Fine mapping of Ne1, the hybrid necrosis gene complementary to Ne2 in common wheat (Triticum aestivum L.).

KEY MESSAGE: Apart from confinement of Ne1 to a 4.45 Mb genomic segment, markers closely linked to Ne2 were identified and incomplete dominance of both genes in conditioning necrosis severity was shown. Hybrid necrosis in plants is characterized by premature death of leaves or plants in F1 hybrids. Interaction of two complementary dominant genes Ne1 and Ne2 in wheat (Triticum aestivum L.) is known to cause hybrid necrosis. However, the mechanism underlying this necrosis is still elusive. To obtain markers closely-linked to these two genes, Ne1-carrying cultivar Zheng891 was crossed with Ne2-carrying cultivar Pan555. Using BC1F1 plants derived from crosses of the F1 plants with the two parental lines, Ne1 and Ne2 were mapped to a 2.2 cM interval and a 2.3 cM interval with newly developed markers, respectively. Ne1 was further delimited to a 0.19 cM interval using 2015 Ne2-carrying F2 plants. Xwgrc3146, Xwgrc3147 and Xwgrc3150, three of the four markers co-segregating with Ne1, were all Zheng891-dominant, suggesting that, compared with Pan555, Ne1 is located in a region with substantial sequence diversity. The Ne1 interval is syntenic to chromosomes 5H, 4, 9 and 2 of barley, Brachypodium distachyon, rice and sorghum, respectively, and corresponds to a 4.45 Mb Chinese Spring sequence. Variations in necrosis severity of the F2 plants differing in Ne1 and Ne2 genotypes implied that these two genes are incompletely dominant in determining the timing and severity of necrosis.

Overexpression of a Prefoldin ß subunit gene reduces biomass recalcitrance in the bioenergy crop Populus.

Prefoldin (PFD) is a group II chaperonin that is ubiquitously present in the eukaryotic kingdom. Six subunits (PFD1-6) form a jellyfish-like heterohexameric PFD complex and function in protein folding and cytoskeleton organization. However, little is known about its function in plant cell wall-related processes. Here, we report the functional characterization of a PFD gene from Populus deltoides, designated as PdPFD2.2. There are two copies of PFD2 in Populus, and PdPFD2.2 was ubiquitously expressed with high transcript abundance in the cambial region. PdPFD2.2 can physically interact with DELLA protein RGA1_8g, and its subcellular localization is affected by the interaction. In P. deltoides transgenic plants overexpressing PdPFD2.2, the lignin syringyl/guaiacyl ratio was increased, but cellulose content and crystallinity index were unchanged. In addition, the total released sugar (glucose and xylose) amounts were increased by 7.6% and 6.1%, respectively, in two transgenic lines. Transcriptomic and metabolomic analyses revealed that secondary metabolic pathways, including lignin and flavonoid biosynthesis, were affected by overexpressing PdPFD2.2. A total of eight hub transcription factors (TFs) were identified based on TF binding sites of differentially expressed genes in Populus transgenic plants overexpressing PdPFD2.2. In addition, several known cell wall-related TFs, such as MYB3, MYB4, MYB7, TT8 and XND1, were affected by overexpression of PdPFD2.2. These results suggest that overexpression of PdPFD2.2 can reduce biomass recalcitrance and PdPFD2.2 is a promising target for genetic engineering to improve feedstock characteristics to enhance biofuel conversion and reduce the cost of lignocellulosic biofuel production.

Sex differences in subclinical hypothyroidism and associations with metabolic risk factors: a health examination-based study in mainland China.

