Prediction of epidermal growth factor receptor mutation subtypes in non-small cell lung cancer from hematoxylin and eosin-stained slides using deep learning.

Accurate assessment of epidermal growth factor receptor (EGFR) mutation status and subtype are critical for the treatment of non-small cell lung cancer (NSCLC) patients. Conventional molecular testing methods for detecting EGFR mutations have limitations. In this study, an artificial intelligence-powered deep learning framework was developed for weakly supervised prediction of EGFR mutations in NSCLC from hematoxylin and eosin (H&E)-stained histopathology whole-slide images (WSIs). The study cohort was partitioned into training and validation subsets. Foreground regions containing tumor tissue were extracted from WSIs. A convolutional neural network (CNN) employing a contrastive learning paradigm was implemented to extract patch-level morphological features. These features were aggregated using a vision-transformer-based model to predict EGFR mutation status and classify patient cases. The established prediction model was validated on unseen datasets. In internal validation with a cohort from (USTC)(n=172), the model achieved patient-level areas under the receiver operating characteristic (ROC) curve (AUCs) of 0.927 and 0.907, sensitivities of 81.6% and 93.0%, and specificities of 83.3% and 92.3%, for surgical resection and biopsy specimens in EGFR mutation subtype prediction, respectively. External validation with cohorts from the Second Affiliated Hospital of Anhui Medical University (AMU) and the First Affiliated Hospital of Wannan Medical College (WMC) (n=193) yielded patient-level AUCs of 0.849 and 0.871, sensitivities of 75.7% and 72.1%, and specificities of 90.5% and 90.3% for surgical and biopsy specimens, respectively. Further validation with The Cancer Genome Atlas (TCGA) dataset (n=81) showed an AUC of 0.861, sensitivity of 84.6%, and specificity of 90.5%. Deep learning solutions demonstrate potential advantages for automated, non-invasive, fast, cost-effective, and accurate inference of EGFR alterations from histomorphology. Integration of such artificial intelligence frameworks into routine digital pathology workflows could augment existing molecular testing pipelines.

Reversible Fusion-Fission MXene Fiber-Based Microelectrodes for Target-Specific Gram-Positive and Gram-Negative Bacterium Discrimination.

Inaccurate or cumbersome clinical pathogen diagnosis between Gram-positive bacteria (G+) and Gram-negative (G-) bacteria lead to delayed clinical therapeutic interventions. Microelectrode-based electrochemical sensors exhibit the significant advantages of rapid response and minimal sample consumption, but the loading capacity and discrimination precision are weak. Herein, we develop reversible fusion-fission MXene-based fiber microelectrodes for G+/G- bacteria analysis. During the fissuring process, the spatial utilization, loading capacity, sensitivity, and selectivity of microelectrodes were maximized, and polymyxin B and vancomycin were assembled for G+/G- identification. The surface-tension-driven reversible fusion facilitated its reusability. A deep learning model was further applied for the electrochemical impedance spectroscopy (EIS) identification in diverse ratio concentrations of G+ and G- of (1:100-100:1) with higher accuracy (>93%) and gave predictable detection results for unknown samples. Meanwhile, the as-proposed sensing platform reached higher sensitivity toward E. coli (24.3 CFU/mL) and S. aureus (37.2 CFU/mL) in 20 min. The as-proposed platform provides valuable insights for bacterium discrimination and quantification.

Analysis of PIK3CA mutations in the primary and recurrent tumors of hormone receptor positive/human epidermal growth factor receptor 2 negative breast cancer.

OBJECTIVE: Our aim was to compare the PIK3CA mutation status in matched primary and recurrent tumors of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (BC) to gain insight into the optimization of patient selection and detection time for PIK3CA-targeted therapy. METHODS: The data were from 3035 patients with BC diagnosed at the Breast Disease Center, Peking University First Hospital, between January 2008 and December 2017. Matched primary and recurrent samples were profiled using amplification-refractory mutation system-polymerase chain reaction covering 11 mutational hotspots in PIK3CA. RESULTS: PIK3CA mutations were detected in 54.3% primary tumors and 48.6% corresponding recurrences. PIK3CA mutation was detected in 37.5% cases in the locoregional recurrent group and 40.0% of distant metastasis, without a statistical difference. Besides, PIK3CA mutations were concordant in 88.6% of the matched pairs. For patients treated with neoadjuvant chemotherapy, 100% concordance was observed. However, PIK3CA mutation was neither correlated with clinicopathological features nor associated with clinical outcomes. CONCLUSIONS: Mutations in PIK3CA in HR+/HER2- BC generally progressed to recurrent tumors. The high concordance rate of PIK3CA mutation status between primary tumors and corresponding recurrences suggests that the detection of primary tumors could be a substitute approach when recurrent samples are not easily obtainable.

