Neoadjuvant inetetamab and pertuzumab with taxanes and carboplatin (TCbIP) In locally advanced HER2-positive breast cancer: a prospective cohort study with propensity-matched analysis.

BACKGROUND: Inetetamab is the first domestically developed innovative anti-HER2 monoclonal antibody in China, proven effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remain to be validated. METHODS: This prospective cohort study aimed to evaluate the efficacy and safety of inetetamab combined with pertuzumab, taxanes, and carboplatin (TCbIP) in neoadjuvant therapy for HER2-positive LABC, comparing it to data from patients treated with the TCbHP regimen (trastuzumab combined with pertuzumab, taxanes, and carboplatin) using propensity score matching (PSM). The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints. RESULTS: Forty-four patients with clinical stage IIA-IIIC HER2-positive LABC were prospectively enrolled and treated with the TCbIP regimen. The tpCR rate among 28 patients who completed surgery was 60.7%, comparable to and slightly higher than the TCbHP group in PSM (60.7% vs. 53.6%, P = 0.510). The ORR was 96.4%, and the DCR reached 100.0%. The most common ≥ grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs. CONCLUSION: Neoadjuvant therapy with TCbIP showed good efficacy and safety in patients with HER2-positive LABC and might be another promising option for neoadjuvant treatment. TRIAL REGISTRATION: NCT05749016 (registration date: Nov 01, 2021).

Genome-wide cell-free DNA methylation analyses improve accuracy of non-invasive diagnostic imaging for early-stage breast cancer.

Early detection is crucial to improve breast cancer (BC) patients' outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78-0.79 to 0.93-0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.

Overexpression of IncRNA SAMMSON Promotes Triple-Negative Breast Cancer Cell Proliferation by Interacting with p53.

This study was carried out to explore the role of the long noncoding RNA (lncRNA) SAMMSON in triple-negative breast cancer (TNBC). The research patients in this study included 68 TNBC patients. Cell Counting Kitcck-8 were utilized to determine cell proliferation abilities, respectively. Proteins and mRNAs were estimated by western blot and Methylation-specific polymerase chain reaction, respectively. We found that SAMMSON was upregulated, while p53 was downregulated in cancer (TNBC) tissues than in non-cancer tissues of TNBC patients. SAMMSON expression levels in TNBC tissues increased with the increase of clinical stages of TNBC patients. SAMMSON and p53 were inversely correlated in TNBC tissues. In TNBC cells, SAMMSON overexpression decreased p53 expression, while p53 overexpression failed to affect SAMMSON expression. In addition, SAMMSON overexpression increased TNBC cell proliferation, while p53 overexpression decreased the proliferation rates of TNBC cells. In addition, p53 overexpression attenuated the effects of SAMMSON overexpression. Therefore, overexpression of SAMMSON could promote TNBC cell proliferation by interacting with p53.

Contralateral risk-reducing local therapy in breast cancer patients with BRCA1/2 mutations: systemic review and meta-analysis.

BACKGROUND: Unilateral breast cancer (UBC) patients with germline pathogenic BRCA1/2 variants have a higher risk of developing contralateral breast cancer (CBC) and need contralateral risk-reducing local treatments, including contralateral risk-reducing mastectomy (CRRM) and prophylactic irradiation (CPI). The aim of our study was to systematically explore the efficacy of CRRM and CPI in reducing CBC risk and increasing survival. METHODS: A search was done, and eligible randomized trials and cohort studies should include and compare UBC patients with germline pathogenic BRCA1/2 variants who have and have not received contralateral risk-reducing local treatment. Random-effects meta-analysis was used in this study. Primary outcomes of the studies included overall survival (OS) and the incidence of contralateral breast cancer (CBC), and secondary outcomes included breast cancer-specific survival (BCSS). RESULTS: A total of five studies with 1769 UBC patients with germline pathogenic BRCA1/2 variants were enrolled in our meta-analysis. CRRM was correlated with a lower risk of CBC in UBC patients with germline pathogenic BRCA1/2 variants (summary RR = 0.07; 95%CI 0.03-0.13, I2 = 3%), a significantly increased OS (summary RR, 1.15; 95%CI 1.04-1.26, I2 = 26%) and a significantly increased BCSS (summary RR, 1.18; 95%CI 1.07-1.31, I2 = 64%) compared with surveillance. CPI also decreased the risk of CBC (RR 0.02; 95%CI 0.05-0.88) but did not significantly improve OS (RR 0.97; 95%CI 0.90-1.05) and BCSS (RR 0.97; 95%CI 0.90-1.05) compared with surveillance. CONCLUSIONS: CRRM reduces CBC risk and increases OS and BCSS in UBC patients with germline pathogenic BRCA1/2 variants, and could be offered as a risk-reducing local treatment. For those who oppose CRRM, CPI could be offered for CBC-risk reduction, while its survival benefit is still uncertain.