BACKGROUND: The association between subclinical hypothyroidism (SCH) and metabolic risk factors in the general health examination-based population has been widely explored. However, the results have been inconclusive. Additionally, the sex differences in the prevalence of SCH and the association of SCH with metabolic risk factors remain unknown. METHODS: We conducted this cross-sectional study using data from health examination-based participants between June 2016 and April 2018 in our health examination centre. Sex differences SCH and the association of SCH with metabolic risk factors were explored. RESULTS: The total prevalence of SCH was 3.40% among the 5319 included participants, and 4.90% among the 2306 female participants, which was much higher than the prevalence of 2.26% among the 3013 male participants (p < 0.05). In males, the difference between participants younger than 60 and aged 60 or older was not significant (p = 0.104); while in females, the difference between participants younger than 40 and participants aged 40 or older was statistically significant (p = 0.023). Multivariate logistic regression analysis demonstrated that age (OR = 0.568, p = 0.004), body-mass index (BMI) (OR = 5.029, p < 0.001) and systolic/diastolic blood pressure (SBP/DBP) (OR = 5.243, p < 0.001) were independent predictors of SCH in females, but no metabolic risk factor was significantly associated with SCH in males. Further analysis revealed that the prevalence was much higher in participants with one or two metabolic risk factors than in those with no above metabolic risk factors regardless of age (p < 0.01). CONCLUSIONS: Our study demonstrates that high BMI and/or high blood pressure are associated with SCH in female participants, and the prevalence of SCH among women with one or two metabolic risk factors ranges from 7.69-14.81%, which indicates that in such a population, serum concentrations of TSH and FT4 may be routinely screened in mainland China. Certainly, prospective, large-scale studies with long follow-up period are still necessary to further verify our results.

Transition metal-coordinated graphitic carbon nitride dots as a sensitive and facile fluorescent probe for ß-amyloid peptide detection.

Herein, we developed a sensitive graphitic carbon nitride quantum dot (gCNQD)-based fluorescent strategy for ß-amyloid peptide monomer (Aß) determination down to the ng mL-1 level for the first time. To realize this goal, the nanostructured gCNQDs were firstly coordinated with four transition metal ions (Cu2+, Cu+, Fe3+, Zn2+). Our findings showed that the fluorescence (FL) intensity of gCNQDs was quenched in the presence of these metal ions possibly due to the effective chelation with the nitrogen element in gCNQDs and subsequent photoinduced electron transfer (PET) of gCNQDs. The degree of fluorescence quenching was found to be the most intense with the addition of Cu2+ and therefore, we selected Cu2+ as the quencher for the following Aß determination. Through binding to Cu2+, the introduction of Aß unexpectedly induced a further decline of FL intensity. Importantly, on account of different peptide sequences coexisting in the same cerebral system, including Aß1-11, Aß1-16, Aß1-38, Aß1-40 and Aß1-42, their affinities to Cu2+ could be reflected by the distinguished declining extent of FL intensity. The possible mechanism of Aß sensing by the probe was clarified by TEM characterization. The developed fluorescent biosensor was demonstrated to give a wide linear range from 1 to 700 ng mL-1 and a low detection limit of 0.18 ng mL-1 for Aß1-42. In the end, the proposed fluorescence approach was successfully applied to monitoring of Aß1-42 variations in the cortex and hippocampus of AD rats.

Design of a Biocompatible and Ratiometric Fluorescent probe for the Capture, Detection, Release, and Reculture of Rare Number CTCs.

Circulating tumor cells (CTCs) served as an important biomarker for tumor recurrence and prediction of prognosis. However, selective capture and quantification of CTCs from whole blood was still full of challenge due to the extremely scare number of CTCs. Moreover, how to keep a high cell viability after capture remained to be solved. Here, we described a ratiometric fluorescent probe for the efficient capture and accurate determination of CTCs by conjugating graphitic carbon nitride quantum dots (g-CNQDs) with gold nanoclusters (AuNCs) and further linking with anti-EpCAM antibody to acquire the CTC-specific immune probe. In this probe, AuNCs protected by albumin V bovine played the role as the fluorophore reference and anti-EpCAM-attached g-CNQDs acted as both the response signal and specific recognition element for sensing CTCs. In the presence of CTCs, the quenched fluorescence of the immune probe at 500 nm was recovered due to the detachment of anti-EpCAM from the probe, whereas the intensity at 650 nm was essentially unchanged. This strategy realized the highly sensitive detection of CTCs in whole blood down to one CTC. Furthermore, it was demonstrated that the designed probe allowed capturing living CTCs with minimal cell damage. The subsequent reculture of captured cells for proliferation revealed that after a 7 day proliferation, almost 28 MCF-7 cells were obtained from one target cell. The immune probe was successfully applied into capture and detection of CTCs from clinical cancer patients. Our data suggested the good potential of fluorescent probe for the clinical diagnosis of cancers.

