Prenyllongnols A-D, New Prenylated Acylphloroglucinols that Fight Concanavalin A-Induced Autoimmune Hepatitis.

Autoimmune hepatitis is a serious hepatic disorder with unknown nosogenesis, and natural products have been deemed to be one of the most significant sources of new drugs against this disease. Prenyllongnols A-D (1-4), four undescribed prenylated acylphloroglucinols, were isolated from Hypericum longistylum. Compounds 1-4 exhibited remarkable immunosuppressive activities in murine splenocyte proliferation under the induction of concanavalin A (Con A), and IC50 values ranged from 2.98 ± 0.21 to 6.34 ± 0.72 µM. Furthermore, in a Con A-challenged autoimmune hepatitis mouse model, the mice in the group that were pretreated with isolate 2 significantly ameliorated liver injury and decreased proinflammatory cytokine production. Notably, natural product 2 was the first prenylated acylphloroglucinol to protect against concanavalin A-induced autoimmune hepatitis. This finding underscores the potential of prenylated acylphloroglucinol-type metabolites as promising candidates for designing novel immunosuppressors in the quest for new antiautoimmune hepatitis drugs.

Nomogram for predicting axillary upstaging in clinical node-negative breast cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: The prediction of axillary lymph node status after neoadjuvant chemotherapy (NAC) becoming critical because of the advocation of the de-escalation of axillary management. We investigate associated factors of axillary upstaging in clinical node-negative (cN0) breast cancer patients receiving NAC to develop and validate an accurate prediction nomogram. METHODS: We retrospectively analyzed 1892 breast cancer patients with stage of cT1-3N0 treated by NAC and subsequent surgery between 2010 and 2020 in twenty hospitals across China. Patients randomly divided into a training set and validation set (3:1). Univariate and multivariate logistic regression analysis were performed, after which a nomogram was constructed and validated. RESULTS: In total, pathologic node negativity (ypN0) achieved in 1406 (74.3%) patients and another 486 (25.7%) patients upstaged to pathologic node positive (ypN+). Breast pathologic complete response (bpCR) was achieved in 445 (23.5%) patients and non-bpCR in 1447 (76.5%) patients. A nomogram was established by ER, tumor histology, HER2 status, cycle of NAC treatment, and the bpCR, which were confirmed by multivariate logistic analysis as independent predictors of nodal upstaging in the training cohort (n = 1419). The area under the receiver operating characteristic curve (AUC) of the training cohort and validation cohort (n = 473) were 0.73 (95% CI 0.693-0.751) and 0.77 (95% CI 0.723-0.812) respectively. CONCLUSION: We present a nomogram with a nationwide large sample data which can effectively predict axillary upstaging after neoadjuvant chemotherapy to give better advice for individualized axillary lymph node management of breast cancer.

The nodal positivity rate in breast pCR patients with initially, clinically node-negative breast cancer after neoadjuvant systemic therapy: A systematic review and meta-analysis.

Background: The axillary lymph node positive (ypN+) rate in patients with clinically node-negative (cN0) breast cancer who have achieved breast pathologic complete response (bpCR) after neoadjuvant systemic therapy (NST) is extremely low, and this population has the potential to be exempt from sentinel lymph node biopsy (SLNB). However, an overview of the ypN+ rate in this population for different breast cancer subtypes is lacking. Objective: To provide the pooled ypN+ rate in cN0 patients who achieved bpCR after NST in different breast cancer subtypes defined by hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status. Methods: A systematic literature search was conducted in Embase and PubMed on July 20, 2022. Two authors independently selected studies that met the inclusion criteria and extracted all data. The pooled ypN+ rates for each subtype were calculated by a random-effects model using the Stata 16.0 metaprop command. Results: The pooled analysis of 9609 cN0 patients who achieved bpCR showed that the ypN+ rate was lowest for the HR+/HER2+ (0%) subtype, followed by HR+/HER2- (5.1%), HR-/HER2+ (0.6%), and HR-/HER2- (0.3%). Additionally, 6571 cT1-T2N0 patients who achieved bpCR had a pooled ypN+ rate of 0.6%, and the ypN+ rates for different subtypes were as follows: HR+/HER2+ (1.7%), HR+/HER2- (2.7%), HR-/HER2+ (0.1%), and HR-/HER2- (0.8%). Conclusion: Our results suggested that cN0 patients who achieve bpCR may be exempt from axillary surgery in the HR+/HER2-, HR+/HER2+, and HR-/HER2- subtypes because of the extremely low probability of residual axillary lymph node disease. However, the safety of omitting axillary surgery needs to be further confirmed by prospective studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022351739.

