Comparison of Multiple Quantitative Evaluation Indices of Theoretical Knowledge and Clinical Practice Skills and Training of Medical Interns in Cardiovascular Imaging Using Blended Teaching and the Case Resource Network Platform (CRNP).

BACKGROUND This study aimed to compare multiple quantitative evaluation indices of levels of theoretical knowledge and clinical practice skills in training medical interns in cardiovascular imaging based on the use of the blended teaching (BT) online artificial intelligence (AI) case resource network platform (CRNP), including time and frequency indices and effectiveness of the CRNP. MATERIAL AND METHODS The study included 110 medical interns who were divided into the routine teaching (RT) group (n=55) and the blended teaching (BT) group (n=55). The two were assessed using the mini-clinical evaluation exercise (mini-CEX) that assessed clinical skills, attitudes, and behaviors and using an objective written questionnaire. The following four indices were compared between the RT and BT groups: the X-ray score (XS), the computed tomography angiography (CTA) score (CS), the cardiac magnetic resonance imaging (CMRI) score (MS), and the average score (AS). Seven assessment indicators included: the imaging description (ID), the qualitative diagnosis (QD), the differential diagnosis (DD), examination preparation (EP), interview skill (IS), position display (PD), and human care (HC). Indicators of CRNP use included: number of times (TN), average duration (AD), single maximum duration (SMD), and total duration (TD). RESULTS AS significantly correlated with AD (rAD=0.761) and TD (rTD=0.754), and showed moderate correlation with TN (rTN=0.595), but weak correlation with SMD (rSMD=0.404). CONCLUSIONS Levels of theoretical knowledge and clinical practice skills during medical intern training in cardiovascular imaging based on BT using the CRNP teaching technology improved theoretical knowledge and practical skills.

Bu-Fei decoction and modified Bu-Fei decoction inhibit the growth of non-small cell lung cancer, possibly via inhibition of apurinic/apyrimidinic endonuclease 1.

Human apurinic/apyrimidinic endonuclease 1 (APE1) is a ubiquitous multifunctional protein, which possesses DNA repair and redox activities. High levels of APE1 are associated with chemo­ and radioresistance, and poor prognosis in various types of cancer, including non­small cell lung cancer (NSCLC). Bu­Fei decoction (BFD) is a traditional Chinese herbal formula, which is believed to supplement Qi, clear away heat and nourish the lungs. BFD and modified Bu­Fei decoction (MBFD) have been used in China to treat patients with lung cancer. The present study aimed to evaluate the potential antitumor effects of BFD and MBFD on NSCLC in vitro and in vivo. In addition, the possible contribution of APE1 was examined. MTT assay was used to investigated the anti-tumor activity of BFD and MBFD on H1975 and H292 NSCLC cell lines. The DNA damage of cells in the control and the experimental groups was detected using comet assay. The in vivo anti-tumor effects of BFD and MBFD were evaluated in a NSCLC tumor nude mouse xenograft model. Polymerase chain reaction (PCR), reverse transcription­quantitative PCR (RT­qPCR) analysis and western blot analysis were applied to analyze the mRNA and protein expression levels of APE1 in H1975 and H292 cells, so as to the xenograft tumor tissues. The concentration of APE1 in mice plasma was determined using enzyme linked immunosorbent assay (ELISA). In vitro, BFD and MBFD inhibited the growth of cultured H1975 and H292 NSCLC cells. The results of a comet assay revealed that BFD and MBFD increased DNA damage. Furthermore, the expression levels of APE1 were decreased in response to BFD and MBFD at the mRNA and protein levels. In mice carrying NSCLC xenografts, BFD and MBFD inhibited tumor growth and decreased APE1 expression. In addition, in normal human lung bronchial epithelial BEAS­2B cells, the half maximal inhibitory concentrations of BFD and MBFD were much higher compared with in NSCLC cells, and they had no effect on DNA damage. These results suggested that BFD and MBFD may inhibit the growth of NSCLC, possibly by inhibiting APE1 expression.

Marsdenia tenacissima extract overcomes Axl- and Met-mediated erlotinib and gefitinib cross-resistance in non-small cell lung cancer cells.

Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations. However, the potential efficacy of MTE in NSCLC cells with resistance mediated by Axl and c-Met, and the related molecular mechanisms need to be elucidated. In this study we evaluated the ability of MTE to restore erlotinib/gefitinib sensitivity in TKI resistant HCC827/ER cells and xenograft mice models. Our results demonstrate that MTE overcomes erlotinib and gefitinib resistance driven by Axl and c-Met in vitro and in vivo. Combination therapy significantly suppressed EGFR downstream molecules and the c-Met and Axl activated bypass signaling pathways. Moreover, we observed that MTE is more efficient at restoring resistance to erlotinib than gefitinib. As the Axl and c-Met mediated bypass pathways share the same downstream signaling cascade as EGFR, simultaneous targeting of these pathways is a promising strategy to overcome acquired resistance of TKIs. Our results demonstrate that MTE treatment attenuates Axl phosphorylation and the associated epithelial-mesenchymal transition, suggesting MTE treatment may be a potential therapeutic strategy for overcoming erlotinib and gefitinib cross-resistance in NSCLC, especially for erlotinib resistance.

Taraxacum mongolicum extract induced endoplasmic reticulum stress associated-apoptosis in triple-negative breast cancer cells.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum, commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied. AIM OF THE STUDY: This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line. METHODOLOGY: Dandelion extract was prepared and purified, and then its chemical composition was determined. Cell viability was evaluated by MTT assay. Analysis of cell apoptosis and cell cycle was assessed by flow cytometry. The expression levels of mRNA and proteins were determined by real-time PCR and Western blotting, respectively. Caspase inhibitor Z-VAD-FMK and CHOP siRNA were used to confirm the cell apoptosis induced by dandelion extract. RESULTS: Dandelion extract significantly decreased MDA-MB-231cell viability, triggered G2/M phase arrest and cell apoptosis. Concurrently, it caused a markedly increase of cleaved caspase-3 and PARP proteins. Caspase inhibitor Z-VAD-FMK abolished the apoptosis triggered by dandelion extract. The three ER stress-related signals were strongly induced after dandelion treatment, including increased mRNA expressions of ATF4, ATF6, XBP1s, GRP78 and CHOP genes, elevated protein levels of phosphorylated PERK, eIF-2α, IRE1, as well as the downstream molecules of CHOP and GRP78. MDA-MB-231 cells transfected with CHOP siRNA significantly reduced apoptosis induced by dandelion extract. The underlying mechanisms at least partially ascribe to the strong activation of PERK/p-eIF2α/ATF4/CHOP axis. CONCLUSION: ER stress related cell apoptosis accounted for the anti-cancer effect of dandelion extract, and these findings support dandelion extract might be a potential therapeutic approach to treat TNBC.

Chinese medicine Bu-Fei decoction attenuates epithelial-mesenchymal transition of non-small cell lung cancer via inhibition of transforming growth factor ß1 signaling pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Bu-Fei decoction (BFD) has been utilized to treat patients with Qi deficiency for decades, with the advantages of invigorating vital energy, clearing heat-toxin and moistening lung, etc. According to previous clinical experience and trials, BFD has been found to indeed improve life quality of lung cancer patients and prolong survival time. Nevertheless, little is known on its potential mechanisms so far. Being regarded as a pivotal cytokine in the tumor microenvironment, transforming growth factor ß (TGF-ß) stands out as a robust regulator of epithelial-mesenchymal transition (EMT), which is closely linked to tumor progression. AIM OF THE STUDY: The present study was designed to explore whether BFD antagonized EMT via blocking TGF-ß1-induced signaling pathway, and then help contribute to create a relatively steady microenvironment for confining lung cancer. MATERIALS AND METHODS: This experiment was performed in lung adenocarcinoma A549 cells both in vitro and in vivo. In detail, the influences mediated by TGF-ß1 alone or in combination with different concentrations of BFD on migration were detected by wound healing and transwell assays, and the effects of BFD on cell viability were determined by cell counting kit-8 (CCK-8) assay. TGF-ß1, EMT relevant proteins and genes were evaluated by western blotting, confocal microscopy, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and enzyme-linked immuno sorbent assay (ELISA). Female BALB/C nude mice were subcutaneously implanted A549 cells and given BFD by gavage twice daily for 28 days. The tumor volume was monitored every 4 days to draw growth curve. The tumor weight, expression levels of EMT-related protein in tumor tissues and TGF-ß1 serum level were evaluated, respectively. RESULTS: BFD only exerted minor effects on A549 cell proliferation and this was in accordance with the in vivo result, which showed that the tumor growth and weight were not be restrained by BFD administration. However, the data elucidated that BFD could dose-dependently suppress EMT induced by TGF-ß1 in vitro via attenuating canonical Smad signaling pathway. In the A549 xenograft mouse model, BFD also inhibited protein markers that are associated with EMT and TGF-ß1 secretion into serum. CONCLUSIONS: Based on these above data, the conclusion could be put forward that BFD probably attenuated TGF-ß1 mediated EMT in A549 cells via decreasing canonical Smad signaling pathway both in vitro and in vivo, which may help restrain the malignant phenotype induced by TGF-ß1 in A549 cells to some extent.