Predictive Value of Clinicopathological Characteristics for Sentinel Lymph Node Metastasis in Early Breast Cancer.

BACKGROUND Sentinel lymph node biopsy (SLNB) is one of the preferred treatments for breast cancer including clinically negative lymph node breast cancer. However, for 60-70% of patients this invasive axilla surgery is unnecessary. Our study aimed to identify the predictors for sentinel lymph node (SLN) metastasis in early breast cancer patients and provide evidence for rational decision-making in specified clinical situations. MATERIAL AND METHODS Medical records of 417 breast cancer patients who were treated with a breast surgical procedure and SLNB in Ningbo Medical Center Lihuili Eastern Hospital were retrospectively reviewed. Univariate analysis and multivariate logistic regression analysis were used to analyze the correlation between SLN metastasis and clinicopathological characteristics, including patient age, menstrual status, body mass index (BMI), family history, tumor size, laterality of tumor, histological grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67 index, and molecular subtypes of the tumor. RESULTS In the cohort of 417 cases, the ratio of SLNM was 23.0%. Univariate analysis found that age, tumor size, histological grade, and Ki67 index were associated with SLN metastasis. However, age, tumor size, and histological grade were the only three independent predictors for SLN metastasis by multivariate logistic regression analysis. When these three factors were considered together, three different levels of SLN metastasis groups could be classified: low-risk group with the ratio of 14.3%, moderate-risk group with the ratio of 31.4%, and high-risk group with the ratio of 66.7%. CONCLUSIONS Our study demonstrated that age, tumor size, and histological grade were three independent predictive factors for SLN metastasis in early breast cancer patients. This finding may help surgeons in the decision-making process for early breast cancer patients before considering axilla surgical procedure.

A new species of Neobelocera Ding & Yang (Hemiptera: Delphacidae: Delphacinae: Tropidocephalini) from China, with a key to species of the genus.

Neobelocera medogensis sp. nov. (Hemiptera: Delphacidae: Delphacinae: Tropidocephalini) is described and illustrated from Mȇdog, Tibet, China. The new species can be easily separated from other known species in the genus Neobelocera by the color of tegmina and the form of the male genitalia. A key for separation of all known species of Neobelocera is also provided.

Therapy for Hormone Receptor-Positive, Human Epidermal Growth Receptor 2-Negative Metastatic Breast Cancer Following Treatment Progression via CDK4/6 Inhibitors: A Literature Review.

Endocrine therapy (ET) with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is currently the first-line standard treatment for most patients with hormone receptor-positive (HR+) and human epidermal growth receptor 2-negative (HER2-) metastatic or advanced breast cancer. However, the majority of tumors response to and eventually develop resistance to CDK4/6is. The mechanisms of resistance are poorly understood, and the optimal postprogression treatment regimens and their sequences continue to evolve in the rapidly changing treatment landscape. In this review, we generally summarize the mechanisms of resistance to CDK4/6is and ET, and describe the findings from clinical trials using small molecule inhibitors, antibody-drug conjugates and immunotherapy, providing insights into how these novel strategies may reverse treatment resistance, and discussing how some have not translated into clinical benefit. Finally, we provide rational treatment strategies based on the current emerging evidence.

Comparison of the prognosis of medullary breast carcinoma and invasive ductal carcinoma: a SEER-based study.

Background: Medullary breast carcinoma (MBC) is a rare type of breast cancer. Our study aimed to compare the differences in clinical characteristics and prognosis between MBC and invasive ductal carcinoma (IDC), and to further develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in MBC patients. Methods: A total of 179,613 patients from the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015, including 596 MBC patients, were analyzed using the Kaplan-Meier method and propensity score matching (PSM) to compare patients' OS and CSS. Cox proportional hazard regression model was used to determine independent prognostic factors for OS and CSS in MBC patients. Nomograms were constructed based on Cox regression analysis whereas receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive accuracy. Results: There were significant differences in the clinical characteristics between MBC and IDC. According to the logrank test, MBC had better OS and CSS than IDC before and after PSM. Cox multivariate analysis showed that age, race, tumor size, lymph node (LN), and radiation therapy were independent prognostic factors for OS, whereas age, tumor size, American Joint Committee on Cancer (AJCC) stage, laterality, type of surgery, and chemotherapy were independent prognostic factors for CSS. Nomograms of OS and CSS were constructed based on independent prognostic factors. Conclusions: MBC had better OS and CSS than IDC. Nomograms based on clinicopathological features were sufficiently accurate in predicting the OS and CSS for MBC patients, which can effectively predict the survival risk of MBC patients and guide clinicians to provide more effective treatment measures.