ERK Inhibition Promotes Engraftment of Allografts by Reprogramming T-Cell Metabolism.

Extracellular regulated protein kinases (ERK) signaling is a master regulator of cell behavior, life, and fate. Although ERK pathway is shown to be involved in T-cell activation, little is known about its role in the development of allograft rejection. Here, it is reported that ERK signaling pathway is activated in allograft-infiltrating T cells. On the basis of surface plasmon resonance technology, lycorine is identified as an ERK-specific inhibitor. ERK inhibition by lycorine significantly prolongs allograft survival in a stringent mouse cardiac allotransplant model. As compared to untreated mice, lycorine-treated mice show a decrease in the number and activation of allograft-infiltrated T cells. It is further confirmed that lycorine-treated mouse and human T cells are less responsive to stimulation in vitro, as indicated by their low proliferative rates and decreased cytokine production. Mechanistic studies reveal that T cells treated with lycorine exhibit mitochondrial dysfunction, resulting in metabolic reprogramming upon stimulation. Transcriptome analysis of lycorine-treated T cells reveals an enrichment in a series of downregulated terms related to immune response, the mitogen-activated protein kinase cascade, and metabolic processes. These findings offer new insights into the development of immunosuppressive agents by targeting the ERK pathway involved in T-cell activation and allograft rejection.

Evaluation of outcome of chemotherapy for breast cancer patients older than 70 years: A SEER-based study.

Background: With the aging of the population, the number of elderly breast cancer cases has increased. However, there is a lack of effective randomized clinical trial data to support whether elderly patients should receive chemotherapy. Our goal was to observe the relationship between chemotherapy and breast cancer-specific survival (BCSS) in elderly breast cancer patients and to identify those who could benefit from chemotherapy. Methods: We collected the data of patients who were diagnosed with invasive ductal carcinoma and older than 70 years in the SEER database from 1995 to 2016. The independent predictors of BCSS were identified by Cox regression analysis. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to eliminate confounding factors. Results: A total of 142,537 patients were collected, including 21,782 patients in the chemotherapy group and 120,755 patients in the non-chemotherapy group. We identified the same potential predictors of BCSS after PSM and IPTW, such as age, race, grade, stage, therapy, subtype. A nomogram for predicting 3-year, 5-year and 10-year BCSS was constructed. The 3-year, 5-year and 10-year AUCs of the nomogram were 0.842, 0.819, and 0.788. According to the risk stratification of model predictive scores, patients in the high-risk group achieved the greatest improvement in BCSS after receiving chemotherapy. Conclusions: Our study suggests that women older than 70 years with larger tumors, higher grade, positive nodes, negative hormone receptor and inactive local therapy gain prognostic benefits from chemotherapy, but for those with low- and median-risk, conventional chemotherapy should be administered cautiously.

Inhibition of Posterior Capsule Opacification by Adenovirus-Mediated Delivery of Short Hairpin RNAs Targeting TERT in a Rabbit Model.