Recent highlights of Chinese medicine for advanced lung cancer.

Owing to its unique superiority in improving quality of life and prolonging survival time among advanced lung cancer patients, Chinese medicine (CM) has, in recent years, received increased attentions worldwide. We utilized a bibliometric statistical method based on MEDLINE/GoPubMed to conduct a comprehensive analysis of the current application status of CM in lung cancer, by including annual and accumulated publications, origin distribution of countries and journals, and keywords with a higher frequency score. Then the relevant clinical trials and mechanistic studies were systematically summarized within the field according to research types. We have raised potential problems and provided potentially useful reference information that could guide similar studies in the future. The basic experimental results are highly consistent with clinical trials, leading us to conclude that CM can offer better overall therapeutic benefits when used in combination with routine Western medicine for patients with advanced lung cancer.

High-performance liquid chromatography coupled with tandem mass spectrometry technology in the analysis of Chinese Medicine Formulas: A bibliometric analysis (1997-2015).

There is a recognized challenge in analyzing traditional Chinese medicine formulas because of their complex chemical compositions. The application of modern analytical techniques such as high-performance liquid chromatography coupled with a tandem mass spectrometry has improved the characterization of various compounds from traditional Chinese medicine formulas significantly. This study aims to conduct a bibliometric analysis to recognize the overall trend of high-performance liquid chromatography coupled with tandem mass spectrometry approaches in the analysis of traditional Chinese medicine formulas, its significance and possible underlying interactions between individual herbs in these formulas. Electronic databases were searched systematically, and the identified studies were collected and analyzed using Microsoft Access 2010, Graph Pad 5.0 software and Ucinet software package. 338 publications between 1997 and 2015 were identified, and analyzed in terms of annual growth and accumulated publications, top journals, forms of traditional Chinese medicine preparations and highly studied formulas and single herbs, as well as social network analysis of single herbs. There is a significant increase trend in using high-performance liquid chromatography coupled with tandem mass spectrometry related techniques in analysis of commonly used forms of traditional Chinese medicine formulas in the last 3 years. Stringent quality control is of great significance for the modernization and globalization of traditional Chinese medicine, and this bibliometric analysis provided the first and comprehensive summary within this field.

Injectable Chinese herbal formula Kang'ai for nonsmall cell lung cancer: Trial sequential analysis of 2,259 participants from 31 randomized controlled trials.

OBJECTIVE: The aim was to evaluate the efficacy and safety of Kang' ai (KA) injection for patients with nonsmall cell lung cancer (NSCLC). Furthermore, to identify if more trials are needed before reliable conclusions could be drawn with regard to these outcomes. MATERIALS AND METHODS: We searched the Cochrane library, PubMed, EMBASE, VIP, CBMdisc, and CNKI in September 2012, and then an additional updated search was conducted in January 2013. Only relevant randomized controlled trials (RCTs) on KA injection plus first-line cisplatin-based chemotherapy in the treatment of NSCLC were identified. Trials' data was reviewed and extracted by two reviewers independently. The quality of included studies was assessed according to a statement from Cochrane Handbook. RevMan 5 Software and Trial sequential analysis (TSA) software were applied for data analyses. RESULTS: A total of 31 RCTs involving 2259 patients were included. The results of meta-analysis showed that compared with chemotherapy alone, the combination of KA injection plus chemotherapy had a statistically significant benefit in improving clinical response rate (relative risk [RR] =1.29, 95% confidence interval [CI]: 1.17-1.41, P < 0.00001), clinical benefit rate (RR = 1.19, 95% CI: 1.14-1.25, P < 0.00001) and quality of life (RR = 1.79, 95% CI: 1.63-1.98, P < 0.00001); hematological toxicity (white blood cell) (RR = 0.71, 95% CI: 0.66-0.76, P < 0.00001) and nonhematological toxicity (nausea and vomiting) (RR = 0.73, 95% CI: 0.65-0.83, P < 0.00001) were improved as well. TSA showed that all cumulative Z-score crossed their monitoring boundaries, demonstrating that no more trials are needed before reliable conclusions could be drawn. CONCLUSION: Current evidence presented that KA injection might improve the therapeutic effect when combined with chemotherapy. Moreover, no more trials are needed in future according to TSA. Nevertheless, additional randomized studies investigating KA injection are needed to be further evaluated.

MicroRNA-33a-3p suppresses cell migration and invasion by directly targeting PBX3 in human hepatocellular carcinoma.

