression and allergy-related outcomes. The prevalence of AR and depression was 34.2% and 6.8%, respectively. The odds of depression were 8.6% higher in participants with AR patients compared those without AR [odds ratio (OR) = 1.739, 95% confidence interval (CI): (1.034, 2.933)], while the odds of depression in participants with allergic sensitization and without allergic sensitization were not found significant difference. Allergy is positively associated with depression disorder, and patients with allergy-related outcomes, such as AR, may be at higher risk of depression, while the IgE level was not founded to be related with depression. In the treatment of AR patients with depression symptoms, early detection and management of mental problems are of importance.

Prevalence and risk factors of work-related musculoskeletal disorders among emerging manufacturing workers in Beijing, China.

Objective: The workers in emerging manufacturing are at decreased risk of traditional occupational diseases, while probably at increased risk of work-related musculoskeletal disorders (WMSDs). This study aimed to investigate the prevalence and risk factors of WMSDs among emerging manufacturing workers in Beijing. Methods: A total of 3,359 valid questionnaires were collected from 10 enterprises in the electronics, pharmaceutical, and motor manufacturing industries. The prevalence of WMSDs was assessed using the Nordic Musculoskeletal Questionnaire. The work posture load was evaluated through a questionnaire. Results: The results showed that the highest prevalence of WMSDs was observed in part of the neck (15.0%), followed by the lower back (12.5%), shoulders (11.2%), and upper back (7.1%). Female workers, workers aged older than 35 years, workers with a BMI of ≥28 kg/m2, longer working experience, never exercised had a higher prevalence of WMSDs. Logistic regression analysis showed that female workers, workers aged older than 35 years, with a middle school education and college degree, and workers who never exercised had a higher risk of WMSDs. In addition, workers who sat for long during work, worked hard with upper limbs or hands, worked in uncomfortable postures, and performed repetitive operations were positively related with the increased risk of WMSDs. Conclusion: These findings suggested that WMSDs were prevalent among emerging manufacturing workers in Beijing, China, while efforts should be made to reshape the risk factors associated with WMSDs, such as prolonged sitting, uncomfortable positions, and repetitive operations. Encouraging exercise and promoting ergonomic interventions probably be also benefit to induce the risk of WMSDs.

The Value of Neoadjuvant Anthracycline-Based Regimens for HER2-Positive Breast Cancer: A Systematic Review and Meta-analysis Including 1366 Patients.

Background: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. Methods: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. Results: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013). Conclusions: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

A comprehensive analysis of Fanconi anemia genes in Chinese patients with high-risk hereditary breast cancer.

BACKGROUND: Four Fanconi anemia (FA) genes (BRCA1, BRCA2, PALB2 and RAD51C) are defined as breast cancer (BC) susceptibility genes. Other FA genes have been inconsistently associated with BC. Thus, the role of other FA genes in BC should be explored in specific populations. METHODS: Mutations in 16 FA genes were screened with a 98-gene panel sequencing assay in a cohort of 1481 Chinese patients with high-risk hereditary BC. The association between mutations and clinicopathological characteristics as well as prognosis was analyzed. The risk of BC in carriers of FA gene mutations was assessed in the Genome Aggregation Database and the Westlake Biobank for Chinese cohort. RESULTS: A total of 2.57% (38/1481) BC patients were identified who had 12 other FA gene germline mutations. Among them, the most frequently mutated gene was FANCA (8/1481, 0.54%). These 38 patients carried 35 distinct pathogenic/likely pathogenic variants, of which 21 were novel. We found one rare FANCB deleterious variant (c.1327-3dupT) in our cohort. There was a statistically significant difference in lymph node status between FA gene mutation carriers and non-carriers (p = 0.041). We observed a trend that mutation carriers had larger tumor sizes, lower estrogen receptor (ER) and progesterone receptor (PR) positivity rates, and lower 3.5-year invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS) rates than non-carriers (tumor size > 2 cm: 51.43% vs. 45.63%; ER positivity rates: 51.43% vs. 60.81%; PR positivity rates: 48.57% vs. 55.16%; 3.5-year iDFS rates: 58.8% vs. 66.7%; 3.5-year DRFS rates: 58.8% vs. 68.8%). The frequency of the mutations in FANCD2, FANCM and BRIP1 trended to be higher among BC cases than that in controls (p = 0.055, 0.08 and 0.08, respectively). CONCLUSION: This study comprehensively estimated the prevalence, clinicopathological characteristics, prognosis and risk of BC associated with deleterious variants in FA genes in Chinese high-risk hereditary BC patients. It enriches our understanding of the role of FA genes with BC.

