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Tissue remodeling/fibrosis is a main feature of idiopathic pulmonary fibrosis (IPF), which results in the replacement of normal lung parenchyma with a collagen-rich extracellular matrix produced by fibroblasts and myofibroblasts. Epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells is a key process in IPF, which leads to fibroblasts and myofibroblasts accumulation and excessive collagen deposition. DEC1, a structurally distinct class of basic helix-loop-helix proteins, is associated with EMT in cancer. However, the functional role of DEC1 in pulmonary fibrosis (PF) remains elusive. Herein, we aimed to explore DEC1 expression in IPF and bleomycin (BLM)-induced PF in mice and the mechanisms underlying the fibrogenic effect of DEC1 in PF in vivo and in vitro by Dec1-knockout (Dec1 -/-) mice, knockdown and overexpression of DEC1 in alveolar epithelial cells (A549 cells). We found that the expression of DEC1 was increased in IPF and BLM-injured mice. More importantly, Dec1 -/- mice had reduced PF after BLM challenge. Additionally, DEC1 deficiency relieved EMT development and repressed the PI3K/AKT/GSK-3β/β-catenin integrated signaling pathway in mice and in A549 cells, whereas DEC1 overexpression in vitro had converse effects. Moreover, the PI3K/AKT and Wnt/β-catenin signaling inhibitors, LY294002 and XAV-939, ameliorated BLM-meditated PF in vivo and relieved EMT in vivo and in vitro. These pathways are interconnected by the GSK-3β phosphorylation status. Our findings indicated that during PF progression, DEC1 played a key role in EMT via the PI3K/AKT/GSK-3β/β-catenin integrated signaling pathway. Consequently, targeting DEC1 may be a potential novel therapeutic approach for IPF.Dickkopf-1 (DKK1) is a well-characterized Wnt inhibitor and component of the Wnt/β-catenin signaling pathway, whose dysregulation is associated with multiple abnormal pathologies including osteoporosis, Alzheimer's disease, diabetes, and various cancers. The Wnt signaling pathway has fundamental roles in cell fate determination, cell proliferation, and survival; thus, its mis-regulation can lead to disease. Although DKK1 is involved in other signaling pathways, including the β-catenin-independent Wnt pathway and the DKK1/CKAP4 pathway, the inhibition of DKK1 to propagate Wnt/β-catenin signals has been validated as an effective way to treat related diseases. In fact, strategies for developing DKK1 inhibitors have produced encouraging clinical results in different pathological models, and many publications provide detailed information about these inhibitors, which include small molecules, antibodies, and nucleic acids, and may function at the protein or mRNA level. However, no systematic review has yet provided an overview of the various aspects of their development and prospects. Therefore, we review the DKK1 inhibitors currently available or under study and provide an outlook on future studies involving DKK1 and drug discovery.Background Tumor mutational burden (TMB) is a genomic biomarker that can predict favorable responses to immune checkpoint inhibitors (ICIs). Although we have better understanding of TMB in cancer immunity and cancer immunotherapy, the relationship between TMB and the clinical efficacy of ICIs remains unknown in the treatment of melanoma patients. Here, we conduct a systematic review and meta-analysis to evaluate the predictive value of TMB on the efficacy of ICIs in patients with melanoma. Methods We systematically collected data from PubMed, Embase, Cochrane Library, CNKI, China Biomedical Database (CBM), and Wanfang Database. read more The end date was set to 26 June 2021. We included retrospective studies or clinical trials of ICIs that reported hazard ratios (HRs) for overall survival and/or progression-free survival according to TMB. Data for 1,493 patients from 15 studies were included. In addition, pooled effect size, heterogeneity analysis, sensitivity analysis, publication bias detection, and subgroup analysisCI should be further determined in more randomized controlled trials in the future.Prunus mira Koehne, a Prunus plant in the Rosaceae family, is named ཁམབུ། in Tibetan and "Guang he tao" in Chinese. It is mainly distributed in Tibet Autonomous Region, Yunnan Province, and Sichuan Province in China. It is also a rare "living fossil group" of peach genetic resources in the world. It is used in traditional Chinese medicine for the treatment of dysmenorrhea, injury, intestinal dryness, constipation, and other diseases, and is used in Tibetan medicine for the treatment of hair, eyebrows, and beard shedding. In this article, the botanical characteristics, medicinal history, modern applied research, and ethnobotanical investigation of P. mira were recorded and evaluated. P. mira was first recorded in Dumu Materia Medica. P. mira in Sichuan Province is mainly distributed in Ganzi Tibetan Autonomous Prefecture, and has certain economic and medicinal value. P. mira has high nutritional composition. It is made into high-quality edible oil, cosmetic base oil, fruit juice, fruit wine, fruit vinegar, "Liang guo", and other products. Oleic acid and linoleic acid are the main fat-soluble components of P. mira, which has an anti-inflammatory medicinal value and promotes hair growth. Its longevity and cold resistance can bring great genetic value and play an important role in maintaining peach genetic diversity. At present, there are few studies on the pharmacological effects of specific active components of P. mira and there are also few clinical studies. We can continue to study these aspects in the future. At the same time, products of P. mira have great market potential. All in all, P. mira is very worthy of further research and development.

