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Abstract Background The rates of chemotherapy-induced amenorrhea (CIA) associated with docetaxel-based regimens reported by previous studies are discordant. For navelbine-based chemotherapies, rates of CIA have seldom been reported. Methods Of 170 premenopausal patients recruited between January 2003 and September 2008, 78 were treated with fluorouracil plus epirubicin and cyclophosphamide (FEC), 66 were treated with docetaxel plus epirubicin (TE), and 26 were treated with navelbine plus epirubicin (NE). Patient follow-up was carried up every 3-4 months during the first year, then every 9-12 months during subsequent years. Results In univariate analysis, the rates of CIA were 44.87% for the FEC regimen, 30.30% for the TE regimen and 23.08% for the NE regimen (P = 0.068). Significant differences in the rates of CIA were not found between the FEC and TE treatment groups (P > 0.05), but were found between the FEC and NE treatment groups (P < 0.05). Furthermore, no significant differences were found between the TE and NE regimens (P > 0.05). Tamoxifen use was a significant predictor for CIA (P = 0.001), and age was also a significant predictor (P < 0.001). In multivariate analysis, age (P < 0.001), the type of chemotherapy regimens (P = 0.009) and tamoxifen use (P = 0.003) were all significant predictors. Conclusions Age and administration of tamoxifen were found to be significant predictive factors of CIA, whereas docetaxel and navelbine based regimens were not associated with higher rates of CIA than epirubicin-based regimen.

the surgery practice teaching is an important transition for medical students from the theoretical study to the practice operation, and it is also the key to the medical students' surgical skills. By standardizing teaching contents, the reasonable use of network system, increasing layers of assessment and use the Objective Structured Clinical Examination (Objective Structured Clinical Examination, the OSCE), we want to strengthen the combination of theory and practice of the learning process based practice of surgery medical students, encourage students to play the subjective initiative and independent thinking. What's more, we hope students take effective use of the resources and time to improve themselves. Comparison study in the class of 2010 students showed that these means had not only achieved good teaching results, improved the teaching quality, but also got good grades in the national skills contest, laid a solid foundation for surgery medical students. [ABSTRACT FROM AUTHOR]

For the actual dilemma of intensified doctor-patient conflicts and the lack of teaching resources, we take advantage of the current social digitization, networking and informatization and explore construction and application of the surgical practice teaching platform. The teaching on network is an important useful supplement of clinical teaching. The teaching and research section of surgery in Nanjing Medical University focus on the current developed network technology and the high popularization of student computers and build autonomous learning platform with the aid of network technology. The platform includes virtual operating room, stereoscopic experimental teaching material and quality management through the network about "trinity" on surgical practice teaching. Through the training platform, the students get high scores in the three consecutive session of the contest of undergraduates' clinical skils of national medical coneges. Passing rate of practitioners practice exams within the graduates from our university is over 80. It can improve the medical students' surgical ability, effectively promote the construction of teachers team, and it is a good leading and exemplary role for the medical schools in China. [ABSTRACT FROM AUTHOR]

As the first complete annotation under the relevant Chinese context, Mao Zhuan is affected by two contexts: the context of the Chinese language itself and the relevant extra-lingual context. These two have different influences on the explanations, especially when they are in conflict. Because of this, there are numerous possibilities when the explanation in Mao Zhuan agrees with different contexts. Generally, the extra-lingual context restricts the one of language, which is to explain and supplement the meaning of the Confucian classics by word meaning explanation. However, the explanation is based on the relevant language phenomena. [ABSTRACT FROM AUTHOR]

This paper described the surgical teaching laboratory construction in Nanjing Medical University, in accordance with the requirements of the national experimental teaching demonstration center. This lab reform focuses on surgery practice from the experimental teaching ideas, teaching system, teaching team, laboratory equipment, environment and lab operation, management mechanism and so on. We innovate practice teaching idea and establish the experimental teaching demonstration center of Jiangsu Province. We design experiment teaching contents, manufacture simple teaching equipments and increase improving and innovating experiments in order to build a surgical practice teaching style. We strengthen the construction of experiment teaching team and make it stable to improve the teachers initiative and creativity. We strengthen the education of laboratory principles and set up advanced management mode to ensure the safety of laboratories and to make sure that the laboratory run well. Our struggle has obtained the remarkable effect in basic experiment teaching, it cultivates medical students with clinical skills, clinical thinking ability, communication ability and innovative ability. [ABSTRACT FROM AUTHOR]