Effect of Aggressive Intravenous Fluid Resuscitation Versus Nonaggressive Fluid Resuscitation in the Treatment of Acute Pancreatitis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Despite the need for active fluid therapy, fluid management of most acute pancreatitis (AP) cases is still supportive. The aim of this review is to compare the effect of aggressive versus nonaggressive intravenous (IV) fluid resuscitation in the treatment of acute pancreatitis. METHODS: A systematic search of medical databases, such as Medline, Google Scholar, Science Direct, Cochrane Central, was conducted for publication until April 2022. We included randomized controlled trials or cohort (prospective and retrospective) studies reporting the outcomes of AP in patients that were managed with aggressive and nonaggressive IV fluid resuscitation. The primary outcome of interest was in-hospital mortality. RESULTS: Fourteen trials involving 3423 acute pancreatitis patients were included in the review. We did not observe any differences in the risk of mortality, persistent organ failure, and systemic inflammatory response syndrome in both study groups. However, there was an increased risk of development of pancreatic necrosis, renal failure, and respiratory failure in the aggressive fluid therapy group compared with nonaggressive therapy. The funnel plot showed no publication bias. CONCLUSIONS: Aggressive fluid therapy did not improve mortality rates in acute AP patients and was associated with an increased risk of acute renal failure, and respiratory failure.

Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

INTRODUCTION: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer (ClinicalTrials.gov identifier: NCT03756064). METHODS: Sixty-nine women with HER2-positive early (T1-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) were recruited from October 1, 2019, to June 1, 2021. Before surgery, patients received 6 cycles of orally pyrotinib (400 mg once per day), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), docetaxel (75 mg/m2), and carboplatin (AUC = 6 mg/mL·min) or orally placebo, trastuzumab, and docetaxel, and carboplatin every 3 weeks. The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by age, hormone receptor status, tumor stage, nodal status, cTNM stage, and Ki-67 level was used to compare rates between treatment groups. RESULTS: In total, 69 female patients were randomized (pyrotinib, 36; and placebo, 33; median age, 53 [31-69] years). In the intention-to-treat population, total pathologic complete response rates were 65.5% (19/29) in the pyrotinib group and 33.3% (10/30) in the placebo group (difference, 32.2%, p = 0.013). Diarrhea was been reported in 86.1% of patients (31/36) in the pyrotinib group as the most common adverse events (AEs) and 15.2% of patients (5/33) in the placebo group. But no grade 4 or 5 AEs were reported. CONCLUSION: Treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin resulted in a statistically significant improvement in the total pathologic complete response rate versus placebo, trastuzumab, docetaxel, and carboplatin for the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer in Chinese patients. Safety data were in line with the known pyrotinib safety profile and generally comparable between treatment groups.

Long non-coding RNAs in breast cancer stem cells.

Breast cancer, one of the most commonly diagnosed cancers worldwide, is a heterogeneous disease with high rates of recurrence and metastasis that contribute to its high mortality rate. Breast cancer stem cells (BCSCs) are a small but significant subset of heterogeneous breast cancer cells that possess stem cell characteristics such as self-renewal and differentiation abilities that may drive metastasis and recurrence. Long non-coding RNAs (lncRNAs) are a class of RNAs that are longer than 200 nucleotides in length and do not possess protein-coding properties. An increasing number of studies have shown that some lncRNAs are abnormally expressed in BCSCs, and have great biological significance in the occurrence, progression, invasion, and metastasis of various cancers. However, the importance of lncRNAs, as well as the molecular mechanisms that regulate and promote the stemness of BCSCs, are still poorly understood. In the current review, we aim to summarize recent studies that highlight the role of lncRNAs in tumor occurrence and progression through BCSCs. In addition, the utility of lncRNAs as biomarkers of breast cancer progression, and their potential use as therapeutic targets for treatment of breast cancer, will be discussed.

Exposure to household dust, allergens, and endotoxin and allergy-related outcomes alternation in the general U.S. population.