Primary lymphoma of the female genital tract masquerading as gynecological malignancy.

BACKGROUND: Primary lymphoma of the female genital tract (PLFGT) is a rare malignant tumor in the female reproductive system, with a low incidence and few clinical reports. The aim of this study is to report our institutional experience with this rare malignancy and emphasize the need for increasing the awareness about PLFGT presenting with gynecologic symptoms. METHODS: The medical records of patients diagnosed with PLFGT from March 2014 to November 2022 in the First Affiliated Hospital of Wannan Medical College were reviewed. Histological classification and staging were based on the World Health Organization and Ann Arbor systems, respectively. RESULTS: There were 13 patients with diagnosis of PLFGT and the median length of follow-up was 31 months (0-102 months). The main clinical symptoms included postmenopausal vaginal bleeding, pelvic mass and abdominal pain. Serum LDH increased in 10 patients and serum CA125 elevated in 2 patients. The tumor of ovarian or uterine presented as solid masses in CT or MRI, and ascites was rare. The histological subtypes were diffuse large B-cell (n = 12) and follicular (n = 1) lymphoma. Tumors were located in ovary (n = 8), uterus (n = 3), and cervix (n = 2). According to the Ann Arbor staging system, 6 cases were classified as stage II and 7 cases were classified as stage IV, respectively. A total of 10 patients underwent surgery. Combination chemotherapy was used in 10 patients. Eight patients had tumor-free survival, 1 patient had recurrent disease, 3 patients died and 1 patient lost to follow-up. The median survival time was 32 months (1-102 months). CONCLUSION: PLFGT usually presents as gynecological symptoms and solid masses in pelvis. Surgery or biopsy was the way to obtain the pathologic diagnosis, and combination chemotherapy is the efficient method for PLFGT. Making an accurate preoperative diagnosis is of paramount importance to avoid radical gynecologic surgery.

EEG-Based Emotion Recognition with Consideration of Individual Difference.

Electroencephalograms (EEGs) are often used for emotion recognition through a trained EEG-to-emotion models. The training samples are EEG signals recorded while participants receive external induction labeled as various emotions. Individual differences such as emotion degree and time response exist under the same external emotional inductions. These differences can lead to a decrease in the accuracy of emotion classification models in practical applications. The brain-based emotion recognition model proposed in this paper is able to sufficiently consider these individual differences. The proposed model comprises an emotion classification module and an individual difference module (IDM). The emotion classification module captures the spatial and temporal features of the EEG data, while the IDM introduces personalized adjustments to specific emotional features by accounting for participant-specific variations as a form of interference. This approach aims to enhance the classification performance of EEG-based emotion recognition for diverse participants. The results of our comparative experiments indicate that the proposed method obtains a maximum accuracy of 96.43% for binary classification on DEAP data. Furthermore, it performs better in scenarios with significant individual differences, where it reaches a maximum accuracy of 98.92%.

Real-Time EEG-Based Emotion Recognition.

Most studies have demonstrated that EEG can be applied to emotion recognition. In the process of EEG-based emotion recognition, real-time is an important feature. In this paper, the real-time problem of emotion recognition based on EEG is explained and analyzed. Secondly, the short time window length and attention mechanisms are designed on EEG signals to follow emotion change over time. Then, long short-term memory with the additive attention mechanism is used for emotion recognition, due to timely emotion updates, and the model is applied to the SEED and SEED-IV datasets to verify the feasibility of real-time emotion recognition. The results show that the model performs relatively well in terms of real-time performance, with accuracy rates of 85.40% and 74.26% on SEED and SEED-IV, but the accuracy rate has not reached the ideal state due to data labeling and other losses in the pursuit of real-time performance.

Preparation and Application of Amino-Terminated Hyperbranched Magnetic Composites in High-Turbidity Water Treatment.