During the last decade, partial breast irradiation (PBI) has gained traction as a relevant treatment option for patients with early-stage low-risk breast cancer after breast-conserving surgery. The TARGIT-A prospective randomized trial compared a "risk-adapted" intraoperative radiotherapy (IORT) approach with 50-kv X-rays (INTRABEAM®) as the PBI followed by optional whole-breast irradiation (WBI) and conventional adjuvant WBI in terms of observed 5-year in-breast recurrence rates. Recently, long-term data were published. Since the first publication of the TARGIT-A trial, a broad debate has been emerged regarding several uncertainties and limitations associated with data analysis and interpretation. Our main objective was to summarize the data, with an emphasis on the updated report and the resulting implications.

From our point of view, the previously unresolved questions still remain and more have been added, especially with regard to the study design, a change in the primary outcome measure, the significant number of patients lost to follow-up, and the lack of a subgroup analysis according to risk factors and treatment specifications.

Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI "the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery."

Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI "the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery."

The study aim was to evaluate if mTOR inhibitors can be considered as a treatment option for HR+ HER2- metastatic breast cancer (MBC) after progression on CDK4/6 inhibitors in clinical practice.

We retrospectively collected the clinicopathological data of patients with HR+ HER2- MBC treated with CDK4/6 inhibitors and subsequent therapies at our institution between 2014 and 2020. The patients were divided into 3 groups according to the type of subsequent treatment (A) exemestane plus everolimus, (B) endocrine monotherapy, and (C) chemotherapy. Overall survival (OS) was estimated by using the Kaplan-Meier method and compared by using the log-rank test. The efficacy and adverse events (AEs) of each subsequent treatment were assessed by using Fisher's exact tests.

Eighty-six patients (34 in group A, 20 in group B, 32 in group C) were included. The most common endocrine therapy in group B was fulvestrant (40%). The major chemotherapy regimen in group C was eribulin (25%). The median OS times after stopping CDK4/6 inhibitors were 34.5 months (95% confidence interval, 17.2 to NA), 13.6 months (3.9 to NA), and 19.5 months (18.8 to NA) in group A, group B, and group C, respectively. The only significant difference in OS was observed between group A and group B (20.9 months;

= 0.003). There was no difference in the incidence of grade 3 AEs between groups A and C or in the frequency of treatment discontinuation because of AEs among the 3 groups.

Our study shows that mTOR inhibitors might be an effective treatment option for patients with HR+ HER2- MBC previously treated with CDK4/6 inhibitors.

Our study shows that mTOR inhibitors might be an effective treatment option for patients with HR+ HER2- MBC previously treated with CDK4/6 inhibitors.

Periductal mastitis (PDM) is a complex benign breast disease with a prolonged course and a high risk of recurrence after treatment. There are many available treatments for PDM, but none is widely accepted. This study aims to evaluate the various treatment failure rates (TFR) of different invasive treatment measures by looking at recurrence and persistence after treatment. In this way, it sets out to inform better clinical decisions in the treatment of PDM.

We searched PubMed, Embase, and Cochrane Library databases for eligible studies about different treatment regimens provided to PDM patients that had been published before October 1, 2019. We included original studies written in English that reported the recurrence and/or persistence rates of each therapy. Outcomes were presented as pooled TFR and 95% CI for the TFR.

We included 27 eligible studies involving 1,066 patients in this study. We summarized 4 groups and 10 subgroups of PDM treatments, according to the published studies. Patients treated minihe treatment options, seemed to yield good outcomes and may be the first-line treatment for PDM patients. Minor excision methods, except for primary closure alone, might be enough for most PDM patients. Major excision, especially with radial incision, was a highly effective salvage therapy. The major plastic surgery technique was also acceptable as an alternative treatment for patients with large lesions and concerns about breast appearance. Incision and drainage and minor excision with primary closure alone should be avoided for PDM patients. Further research is still needed to better understand the etiology and pathogenesis of PDM and explore more effective treatments for this disease.

The aim of this study was to measure the expression of PD-L1, CD1a (a marker for immature dendritic cells), and CD83 (a marker for mature dendritic cells) and further examine the associations of PD-L1, CD83, and CD1a with overall survival (OS) in triple-negative breast carcinoma patients.

PD-L1, CD1a, and CD83 expression in breast carcinoma tissues and CD83 expression in lymph node tissues were examined by immunohistochemistry and tissue microarray in 159 patients. Patients were classified into the low, medium, and high PD-L1, CD1a, and CD83 levels. Pearson χ

test was used to analyze the correlations between PD-L1, CD1a, and CD83. The Kaplan-Meier method was used to calculate the OS. Multivariate analysis was used to identify determinants of 3- and 5-year OS.

25.1, 25.8, and 49.1% of the patients had low, medium, and high PD-L1 levels, respectively. PD-L1 levels significantly correlated with CD1a (

= 0.30409,

< 0.001) and CD83 levels (

= 0.6146,

< 0.001) in breast carcinoma tissue, as well as CD83 levels (

= 0.