Photonic integrated quantum key distribution receiver for multiple users.

Integrated photonics has the advantages of miniaturization, low cost, and CMOS compatibility, and it provides a stable, highly integrated, and practical platform for quantum key distribution (QKD). While photonic integration of optical components has greatly reduced the overall cost of QKD systems, single-photon detectors (SPDs) have become the most expensive part of a practical QKD system. In order to circumvent this obstacle and make full use of SPDs, we have designed and fabricated a QKD receiver chip for multiple users. Our chip is based on a time-division multiplexing technique and makes use of a single set of SPDs to support up to four users' QKD. Our proof-of-principle chip-based QKD system is capable of producing an average secret key rate of 13.68 kbps for four users with a quantum bit error rate (QBER) as low as 0.51% over a simulated distance of 20 km in fiber. Our result clearly demonstrates the feasibility of multiplexing SPDs for setting QKD channels with different users using photonic integrated chip and may find applications in the commercialization of quantum communication technology.

The Association Between Body Size and Breast Cancer in Han Women in Northern and Eastern China.

INTRODUCTION: Although obesity has been reported worldwide as a risk factor for breast cancer, there are still some inconsistencies regarding the association between obesity and breast cancer. Body mass index (BMI) is used most to assess the extent of obesity; however, the association of other body size characteristics, such as waist and hip circumference, with susceptibility to breast cancer in Chinese Han women needs to be better assessed. PATIENTS AND METHODS: Female Chinese Han patients (N = 2,800) were recruited from 21 hospitals in northern and eastern China from April 2012 to April 2013 for a case-control study. The significant differences of factors related to body size between the breast-cancer case and control groups were determined by Student's t test and chi-square tests. RESULTS: Premenopausal women with breast cancer had higher BMI and larger waist and hip circumferences (p = 2 × 10-4, <1 × 10-6, and 2 × 10-5, respectively). However, these body-size factors were not associated with postmenopausal breast cancer (p = .45, 0.32, and 0.12, respectively). BMI between 28 and 30 kg/m2 or greater than 32 kg/m2 was related to breast cancer incidence in the overall study population and in premenopausal women but not in the postmenopausal group. CONCLUSION: Obesity is significantly associated with breast cancer in Chinese Han premenopausal women but not in postmenopausal women. Thus, it is important to realize that weight control, as well as avoiding abdominal obesity, should be considered as one of the most effective methods of reducing breast cancer risk. IMPLICATIONS FOR PRACTICE: To better understand the characteristics and risk factors for breast cancer in Han women in northern and eastern China, a case-control study of 2,800 Chinese Han women was conducted. Obesity was significantly associated with breast cancer in Chinese Han premenopausal women but not in postmenopausal women. Consequently, controlling body weight and avoiding abdominal obesity should be considered as one of the most effective methods of reducing breast cancer susceptibility. However, the diversity between this study's finding among Chinese Han women and other data previously reported among European and American populations still needs further investigation.

