Implementing mind mapping in small-group learning to promote student engagement in the medical diagnostic curriculum: a pilot study.

BACKGROUND: Medical diagnostics is a pivotal bridge curriculum that receives much less attention from undergraduates in non-clinical medicine health profession programs with less student engagement and poor performance. Mind mapping is an active learning strategy for graphically presenting radiant thinking to culture clinical reasoning. The purpose of this study was to explore whether students' comprehensive diagnostic skills are enhanced through increased student engagement by employing mind mapping. METHODS: We implemented mind mapping in small-grouped workshops with 86 junior undergraduates from preventive medicine program, for physical diagnostic sessions including physical examination (PE) maneuver, electrocardiogram (ECG) interpretation and medical history collection. We also conducted assessments of the above skills, as well as online surveys regarding their expectation on this course, self-evaluation of mind mapping in teaching and the learning process of all the modules. RESULTS: Group members employing mind mapping in all PE sessions obtained higher scores in the heart and lung systems during the PE maneuver exam. Similarly, groups that made more in-depth mind maps achieved higher scores on the ECG quiz. In addition, groups displaying mind maps for history taking from normal classes and reformed class exhibited greater completeness of medical history with both standardized patients and real patients, which was consistent with increased collection of accompanying symptoms. Mind mapping was valued by the majority of students for its benefits in terms of acquiring PE maneuver, theoretical knowledge, medical history collection and medical records writing, clinical reasoning, communication skills, sense of teamwork and cooperation, professionalism and humanistic literacy. DISCUSSION: The visual feature of mind mapping evoked extensive behavioral engagement in all groups, as did cognitive and emotional engagement, as the majority of students expressed their willingness and affective reactions. In the short term, the positive feedbacks encourage growing engagement. The continuous benefits of mind mapping require long-term observation.

Airway-invasion-associated pulmonary computed tomography presentations characteristic of invasive pulmonary Aspergillosis in non-immunocompromised adults: a National Multicenter Retrospective Survey in China.

BACKGROUND: The European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria are widely used in the diagnosis of invasive pulmonary aspergillosis (IPA), but they only apply to immunocompromised patients. We here aimed to identify clinical characteristics helpful to the diagnosis of IPA in non-immunocompromised patients. METHODS: This is a multicenter retrospective study. Data were collected from adult patients with IPA admitted to 15 tertiary hospitals in China from 2010 to 2016. RESULTS: We included 254 patients in the study, of whom 66 (26.0%) were immunocompromised, and 188 (74.0%) were not. Airway-invasion-associated computed tomography (CT) signs including patchy exudation along the airway (67.6% vs. 45.5%, P = 0.001) and thickened airway wall (42.0% vs. 16.7%, P < 0.001) were more common in non-immunocompromised patients than in immunocompromised ones, and angio-invasive CT signs were more common in immunocompromised patients (55.3% vs.72.7%, P = 0.013). Typical angio-invasive CT signs were delayed in non-immunocompromised IPA patients, whereas airway-invasive signs appear earlier. Host immunocompromised condition was associated with ICU admission and/or intubation (OR 1.095; 95% CI 1.461-6.122; P = 0.003). Poor prognosis (35.5% vs. 21.1%, P = 0.005) was more common in immunocompromised patients. CONCLUSION: Airway-invasion-associated CT presentations at early stages of the disease are characteristic of IPA in non-immunocompromised hosts.

[Congenital intracapsular hemorrhage of pulmonary cyst complicated with infection: A case report].

Congenital pulmonary cyst is a common benign disease in the lung, but intracapsular hemorrhage combined with infection is rare, which is easy to be misdiagnosed. A 14-year-old male patient presented fever for one week and companied with right chest pain and blood in sputum for 5 days. The external hospital diagnosed the disease as "the cause of pleural effusion" which the patient still had fever and intraluminal active hemorrhage after performing closed drainage of pleural cavity, draining haemorrhagic fluid, and the treatment of anti-infection, thoracic irrigation, and thoracoscope. Because of no effect after angiography and vascular embolization treatment, emergency thoracotomy was performed. Postoperative pathology proved it to be congenital pulmonary cyst with intracapsular hemorrhage and infection. Intracapsular hemorrhage in congenital pulmonary cyst with infection is easy to be confused with intrapleural hemorrhage in imaging. What's more, invasive operation will increase the difficulty in imaging differentiation. Clinicians should pay a great attention to the initial images of patients.

Reversing Mechanoinductive DSP Expression by CRISPR/dCas9-mediated Epigenome Editing.

