Quality of life and survival analyses of breast cancer cases treated with integrated traditional Chinese and Western medicine.

BACKGROUND: Breast cancer (BC) is the second leading cause of tumor-related mortality after lung cancer. Chemotherapy resistance remains a major challenge to progress in BC treatment, warranting further exploration of feasible and effective alternative therapies. AIM: To analyzed the quality of life (QoL) and survival of patients with BC treated with integrated traditional Chinese and Western medicine (TCM-WM). METHODS: This study included 226 patients with BC admitted to the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine between February 2018 and February 2023, including 100 who received conventional Western medicine treatment (control group) and 126 who received TCM-WM treatment (research group). The total effective rate, side effects (alopecia, nausea and vomiting, hepatorenal toxicity, and myelosuppression), QoL assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), 1-year overall survival (OS), recurrence and metastasis rates, and serum inflammatory factors [interleukin (IL)-6, IL-10, and tumor necrosis factor alpha] were comparatively analyzed. RESULTS: The research group showed statistically better overall efficacy, EORTC QoL-C30 scores, and 1-year OS than the control group, with markedly lower side effects and 1-year recurrence and metastasis rates. Moreover, the posttreatment levels of serum inflammatory in the research group were significantly lower than the baseline and those in the control group. CONCLUSION: Overall, TCM-WM demonstrated significantly improved therapeutic efficacy while ensuring drug safety in BC, which not only improved patients' QoL and prolonged survival, but also significantly inhibited the inflammatory response.

Programmable "triple attack" cancer therapy through in situ activation of disulfiram toxification combined with phototherapeutics.

Effectively and completely eliminating residual tumor cells is the key to reducing the risk of tumor metastasis and recurrence. Designing an "ideal" nanoplatform for programmable cancer therapy has great prospects for completely eliminating residual tumor cells. Herein, an intelligent nanoplatform of disulfiram (DSF)-loaded CuS-tannic acid nanohexahedrons (denoted as "DSF-CuS@TA") with thermal- and pH-sensitive degradation, as well as near-infrared (NIR-II) phototherapeutics properties, was constructed. And then, it was employed for in situ DSF toxification activation programmable "triple attack" cancer therapy. After accumulating in the tumor, DSF-CuS@TA first releases the loaded Cu(DTC)2, and simultaneously degrades and releases Cu2+ and DSF under mildly acidic stimulation to trigger instant intratumoral Cu(DTC)2 chelation, thereby achieving the "first strike." Next, under irradiation by a NIR-II laser, light energy is converted into heat to generate NIR-II photothermal therapy, thereby achieving the second strike. Subsequently, under thermal stimulation, DSF-CuS@TA degrades further, triggering the chelation of Cu(DTC)2 for a second time to reach the third strike. As expected, in vitro and in vivo studies showed that the synergistic integration of DSF-based programmed chemotherapy and NIR-II phototherapeutics could achieve effective tumor removal. Therefore, we propose a novel type of programmed therapy against cancer by designing a nanoplatform via "nontoxicity-to-toxicity" chemical chelation transformation.

Simultaneous electrocoagulation and E-peroxone coupled with ultrafiltration membrane for shale gas produced water treatment.

Membrane fouling caused by the organics-coated particles was the main obstacle for the highly efficient shale gas produced water (SGPW) treatment and recycling. In this study, a novel hybrid electrocoagulation (EC) and E-peroxone process coupled with UF (ECP-UF) process was proposed to examine the efficacy and elucidate the mechanism for UF fouling mitigation in assisting SGPW reuse. Compared to the TMP (transmembrane pressure) increase of -15 kPa in the EC-UF process, TMP in ECP-UF system marginally increased to -1.4 kPa for 3 filtration cycles under the current density of 15 mA/cm2. Both the total fouling index and hydraulically irreversible fouling index of the ECP-UF process were significantly lower than those of EC-UF process. According to the extended Derjaguin-Landau-Verwey-Overbeek theory, the potential barriers was the highest for ECP-UF processes due to the substantial increase of the acid-base interaction energy in ECP-UF process, which was well consistent with the TMP and SEM results. Turbidity and TOC of ECP-UF process were 63.6% and 45.8% lower than those of EC-UF process, respectively. According to the MW distribution, the variations of compounds and their relative contents were probably due to the oxidation and decomposing products of the macromolecular organics. The number of aromatic compound decreased, while the number of open-chain compounds (i.e., alkenes, alkanes and alcohols) increased in the permeate of ECP-UF process. Notably, the substantial decrease in the relative abundance of di-phthalate compounds was attributed to the high reactivity of these compounds with ·OH. Mechanism study indicated that ECP could realize the simultaneous coagulation, H2O2 generation and activation by O3, facilitating the enhancement of ·OH and Alb production and therefore beneficial for the improved water quality and UF fouling mitigation. Therefore, the ECP-UF process emerges as a high-efficient and space-saving approach, yielding a synergistic effect in mitigating UF fouling for SGPW recycling.