PURPOSE: Posterior capsule opacification (PCO) is the most common postoperative complication after cataract surgery and cannot yet be eliminated. Here, we investigated the inhibitory effects of telomerase reverse transcriptase (TERT) gene silencing on PCO in a rabbit model. METHODS: After rabbit lens epithelial cells (LECs) were treated with adenovirus containing short hairpin RNAs (shRNA) targeting TERT (shTERT group), adenovirus containing scramble nonsense control shRNA (shNC group) or PBS (control group), quantitative real-time polymerase chain reaction and Western blotting were used to measure the expression levels of TERT, and a scratch assay was performed to assess the LEC migration. New Zealand white rabbits underwent sham cataract surgery followed by an injection of adenovirus carrying shTERT into their capsule bag. The intraocular pressure and anterior segment inflammation were evaluated on certain days, and EMT markers (α-SMA and E-cadherin) were evaluated by Western blotting and immunofluorescence. The telomerase activity of the capsule bag was detected by ELISA. At 28 d postoperatively, hematoxylin and eosin staining of the cornea and iris and electron microscopy of the posterior capsule were performed. RESULTS: Application of shTERT to LECs downregulated the expression levels of TERT mRNA and protein. The scratch assay results showed a decrease in the migration of LECs in the shTERT group. In vivo, shTERT decreased PCO formation after cataract surgery in rabbits and downregulated the expression of EMT markers, as determined by Western blotting and immunofluorescence. In addition, telomerase activity was suppressed in the capsule bag. Despite slight inflammation in the iris, histologic results revealed no toxic effects in the cornea and iris. CONCLUSION: TERT silencing effectively reduces the migration and proliferation of LECs and the formation of PCO. Our findings suggest that TERT silencing may be a potential preventive strategy for PCO.

Highly Efficient and Chemoselective Tandem Hydroformylation-Hydrogenation of Alkenes to Alcohols over g-CN Supported Bimetallic Rh and Co Nanoparticles Catalysts.

The objective of the tandem hydroformylation-hydrogenation of alkenes to corresponding alcohols was to design an efficient and stable heterogeneous catalyst. To this end, a series of novel heterogeneous graphitic carbon nitride (g-CN) supported bimetallic Rh-Co nanoparticle catalysts (Rh-Co/g-CN) were prepared and subsequently studied for this one-pot two-step reaction. The lamellar structure makes Rh and Co nanoparticles with diameters of <1 nm and 20 nm, respectively, homogeneously deposited on the surface of g-CN layers, exhibit remarkable conversion of styrene (99.9 %) and chemoselectivity for alcohol (87.8 %). More importantly, Co nanoparticles are found to play an important role in the improvement of the chemoselectivity for alcohol due to the formation of catalytic active species [HCo(CO)y ]. Besides the detailed investigation of the catalytic properties of Rh-Co/g-CN under different reaction conditions, the reuse of Rh-Co/g-CN was conducted for five times and no evident decrease in the activity and chemoselectivity was observed. Therefore, we expect that this work could offer an initial insight into g-CN-based heterogeneous catalyst on the tandem hydroformylation-hydrogenation reaction.

New Insight into the Concanavalin A-Induced Apoptosis in Hepatocyte of an Animal Model: Possible Involvement of Caspase-Independent Pathway.

Concanavalin A (Con A) is known to be a T-cell mitogen and has been shown to induce hepatitis in mice through the triggering of conventional T cells and NKT cells. However, it remains unknown whether Con A itself can directly induce rapid hepatocyte death in the absence of a functional immune system. Here, by using an immunodeficient mouse model, we found Con A rapidly induced liver injury in vivo despite a lack of immunocyte involvement. We further observed in vitro that hepatocytes underwent a dose-dependent but caspase-independent apoptosis in response to Con A stimulation in vitro. Moreover, transcriptome RNA-sequencing analysis revealed that apoptosis pathways were activated in both our in vivo and in vitro models. We conclude that Con A can directly induce rapid but non-classical apoptosis in hepatocytes without the participation of immunocytes. These findings provide new insights into the mechanism of Con A-induced hepatitis.

Blood loss during liver transplantation is a predictor of postoperative thrombosis.