Sex-specific differences in the associations of metabolic syndrome or components with gallstone disease in Chinese euthyroid population.

In euthyroid population, it is uncertain whether there is sex-specific difference in the associations of metabolic syndrome (MetS) or its components with gallstone disease (GSD); in general population, MetS increases the risk of GSD. This was a cross-sectional study to investigate the sex-specific difference in the prevalence of MetS according to GSD status and the associations of MetS or its components with GSD in Chinese euthyroid population. The total prevalence of GSD was 8.1% (6.5% in men and 11.0% in women, with a significant difference (p < 0.001)). The total presence of MetS was 10.7% (12.1% in men and 8.2% in women,with a significant difference (p = 0.001)). The age-adjusted odds ratio of MetS for GSD was 2.775 in men (p < 0.001), 2.543 in women (p = 0.007) and 2.503 in the oveall samples (p < 0.001). Univariate analysis revealed that fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C) and thyroid-stimulating hormone (TSH) were associated with the prevalence of GSD. After adjustment for age, multivariate logistic regression analysis demonstrated that above three parameters were still significantly associated with the risk of GSD in general population; FPG and HDL-C but not TSH levels were significantly associated with the risk of GSD in men; and FPG and TSH levels but not HDL-C in women. Our study demonstrated that in euthyroid population, MetS appeared to be strongly associated with GSD regardless of sex, and FPG and TSH were two independent risk factors for GSD in men, while FPG and HDL-C in women.

Development and validation of an ultrasonography and clinicopathological features-based nomogram for non-sentinel lymph node metastasis.

Background: With the development of precise treatment for breast cancer, the current trend of clinical treatment aims to limit axillary surgery as much as possible. At present, there is an unmet need to predict the probability of patients with a low risk of non-sentinel lymph node (SLN) metastasis and determine whether the omission of axillary lymph node dissection (ALND) is appropriate. Methods: We retrospectively analyzed the data of patients with breast cancer who underwent sentinel lymph node biopsy (SLNB) and ALND. The patients were randomly assigned to training and validation sets. The associations between non-SLN metastasis (NSLNM) and ultrasonography and clinicopathological characteristics were assessed by multivariate logistic regression. Then, a nomogram model was constructed and validated using the calibration curve and the receiver operating characteristic curve. Results: Vascular infiltration, positive SLN number, negative SLN number, human epidermal growth factor receptor 2 (HER2) status, and lymph node shape were identified as independent predictive factors for positive NSLNM. The areas under the curve of the nomogram model to predict NSLNM were 0.793 and 0.780 in the training and validation sets, respectively, and P=0.161 and P=0.768 in the Hosmer-Lemeshow goodness of fit test, respectively. Conclusions: A nomogram model based on ultrasonography and clinicopathological features predicting NSLNM was established in our study, which is helpful for accurately assessing the risk of NSLNM in invasive breast cancer and providing evidence for individual surgical procedures involving axillary lymph nodes.

Prognostic factors for hormone receptor-positive breast cancer with liver metastasis and establishment of novel nomograms for prediction: a SEER-based study.