A new strategy for the treatment of heavily pretreated metastatic breast cancer: A case report and review of the literature.

BACKGROUND: Breast cancer is one of the most common type of cancers worldwide and remains a critical health issue. Although there are numerous treatment options for advanced metastatic breast cancer, the results are not satisfactory, particularly for triple-negative breast cancer. New treatment modalities need to be explored. CASE PRESENTATION: We present the case of a breast cancer patient with multiple metastases who achieved a good response and tolerance to the combination treatment of utidelone plus capecitabine. After being treated with 10 cycles of combined treatment, the patient is now in a good general condition with a progression-free survival time of 10 months. CONCLUSION: To our knowledge, this is the first report of utidelone plus capecitabine successfully treating a patient with heavily pretreated metastatic breast cancer. This combined treatment offers a new option for patients with multi-drug resistant breast cancer.

A comparative study of melanocytic nevi classification with dermoscopy and high-frequency ultrasound.

BACKGROUND: Melanocytic nevi (MN) can be classified into three subtypes according to the depth of the nests of nevus cells which is important for management. High-frequency ultrasound (HF-US) can clearly reveal the lesion size, contour, depth, and internal structures. However, the HF-US studies of MN according to subtypes are limited. We aimed to describe the HF-US features of MN and explore its value in accurate classification. MATERIALS AND METHODS: This retrospective study was conducted from January 2018 to November 2019. Eighty-five patients with MN were included and examined by 50 and 20 MHz HF-US. The HF-US features were recorded including morphological flatness, depth, shape, boundary, internal echogenicity, hyperechoic spots, lateral acoustic shadow, posterior echoic patterns, mushroom signs, and straw-hat signs. Each image was evaluated by two physicians independently, and the consistency was tested. RESULTS: Eleven lesions could not be detected by HF-US. The rest 74 lesions underwent ultrasonic analysis. MN appeared as strip-shaped or oval, hypoechoic areas localized in the epidermis and dermis under ultrasonography. A strong consistency between HF-US and dermoscopy of determining the lesion depth was achieved (κ = 0.935, p < 0.001). The hyperechoic spots were found in 57.6% intradermal nevi. The mushroom signs were seen in 34.8% intradermal nevi, and the straw-hat signs were seen in all the compound nevi. CONCLUSION: MN can be correctly classified using HF-US, and it had a strong correlation with dermoscopic and clinical classification. HF-US could further reveal the internal morphological features of MN, which may support more precise classification and management.

A Deep Learning Based Framework for Diagnosing Multiple Skin Diseases in a Clinical Environment.