Liver transplantation (LT) is an effective way to cure end-stage liver diseases (ESLDs), which have generally been regarded as examples of acquired bleeding disorders. However, postoperative thrombosis after LT is recognised and remains a life-threatening complication. This study aimed to show that blood loss during LT is a predictor of postoperative thrombosis and to establish a predictive model. We analysed the medical records of all patients who underwent LT at the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to April 2019 to identify the risk factors for post-transplant thrombosis. The predictive nomogram was established based on independent predictors identified by logistic regression analysis. Blood loss during LT of ≥31.25 mL/kg can predict postoperative thrombosis, and the nomogram achieved an accurate prediction.

Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer.

Background: Cuproptosis is a newly discovered programmed cell death dependent on overload copper-induced mitochondrial respiration dysregulation. The positive response to immunotherapy, one of the most important treatments for invasive breast cancer, depends on the dynamic balance between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). However, cuproptosis-related genes (CRGs) in clinical prognosis, immune cell infiltration, and immunotherapy response remain unclear in breast cancer progression. Methods: The expression and mutation patterns of 12 cuproptosis-related genes were systematically evaluated in the BRCA training group. Through unsupervised clustering analysis and developing a cuproptosis-related scoring system, we further explored the relationship between cuproptosis and breast cancer progression, prognosis, immune cell infiltration, and immunotherapy. Results: We identified two distinct CuproptosisClusters, which were correlated with the different patterns between clinicopathological features, prognosis, and immune cell infiltration. Moreover, the differences of the three cuproptosis-related gene subtypes were evaluated based on the CuproptosisCluster-related DEGs. Then, a cuproptosis-related gene signature (PGK1, SLC52A2, SEC14L2, RAD23B, SLC16A6, CCL5, and MAL2) and the scoring system were constructed to quantify the cuproptosis pattern of BRCA patients in the training cohort, and the testing cohorts validated them. Specifically, patients from the low-CRG_score group were characterized by higher immune cell infiltration, immune checkpoint expression, immune checkpoint inhibitor (ICI) scores, and greater sensitivity to immunotherapy. Finally, we screened out RAD23B as a favorable target and indicated its expression was associated with breast cancer progression, drug resistance, and poor prognosis in BRCA patients by performing real-time RT-PCR, cell viability, and IC50 assay. Conclusions: Our results confirmed the essential function of cuproptosis in regulating the progression, prognosis, immune cell infiltration, and response to breast cancer immunotherapy. Quantifying cuproptosis patterns and constructing a CRG_score could help explore the potential molecular mechanisms of cuproptosis regulating BRCA advancement and provide more effective immunotherapy and chemotherapy targets.

Identification of necroptosis-related subtypes and prognosis model in triple negative breast cancer.

Background: Necroptosis is considered to be a new form of programmed necrotic cell death, which is associated with metastasis, progression and prognosis of various types of tumors. However, the potential role of necroptosis-related genes (NRGs) in the triple negative breast cancer (TNBC) is unclear. Methods: We extracted the gene expression and relevant clinicopathological data of TNBC from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases. We analyzed the expression, somatic mutation, and copy number variation (CNV) of 67 NRGs in TNBC, and then observed their interaction, biological functions, and prognosis value. By performing Lasso and COX regression analysis, a NRGs-related risk model for predicting overall survival (OS) was constructed and its predictive capabilities were verified. Finally, the relationship between risk_score and immune cell infiltration, tumor microenvironment (TME), immune checkpoint, and tumor mutation burden (TMB), cancer stem cell (CSC) index, and drug sensitivity were analyzed. Results: A total 67 NRGs were identified in our analysis. A small number of genes (23.81%) detected somatic mutation, most genes appeared to have a high frequency of CNV, and there was a close interaction between them. These genes were remarkably enriched in immune-related process. A seven-gene risk_score was generated, containing TPSG1, KRT6A, GPR19, EIF4EBP1, TLE1, SLC4A7, ESPN. The low-risk group has a better OS, higher immune score, TMB and CSC index, and lower IC50 value of common therapeutic agents in TNBC. To improve clinical practicability, we added age, stage_T and stage_N to the risk_score and construct a more comprehensive nomogram for predicting OS. It was verified that nomogram had good predictive capability, the AUC values for 1-, 3-, and 5-year OS were 0.847, 0.908, and 0.942. Conclusion: Our research identified the significant impact of NRGs on immunity and prognosis in TNBC. These findings were expected to provide a new strategy for personalize the treatment of TNBC and improve its clinical benefit.