Background: The prognosis of patients with hormone receptor (HR)-positive breast cancer with liver metastasis (BCLM) remains dismal and varies widely from person to person. Thus, we sought to construct nomograms to predict overall survival (OS) and breast cancer-specific survival (BCSS) in patients with HR-positive BCLM using data from the Surveillance, Epidemiology and End Results (SEER) database. Methods: The data of patients with BCLM, who had received HR-positive diagnoses between 2010 and 2016, were collected from the SEER database. A Cox proportional hazards model was used to evaluate and identify the independent risk factors for OS and BCSS. Subsequently, two new nomograms were developed. Finally, the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) results were evaluated. Results: The data of 1,780 patients diagnosed between 2010 and 2015 were used to build the nomogram models. Using both univariate and multivariate Cox regression analyses, nine variables, including age, marital status, grade, human epidermal growth factor receptor 2 (HER2) status, chemotherapy, surgery, bone metastasis, lung metastasis, and brain metastasis, were found to be significantly associated with OS. Conversely, 10 variables, including age, marital status, T stage, grade, HER2 status, chemotherapy, surgery, bone metastasis, lung metastasis, and brain metastasis, were identified as independent risk factors for BCSS. Using the risk factors listed above, we created 1-, 2-, and 3-year survival nomograms for OS and BCSS, respectively. Subsequently, the data of 312 patients, who had been diagnosed in 2016, were used for the external validation. These results, including the ROC curve, calibration curve, and DCA results, showed that our nomogram had strong predictive power. Conclusions: Nomograms can effectively and reliably predict a patient's prognosis and could be useful in clinical decision making. The nomograms had strong discrimination, calibration, and clinical values. More aggressive treatment and closer monitoring should be considered when treating high-risk individuals.

Preparation of Al3Ti-Al2O3/Al Inoculant and Its Inoculation Effect on Al-Cu-Mn Alloy.

The grain size plays a pivotal role in determining the properties of the alloy. The grain size can be significantly decreased by adding inoculants. Aiming to address the shortcomings of existing inoculants, the Al3Ti-Al2O3/Al inoculant was successfully prepared using Al-Ti master alloy and Al2O3 whiskers as raw materials. With the aid of ultrasonic energy, the Al2O3 whiskers were uniformly dispersed within the inoculants. Under the combined action of ultrasonic and titanium, the Al2O3 whiskers were broken into small particles at high temperature. To enhance the morphology of Al3Ti and achieve even particle dispersion throughout the matrix, vacuum rapid quenching treatment was applied to the inoculant. The SEM test results indicated a significant reduction in particle size after vacuum rapid quenching. The Al3Ti-Al2O3/Al inoculants exhibited excellent grain refinement effects on the weldable Al-Cu-Mn alloy. Crystallographic calculations and HRTEM analysis revealed that Al2O3 and Al have orientation relationships, indicating their potential as effective heterogeneous nucleation sites. The mechanical properties of the Al-Cu-Mn alloy were obviously improved after the Al3Ti-Al2O3/Al inoculant was added.

Validation of the Prognostic Stage from the American Joint Committee on Cancer 8th Staging Manual in Luminal B-Like Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

PURPOSE: The 8th edition American Joint Committee on Cancer (AJCC) prognostic staging system (PS) has been validated numerous times; however, the prognostic value of PS for breast cancer based on molecular subtype has rarely been explored. This study aimed to investigate the prognostic value of PS in Chinese patients with luminal B-like human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: A total of 407 eligible cases were included in the study. All of the cases were restaged using the 8th edition AJCC Anatomic Staging System (AS) and PS. The Kaplan-Meier method was used to calculate estimated survival and the Log rank test was used to compare the survival differences between groups. RESULTS: The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 90.3% and 93.5%, respectively, and there were statistically significant differences in the 5-year DSS and 5-year OS rates among the different anatomic and prognostic stage groups. The application of the PS resulted in the assignment of 215 (52.8%) patients to a different group. Different prognostic stage groups restaged from anatomic Stage III had significant differences in both DSS (χ 2 = 4.366, p = 0.037) and OS (χ 2 = 7.549, p = 0.006); additionally, different prognostic stage groups from the anatomic Stage II group had significant differences in DSS (χ 2 = 7.724, p = 0.021) but no significant differences in OS (χ 2 = 5.182, p = 0.075). However, different prognostic stage groups from anatomic Stage I had no significant differences in either DSS (χ 2= 0.159, p = 0.690) or OS (χ 2 = 0.099, p = 0.753). CONCLUSION: The 8th edition AJCC PS refined the anatomic stage grouping in luminal B-like HER2-negative breast cancer and could lead to a more personalized approach to breast cancer treatment.