Background: Numerous studies have attempted to apply artificial intelligence (AI) in the dermatological field, mainly on the classification and segmentation of various dermatoses. However, researches under real clinical settings are scarce. Objectives: This study was aimed to construct a novel framework based on deep learning trained by a dataset that represented the real clinical environment in a tertiary class hospital in China, for better adaptation of the AI application in clinical practice among Asian patients. Methods: Our dataset was composed of 13,603 dermatologist-labeled dermoscopic images, containing 14 categories of diseases, namely lichen planus (LP), rosacea (Rosa), viral warts (VW), acne vulgaris (AV), keloid and hypertrophic scar (KAHS), eczema and dermatitis (EAD), dermatofibroma (DF), seborrheic dermatitis (SD), seborrheic keratosis (SK), melanocytic nevus (MN), hemangioma (Hem), psoriasis (Pso), port wine stain (PWS), and basal cell carcinoma (BCC). In this study, we applied Google's EfficientNet-b4 with pre-trained weights on ImageNet as the backbone of our CNN architecture. The final fully-connected classification layer was replaced with 14 output neurons. We added seven auxiliary classifiers to each of the intermediate layer groups. The modified model was retrained with our dataset and implemented using Pytorch. We constructed saliency maps to visualize our network's attention area of input images for its prediction. To explore the visual characteristics of different clinical classes, we also examined the internal image features learned by the proposed framework using t-SNE (t-distributed Stochastic Neighbor Embedding). Results: Test results showed that the proposed framework achieved a high level of classification performance with an overall accuracy of 0.948, a sensitivity of 0.934 and a specificity of 0.950. We also compared the performance of our algorithm with three most widely used CNN models which showed our model outperformed existing models with the highest area under curve (AUC) of 0.985. We further compared this model with 280 board-certificated dermatologists, and results showed a comparable performance level in an 8-class diagnostic task. Conclusions: The proposed framework retrained by the dataset that represented the real clinical environment in our department could accurately classify most common dermatoses that we encountered during outpatient practice including infectious and inflammatory dermatoses, benign and malignant cutaneous tumors.

Identification of hub genes in triple-negative breast cancer by integrated bioinformatics analysis.

BACKGROUND: Triple negative breast cancer (TNBC) is usually aggressive and accompanied by a poor prognosis. The molecular biological mechanism of TNBC pathogenesis is still unclear, and requires more detailed research. The aim of this study was to screen and verify potential biomarkers of TNBC, and provide new clues for the treatment and diagnosis of TNBC. METHODS: In this work, GSE76250 was downloaded from the Gene Expression Omnibus (GEO) database and included 165 TNBC samples and 33 paired normal breast tissues. The R software and its related software package were used for data processing and analysis. Compared with normal tissues, genes with a false discovery rate (FDR) <0.01 and log fold change (logFC) ≥1 or ≤-1 were identified as differentially expressed genes (DEGs) by limma package. Survival prognoses were analyzed by Kaplan-Meier plotter database. RESULTS: In total, 160 up-regulated and 180 down-regulated genes were identified. The biological mechanism of enrichment analysis presented that DEGs were significantly enriched in chromosome segregation, extracellular matrix, and extracellular matrix structural constituent, among others. A total of 8 hub genes (CCNB1, CDK1, TOP2A, MKI67, TTK, CCNA2, BUB1, and PLK1) were identified by the protein-protein interaction network (PPIN) and Cytoscape software. Survival prognosis of these hub genes showed that they were negatively correlated with overall survival. CONCLUSIONS: The 8 hub genes and pathways that were identified might be involved in tumorigenesis and become new candidate biomarkers for TNBC treatment.

The synergistic effect of electrocoagulation coupled with E-peroxone process for shale gas fracturing flowback water treatment.

Electrocoagulation (EC) coupled with E-peroxone process (ECP) was a promising and cost-effective integrated technology for shale gas fracturing flowback water (SGFFW) treatment. In this study, the ECP process was comprehensively compared with two sequential processes (EC followed by E-peroxone (EC-E-peroxone) and E-peroxone followed by EC (E-peroxone-EC)) to elucidate the synergistic effect of this coupled process. In EC-E-peroxone process, COD decreased by 89.2%, while COD decreased by 82.5% for 180 min in E-peroxone-EC process. However, COD removal efficiency was 82.4% in ECP for only 90 min. Average current efficiency of the ECP process was 29.9%, which was twice than that of the sequential processes. The enhancement factor was calculated to be 1.63, demonstrating the substantial significant synergistic effects for ECP. Only low MW components could be observed for the EC-E-peroxone (average MW = 533 Da with PD ≈ 1) and ECP process (MW = 538 Da with PD ≈ 1). These results suggested that EC-E-peroxone and ECP process had much stronger oxidation ability, demonstrating the enhancement of OH production induced by the Al-based coagulants might be responsible for the significant enhancement of COD removal. These results indicated there could be a synergistic effect between EC and ozone in addition to EC and E-peroxone reactions. Compared to the two sequential processes, ECP was a high efficiency and space-saving electrochemical system with simultaneous coagulation and enhanced OH generation by the products of anode and the cathode.

miR-454 performs tumor-promoting effects in oral squamous cell carcinoma via reducing NR3C2.