A Novel Risk-Scoring System to Identify the Potential Population Benefiting From Adjuvant Chemotherapy for Node-Negative TNBC Patients With Tumor Size Less Than 1 cm.

Background and Objectives: Whether chemotherapy is needed in node-negative triple-negative breast cancer (TNBC) patients with tumor size less than 1 cm is still controversial. In our research, we constructed a novel risk-scoring system to identify the potential TNBC patients benefiting from adjuvant chemotherapy in T1miN0M0, T1aN0M0, and T1bN0M0 stages. Methods: Relevant data were extracted from the SEER database. We applied Kaplan-Meier curves and the Cox hazards model for survival analysis and developed a nomogram of overall survival. The X-tile software was used for risk stratification. The information of TNBC patients treated in the First Affiliated Hospital of Xi'an Jiaotong University was used for the application of the model. Results: A total of 4266 patients who met the criteria of our study were included. T stage, age, race, surgery, and radiotherapy state were used to create the nomogram of overall survival. According to the total risk score, the patients were divided into high-risk (score g 73), median-risk (38 ≤ score < 73), and low-risk (score <38) groups. Chemotherapy can prolong the overall survival of patients in the median-risk and high-risk groups, while patients in the low-risk group can be exempted from chemotherapy. In addition, we also used the risk-scoring system in real-world patients as application and verification. Conclusion: We constructed a novel risk-scoring system that can be used as a chemotherapy decision-making tool for node-negative TNBC patients with tumor size less than 1 cm. Tumor size should not be the only criterion for chemotherapy treatment decision-making.

Bioinformatics analysis for the role of CALR in human cancers.

Cancer is one of the most important public health problems in the world. The curative effect of traditional surgery, radiotherapy and chemotherapy is limited and has inevitable side effects. As a potential target for tumor therapy, few studies have comprehensively analyzed the role of CALR in cancers. Therefore, by using GeneCards, UALCAN, GEPIA, Kaplan-Meier Plotter, COSMIC, Regulome Explorer, String, GeneMANIA and TIMER databases, we collected and analyzed relevant data to conduct in-depth bioinformatics research on the CALR expression in Pan-cancer to assess the possibility of CALR as a potential therapeutic target and survival biomarker. We studied the CALR expression in normal human tissues and various tumors of different stages, and found that CALR expression was associated with relapse free survival (RFS). We verified the expression of CALR in breast cancer cell lines by vitro experiments. Mutations of CALR were widely present in tumors. CALR interacted with different genes and various proteins. In tumors, a variety of immune cells are closely related to CALR. In conclusion, CALR can be used as a biomarker for predicting prognosis and a potential target for tumor molecular and immunotherapy.

HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/ß-catenin pathway activation.

Calreticulin (CALR) is a multifunctional protein that participates in various cellular processes, which include calcium homeostasis, cell adhesion, protein folding, and cancer progression. However, the role of CALR in breast cancer (BC) is unclear. Here, we report that CALR is overexpressed in BC compared with normal tissue, and its expression is correlated with patient mortality and stemness indices. CALR expression was increased in mammosphere cultures, CD24-CD44+ cells, and aldehyde dehydrogenase-expressing cells, which are enriched for breast cancer stem cells (BCSCs). Additionally, CALR knockdown led to BCSC depletion, which impaired tumor initiation and metastasis and enhanced chemosensitivity in vivo. Chromatin immunoprecipitation and reporter assays revealed that hypoxia-inducible factor 1 (HIF-1) directly activated CALR transcription in hypoxic BC cells. CALR expression was correlated with Wnt/ß-catenin pathway activation, and an activator of Wnt/ß-catenin signaling abrogated the inhibitory effect of CALR knockdown on mammosphere formation. Taken together, our results demonstrate that CALR facilitates BC progression by promoting the BCSC phenotype through Wnt/ß-catenin signaling in an HIF-1-dependent manner and suggest that CALR may represent a target for BC therapy.