Present situation and analysis of factors affecting perimenopausal syndrome among clinical nurses-a cross-sectional survey.

BACKGROUND: The quality of life of women is seriously affected by perimenopausal symptoms and related diseases. Clinical nurses often suffer from job burnout due to high pressure and intensity of work and life, which is easy to induce and aggravate perimenopausal syndrome. Nursing occupational environment varies greatly in different economic regions, but relevant studies are limited to northern cities, and are often confined to the second and third grade hospitals or a hospital in a certain region, lacking multi-center studies on hospitals of different grades. Therefore, it is necessary to understand the occurrence of perimenopausal syndrome in clinical nurses in Chongqing and its influencing factors, so as to provide reference for managers to take targeted intervention measures. METHODS: The investigation was conducted using the method of stratified random cluster sampling. A questionnaire survey was conducted among 933 clinical nurses aged from 40 to 55 in primary, secondary and tertiary hospitals. Kupperman's total symptom score ranged from 0 to 63, while a score of ≥7 can determine the existence of perimenopausal syndrome. RESULTS: Among the 933 clinical nurses surveyed, 662 (70.95%) had perimenopausal syndrome, the results of the multivariate unconditional logistic regression analysis showed that The age ranges from 51 to 55 (OR =2.035, 95% CI: 1.070-3.872), the presence of chronic diseases (OR =1.659, 95% CI: 1.095-2.512), menopause (OR =1.989, 95% CI: 1.198-3.303), moderate family function impairment (OR =1.940, 95% CI: 1.356-2.776), severe family dysfunction weekly (OR =2.309, 95% CI: 1.178-4.524), never participation in sports (OR =3.328, 95% CI: 1.657-6.684) and exercising 1-5 times per week (OR =2.689, 95% CI: 1.516-4.768) were risk factors for perimenopausal syndrome in clinical nurses, basic security (OR =0.939, 95% CI: 0.887-0.994), and sufficient manpower (OR =0.915, 95% CI: 0.855-0.979) were protective factors for perimenopausal syndrome in clinical nurses. CONCLUSIONS: The incidence of perimenopausal syndrome in clinical nurses at all levels of hospitals situated in Chongqing is relatively high. It is suggested that nursing managers should attach great importance to the physical and mental condition of this population and timely take targeted intervention measures to prevent or alleviate the occurrence and development of perimenopausal syndrome in clinical nurses.

An autophagy-related long non-coding RNA prognostic model and related immune research for female breast cancer.

Introduction: Breast cancer (BRCA) is the most common malignancy among women worldwide. It was widely accepted that autophagy and the tumor immune microenvironment play an important role in the biological process of BRCA. Long non-coding RNAs (lncRNAs), as vital regulatory molecules, are involved in the occurrence and development of BRCA. The aim of this study was to assess the prognosis of BRCA by constructing an autophagy-related lncRNA (ARlncRNA) prognostic model and to provide individualized guidance for the treatment of BRCA. Methods: The clinical data and transcriptome data of patients with BRCA were acquired from the Cancer Genome Atlas database (TCGA), and autophagy-related genes were obtained from the human autophagy database (HADb). ARlncRNAs were identified by conducting co­expression analysis. Univariate and multivariate Cox regression analysis were performed to construct an ARlncRNA prognostic model. The prognostic model was evaluated by Kaplan-Meier survival analysis, plotting risk curve, Independent prognostic analysis, clinical correlation analysis and plotting ROC curves. Finally, the tumor immune microenvironment of the prognostic model was studied. Results: 10 ARlncRNAs(AC090912.1, LINC01871, AL358472.3, AL122010.1, SEMA3B-AS1, BAIAP2-DT, MAPT-AS1, DNAH10OS, AC015819.1, AC090198.1) were included in the model. Kaplan-Meier survival analysis of the prognostic model showed that the overall survival(OS) of the low-risk group was significantly better than that of the high-risk group (p< 0.001). Multivariate Cox regression analyses suggested that the prognostic model was an independent prognostic factor for BRCA (HR = 1.788, CI = 1.534-2.084, p < 0.001). ROCs of 1-, 3- and 5-year survival revealed that the AUC values of the prognostic model were all > 0.7, with values of 0.779, 0.746, and 0.731, respectively. In addition, Gene Set Enrichment Analysis (GSEA) suggested that several tumor-related pathways were enriched in the high-risk group, while several immune­related pathways were enriched in the low-risk group. Patients in the low-risk group had higher immune scores and their immune cells and immune pathways were more active. Patients in the low-risk group had higher PD-1 and CTLA-4 levels and received more benefits from immune checkpoint inhibitors (ICIs) therapy. Discussion: The ARlncRNA prognostic model showed good performance in predicting the prognosis of patients with BRCA and is of great significance to guide the individualized treatment of these patients.