Mao Shi Guxun Zhuan (≪ ... ≫), the first complete annotation of Shijing(≪ ... ≫) made according to the contextual clues, displays various types of the method to explain one word through another. In the book, the linguistic context is used to activate the differential sememe between synonymous units, making it possible to differentiate the synonymous items paradigmatically associated with each other in terms of their grammatical and semantic properties. Accordingly, the words used for explanation are multiplied in the annotations. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the primary tumor features derived from conventional ultrasound (US) and contrast-enhanced US (CEUS) facilitate the prediction of positive axillary lymph nodes (ALNs) in breast cancer diagnosed as Breast Imaging Reporting and Data System (BI-RADS) category 4., Methods: A total of 240 women with breast cancer who underwent preoperative conventional US, strain elastography, and CEUS between September 2016 and December 2019 were included. The multiple parameters of the primary tumor were obtained, and univariate and multivariate analyses were performed to predict positive ALNs. Then three prediction models (conventional US features, CEUS features, and the combined features) were developed, and the diagnostic performance was evaluated with receiver operating characteristic curves., Results: On conventional US, the traits of large size and the non-circumscribed margin of the primary tumor were marked as two independent predictors. On CEUS, the features of vessel perforation or distortion and the enhanced range of the primary tumor were marked as two independent predictors for positive ALNs. Three prediction models were then developed: model A (conventional US features), model B (CEUS features), and model C (model A plus B). Model C yielded the highest area under the curve (AUC) of 0.82 [95% confidence interval (CI), 0.75-0.88] compared with model A (AUC 0.74; 95% CI, 0.68-0.81; P = 0.008) and model B (AUC 0.72; 95% CI, 0.65-0.80; P < 0.001) as per the DeLong test., Conclusion: CEUS, as a non-invasive examination technique, can be used to predict ALN metastasis. Combining conventional US and CEUS may produce favorable predictive accuracy for positive ALNs in BI-RADS category 4 breast cancer.

Inhibitors targeting the antiapoptotic molecule BCL-2 have therapeutic potential for the treatment of acute myeloid leukaemia (AML); however, BCL-2 inhibitors such as venetoclax exhibit limited monotherapy efficacy in relapsed or refractory human AML. PI3Kδ/AKT signalling has been shown to be constitutively active in AML patients. Here, we demonstrate that the combination of BCL-2 and PI3Kδ inhibitors exerts synergistic antitumour effects both in vitro and in vivo in AML. Cotreatment with venetoclax and the specific PI3Kδ inhibitor idelalisib significantly enhanced antiproliferative effects and induced caspase-dependent apoptosis in a panel of AML cell lines. The synergistic effects were mechanistically based on the inactivation of AKT/4E-BP-1 signalling and the reduction of MCL-1 expression, which diminished the binding of Bim to MCL-1. Notably, compared with the parental FLT3-ITD-positive MV-4-11, the acquired FLT3 inhibitor quizartinib-resistant xenograft model carrying the F691L mutation, exhibited a markedly higher sensitivity to venetoclax. Furthermore, venetoclax combined with idelalisib led to tumour regression in all animals in this quizartinib-resistant AML model. Thus, these data indicate that combined inhibition of BCL-2 and PI3Kδ may be a promising strategy in AML, especially for patients with FLT3-ITD and/or FLT3-TKD mutations., Competing Interests: None., (AJCR Copyright © 2022.)

In the current study, we sought to evaluate the diagnostic efficacies of conventional ultrasound (US), contrast-enhanced US (CEUS), combined US and CEUS and magnetic resonance imaging (MRI) in detecting focal solid breast lesions. Totally 117 patients with 120 BI-RADS category 4A-5 breast lesions were evaluated by conventional US and CEUS, and MRI, respectively. SonoVue was used as contrast agent in CEUS and injected as an intravenous bolus; nodule scan was performed 4 minutes after bolus injection. A specific sonographic quantification software was used to obtain color-coded maps of perfusion parameters for the investigated lesion, namely the time-intensity curve. The pattern of contrast enhancement and related indexes regarding the time-intensity curve were used to describe the lesions, comparatively with pathological results. Histopathologic examination revealed 46 benign and 74 malignant lesions. Sensitivity, specificity, and accuracy of US in detecting malignant breast lesions were 90.14%, 95.92%, and 92.52%, respectively. Meanwhile, CE-MRI showed sensitivity, specificity, and accuracy of 88.73%, 95.92%, and 91.67%, respectively. The area under the ROC curve for combined US and CEUS in discriminating benign from malignant breast lesions was 0.936, while that of MRI was 0.923, with no significant difference between them, as well as among groups. The time-intensity curve of malignant hypervascular fibroadenoma and papillary lesions mostly showed a fast-in/fast-out pattern, with no good correlation between them (kappa < 0.20). In conclusion, the combined use of conventional US and CEUS displays good agreement with MRI in differentiating benign from malignant breast lesions.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with no protein-coding capacity. Transcribed ultraconserved regions (T-UCRs) are a type of lncRNA and are conserved among human, chick, dog, mouse and rat genomes. These sequences are involved in cancer biology and tumourigenesis. Nevertheless, the clinical significance and biological mechanism of T-UCRs in breast cancer remain largely unknown. The expression of uc.38, a T-UCR, was down-regulated in both breast cancer tissues and breast cancer cell lines. However, uc.38 was expressed at significantly lower levels in larger tumours and tumours of more advanced stages. Based on the results of in vitro and in vivo experiments, up-regulation of uc.38 expression inhibited cell proliferation and induced cell apoptosis. Thus, uc.38 suppressed breast cancer. Additional experiments revealed that uc.38 negatively regulated the expression of the pre-B-cell leukaemia homeobox 1 (PBX1) protein and subsequently affected the expression of Bcl-2 family members, ultimately inducing breast cancer cell apoptosis. Describing the uc.38/PBX1 axis has improved our understanding of the molecular mechanisms involved in breast cancer apoptosis and has suggested that this axis is a potential therapeutic target for breast cancer., Competing Interests: None.