BACKGROUND: Aberrant miRNAs expression regulates the occurrence and progression of a variety of cancers, including oral squamous cell carcinoma (OSCC). This study aims to illustrate the potential effects of miR-454/nuclear receptor subfamily 3 group C member 2 (NR3C2) on the biological behaviors of OSCC cells. METHODS: GEO database was applied to detect and analyze the expression of miR-545 and NR3C2 in OSCC tissues. Two OSCC cell lines including CAL27 and Tca-83 were utilized to determine the function of miR-454/NR3C2 on OSCC cells biological behaviors. miR-454 and NR3C2 expressions were regulated by miR-454 mimic/inhibitor and pcDNA3.1-NR3C2/si-NR3C2, respectively. Cells biological behaviors were evaluated by cell proliferation, colony formation, and transwell assays. RESULTS: The data collected from GEO database indicated that miR-454 expression was upregulated in OSCC tissues; however, the expression of NR3C2 assumed a downward trend. In vitro experiments, the expression trend of miR-454 in OSCC cell lines was consistent with that of the trend in tissues, and the OSCC cells growth and movement abilities significantly decreased after miR-454 depletion. Through co-transfection experiments, we explored that the abilities of OSCC cell proliferation, colony formation, invasion, and migration obviously reduced after miR-454 depletion, but these phenomena were mitigated to some extent after NR3C2 silencing. CONCLUSION: The study illustrates that miR-454 acts as an active regulator to facilitate OSCC cells growth, colony formation, invasion, and migration by targeting NR3C2, which may afford a novel perspective and possibility for the targeted treatment of OSCC.

Genomic identification and characterization of MYC family genes in wheat (Triticum aestivum L.).

BACKGROUND: MYC transcriptional factors are members of the bHLH (basic helix-loop-helix) superfamily, and play important roles in plant growth and development. Recent studies have revealed that some MYCs are involved in the crosstalk between Jasmonic acid regulatory pathway and light signaling in Arabidopsis, but such kinds of studies are rare in wheat, especially in photo-thermo-sensitive genic male sterile (PTGMS) wheat line. RESULTS: 27 non-redundant MYC gene copies, which belonged to 11 TaMYC genes, were identified in the whole genome of wheat (Chinese Spring). These gene copies were distributed on 13 different chromosomes, respectively. Based on the results of phylogenetic analysis, 27 TaMYC gene copies were clustered into group I, group III, and group IV. The identified TaMYC genes copies contained different numbers of light, stress, and hormone-responsive regulatory elements in their 1500 base pair promoter regions. Besides, we found that TaMYC3 was expressed highly in stem, TaMYC5 and TaMYC9 were expressed specially in glume, and the rest of TaMYC genes were expressed in all tissues (root, stem, leaf, pistil, stamen, and glume) of the PTGMS line BS366. Moreover, we found that TaMYC3, TaMYC7, TaMYC9, and TaMYC10 were highly sensitive to methyl jasmonate (MeJA), and other TaMYC genes responded at different levels. Furthermore, we confirmed the expression profiles of TaMYC family members under different light quality and plant hormone stimuli, and abiotic stresses. Finally, we predicted the wheat microRNAs that could interact with TaMYC family members, and built up a network to show their integrative relationships. CONCLUSIONS: This study analyzed the size and composition of the MYC gene family in wheat, and investigated stress-responsive and light quality induced expression profiles of each TaMYC gene in the PTGMS wheat line BS366. In conclusion, we obtained lots of important information of TaMYC family, and the results of this study was supposed to contribute novel insights and gene and microRNA resources for wheat breeding, especially for the improvement of PTGMS wheat lines.

Long non-coding RNA Igf2as controls hepatocellular carcinoma progression through the ERK/MAPK signaling pathway.