Myocardin/microRNA-30a/Beclin1 signaling controls the phenotypic modulation of vascular smooth muscle cells by regulating autophagy.

Upon vascular injury, vascular smooth muscle cells (VSMCs) change from a contractile phenotype to a synthetic phenotype, thereby leading to atherogenesis and arterial restenosis. Myocardin (MYOCD) is essential for maintaining the contractile phenotype of VSMCs. Deletion of MYOCD in VSMCs triggers autophagy. However, the molecular mechanism underlying the effect of MYOCD on autophagy is not clear. In this study, knockdown of MYOCD in human aortic VSMCs (HA-VSMCs) triggered autophagy and diminished the expression of SMC contractile proteins. Inhibition of autophagy in MYOCD-knockdown cells restored the expression of contractile proteins. MYOCD activated the transcription of miR-30a by binding to the CArG box present in its promoter, as confirmed by luciferase reporter and chromatin immune coprecipitation assays, while miR-30a decreased the expression of autophagy protein-6 (ATG6, also known as beclin1) by targeting its 3'UTR. Restoring the expression of miR-30a in MYOCD-knockdown cells upregulated the levels of contractile proteins. Treatment of VSMCs with platelet-derived growth factor type BB (PDGF-BB) resulted in the transformation of VSMCs to a proliferative phenotype. A low level of miR-30a was observed in PDGF-BB-treated HA-VSMCs, and re-expression of miR-30a led to a decrease in proliferative marker expression. Furthermore, using a wire injury mouse model, we found that miR-30a expression was significantly downregulated in the arterial tissues of mice and that restoration of miR-30a expression at the injured site abolished neointimal formation. Herein, MYOCD could inhibit autophagy by activating the transcription of miR-30a and that miR-30a-mediated autophagy defects could inhibit intimal hyperplasia in a carotid arterial injury model.

Treatment patterns, effectiveness, and patient-reported outcomes of palbociclib therapy in Chinese patients with advanced breast cancer: A multicenter ambispective real-world study.

BACKGROUND: Palbociclib was the only available cyclin-dependent kinase 4/6 inhibitor in China until very recently, and its effect has not been systemically evaluated among Chinese patients. This study aims to assess the efficacy, safety and patient-reported outcomes (PROs) of palbociclib plus endocrine therapy (ET) in real-world China. METHODS: An ambispective cohort study was conducted on patients with advanced HR+HER2- breast cancer who received palbociclib between July 2018, and November 2020 and were enrolled from 12 hospitals. Treatment patterns, survival outcomes, and safety events were documented, and PROs (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items [EORTC QLQ-C30] and EuroQoL 5 dimensions [EQ-5D]) were analyzed. The Kaplan-Meier method was used to visualize and estimate the median progression-free survival (mPFS). Log-rank tests, Cox regressions, t tests, and chi-square tests were performed for comparison. RESULTS: A total of 190 patients (median follow-up of 18.0 months) were enrolled. Palbociclib was mostly combined with aromatase inhibitors (66.3%), fulvestrant (32.6%), and tamoxifen (1.1%). The mPFS values were 21.0, 14.0, and 7.0 months with palbociclib administered in first- (n = 83), second- (n = 41) and subsequent-line settings (n = 66), respectively. Endocrine sensitivity was significantly associated with patient prognosis (mPFS: 23.0, 12.0, and 6.0 months for endocrine naïve, acquired, and primary resistant patients, respectively, p < 0.01). The outcome was worse for patients who failed to meet the inclusion criteria of PALOMA-3 than for those who met the criteria (later-line: 6.0 months vs. 9.0 months). The most common adverse events (AEs) were neutropenia (74.2%; grade 3/4: 30.0%), fatigue (48.4%), anemia (32.6%), and thrombocytopenia (22.1%). PRO data suggested that palbociclib plus ET significantly improved cognitive and emotional function, pain symptoms, and overall quality of life. CONCLUSIONS: Palbociclib is effective for front-line use and for treating endocrine-sensitive patients in real-world China and is generally well tolerated. The prevalence of AEs in the Chinese population is different from that reported in the PALOMA-2/3 trials.