Silencing ARL11 relieved atherosclerotic inflammation and lipid deposition via retraining JAK2/STAT1 pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS), an arterial vasculature disease, is characterized by abnormal lipid accumulation and inflammatory response. ADP ribosylation factor like GTPase 11 (ARL11) is linked to multifarious processes in cells. This study aims to clarify the underlying mechanism of ARL11 in AS. METHODS: ApoE-/- mice fed with high-fat diet were used as mouse model of AS. Gene expression in AS was determined by mRNA-sequencing. ARL11 expression was detected by real-time PCR, Western blot and immunofluorescence. M1 polarization of macrophages was indicated by TNF-α and IL-6 levels as detected with ELISA, and iNOS expression determined by real-time PCR and Western blot. The role of ARL11 during AS was explored through loss-of-function analysis. RESULTS: There were 1301 upregulated and 1110 downregulated genes during AS. These differentially expressed genes (DEGs) were mainly enriched in pathways and terms which are involved in inflammation. Moreover, Arl11 was highly expressed in AS models. Downregulation of Arl11 decreased lipid deposition and atherosclerotic plaques in the aortas of AS mice, and declined inflammatory cytokines and M1 polarization of macrophages induced by IFN-γ. Furthermore, ARL11 interacted with JAK2 and p-JAK2 and modulated their degradation, thus inhibiting the activation of JAK2/STAT1 pathway. CONCLUSIONS: ARL11 promoted the development of AS via interacting with JAK2 and activating JAK2/STAT1 pathway. Thus, silencing ARL11 may prevent the process of AS and be a novel way to treat AS.

Construction and validation of a ubiquitination-related prognostic risk score signature in breast cancer.

Background: Breast cancer (BC) is a highly common form of cancer that occurs in many parts of the world. However, early -stage BC is curable. Many patients with BC have poor prognostic outcomes owing to ineffective diagnostic and therapeutic tools. The ubiquitination system and associated proteins were found influencing the outcome of individuals with cancer. Therefore, developing a biomarker associated with ubiquitination genes to forecast BC patient outcomes is a feasible strategy. Objective: The primary goal of this work was to develop a novel risk score signature capable of accurately estimate the future outcome of patients with BC by targeting ubiquitinated genes. Methods: Univariate Cox regression analysis was conducted utilizing the E1, E2, and E3 ubiquitination-related genes in the GSE20685 dataset. Genes with p < 0.01 were screened again using the Non-negative Matrix Factorization (NMF) algorithm, and the resulting hub genes were composed of a risk score signature. Patients were categorized into two risk groups, and the predictive effect was tested using Kaplan-Meier (KM) and Receiver Operating Characteristic (ROC) curves. This risk score signature was later validated using multiple external datasets, namely TCGA-BRAC, GSE1456, GSE16446, GSE20711, GSE58812 and GSE96058. Immuno-microenvironmental, single-cell, and microbial analyses were also performed. Results: The selected gene signature comprising six ubiquitination-related genes (ATG5, FBXL20, DTX4, BIRC3, TRIM45, and WDR78) showed good prognostic power in patients with BC. It was validated using multiple externally validated datasets, with KM curves showing significant differences in survival (p < 0.05). The KM curves also demonstrated superior predictive ability compared to traditional clinical indicators. Single-cell analysis revealed that Vd2 gd T cells were less abundantin the low-risk group, whereas patients in the high-risk group lacked myeloid dendritic cells. Tumor microbiological analysis revealed a notable variation in microorganism diversity between the high- and low-risk groups. Conclusion: This study established an risk score signature consisting of six ubiquitination genes, that can accurately forecast the outcome of patients with BC using multiple datasets. It can provide personalized and targeted assistance to provide the evaluation and therapy of individuals having BC.

Discovery of Natural Ah Receptor Antagonists from Salvia miltiorrhiza Bunge and Synthesis of Analogs for Tumor Immunotherapy.

IDO/TDO/Kyn/AhR signaling plays a crucial role in regulating innate and adaptive immunity, and targeting Ah receptor (AhR) inhibition can potentially redirect immune cells toward an antitumoral phenotype. Therefore, AhR is an attractive drug target for novel small molecule cancer immunotherapies. In this study, natural products tanshinolic A-D (1-4), the first adducts composed of ortho-naphthoquinone-type tanshinone and phenolic acid featuring a unique 1,4-benzodioxan hemiacetal structure, were isolated and characterized from the roots of Salvia miltiorrhiza Bunge. Luciferase reporter gene assay revealed that these adducts exhibited significant AhR inhibitory activity. A linear strategy was developed to construct a cis-3,4-disubstituted 1,4-benzodioxan hemiacetal structure. Encouragingly, in both in vitro and in vivo experiments, (±)-13e demonstrated the ability to inhibit tumor cell proliferation, promote INF-γ secretion in CD8+ T cells, and inhibit PD-1/PD-L1 signal transduction, which could exert tumor inhibition properties by inhibiting AhR activity, positioning it as a promising candidate for tumor immunotherapy.