An ideal mouse model should closely mimic a clinical situation. However, for most models available, this is not the case since clinical trials frequently fail to reproduce the highly encouraging therapeutic results obtained from pre-clinical studies performed using mouse models. In this study, in the process of extending the application of our previously established breast tissue-derived orthotopic and metastatic (BOM) model, the human breast cancer cell line MDA-MB-231 failed to exhibit any osteotropic features that differed from previous studies. Our observations suggest that a human tissue-specific microenvironment could be an essential requirement for a successful mouse model of breast cancer. Here, multiple in vivo breast cancer models were used to confirm this hypothesis. Human breast tissue and cancellated bone were transplanted subcutaneously to female severe combined immunodeficiency disease (SCID) mice by different assemblies, to build several mouse models termed 'breast-breast', 'breast-bone', 'bone-bone', 'MFP (mouse mammary fat pad)-bone', and 'MFP-breast' models. Two human breast cancer cell lines, MDA-MB-231 and MDA-MB-231BO, and the mouse breast cancer cell line TM40D were used. All cancer cells were labeled with GFP for gross observation. In addition, transplanted human tissues and various mouse tissues including bone, lung, liver, mesentery were examined microscopically. Based on morphological, immunohistochemical, and enzymohistochemical evidence obtained from several comparative experiments in 'breast-breast', 'breast-bone' and 'bone-bone' models, the BOM model was proved to be feasible and reliable. The organ tropism of the breast cancer cell line, which was derived from a mouse model by intracardiac inoculation in a pure mouse microenvironment, was reconsidered. The behavior of breast cancer cells in the mouse model was altered in response to the varying microenvironment. The results in this study suggest the human tissue-specific micro-environment is most likely an essential requirement in mouse models of breast cancer.

Background: A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis., Methods: Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1 x 10(5), 1 x 10(6) human breast cancer stem-like cells, and 1 x 10(6) parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1 x 10(6) MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR)., Results: Our results demonstrated that cells in implanted human bones of group B, which received 1 x 10(6) cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P = 0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest., Conclusions: In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.

Objective: To investigate the therapeutic potential of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, and to analyze TRAIL-induced apoptosis in Jurkat cells., Methods: Expression of TRAIL receptors (DR4 and DR5) was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Cytotoxic effects were determined by colony formation assay and a cell counting kit. The effects of recombinant TRAIL on apoptosis of Jurkat cells were determined by DNA fragmentation (DNA ladder) and PI staining. Changes in mitochondrial membrane potential were detected with JC-1 fluorescence., Results: TRAIL inhibited the proliferation and induced internucleosomal DNA fragmentation (characteristic of apoptosis) and loss of mitochondrial membrane potential., Conclusion: Recombinant soluble TRAIL can be used as a therapy for cancer.

Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was performed on total RNA of resistant-line TAM104R and susceptible-line TAM104S using 33 primers designed according to conservative domain of plant R-genes and the sequence of barley powdery mildew resistance genes Mlo, Mla1, Mla6 and wheat leaf rust resistance gene Lrk10. A polymorphic cDNA fragment TaZF was cloned and sequenced. The Open Reading Frame (ORF) of TaZF is comprised of 822 base pairs which encodes a zinc finger-like DNA or RNA-binding protein with 273 amino acids and molecular weight of 31 kD. TaZF is more than one copy gene in TAM104R genome based on southern blot. It is constitutively expressed, but level of expression was enhanced in tissue infected by Erysiphe Graminis. There is no intron in TaZF genome DNA.