It has been widely reported that the general population was at an increased risk of allergy diseases, which probably be related with household allergens exposure. However, the difference of local and systemic allergic reactions exposure to allergens has not been reported in the general population previously. The data of 1094 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 data bank were analyzed. Dust, allergens (Bia g 1, Bia g 2, Can f 1, Feld 1, Derp 1, Mus m 1, Rat n 1, Alternaria alternate, and Aspergillus fumigatus), and endotoxin, were measured to estimate sensitizing source exposure. And allergy-related outcomes indicators including hay fever, sneezing, allergic rhinitis (AR), immunoglobulin E (IgE), and allergic sensitization, were evaluzted to estimate local and systemic allergic reactions. Multiple linear regression and logistic regression models were used to examine the associations of sensitizer and allergy-related outcomes. The mean or median concentration of dust and endotoxin were 0.66 g and 12.98 EU/mg dust. The Derp 1, Mus m 1, Rat n 1, Alternaria alternate, and Aspergillus fumigatus were the main allergens in the dust, with the concentrations of 30.66 ng/g dust, 30.73 ng/g dust, 5.94 ng/g dust, 5.20 ng/g dust, and 207.68 µg/g dust, respectively. The prevalence of AR was 34.2% among the general population. After controlling for sociodemographic factors, we found that the allergens, such as Can f 1 and Feld 1, were positively associated with AR. The prevalence of allergic sensitization was about 20%. Dust and endotoxin were found positively associated with allergic sensitization, while Bia g 2, Rat n 1, Alternaria alternate, and Aspergillus fumigatus were inversely associated with that. Dust and endotoxin probably be associated with higher risk of local allergic reactions, while some allergens, such as Bia g 2, Rat n 1, Alternaria alternate, and Aspergillus fumigatus probably be associated with lower risk of systemic allergic reactions.

α-Cyperone ameliorates depression in mammary gland hyperplasia and chronic unpredictable mild stress rat by regulating hormone, inflammation, and oxidative stress.

BACKGROUND: Hyperplasia of mammary gland (HMG) is caused by endocrine disorders, and patients are prone to anxiety and depression. α-Cyperone has a variety of pharmacological activities including antidepressant. The purpose of this study was to explore the effect and its possible mechanism of α-Cyperone on HMG-associated depression rats. METHODS: The depression model was constructed using chronic unpredictable mild stress (CUMS), while the HMG model was induced by estrogen, with or without α-Cyperone intervention. The effect of α-Cyperone on the depression-like phenotype of model rats was measured by sucrose preference test (SPT), forced swim test (FST), and open field test (OFT). Dendritic spines density in ventral medial prefrontal cortex (vmPFC) neurons was evaluated by Golgi staining. The second pair of nipple height, diameter, organ index, and oxidative stress-related factors were analyzed. Serum sex hormone concentration, histopathological changes, inflammatory factor expression, and p65 were evaluated by enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, real-time quantitative PCR and western blot, respectively. RESULTS: The sucrose preference rate, dendritic spine density decreased, and immobility time increased in CUMS rats; α-Cyperone reversed the effect of CUMS on depression-like behavior and dendritic spine density in rats. α-Cyperone reduced nipple height and diameter, uterine index, estradiol concentration, increased ovary, thymus, spleen index, progesterone, and testosterone concentration, relieved pathological damage, oxidative stress, depression-like behavior, and inflammatory reaction in HMG combine CUMS rats. In addition, α-Cyperone inhibited the phosphorylation of p65 in HMG and CUMS rats. CONCLUSIONS: α-Cyperone has an effective therapeutic effect on HMG combined with CUMS rats.

Physical activity (PA) influences the risk of depression associated with long working hours.

BACKGROUND: Growing evidences showed that long working hours is associated with depression epidemic, but few studies investigate whether physical activity (PA) could modify the risk of depression associated with long working hours, which was the purpose of the present study. METHODS: A cross-sectional data obtained from the National Health and Nutrition Examination Survey 2015-2018. According to the criteria of International Labour Organization, long working hours was defined as >40 h/wk. The Nine-item Patient Health Questionnaire (PHQ-9) was used to identify depression. Binary logistic regression and restricted cubic spline (RCS) models were used to estimate the associations between long working hours and depression, furthermore to estimate the association of PA. RESULTS: 5958 participants were included in the study. The results indicated that 3074 (51.6 %) of participants worked >40 h/wk. The prevalence of depression was 7.7 %. Logistic regression analysis indicated a positive association between long working hours and depression [OR = 1.738, 95 CI (1.427, 2.117)], and the results were still robust after controlling other confounding factors. RCS models indicated that the high intensity PA group had the lowest risk of depression, followed by low intensity PA group and no PA group. CONCLUSION: Long working hours probably be associated with depression, while PA can modify the risk to some degree.