Role of aggressive locoregional surgery in treatment strategies for ipsilateral supraclavicular lymph node metastasis of breast cancer: a real-world cohort study.

Background: Breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastases (ISLNM) have unfavorable prognoses. The role of supraclavicular lymph node dissection (SLND) as a surgical intervention in the treatment of this condition remains controversial. In this study, we aimed to evaluate the prognostic factors associated with breast cancer with ISLNM and to assess the potential impact of aggressive locoregional surgical management on patient outcomes. Methods: We conducted a retrospective analysis of 250 breast cancer patients with ISLNM who were treated with curative intent at our institution between 2000 and 2020. The cohort was stratified into groups based on the extent of axillary surgery. The first group, comprising 185 patients, underwent level I/II axillary dissection. The second group, consisting of 65 patients, underwent aggressive locoregional surgery, including levels I/II/III (infraclavicular) dissection in 37 patients and levels I/II/III + SLND in 28 patients. Our study evaluated overall survival (OS) and disease-free survival (DFS) as primary endpoints, and locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) as secondary endpoints. Results: The median follow-up time among all patients was 5.92 years (1.05-15.36 years). The 5-year OS rate was 71.89%, while the DFS rate, LRRFS rate, and DMFS rates were 59.25%, 66.38%, and 64.98%, respectively. A significant difference in OS, DFS, LRRFS, and DMFS was observed between the second group and the first group (p < 0.01). No beneficial impact on recurrence, metastasis, or survival outcomes was observed in the levels I/II/III + SLND group compared to the levels I/II/III dissection group. Multivariate logistic regression analysis revealed that levels I/II/III ± SLND surgery and T stage were associated with OS (p = 0.006 and p = 0.026), while levels I/II/III ± SLND surgery, ER+/HER2-, and histologic grade were associated with DFS (p = 0.032, p = 0.001, p = 0.032). Conclusion: Breast cancer with ISLNM may be considered a locoregional disease, requiring a combination of systemic and local therapies. Aggressive locoregional surgery has been shown to positively impact recurrence, metastasis, and survival outcomes. This approach may provide improved management of the ISLNM for breast cancer patients.

Working from anywhere: yin-yang cognition paradoxes of knowledge sharing and hiding for developing careers in China.

Digital technology coupled with the quarantines caused by the COVID-19 pandemic has made working from anywhere (WFA)-a modern form of remote working-a widespread phenomenon. Given that WFA brings new career challenges to and engenders paradoxes of knowledge exchange among employees, this research aims to examine how the interactions of remote work time (RWT), knowledge sharing (KS), and knowledge hiding (KH) affect career development (CD) from a culturally grounded paradoxical framing of yin-yang harmonizing. The data were collected from Chinese manufacturing employees, and a moderated hierarchical regression analysis was used to examine the hypotheses. The results show an inverted U-shaped relationship between RWT and CD. The interaction of KS and KH is significantly related to CD, and the inverted U-shaped RWT-CD relationship is moderated by the interaction term, in which RWT exerts the most substantial positive impact on CD when KS is high and KH is low. This study offers valuable implications for coping with perplexing employment relationships and increasing career challenges in volatile work environments. The primary originality is to adopt a novel cognitive frame of yin-yang harmonizing to examine the nonlinear effect of remote working and the symbiotic impact of KS and KH on CD, which not only enriches the understanding of flexible work arrangements in the digital economy but also provides novel insights into the interconnectedness of KS and KH and their interacting effects on HRM-related outcomes.

LETMD1, a target of KLF4, hinders endothelial inflammation and pyroptosis: A protective mechanism in the pathogenesis of atherosclerosis.