A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape.

BACKGROUND: The diversity and plasticity behind ER+/PR-/HER2- breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. METHODS: Based on the immune-related gene expression profiles of 411 ER+/PR-/HER2- breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. RESULTS: Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. CONCLUSION: Overall, this study revealed five heterogeneous immune subtypes among ER+/PR-/HER2- breast cancer, also provided important implications for clinical translations.

A systematic analysis of a potential metabolism-related prognostic signature for breast cancer patients.

BACKGROUND: Metabolic pathways play an essential role in breast cancer. However, the role of metabolism-related genes in the early diagnosis of breast cancer remains unknown. METHODS: In our study, RNA sequencing (RNA-seq) expression data and clinicopathological information from The Cancer Genome Atlas (TCGA) and GSE20685 were obtained. Univariate cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed on the differentially expressed metabolism-related genes. Then, the formula of the metabolism-related risk model was composed, and the risk score of each patient was calculated. The breast cancer patients were divided into high-risk and low-risk groups with a cutoff of the median expression value of the risk score, and the prognostic analysis was also used to analyze the survival time between these two groups. In the end, we also analyzed the expression, interaction, and correlation among genes in the metabolism-related gene risk model. RESULTS: The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group in both TCGA and GSE20685 datasets. In addition, after adjusting for different clinicopathological features in multivariate analysis, the metabolism-related risk model remained an independent prognostic indicator in TCGA dataset. CONCLUSIONS: In summary, we systematically developed a potential metabolism-related gene risk model for predicting prognosis in breast cancer patients.

Heat Storage of Paraffin-Based Composite Phase Change Materials and Their Temperature Regulation of Underground Power Cable Systems.

Excessive heat accumulation in backfill materials causes thermal fatigue damage in underground power cable systems that significantly affects the cable carrying capacity. To improve the thermal conditions of the system, two types of composite phase change materials (CPCMs) were prepared by incorporating paraffin into porous ceramsite (CS)/expanded graphite (EG) in this study. EG and CS can carry 90 and 40 wt.% paraffin, respectively. The phase change temperature of paraffin/CS and paraffin/EG CPCMs was approximately 65 °C, and the corresponding latent heats were 63.38 J/g and 156.4 J/g, respectively. Furthermore, the temperature regulation by CPCMs was evaluated experimentally by designing a setup to simulate the underground power cable system. The reduction in the maximum temperature of the backfill materials with paraffin/CS CPCM and paraffin/EG CPCM was approximately 7.1 °C and 17.1 °C, respectively, compared to reference samples. A similar conclusion was drawn from the heat flux curves. Therefore, the prepared CPCMs could significantly alleviate temperature fluctuations, where the paraffin/EG CPCM provided better temperature regulation than paraffin/CS CPCM. Both materials have potential applications for use in backfill materials for underground power cable systems.

Mining the prognostic significance of the GINS2 gene in human breast cancer using bioinformatics analysis.