Molecular Mechanism of Secondary Endocrine Resistance in Luminal Breast Cancer.

OBJECTIVE: The molecular mechanism of secondary resistance in Luminal breast cancer was studied to provide new ideas for the treatment of breast cancer. METHODS: The sensitivity of the downregulation of myeloid leukemia factor 1-interacting proteins (MLF1IP) to Tamoxifen (TAM) was tested by the Cell Counting Kit-8 (CCK-8). The apoptosis of MLF1IP-mediated resistance was analyzed by flow cytometry (FCM) with/without TAM. Western blot was used in detecting various kinds of apoptosis and the expression of the protein related to the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway to study the molecular mechanism of secondary endocrine resistance in Luminal breast cancer. RESULTS: The downregulation of MLF1IP could significantly increase the drug sensitivity of Michigan Cancer Foundation-7 (MCF-7) cells and also inhibit the proliferation of MCF-7 cells under the stimulation of drugs. Western blot results showed that the expression of Bcl-2-associated X (BAX), Caspase3, Caspase7, and Caspase9 proteins increased when MLF1IP was downregulated. The results of the PI3K/AKT signaling pathway revealed that the phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein expression of MCF7-shRNA was higher than that of MCF7-NC cells, while the expression of p-AKT was lower than that of MCF7-NC cells. CONCLUSIONS: (1) MLF1IP-related apoptosis resistance plays an essential role in MLF1IP-mediated secondary resistance of breast cancer cells. (2) MLF1IP promotes AKT phosphorylation by inhibiting the PTEN expression, thus activating the PI3K/AKT signaling pathway and causing the secondary resistance of Luminal breast cancer. (3) MLF1IP can be used as a factor to predict the endocrine resistance of Luminal breast cancer.

Interpectoral Lymph Node Dissection Can Be Spared in pN0/N1 Invasive Breast Cancer Undergoing Modified Radical Mastectomy: Single-Institution Experience from Mainland China.

PURPOSE: Interpectoral lymph nodes (IPNs) are one of the lymphatic drainage pathways in breast cancer. However, the clinical significance of IPN dissection is controversial, and there is no international consensus regarding the management of IPN for resectable breast cancer. Our study aims to identify the independent predictors of IPN metastasis in invasive breast cancer (IBC) and provide some evidence for rational decision-making. METHODS: Data from 214 IBC patients who were treated with modified radical mastectomy (MRM) plus IPN dissection or biopsy in Ningbo Medical Center Lihuili Hospital were retrospectively reviewed. Univariate analysis and multivariate logistic regression analysis were used to analyse the correlations between IPN occurrence or metastasis and clinicopathological characteristics. RESULTS: The occurrence rate of IPN in overall population was 75.2%. Univariate analysis showed that tumour size, involvement of axillary lymph nodes (ALNs), histological grading, Ki67 index and molecular subtype were associated with the occurrence of IPN. However, involvement of ALN was the only independent predictor by multivariate logistic regression analysis. In 161 patients whose IPNs were detected, 46 (28.6%) patients had one or more metastatic IPNs. Univariate analysis showed that tumour size, involvement of ALN, oestrogen receptor status and molecular subtype were associated with IPN metastasis. However, involvement of ALN was the only predictor by multivariate logistic regression analysis. In total, 0%, 5.0%, 26.1% and 84.2% of pN0, pN1, pN2, and pN3 patients had metastatic IPNs, respectively. CONCLUSION: The relatively low rate of IPN metastasis in patients with pN0/N1 breast cancer suggests that IPN dissection can be safely spared in patients with low tumour burden in axillary lymph nodes (pN0/N1), when MRM even breast conservation surgery is performed.