Atherosclerosis (AS), a metabolic disorder, is usually caused by chronic inflammation. LETM1 Domain-Containing Protein 1 (LETMD1) is a mitochondrial outer membrane protein required for mitochondrial structure. This study aims to evaluate the functional role of LETMD1 in endothelial pathogenesis of AS. Oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) and high-fat diet apolipoprotein E-deficient (ApoE-/-) mice were used to establish in vitro and in vivo models, respectively. Recombinant adenovirus vectors were constructed to investigate the role of LETMD1 in AS. mRNA sequencing was used to explore the effect of LETMD1 overexpression on gene expression in ox-LDL-induced HUVECs. A dual-luciferase reporting assay and chromatin immunoprecipitation (ChIP)-PCR were further conducted to verify the relationship between KLF4 and LETMD1. Results showed that LETMD1 was highly expressed in the aortas of atherosclerotic animals. LETMD1 overexpression reduced the expression of inflammatory factors, pyroptosis, ROS production, and NF-κB activation in ox-LDL-induced HUVECs, whereas LETMD1 knockdown had the opposite impact. LETMD1 overexpression was involved in regulating gene expression in ox-LDL-induced HUVECs. Overexpression of LETMD1 in mice reduced serum lipid levels as well as atherosclerotic lesions in the aortic roots. Furthermore, LETMD1 overexpression suppressed inflammatory reactions, cell pyroptosis, nuclear p65 protein level, cell apoptosis, and ROS generation in the aortas of AS mice. KLF4 (Krüppel-like factor 4) was found to be the transcriptional regulator of LETMD1. In conclusion, LETMD1, a target of KLF4, hinders endothelial inflammation and pyroptosis, which is a mechanism inhibiting the development of atherosclerosis.

Identifying clinicopathological risk factors for regional lymph node metastasis in Chinese patients with T1 breast cancer: a population-based study.

Objectives: To analyze clinicopathological risk factors and regular pattern of regional lymph node metastasis (LNM) in Chinese patients with T1 breast cancer and the effect on overall survival (OS) and disease-free survival (DFS). Materials and methods: Between 1999 and 2020, breast cancer patients meeting inclusion criteria of unilateral, no distant metastatic site, and T1 invasive ductal carcinoma were reviewed. Clinical pathology characteristics were retrieved from medical records. Survival analysis was performed using Kaplan-Meier methods and an adjusted Cox proportional hazards model. Results: We enrolled 11,407 eligible patients as a discovery cohort to explore risk factors for LNM and 3484 patients with stage T1N0 as a survival analysis cohort to identify the effect of those risk factors on OS and DFS. Compared with patients with N- status, patients with N+ status had a younger age, larger tumor size, higher Ki67 level, higher grade, higher HR+ and HER2+ percentages, and higher luminal B and HER2-positive subtype percentages. Logistic regression indicated that age was a protective factor and tumor size/higher grade/HR+ and HER2+ risk factors for LNM. Compared with limited LNM (N1) patients, extensive LNM (N2/3) patients had larger tumor sizes, higher Ki67 levels, higher grades, higher HR- and HER2+ percentages, and lower luminal A subtype percentages. Logistic regression indicated that HR+ was a protective factor and tumor size/higher grade/HER2+ risk factors for extensive LNM. Kaplan-Meier analysis indicated that grade was a predictor of both OS and DFS; HR was a predictor of OS but not DFS. Multivariate survival analysis using the Cox regression model demonstrated age and Ki67 level to be predictors of OS and grade and HER2 status of DFS in stage T1N0 patients. Conclusion: In T1 breast cancer patients, there were several differences between N- and N+ patients, limited LNM and extensive LNM patients. Besides, HR+ plays a dual role in regional LNM. In patients without LNM, age and Ki67 level are predictors of OS, and grade and HER2 are predictors of DFS.

KPNA2 Silencing, Regulated by E3 Ubiquitin Ligase FBXW7, Alleviates Endothelial Dysfunction and Inflammation Through Inhibiting the Nuclear Translocation of p65 and IRF3: A Possible Therapeutic Approach for Atherosclerosis.

Atherosclerosis (AS), characterized by a maladaptive inflammatory response, is one of the most common causes of death among the elderly. Karyopherin subunit alpha 2 (KPNA2), a member of the nuclear transport protein family, has been reported to play a pro-inflammatory role in various pathological processes by regulating the nuclear translocation of pro-inflammatory transcription factors. However, the function of KPNA2 in AS remains unknown. ApoE-/- mice were fed high-fat diets for 12 weeks to establish an AS mice model. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish an AS cell model. We found that KPNA2 was upregulated in the aortic roots of atherosclerotic mice and LPS-stimulated cells. KPNA2 knockdown inhibited LPS-induced secretion of pro-inflammatory factors and monocyte-endothelial adhesion in HUVECs, whereas KPNA2 overexpression exerted the opposite effects. p65 and interferon regulatory factor 3 (IRF3), the transcription factors known to regulate the transcription of pro-inflammatory genes, interacted with KPNA2, and their nuclear translocations were blocked following KPNA2 silencing. Furthermore, we found that KPNA2 protein level was decreased by E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBXW7), which was downregulated in the atherosclerotic mice. FBXW7 overexpression induced ubiquitination with subsequent proteasomal degradation of KPNA2. Meanwhile, the effects of KPNA2 deficiency on atherosclerotic lesions were further confirmed by in vivo experiments. Taken together, our study indicates that KPNA2 downregulation, regulated by FBXW7, may alleviate endothelial dysfunction and related inflammation in the progression of AS by suppressing the nuclear translocation of p65 and IRF3.