MicroRNAs (miRNAs) have been shown to function as either oncogenes or tumor suppressors by negatively regulating target genes involved in tumor initiation and progression. In this study, we demonstrated that down-regulation of miR-33a-3p in human primary hepatocellular cancer (HCC) specimens was significantly associated with metastases and poor survival. Over-expression of miR-33a-3p in HepG2 cells remarkably suppressed not only cell growth, migration and invasion, but also tumor growth and metastases in the chick embryo chorioallantoic membrane (CAM) assay, and down-regulated Pre-B-Cell Leukemia Homeobox 3 (PBX3) expression. Conversely, inhibition of miR-33a-3p in Bel-7402 cells resulted in increased of cell growth, spreading and invasion. Furthermore, rescue experiments by over-expression PBX3 completely eliminated the inhibitory effects of miR-33a-3p on tumor growth and metastasis, both in vitro and in vivo. The luciferase assay showed that 3'-untranslated regions (3'-UTRs) of PBX3 were inhibited significantly by miR-33a-3p, while mutations in the miR-33a-3p pairing residues rescued the luciferase expression. Taken together, our findings suggest that miR-33a-3p suppressed the malignant phenotype while also inhibiting PBX3 expression in hepatocellular cancer, implying that miR-33a-3p may be a promising biomarkers and therapy target for HCC intervention.

Simultaneous determination of gefitinib and its major metabolites in mouse plasma by HPLC-MS/MS and its application to a pharmacokinetics study.

Gefitinib (Iressa) is the first oral EGFR tyrosine kinase inhibitor and it brings benefits to non-small cell lung cancer patients with EGFR mutation. In this study, a simple, rapid and credible high performance liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous quantification of gefitinib and its main metabolites M523595, M537194, M387783 and M608236 in NSCLC tumor-bearing mouse plasma. Sample extraction was done by protein precipitation using acetonitrile containing dasatinib as the internal standard. The chromatography run time was 6min using an Agilent RRHD SB-C18 column with a gradient of acetonitrile and water (0.1% formic acid, v/v). The mass analysis was performed by a triple quadrupole mass spectrometry in positive multiple reaction monitoring mode. The calibration range was 0.5-100ng/mL for M608236 and 1-200ng/mL for other analytes with the correlation coefficients (r(2))≥0.99. For quality control samples, inter- and intra-assay precision was less than 15% and accuracies ranged from 92.6% to 107.58% for all analytes. The extraction recoveries were in the range of 86-105% and no significant matrix effect was observed. This simple and reproducible high-throughput method was successfully applied to the pharmacokinetic study of gefitinib and its major metabolites in mouse.

Recent highlights of experimental research for inhibiting tumor growth by using Chinese medicine.

To give an overview of contemporary experimental research using Chinese medicine (CM) for the treatment of cancer. As an integral part of mainstream medicine in the People's Republic of China, CM emphasizes improvements in holistic physical condition instead of merely killing tumor cells, which is consistent with the current medical model that advocates patient-oriented treatment. Great progress has been made in experimental research, and the principle aspects include anti-tumor angiogenesis, inducing apoptosis and differentiation, reversing multidrug resistance, and improving immune function. As a current hot topic in cancer research, tumor microenvironment (TME) highlights the mutual and interdependent interaction between tumor cells and their surrounding tissues, and the CM treatment concept bears a striking resemblance to it. To date, primary points of TME include extracellular matrix remodeling, inflammation, hypoxia, and angiogenesis, but trials using CM with a focus on TME are rare. Despite considerable recent development, experimental research on CM for solving cancer issues appears insufficient. Greater efforts in this field are urgently needed.

Hand-Sewn Versus Stapled Esophagogastric Anastomosis in the Neck: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