RATIONALE: DSP (desmoplakin), the most abundant component of desmosomes, which maintain the mechanical integrity of epithelium, is a genome-wide association study-identified genetic risk locus in human idiopathic pulmonary fibrosis (IPF). Subjects with IPF express a significantly higher level of DSP than control subjects. OBJECTIVES: Determine potential mechanisms by which DSP is regulated in lung fibrosis. METHODS: Matrigel-coated soft and stiff polyacrylamide gels were made to simulate the stiffness of normal and fibrotic lungs. Quantitative chromatin immunoprecipitation and electrophoretic mobility shift assay were used to evaluate transcription factor binding to the DSP promoter. Targeted DNA methylation was achieved by CRISPR (clustered regularly interspaced short palindromic repeats)/dCas9 (deactivated CRISPR-associated protein-9 nuclease)-mediated Dnmt3A (DNA methyltransferase 3A) expression under the guidance of sequence-specific single guide RNAs. MEASUREMENTS AND MAIN RESULTS: Stiff matrix promotes DSP gene expression in both human and rodent lung epithelial cells as compared with soft matrix. A conserved region in the proximal DSP promoter is hypermethylated under soft matrix conditions and becomes hypomethylated/demethylated under stiff matrix conditions. Demethylation of this conserved DSP promoter region is associated with transactivation of transcription factor EGR1 (early growth response protein 1), resulting in EGR1-dependent DSP overexpression. Targeted DNA methylation by CRISPR/dCas9/Dnmt3A-mediated epigenome editing blocks EGR1 binding to the DSP promoter and inhibits stiff matrix-induced DSP overexpression. CONCLUSIONS: DSP is a matrix stiffness-regulated mechanosensitive gene. CRISPR/dCas9-Dnmt3A-mediated epigenome editing reverses DSP overexpression by reestablishment of the epigenetic control of DSP under the mechanically homeostatic environment. It provides a useful tool for investigations of the functional role of DSP in the pathogenesis of lung fibrosis.

Mechanosensing by the α6-integrin confers an invasive fibroblast phenotype and mediates lung fibrosis.

Matrix stiffening is a prominent feature of pulmonary fibrosis. In this study, we demonstrate that matrix stiffness regulates the ability of fibrotic lung myofibroblasts to invade the basement membrane (BM). We identify α6-integrin as a mechanosensing integrin subunit that mediates matrix stiffness-regulated myofibroblast invasion. Increasing α6-expression, specifically the B isoform (α6B), couples ß1-integrin to mediate MMP-2-dependent pericellular proteolysis of BM collagen IV, leading to myofibroblast invasion. Human idiopathic pulmonary fibrosis lung myofibroblasts express high levels of α6-integrin in vitro and in vivo. Genetic ablation of α6 in collagen-expressing mesenchymal cells or pharmacological blockade of matrix stiffness-regulated α6-expression protects mice against bleomycin injury-induced experimental lung fibrosis. These findings suggest that α6-integrin is a matrix stiffness-regulated mechanosensitive molecule which confers an invasive fibroblast phenotype and mediates experimental lung fibrosis. Targeting this mechanosensing α6(ß1)-integrin offers a novel anti-fibrotic strategy against lung fibrosis.

High-Magnitude and/or High-Frequency Mechanical Strain Promotes Peripapillary Scleral Myofibroblast Differentiation.

PURPOSE: To determine the effects of altered mechanical strain on human peripapillary scleral (ppSc) fibroblast-to-myofibroblast differentiation. METHODS: Eight human ppSc fibroblast cultures were isolated from three paired eyes and two unilateral eyes of five donors using an explant approach. Human ppSc fibroblast isolates were subjected to 1% and 4% cyclic strain at 0.05 to 5 Hz for 24 hours. Levels of α smooth muscle actin (αSMA) mRNA and protein were determined by real-time PCR and immunoblot. Incorporation of αSMA into actin stress fibers was evaluated by confocal immunofluorescent microscopy. Myofibroblast contractility was measured by fibroblast-populated three-dimensional collagen gel contraction assay and phosphorylation of myosin light chain (MLC20). RESULTS: Human ppSc fibroblasts contained 6% to 47% fully differentiated myofibroblasts before strain application; 4% cyclic strain increased αSMA mRNA and protein expression in ppSc fibroblasts compared with 1% strain applied at 5 Hz, but not at lower frequencies. Seven of eight ppSc fibroblast isolates responded to high-magnitude and high-frequency strain with increased cellular contractility and increased MLC20 phosphorylation. In addition, increasing strain frequency promoted αSMA expression in ppSc fibroblasts under both 1% and 4% strain conditions. CONCLUSIONS: High-magnitude and/or high-frequency mechanical strain promotes differentiation of human ppSc fibroblasts into contractile myofibroblasts, a fibroblast phenotypic change known to be key to tissue injury-repair responses. These findings suggest that the cellular constituent of ppSc may play an important role in the regulation of optic nerve head biomechanics in response to injurious IOP fluctuations.