Microbiome and its implications in oncogenesis: a Mendelian randomization perspective.

The human microbiome, an intricate ecological network, has garnered significant attention due to its potential implications in oncogenesis. This paper delves into the multifaceted relationships between the microbiome, its metabolites, and cancer development, emphasizing the human intestinal tract as the primary microbial habitat. Highlighting the potential causative associations between microbial disturbances and cancer progression, we underscore the role of specific bacterial strains in various cancers, such as stomach and colorectal cancer. Traditional causality assessment methods, like randomized controlled trials (RCTs), have limitations. Therefore, we advocate using Mendelian Randomization (MR) as a powerful alternative to study causal relationships, leveraging genetic variants as instrumental variables. With the proliferation of genome-wide association studies, MR harnesses genetic variations to infer causality, which is especially beneficial when addressing confounders like diet and lifestyle that can skew microbial research. We systematically review MR's application in understanding the microbiome-cancer nexus, emphasizing its strengths and challenges. While MR offers a unique perspective on causality, it faces hurdles like horizontal pleiotropy and weak instrumental variable bias. Integrating MR with multi-omics data, encompassing genomics, transcriptomics, proteomics, and metabolomics, holds promise for future research, potentially heralding groundbreaking discoveries in microbiology and genetics. This comprehensive review underscores the critical role of the human microbiome in oncogenesis and champions MR as an indispensable tool for advancing our understanding in this domain.

Construction of a prognostic 6-gene signature for breast cancer based on multi-omics and single-cell data.

Background: Breast cancer (BC) is one of the females' most common malignant tumors there are large individual differences in its prognosis. We intended to uncover novel useful genetic biomarkers and a risk signature for BC to aid determining clinical strategies. Methods: A combined significance (p combined) was calculated for each gene by Fisher's method based on the RNA-seq, CNV, and DNA methylation data from TCGA-BRCA. Genes with a p combined< 0.01 were subjected to univariate cox and Lasso regression, whereby an RS signature was established. The predicted performance of the RS signature would be assessed in GSE7390 and GSE20685, and emphatically analyzed in triple-negative breast cancer (TNBC) patients, while the expression of immune checkpoints and drug sensitivity were also examined. GSE176078, a single-cell dataset, was used to validate the differences in cellular composition in tumors between TNBC patients with different RS. Results: The RS signature consisted of C15orf52, C1orf228, CEL, FUZ, PAK6, and SIRPG showed good performance. It could distinguish the prognosis of patients well, even stratified by disease stages or subtypes and also showed a stronger predictive ability than traditional clinical indicators. The down-regulated expressions of many immune checkpoints, while the decreased sensitivity of many antitumor drugs was observed in TNBC patients with higher RS. The overall cells and lymphocytes composition differed between patients with different RS, which could facilitate a more personalized treatment. Conclusion: The six genes RS signature established based on multi-omics data exhibited well performance in predicting the prognosis of BC patients, regardless of disease stages or subtypes. Contributing to a more personalized treatment, our signature might benefit the outcome of BC patients.

How Do Government Policies Promote Green Housing Diffusion in China? A Complex Network Game Context.