In order to separate the colloidal in high-turbidity water, a kind of magnetic composite (Fe3O4/HBPN) was prepared via the functional assembly of Fe3O4 and an amino-terminal hyperbranched polymer (HBPN). The physical and chemical characteristics of Fe3O4@HBPN were investigated by different means. The Fourier Transform infrared spectroscopy (FTIR) spectra showed that the characteristic absorption peaks positioned at 1110 cm-1, 1468 cm-1, 1570 cm-1 and 1641 cm-1 were ascribed to C-N, H-N-C, N-H and C=O bonds, respectively. The shape and size of Fe3O4/HBPN showed a different and uneven distribution; the particles clumped together and were coated with an oil-like film. Energy-dispersive spectroscopy (EDS) displayed that the main elements of Fe3O4/HBPN were C, N, O, and Fe. The superparamagnetic properties and good magnetic response were revealed by vibrating sample magnetometer (VSM) analysis. The characteristic diffraction peaks of Fe3O4/HBPN were observed at 2θ = 30.01 (220), 35.70 (311), 43.01 (400), 56.82 (511), and 62.32 (440), which indicated that the intrinsic phase of magnetite remained. The zeta potential measurement indicated that the surface charge of Fe3O4/HBPN was positive in the pH range 4-10. The mass loss of Fe3O4/HBPN in thermogravimetric analysis (TGA) proved thermal decomposition. The -C-NH2 or -C-NH perssad of HBPN were linked and loaded with Fe3O4 particles by the N-O bonds. When the Fe3O4/HBPN dosage was 2.5 mg/L, pH = 4-5, the kaolin concentration of 1.0 g/L and the magnetic field of 3800 G were the preferred reaction conditions. In addition, a removal efficiency of at least 86% was reached for the actual water treatment. Fe3O4/HBPN was recycled after the first application and reused five times. The recycling efficiency and removal efficiency both showed no significant difference five times (p > 0.05), and the values were between 84.8% and 86.9%.

Preparation and Application of Magnetic Composites Using Controllable Assembly for Use in Water Treatment: A Review.

The use of magnetic composites in wastewater treatment has become widespread due to their high flocculating characteristics and ferromagnetism. This review provides an analysis and summary of the preparation and application of magnetic composites through controllable assembly for use in wastewater treatment. The applications of magnetic composites include the treatment of dye wastewater, heavy metal wastewater, microalgae suspensions, and oily wastewater. Additionally, the recycling and regeneration of magnetic composites have been investigated. In the future, further research could be focused on improving the assembly and regeneration stability of magnetic composites, such as utilizing polymers with a multibranched structure. Additionally, it would be beneficial to explore the recycling and regeneration properties of these composites.

A multicenter study on efficacy of dual-target neoadjuvant therapy for HER2-positive breast cancer and a consistent analysis of efficacy evaluation of neoadjuvant therapy by Miller-Payne and RCB pathological evaluation systems (CSBrS-026).

Objective: The aim of this study was to investigate the factors influencing pathological complete response (pCR) rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab (H) + pertuzumab (P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden (RCB) systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2 (HER2)+ breast cancer was analyzed. Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery (CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry (IHC) 3+/hormone receptor (HR)-, IHC3+/HR+, IHC2+ in situ hybridization (ISH)+/HR- and IHC2+ ISH+/HR+ groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed. Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals; 18,853 (24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target (H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate (P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0% (κ=0.717, P<0.001). Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+ breast cancer.

Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study.

PURPOSE: For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI). METHODS: We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0-1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0-1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician. RESULTS: A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4-104 months), patients who had PEPI 0-1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5-99.9%) for PEPI 0-1 or pCR group vs. 93.7% (95% CI 89.6-97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases. CONCLUSION: PEPI 0-1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted. CLINICAL TRIAL REGISTRATION: NCT01613560.

True hermaphroditism with sex cord tumor with annular tubules (SCTAT): a rare case report and review of the literature.