Long non-coding RNAs (lncRNAs) serve an important role in numerous human diseases, including cancer. Abnormal expression of lncRNAs has been associated with a number of tumor types; however, the underlying mechanisms through which lncRNA functions have yet to be elucidated. The present study primarily focuses on insulin-like growth factor 2 antisense 1 (Igf2as), a lncRNA reported to be differentially expressed in hepatocellular carcinoma (HCC). Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the level of Igf2as in HCC cells and tissues. Flow cytometry was used to determine the level of cell apoptosis following Igf2as suppression and western blot analysis was used to identify altered protein expression levels. The results demonstrated that Igf2as was upregulated in HCC cells and tissues, and that the inhibition of Igf2as using a targeted small interfering RNA (si-Igf2as), significantly decreased cell proliferation and increased apoptosis. Western blot analysis identified that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway was inhibited in cells transfected with si-Igf2as. In addition, cell migration was markedly reduced by the knockdown of Igf2as. These results suggest that lncRNA Igf2as may control hepatocellular progression primarily through the regulation of the ERK/MAPK signaling pathway.

Identification of two candidate innate immune genes by transcriptional profiling and RNA interference in mouse mammary gland epithelial cells stimulated with lipopolysaccharide.

Mammary epithelial cells (MECs) play an important role in immune responses and inflammatory diseases such as mastitis, which is mainly attributed to the activation of Toll-like receptors and the release of cytokines. However, the overall change of gene expression and biological pathways of MECs to microbial factors stimulation remains unknown. Here, we analyzed the gene expression profile in mouse MECs treated with lipopolysaccharide (LPS) for 24 h. Microarray analysis revealed that about 1548 genes differentially expressed, these genes mainly involved in 346 gene ontology terms and 128 molecular pathways, and particularly, some innate immune-associated pathways were significant. By analyzing data for pathway relation network, we prioritized differentially expressed genes with respect to LPS. The importance of changes, indicating that RNA interference-mediated inhibition of two genes identified in this analysis, transforming growth factor beta 1 (Tgf-ß1) and platelet-derived growth factor B (Pdgfb), reduced interleukin (IL)-6 and tumor necrosis factor α production respectively, in gene expression was verified. These findings delineate mouse MECs gene response patterns induced by LPS and identify Tgf-ß1 and Pdgfb that have been closely related to innate immunity.

Downregulation of pigment epithelium-derived factor in condyloma acuminatum.

OBJECTIVES: To investigate pigment epithelium-derived factor (PEDF) mRNA and protein levels in condyloma acuminatum, and their relationship with angiogenesis and keratinocyte proliferation. METHODS: Lesions from male patients with condyloma acuminatum and skin from healthy male (control) subjects were collected. Levels of PEDF protein and its corresponding mRNA (SERPINF1) were determined via Western blotting and reverse transcription-polymerase chain reaction, respectively. Immunohistochemical staining for Ki-67 and CD34 was performed to calculate keratinocyte proliferation index (PI) and microvessel density (MVD), respectively. RESULTS: Levels of both PEDF protein and SERPINF1 mRNA were significantly lower in lesions from patients with condyloma acuminatum (n = 30) than in skin from healthy control subjects (n = 30). There were significant negative correlations between PEDF levels and both PI and MVD. CONCLUSIONS: The reduction in PEDF levels in condyloma acuminatum was associated with an increase in angiogenesis and cell proliferation. PEDF may be involved in the pathogenesis of condyloma acuminatum.

Energy budget, behavior and leptin in striped hamsters subjected to food restriction and refeeding.

Food restriction induces a loss of body mass that is often followed by rapid regaining of the lost weight when the restriction ends, consequently increasing a risk of development of obesity. To determine the physiological and behavioral mechanisms underlining the regaining, striped hamsters were restricted to 85% of initial food intake for 4 weeks and refed ad libitum for another 4 weeks. Changes in body mass, energy budget, activity, body composition and serum leptin level were measured. Body mass, body fat mass and serum leptin level significantly decreased in food-restricted hamsters, and increased when the restriction ended, showing a short "compensatory growth" rather than over-weight or obesity compared with ad libitum controls. During restriction, the time spent on activity increased significantly, which was opposite to the changes in serum leptin level. Food intake increased shortly during refeeding, which perhaps contributed to the rapid regaining of body mass. No correlation was observed between serum leptin and energy intake, while negative correlations were found in hamsters that were refed for 7 and 28 days. Exogenous leptin significantly decreased the time spent on activity during food restriction and attenuated the increase in food intake during refeeding. This suggests that low leptin in restricted animals may function as a starvation signal to induce an increase in activity behavior, and high leptin likely serves as a satiety signal to prevent activity during refeeding. Leptin may play a crucial role in controlling food intake when the restriction ends, and consequently preventing overweight.