To reduce energy consumption and environmental pollution in the construction industry, many countries have focused on the development of green housing (GH), which is a type of green building for residential use. In China, the local governments have introduced various incentive policies to encourage the development of GH; however, its scale is still small and unevenly distributed. This implies a necessity to optimize the policies that apply to the GH incentive. To promote GH diffusion, we built an evolutionary game model on a complex network to analyze the impacts of government policies on GH pricing and demand and the profits of real estate enterprises developing GH. By implementing simulations, we further explored the incentive effect and operational mechanism of the government policies. The results show that the subsidy policy, the preferential policy for GH, and the restriction policy for ordinary housing can effectively promote the diffusion of GH to 0.6752, 0.506, and 0.5137 respectively. Meanwhile, the incentive effect of the enterprise subsidy policy and GH preferential policy gradually decreases with the increase in policy strength. In terms of the demand side, the consumer subsidy policy could promote GH diffusion to 0.7097. If the subsidy is below 120 CNY/m2, the effect of the consumer subsidy policy is less powerful than that of the enterprises subsidy policy; conversely, the former is slightly more effective than the latter. The outcome of the study has managerial implications on governmental decision-making, especially on the strategy design of incentive policies for GH.

Promotion strategy for online healthcare platform during the COVID-19 pandemic: Evidence from Spring Rain Doctor in China.

Introduction: Online healthcare platform (OHP) is a new form of medical treatment that solves the problems of an unbalanced distribution of medical resources in China. Especially during the COVID-19 pandemic, OHP has greatly reduced the medical pressure of the hospital and the risk of cross-infection. Methods: Based on self-determination theory (SDT) (Ryan and Deci, 2000), privacy calculus theory (PCT) (Culnan, 1999) and perceived value theory (PVT) (Choi, 2004), this study uses evolutionary game theory to analyze behavioral strategies and their dynamic evolution in the promotion of OHP. Moreover, we conduct numerical simulations with the help of program compilation. Results: The results demonstrate that (1) both the qualification inspection of doctors and the investment in information protection influence doctors' participation in and patients' usage of OHP; (2) both the initial probabilities of doctor participation and patient usage influence the multi-game results; (3) the trend of doctors joining OHP is affected by registration cost, time cost, and reputation loss; and (4) the trend of patients using online healthcare is mainly decided by the cost. Conclusion: This study takes the Spring Rain Doctor as an example to verify the game results. To further popularize online medical treatment among patients, the platform should attach importance to the inspection of doctors and the protection of privacy information and strengthen its publicity in remote places.

Antibacterial Effect of Eugenol on Shigella flexneri and Its Mechanism.

Shigella flexneri (Sh. flexneri), which can be found in food and the environment, is a widespread food-borne pathogen that causes human diarrhea termed "shigellosis". In this study, eugenol, a natural active substance, was investigated for its antibacterial activity against Sh. flexneri. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of eugenol against Sh. flexneri ATCC 12022 was 0.5 and 0.8 mg/mL. The growth curves and inhibitory effect in LB broth, PBS, vegetable juice, and minced pork showed that eugenol had a good activity against Sh. flexneri. Research findings indicated the superoxide dismutase activity of Sh. flexneri was inhibited after eugenol treatment, resulting in concentrations of intracellular reactive oxygen species and an increase in malondialdehyde. The flow cytometry analysis and field emission scanning electron microscopy results revealed obvious damage to cell membrane integrity and changes in the morphology of Sh. flexneri. In addition, the intracellular ATP concentration leaked from 0.5 µM to below 0.05 µM and the membrane potential showed a concentration-dependent depolarization after eugenol treatment. In summary, eugenol exerted strong antibacterial activity and has the potential to control Sh. flexneri in the food industry.

A review of studies on omitting surgery after neoadjuvant chemotherapy in breast cancer.

The advancement in systemic neoadjuvant therapy has significantly increased the pathological complete response (pCR) rate in breast cancer. As surgeries inevitably affect patients physically and psychologically and the accuracy of pCR prediction and diagnosis by minimal invasive biopsy is improving, the necessity of surgery in neoadjuvant chemotherapy (NAC) patients who achieve pCR is under debate. Thus, we conducted a literature review of studies on the selective omission of breast surgery after NAC for breast cancer patients. We summarized the existing predictive models and technologies to predict and diagnose pCR after NAC. Our research indicates that, for nearly half a century, the extent of surgery on both breast and axillary lymph nodes is decreasing, while more precise systematic treatments are increasing. NAC has advanced significantly and its pCR rates have improved, so surgery may be omitted in certain patients. However, accurately predicting pCR after NAC is still a challenge. We also described the design for a randomized clinical trial and the potential problems of omitting surgical treatment after NAC. In summary, the decrease in breast cancer surgery is an unavoidable trend, and more high-quality clinical trials need to be conducted.