BACKGROUND: True hermaphroditism is a rare condition. It is defined as the presence of both testicular and ovarian tissues in the same individual. Sex cord tumour with annular tubules (SCTAT) is a rare stromal tumour of the sex cord that occurs mostly in the ovaries. CASE PRESENTATION: A 16-year-old girl presented to the gynaecology department with primary amenorrhea. Gynaecological examination revealed an enlarged clitoris that looked like a small penis. The chromosome karyotype was chimaera. The postoperative pathology confirmed true hermaphroditism with SCTAT. The patient underwent hormonal replacement after an operation and had no evidence of recurrence for 6 months. CONCLUSION: Cases of true hermaphroditism with SCTAT are extremely rare conditions. Surgery and hormonal replacement are important for improving the prognosis of such patients.

GNSS Timing Performance Assessment and Results Analysis.

Global Navigation Satellite System (GNSS) timing is a main service function. Each GNSS has its own time performance specification. However, a uniform timing performance assessment methodology and its outcomes do not exist. Firstly, the timing performance specifications of each GNSS are analyzed. Then, time transfer accuracy is considered as the key GNSS timing performance indicator. Secondly, an assessment method for the Coordinated Universal Time (UTC) published by the Bureau International des Poids et Mesures (BIPM) and UTC kept by the National Time Service Center of China (UTC(NTSC)) is proposed. Thirdly, the uncertainty budget of the assessment method is given. The timing performances of BDS, GPS, GLONASS, and Galileo are assessed and compared. The results show that the time transfer accuracy of BDS, GPS, GLONASS, and Galileo was 13.8 ns, 4.5 ns, 16.8 ns, and 4.2 ns, respectively, in 2021, meeting their performance requirements specified by GNSS (30 ns or 40 ns). Meanwhile, the assessment results of GPS and Galileo are much better than requirements, while the assessment results of BDS and GLONASS show fixed time offset and can still be improved further. If the local reference time of GNSS users can be connected with UTC, this assessment method can be used.

Hsa_circ_0040809 regulates colorectal cancer development by upregulating methyltransferase DNMT1 via targeting miR-515-5p.

BACKGROUND: Circular RNAs (circRNAs) are key regulators in the progression of various cancers. Abnormal DNA methylation patterns feature prominently in the regulation of the expression of tumor-related genes. This study is aimed at investigating the molecular mechanism of circ_0040809 affecting colorectal cancer (CRC) progression by regulating DNA methyltransferase 1 (DNMT1). METHODS: circ_0040809 was selected from the circRNA microarray datasets (GSE142837 and GSE138589). Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the expression of circ_0040809, miR-515-5p, and DNMT1 mRNA in paired cancerous and paracancerous tissues of 40 CRC patients, as well as in cell lines. Western blotting was conducted for detecting DNMT1 protein expression in CRC cells. Cell proliferation, migration, and apoptosis were assessed through CCK-8, Transwell, and flow cytometry assays. Bioinformatics and dual-luciferase gene assay were conducted to predict and verify, respectively, the targeted relationships between circ_0040809 and miR-515-5p, as well as between miR-515-5p and DNMT1 mRNA. RESULTS: In CRC tissues and cells, circ_0040809 and DNMT1 expression are markedly increased, whereas miR-515-5p expression is decreased. Also, high circ_0040809 expression is significantly linked to shorter overall survival. Cell function compensation experiments reveal that circ_0040809 silencing inhibits CRC cell proliferation and migration and promotes apoptosis, while circ_0040809 overexpression has the opposite effects. Mechanistically, circ_0040809 competitively binds to miR-515-5p to elevate DNMT1 expression. Rescue assay reveals that overexpressed miR-515-5p partly counteracts the tumor-facilitating impact of circ_0040809. CONCLUSIONS: circ_0040809 facilitates CRC cell proliferation and migration, and inhibits apoptosis, through modulating miR-515-5p/DNMT1 axis. Our study implies that targeting circ_0040809 may be a therapy strategy for CRC treatment.

S100A16 promotes metastasis and progression of pancreatic cancer through FGF19-mediated AKT and ERK1/2 pathways.