A number of studies have demonstrated the crucial functions of GINS2 within the GINS complex in various types of cancer. However, the molecular mechanisms and prognostic value of GINS2 in breast cancer remain unknown. The present study used; BC-GenExMiner, COSMIC, UCSC Xena, The Human Protein Atlas, GEPIA, cBioPortal, GeneMANIA, TIMER and Oncomine, in order to investigate gene expression, co-expression, clinical parameters and mutations in GINS2 in patients with breast cancer. Furthermore, the present study assessed the prognostic value of GINS2 in patients with breast cancer via the Kaplan-Meier plotter database. The results of the present study demonstrated that the mRNA levels of GINS2 were significantly higher in breast cancer tissue compared with normal tissue. In addition, high mRNA expression levels of GINS2 were associated with high Scarff-Bloom-Richardson status grades, a basal-like status and age (≤51 years); however, it was not associated with lymph node metastasis. The survival analysis revealed that increased GINS2 mRNA levels were associated with a worse prognosis for relapse-free survival in all patients with breast cancer, particularly in those with estrogen receptor-positive and progesterone receptor-positive subtypes. In addition, a positive association between the GINS2, CENPM and MCM4 genes was confirmed. The results of the present study suggest that GINS2 could be used as a potential prognostic biomarker for breast cancer. Nevertheless, further studies are necessary to confirm the effects of GINS2 on the pathogenesis and development of patients with breast cancer.

Increased SIX-1 expression promotes breast cancer metastasis by regulating lncATB-miR-200s-ZEB1 axis.

Patients with advanced breast cancer (BC) showed a higher incidence of regional and distant metastases. Sine oculis homeobox homolog 1 (SIX-1) has been confirmed to be a key tumorigenic and metastatic regulator in BC progression. Yet, molecular mechanisms behind SIX-1-induced BC metastases remain largely unknown. Here we found that SIX-1 was frequently up-regulated in BC and correlated with poor outcomes when tested in human BC tissue microarray. Then, we manipulated the expression of SIX-1 by via shRNA-mediated knockdown and lentivirus-mediated overexpression. Transwell assay in vitro and lung metastases model of nude mice in vivo showed that SIX-1 promoted BC cell invasion and migration in vitro, and facilitated metastases in vivo. Mechanistically, SIX-1 could promote the transcription of lncATB, which exerts critical pro-metastatic role in BC by directly binding to the miR-200 family, especially for miR-200c, to induce EMT and promote metastases. In conclusion, SIX-1 exerts its pro-metastatic role in BC through lncATB/miR-200s axis of EMT signalling pathway and could act as an important diagnostic marker as well as a significant therapeutic target for clinically advanced BC.

Effects of acupuncture on breast cancer-related lymphoedema: A systematic review and meta-analysis.

BACKGROUND: Lymphoedema is a common complication of axillary dissection surgery, especially for breast cancer patients. Approximately 20% of breast cancer survivors develop breast cancer-related lymphoedema (BCRL). Acupuncture (AC) has become an alternative treatment for BCRL. In this study, we investigated whether AC was a good method for treating limb oedema in women after breast cancer surgery. METHODS: We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) to evaluate the effectiveness of AC in the prevention of BCRL. Searching strategies were performed with the following keywords: "Breast cancer," "Acupuncture," "neoplasm," and "lymphoedema," with derivations and different combinations of these keywords. The following databases were searched: PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, WanFang, and CBM. Studies published in English and Chinese were considered for inclusion in this study. Study selection, risk of bias assessment and data extraction were independently conducted. Statistical analyses were conducted with RevMan software (version 5.3). RESULTS: Eight studies were identified by the search strategy, and 519 patients were included in this study. The effective rate was higher (odds ratios (OR): 4.23; 95% confidence interval (CI): 2.11 to 8.49; Z = 4.07, p < 0.0001) in the experimental group than that in the control group. There were no significant improvements in the front flexion (mean difference (MD): 0.19; 95% CI: -3.68 to 4.06; Z = 0.09, p = 0.92) or the back extension (MD: 0.42; 95% CI: -2.22 to 3.06; Z = 0.31, p = 0.75) movements of the shoulder between the experimental and control groups. CONCLUSIONS: AC may be an effective method for improving the condition of breast cancer-related lymphoedema. However, due to the high risk of bias and the low quality of the available studies, further high-quality RCTs are needed to confirm the efficacy of AC for breast cancer-related lymphoedema patients.