[Expression of adiponectin in non-small cell lung cancer and its relationship with MMP-9 and angiogenesis].

BACKGROUND: To explore the expression of adiponectin and its relationship with matrix metalloproteinase (MMP)-9 and angiogenesis in non-small cell lung cancer (NSCLC) tissue.
 METHODS: A total of 87 samples of NSCLC and 10 samples of normal lung tissue were collected for detection of adiponectin and MMP-9 expression by immunohistochemical method. Anti-CD34 monoclonal antibody against endothelial marker was used to evaluate microvessel density (MVD).
 RESULTS: The positive rate for adiponectin in NSCLC (49.43%) was significantly lower than that in normal lung tissues (90.00%) while for MMP-9 in NSCLC (59.77%) was significantly higher than that in normal lung tissues (10.00%, P<0.05); MVD in NSCLC (14.58 ± 0.67) was higher than that in normal lung tissues [(0.80 ± 0.12), P<0.05]. In NSCLC, the positive rates of adiponectin and MMP-9 were varied in groups with different lymph node metastasis, tumor size and clinical stage (P<0.05). Meanwhile, MVD value in NSCLC with or without lymph node metastasis was significantly different. There was a negative correlation between adiponectin level and CD34 (MVD) or MMP-9 level (r=-0.22 or r=-0.55, respectively, P<0.05). On the contrary, MMP-9 was positively correlated with MVD (r=0.21, P<0.05). 
 CONCLUSIONS: The decreased expression of adiponectin might be related to the development of NSCLC through negative regulation of MMP-9 expression.
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microRNA-548l is involved in the migration and invasion of non-small cell lung cancer by targeting the AKT1 signaling pathway.

PURPOSE: microRNAs (miRNAs) have been documented playing a critical role in cancer development and progression. In this study, we investigated the role of miR-548l in non-small cell lung cancer (NSCLC) migration and invasion. METHODS: microRNAs microarray analysis was used to detect the differentially expressed miRNAs between various metastatic levels of NSCLC cells and further confirmed by real-time PCR analysis. To facilitate the delineation of the role of selected miR-548l in NSCLC pathology, we detected its expression in 22 NSCLC tissues. Proliferation, apoptosis, invasion and metastasis effects of the miRNA were evaluated using MTT, flow cytometry, wound healing and invasion assay following transfection with mimics and inhibitors. Luciferase assay and Western blot analysis were performed to assess miR-548l binding to AKT1 gene. AKT1 expression in the clinical tissues was evaluated using immunohistochemical staining. RESULTS: The results showed a negative relationship between miR-548l expression and lymph node metastasis of NSCLC. Functional assays showed that over-expression of miR-548l suppressed NSCLC cell migration and invasion. Luciferase assays confirmed that miR-548l could directly bind to the 3' untranslated region of AKT1. Further data showed that the over-expression of AKT1 could rescue the effects of miR-548l in NSCLC cells, and the miR-548l expression was inversely correlated with AKT1 expression in NSCLC tissues. These results indicated that AKT1 was involved in miR-548l-induced suppression of NSCLC cell migration and invasion. CONCLUSION: These results suggested that miR-548l may play a causal role through AKT1 in NSCLC invasion and metastasis.

[Two cases of pulmonary thromboembolism associated with protein C and protein S deficiency and literature review].

To explore the clinical manifestations, diagnosis and treatment of pulmonary thromboembolism associated with protein C (PC)/protein S (PS) deficiency. Two male patients 29 and 26 years old diagnosed with PC deficiency and/or PS deficiency were retrospectively analyzed and related literatures were reviewed. The most common symptoms were pain in the lower limbs with chest pain or decreased vision. Color dopper flow imaging (CDFI) showed lower deep venous phlebothrombosis. Multislice CT angiography (CTA) revealed pulmonary embolism. The level of serum homocysteine (HCY) increased and the level of plasma PC/PS content decreased to PC 57.4%, and PS 28.9% in patient 1, while PS 33.4% in patient 2. Poor routine anticoagulant response was observed. After the diagnosis of PC/PS deficiency, vitamin B6 and B12 anticoagulant therapy was added, and the symptoms in the patients improved significantly. Congenital thrombophilia should be taken into consideration for young patients with lower deep venous thrombosis and pulmonary embolism which occur recurrently without obvious predisposing causes before 40. Plasma PC/PS concentrations or activity help a lot in the diagnosis and treatment.