The S100 protein family genes play a crucial role in multiple stages of tumorigenesis and progression. Most of S100 genes are located at chromosome locus 1q21, which is a region frequently rearranged in cancers. Here, we examined the expression of the S100 family genes in paired pancreatic ductal adenocarcinoma (PDAC) samples and further validated the expression of S100A16 by immunohistochemistry staining. We found that S100A16 is significantly upregulated in clinical PDAC samples. However, its roles in PDAC are still unclear. We next demonstrated that S100A16 promotes PDAC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Knockdown of S100A16 induces PDAC cell cycle arrest in the G2/M phase and apoptosis. Furthermore, we also demonstrated that S100A16 promotes PDAC cell proliferation, migration, and invasion via AKT and ERK1/2 signaling in a fibroblast growth factor 19 (FGF19)-dependent manner. Taken together, our results reveal that S100A16 is overexpressed in PDAC and promotes PDAC progression through FGF19-mediated AKT and ERK1/2 signaling, suggesting that S100A16 may be a promising therapeutic target for PDAC. S100A16 was upregulated in PDAC and associated with prognosis of PDAC patients. S100A16 regulates apoptosis and the cell cycle of pancreatic cancer cells. S100A16 promotes the progression of pancreatic cancer by AKT-ERK1/2 signaling. S100A16 may be a promising therapeutic target for PDAC.

Extramedullary Blast Crisis of Chronic Myelogenous Leukemia With a Skin Lesion: A Case Report and Literature Review.

ABSTRACT: Extramedullary blast crisis of chronic myeloid leukemia (CML) is defined as extramedullary disease composed of blasts regardless of the proliferation of blasts in the bone marrow. The commonly affected sites are the lymph node, central nervous system, bone, skin, and soft tissue. However, skin infiltration of CML patients as the initial presentation while their bone marrow is still in the chronic phase is extremely rare. In this article, we present a case of a 51-year-old woman who was admitted to our hospital complaining about a skin nodule in her right calf and easy fatigability for 1 week. The peripheral blood and bone marrow analysis both supported the diagnosis of CML in the chronic phase, whereas the excisional biopsy specimen obtained from her right calf showed immature cells infiltration, and fluorescence in situ hybridization test was positive for p210 BCR/ABL1 gene rearrangement. Based on the presence of extramedullary myeloid sarcoma, the patient was diagnosed with extramedullary myeloid blast crisis of CML despite the chronic phase in the bone marrow.

Long non-coding RNA AK085865 ablation confers susceptibility to viral myocarditis by regulating macrophage polarization.

Accumulating evidence indicates that regulators of macrophage polarization may exert pivotal functions in the development of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). However, the mechanisms underlying macrophage polarization remain to be explored. Here, we sought to identify novel and functionally important long non-coding RNAs (lncRNAs) during macrophage polarization and to investigate their function and contribution to VM. In this study, we identified the lncRNA AK085865 as an important regulator of macrophage polarization. Knock-down of AK085865 diminished phenotypical expression of M2 macrophages while promoting polarization to the M1 phenotype. Moreover, AK085865-/- mice had increased susceptibility to CVB3-induced VM. We observed striking bias towards M1 macrophages, whereas the M2 population was decreased in AK085865-/- VM mice. Collectively, our findings uncover a critical role of AK085865 in the regulation of macrophage polarization in vitro and in vivo, identifying a new player in the development of VM and providing a potential clinically significant therapeutic target.

MiR-122 is involved in immune response by regulating Interleukin-15 in the orange-spotted grouper (Epinephelus coioides).

Epinephelus coioides is an important economic culture marine fish and is susceptible to various pathogenic diseases. Increasingly evidences showed that miRNAs participated in the regulation of the cell proliferation, differentiation and immune response. MiR-122 has been reported to play an essential role in immune response by triggering an inflammatory reaction. However, the function of miR-122 in response to bacterial infection is unclear in Epinephelus coioides. Herein, we report that miR-122 is involved in response to Aeromonas hydrophila infection of grouper spleen cells (GS). IL-15, IL-6 and IL-1ß are inhibited in overexpression miR-122 GS cells, while induced in silence miR-122 GS cells. In addition, IL-15 is predicted to be the target gene of miR-122, which is further confirmed by LUC. Taken together, we propose that miR-122 regulates the immune response to bacterial infection by triggering IL-15.

Isoquercetin regulates SREBP-1C via AMPK pathway in skeletal muscle to exert antihyperlipidemic and anti-inflammatory effects in STZ induced diabetic rats.