The application of cervical esophagogastric anastomoses was of great concern. However, between circular stapler (CS) and hand-sewn (HS) methods with anastomosis in the neck, which one has better postoperative effects still puzzles surgeons. This study aims to systematically evaluate the effectiveness, security, practicality, and applicability of CS compared with the HS method for the esophagogastric anastomosis after esophageal resection. A systematic literature search, as well as other additional resources, was performed which was completed in January 2013. The relevant randomized controlled trials (RCTs) about the surgical technique for esophageal resection were included. Trial data was reviewed and extracted independently by two reviewers. The quality of the included studies was assessed by the recommended standards basing on Cochrane handbook 5.1.0, and the data was analyzed via RevMan 5 software (version 5.2.0). Nine studies with 870 patients were included. The results showed that in comparing HS to CS methods with cervical anastomosis, no significant differences were found in the risk of developing anastomotic leakages (relative risk (RR) = 1.30, 95 % confidence intervals (CI) 0.87-1.92, p = 0.20), as well as the anastomosis stricture (RR = 0.97, 95 % CI 0.47-1.99, p = 0.93), postoperative mortality (RR = 0.83, 95 % CI 0.43-1.58, p = 0.57), blood loss (mean difference (MD) = 39.68; 95 % CI -6.97, 86.33; p = 0.10) and operative time (MD = 18.05; 95 % CI -3.22, 39.33; p = 0.10). However, the results also illustrated that the CS methods with cervical anastomosis might be less time-consuming and have shorter hospital stay and higher costs. Based upon this meta-analysis, there were no differences in the postoperative outcomes between HS and CS techniques. And the ideal technique of cervical esophagogastric anastomosis following esophagectomy remains under controversy.

Pancreatic duct stents at pancreaticoduodenectomy: a meta-analysis.

BACKGROUND AND OBJECTIVE: Several studies suggested that pancreatic stents had some benefit during pancreatoduodenectomy (PD), but others disagree. Whether pancreatic duct stents could prevent postoperative pancreatic fistula (POPF) is still under controversy. METHODS: Randomized controlled trials published before November 2012 were all aggregated, focusing on the evaluation of pancreatic duct stents during PD. Trial data was reviewed and extracted independently by two reviewers. The quality of the including studies was assessed by the Cochrane handbook 5.1.0. RESULTS: Seven studies were included, with a total of 793 patients. The results showed that compared with nonstents, stents during PD was associated with a significant difference on overall POPF rate (OR = 0.65, 95% CI 0.45-0.95, p = 0.02), POPF grades B and C (OR = 0.45, 95% CI 0.27-0.76, p = 0.003), and hospital stay (MD = -4.28, 95% CI -6.81, -1.75, p = 0.0009). Subgroup analyses showed that the external stent had a significant difference in the incidence of overall POPF (OR = 0.46, 95% CI 0.29-0.73, p = 0.0009), POPF grades B and C (OR = 0.49, 95% CI 0.30-0.79, p = 0.003), postoperative morbidity (OR = 0.63, 95% CI 0.42-0.96, p = 0.03), as well as hospital stay. CONCLUSIONS: Based upon this meta-analysis, there might be potential benefit in reducing POPF thanks to the use of pancreatic duct stents.

Acupuncture and moxibustion for cancer-related fatigue: a systematic review and meta-analysis.

BACKGROUND: Faced with highly prevalent and recalcitrant cancer-related fatigue (CRF), together with the absence of any official guidelines on management, numerous groups have been striving to seek and test alternative therapies including acupuncture and moxibustion. However, different patients have various feedbacks, and the many clinical trials have given rise to varied conclusions. In terms of the therapeutic effect of acupuncture and moxibustion, there exist vast inconsistencies. OBJECTIVE: The aim of the study was to evaluate the auxiliary effectiveness of acupuncture and moxibustion in the treatment of CRF, and to provide more reliable evidence to guide clinical practice. METHODS: Randomized controlled trials (RCTs) published before December 2012 were all aggregated, focusing on evaluation of acupuncture or moxibustion for CRF. The quality of the included studies was assessed basing on Cochrane handbook 5.1.0, and the available data were analyzed with RevMan software (version 5.2.0). Descriptive techniques were performed when no available data could be used. RESULTS: A total of 7 studies involving 804 participants were eligible. With real acupuncture versus sham acupuncture, subjects receiving true acupuncture benefited more in the reduction of fatigue. With real acupuncture versus acupressure or sham acupressure, fatigue level appeared 36% improved in the acupuncture group, but 19% in the acupressure group and only 0.6% with sham acupressure. When real acupuncture plus enhanced routine care was compared with enhanced routine care, the combination group improved mean scores for general fatigue, together with physical and mental fatigue. With real acupuncture versus sham acupuncture or wait list controls, the real acupuncture group displayed significant advantages over the wait list controls at 2 weeks for fatigue improvement and better well-being effects at 6 weeks. When moxibustion plus routine care was compared with routine care alone, the meta-analyses demonstrated the combination had a relatively significant benefit in improving severe fatigue and QLQ-C30. CONCLUSION: Up to the search date, there exist few high quality RCTs to evaluate the effect of acupuncture and moxibustion, especially moxibustion in English. Yet acupuncture and moxibustion still appeared to be efficacious auxiliary therapeutic methods for CRF, in spite of several inherent defects of the included studies. Much more high-quality studies are urgently needed.