[The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer].

OBJECTIVES: To evaluate the benefit of using autofluorescence bronchoscopy (AFB) for the detection and localization of early invasive lung cancer. METHODS: AFB and white light bronchoscopy (WLB) were performed on 198 cases of suspected lung cancer, and the relative sensitivity of WLB plus AFB compared with WLB alone. RESULTS: Included 198 biopsy specimens, and 160 were classified as positive by pathology, including 156 invasive cancer and 4 severe dysplasia. The relative sensitivity to detect intraepithelial neoplasia of WLB + FLB versus WLB was 97.5% and 80.0% respectively, significantly (P < 0.05). CONCLUSION: AFB was more sensitive than WLB in detecting preneoplastic bronchial changes and early lung cancer in high-risk subjects.

[The clinical features of invasive pulmonary aspergillosis in 53 chronic obstructive pulmonary disease patients].

OBJECTIVE: To study the clinical features of invasive pulmonary aspergillosis (IPA) with chronic obstructive pulmonary diseases (COPD), so as to provide evidence for early diagnosis and treatment. METHODS: A retrospective analysis was made upon clinical data, diagnosis, treatment and prognosis of 53 patients with IPA and COPD admitted between January 2005 and February 2011 collected in a respiratory unit of the Second Xiangya Hospital Affiliated Central South University. RESULTS: There were 53 cases of diagnosed as IPA with COPD, with history of using broad-spectrum antibiotics. And there were 43 cases using steroids more than 2 weeks, 51 with obvious breathlessness, and 20 with fever. Early stage didn't present characteristical changes on CT scan. However, after disease progression, 32 cases had maculas shadows and nonspecific consolidations in bilateral lung, 14 with solitary or multiple nodules, 4 with solitary or multiple air crescent sign, and 2 with halo sign. Four patients of COPD with IPA underwent bronchoscopy examination. In fungi pathogeny, sputum positive rate and galactomannan positive rate were 56.6% and 52.8%, respectively. A total of 53 cases received antifungal treatment. Among 37 cases which underwent mechanical ventilation, 24 received noninvasive ventilation and 13 received invasive ventilation. There were 33 cases which were improved and cured, and 20 cases which had no relief after half-a-month treatment or withdrew treatment. Among them, 13 cases died because of multiple-organ failure (5/15) or acute renal failure (8/15). CONCLUSIONS: Early suspected diagnosis, timely examination in allusion to IPA, actively searching for etiological and imaging evidences, early established diagnosis and antifungal treatment would improve prognosis of patients with COPD combined IPA who have history of high doses of corticosteroids, obvious breathlessness and non-response to antibiotics.

[The effects of Tumstatin185-191 on lung adenocarcinoma cell lines and the association with protein kinase B and extracellular regulated protein kinase activation].

OBJECTIVE: to investigate the antitumor effects of tumstatin185-191 as a single agent or combination with cisplatin (DDP) on non-small lung cancer (NSCLC) cell lines A549. In addition, the changes of the protein kinase B(Akt) and extracellular regulated protein kinase (ERK) in cultured NSCLC cells treated by tumstatin185-191 and cisplatin were evaluated. METHODS: A549 cells were treated with tumstatin185-191 and cisplatin. Cell viability was assessed using the modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was measured by flow cytometry. The activation of Akt and Erk were evaluated by Western blotting. RESULTS: Tumstatin185-191 inhibited the proliferation of A549 and the IC(50) values of tumstatin 185-191 was 73.7 micromol/L. After cotreatment with 20 micromol/L tumstatin185-191, IC(50) values of cisplatin in A549 cells reduced from 5.2 micromol/L to 3.5 micromol/L, while 40 micromol/L tumstatin185-191 reduced from 5.2 micromol/L to 1.4 micromol/L. The early apoptosis rate was (19.34 +/- 0.97)% in the cotreatment group, (12.5 +/- 2.1)% in cisplatin group and (9.6 +/- 1.6)% in tumstatin185-191 group (F = 5.74, P < 0.01). The levels of phospho-Akt (p-Akt) and phospho-ERK (p-ERK) in the A549 cells were remarkably lower after being treated with tumstatin 185-191, while tumstatin 185-191 treatment whether alone, or in combination with cisplatin, had the similar effects on the protein levels of p-Akt and p-ERK in A549 cells. CONCLUSION: our data suggest that tumstatin185-191 might enhance the sensitivity of A549 cells to cisplatin. The effects of promoting apoptosis and downregulation of proliferation induced by tumstatin185-191 may be mediated through inactivation of the Akt and ERK pathways.