Diabetes mellitus (DM) is a cluster of metabolic diseases that exhibits high blood glucose levels accompanied by hyperlipidemia and inflammation. DM is the primary risk factor contributes majorly to cardiovascular disease (CVD) mediated morbidity and mortality. The incidence of dyslipidemia seems to attribute considerably to the initiation of CVDs. The beneficial action of isoquercetin on hyperlipidemia and related signaling pathways are not documented yet, hence we decide to carry out this study. The experimental rats were divided into five groups: Group 1, control rats; group 2, isoquercetin control (40 mg/kg b.w); group 3, diabetic rats (STZ-40 mg/kg b.w); group 4, diabetic + isoquercetin (40 mg/kg b.w); and group 5, diabetic + glibenclamide (600 µg/kg b.w). The animals were sacrificed at the end of the experimental duration of 45 days. Results of our analysis reveal that isoquercetin have a major impact on the tissue lipid profile, isoquercetin strongly regulates the expression of various lipid-metabolizing enzymes, C-reactive protein, expression of various inflammatory genes, SREBP-1C genes and proteins and AMP-activated protein kinase-α (AMPK) signaling pathway genes and proteins. Results recommend that isoquercetin can be effective in mitigating the consequences of hyperlipidemia and DM.

Clinicopathological analysis of early-stage breast cancer patients that meet indications for BRCA1/2 genetic testing.

OBJECTIVE: To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2 (BRCA1/2) genetic testing in China. METHODS: Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology, genetic/familial high-risk assessment: Breast and ovarian (Version 2. 2019), a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center, Peking University First Hospital between January 2008 and December 2016. Clinicopathological characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model. RESULTS: A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group, accounting for 34.7% of all breast cancer patients treated in Breast Disease Center, Peking University First Hospital during the study period. Compared with breast cancer patients without indications for BRCA genetic testing, the overall survival (OS) and disease-free survival (DFS) of patients with indications were not significantly different. In the study group, patients with premenopausal status, high T stage, lymph node positive, estrogen receptor (ER) negative, Ki-67>20% and presence of a vascular tumor thrombus had worse prognosis. There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications. CONCLUSIONS: Single-center data showed that more than 30% of patients with early-stage breast cancer had indications for BRCA genetic testing. There was no prognostic difference in patients with or without indications for BRCA genetic testing. Premenopausal status, high T stage, lymph node positive, ER negative, Ki-67>20%, and presence of a vascular tumor thrombus were associated with poor prognosis.

Histo- and clinico-pathological analysis of a large series of triple-negative breast cancer in a single center in China: Evidences on necessity of histological subtyping and grading.

OBJECTIVE: To investigate histo-pathological distribution and clinico-pathological significance in a large Chinese triple-negative breast cancer (TNBC) patients serials based on the latest understanding of its clinico-pathological diversity, and to provide more information to clinicians to improve precision of individualized treatment of TNBC. METHODS: A retrospective analysis was performed on patients with TNBC at Breast Disease Center, Peking University First Hospital between January 2010 and December 2019. Histo- and clinico-pathological characteristics were analyzed by Chi-square test and Student's t-test, and prognoses were calculated using Kaplan-Meier method and a Cox proportionate hazards model. Bonferroni correction was used to correct for multiple comparison. RESULTS: Conventional type of TNBC (cTNBC) were identified in 73.7% of 582 TNBC, while special type of TNBC (sTNBC) were 26.3%, including 71 apocrine carcinoma, 20 medullary carcinoma, 31 metaplastic carcinoma, 18 invasive lobular carcinoma, 7 invasive micropapillary carcinoma, 5 adenoid cystic carcinoma and 1 acinic cell carcinoma. Compared to sTNBC, cTNBC was associated with high histologic grade (P<0.001) and lower androgen receptor (AR) expression (P<0.001). TNM stage of low-grade cTNBC was significantly lower than that of high-grade cTNBC (P=0.002). Although no significant difference, there was a trend that the rate of 5-year disease-free survival (DFS) and 5-year overall survival (OS) were longer in high-grade cTNBC than in high-grade sTNBC (P=0.091 and 0.518), and were longer in low-grade sTNBC than in high-grade sTNBC (P=0.051 and 0.350). Metaplastic carcinomas showed larger tumor size (P=0.008) and higher proliferative Ki67 index (P=0.004) than cTNBCs. CONCLUSIONS: Results from our cohort imply that sub-categorization or subtyping and histological grading could be meaningful in pathological evaluation of TNBC, and need to be clarified in more large collections of TNBC.