[Tumstatin185-191 increases the sensitivity to cisplatin in a cisplatin-resistant human lung adenocarcinoma cell line].

OBJECTIVE: To investigate the effects and related mechanisms of Tumstatin 185-191 as a single agent or in combination with cisplatin on proliferation and apoptosis in a cisplatin-resistant human lung adenocarcinoma cell line A549-DDP cells. METHODS: A549-DDP cells were treated with Tumstatin185-191 and cisplatin at varying concentrations. Cell viability was assessed by a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 50% inhibiting concentration (IC(50)) values of the chemotherapeutic drugs were analyzed by MTT assay. Cell apoptosis was measured by flow cytometry. The activation of Akt and ERK was evaluated by Western blotting. RESULTS: Tumstatin185-191 inhibited the proliferation of A549-DDP cells and its IC(50) value was 80.25 micromol/L. After cotreatment with 20 micromol/L Tum185-191, the IC(50) value of cisplatin in A549-DDP cells reduced from 77.16 micromol/L to 57.97 micromol/L, the reverse index was 1.33, while with 40 micromol/L Tumstatin185-191 the IC(50) was reduced from 77.16 to 26.40 micromol/L and the reverse index was 2.92. The early apoptosis rate was 19.5% +/- 1.1% in the cotreatment group, while 13.3% +/- 1.5% in cisplatin group and 10.2% +/- 2.0% in Tum185-191 group (F = 4.09, P < 0.05). The levels of phospho-Akt (p-Akt) and phospho-ERK (p-ERK) in the A549-DDP cells were remarkably lower after treatment with Tumstatin 185-191. The Tumstatin 185-191 treatment alone or in combination with cisplatin had a similar effect on the protein levels of p-Akt and p-ERK in A549-DDP cells. CONCLUSION: Our data suggest that Tumstatin185-191 may promote apoptosis, downregulate proliferation and partly reverse the drug resistance of A549-DDP cells to cisplatin. The effects induced by Tum185-191 may be mediated through inactivation of the Akt and ERK pathways.

[Application of sequential noninvasive following invasive mechanical ventilation in COPD patients with severe respiratory failure by investigating the appearance of pulmonary-infection-control-window].

OBJECTIVE: To evaluate the application of sequential noninvasive following invasive mechanical ventilation in chronic obstructive pulmonary disease (COPD) patients with severe respiratory failure by investigating the appearance of pulmonary-infection-control-window. METHODS: From November 2001 to October 2004, 76 case of COPD patients with severe respiratory failure due to pulmonary infection were intubated and recruited in the study. When the pulmonary infection was significantly controlled (the time of pulmonary infection control was called PIC window) by the antibiotic and comprehensive therapy, all cases were randomized into noninvasive veatiation group (NIV) and control group. The early extubation was conducted and followed by noninvasive mechanical ventilation via facial mask with bilevel positive airway pressure mode immediately in the NIV group. Conventional invasive synchronized intermittent mandatory ventilation (SIMV) plus pressure support ventilation (PSV) was used as the weaning technique in the control group. RESULTS: Thirty eight cases among 76 patients were in the NIV group, and the rest in the control group. The NIV group and the control group had similar age, sex, APACHE scores, RR, HR, MAP, PaO2 and PaCO2 at the time of commencement and PIC window (P > 0.05). The time of PIC window was (7.5 +/- 1.9) d in the NIV group, and (8.0 +/- 2.5) d in the control group (P > 0.05). In the NIV group, the durations of invasive mechanical ventilation (MV) and total MV were (7.5 +/- 1.9) d and (12.5 +/- 4.0) d respectively, while the durations were (23.5 +/- 9.5) d in the control group (P < 0.05). The durations of RICU stay and hospital stay were shorter than that in the control group. The incidence of ventilation associated pneumonia (VAP) was 18.4% (7/38) in the NIV group, 39.5% (15/38) in the control group respectively (P < 0.05). The incidence of reintubation was 13.2% (5/38) in the NIV group, 34.2% (13/38) in the control group respectively (P < 0.05). Hospital mortality was 7.9% (3/38) in the NIV group, and 28.9% (11/38) in the control group (P < 0.05). CONCLUSION: In those COPD patients requiring intubation and mechanical ventilantion who have severe respiratory failure due to pulmonary infection, sequential noninvasive following invasive mechanical ventilation at the appearance of PIC window can significantly reduce the MV duration, the length of RICU stay and hospital stay, and decrease the occurrence of VAP, reintubation and hospital mortality as well. So it is an efficient strategy to be generalized.