Genomic testing and targeted therapy of non-small cell lung cancer in China: a nationwide survey of physicians and clinical pathologists.

BACKGROUND: Genomic diagnostic testing is necessary to guide optimal treatment for non-small cell lung cancer (NSCLC) patients. The proportion of NSCLC patients whose treatment was selected based on genomic testing is still unknown in many countries or needs further improvement. This survey aimed to assess perception of genomic testing and targeted therapy for NSCLC in clinical pathologists and physicians across China. METHODS: The web-based survey was conducted with 150 clinical pathologists and 450 physicians from oncology, respiratory and thoracic surgery departments from May to September 2020, across 135 cities in China. The participants had >5 years of clinical experience in genomic testing, diagnosis or treatment of NSCLC. RESULTS: Clinical pathologists reported capability of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS-1) testing as 95.3%, 94.7%, and 84.7%, respectively, but only 81.9%, 75.5%, and 65.6% of physicians believed that the pathology department of the hospital is capable of performing the testing. The proportions of sending out specimens for testing were 21.0% and 49.7% as reported from clinical pathologists and physicians, respectively. Testing for EGFR mutation was recommended by physicians most often, followed by ALK and ROS-1 rearrangement. As first-line treatment, among the newly diagnosed patients with EGFR mutation, 77% received tyrosine kinase inhibitors (TKIs) therapy (49% treated with gefitinib); among patients with ALK rearrangement, 71% received TKI (64% treated with crizotinib); among patients with ROS-1 fusion, 65% received TKI (88% treated with crizotinib). CONCLUSIONS: The improvement of the non-tertiary hospital pathology departments' detection capabilities and the physicians' awareness are needed for enhancing the rate of genomic testing and targeted therapy in NSCLC patients in China.

Circ_0002395 promotes aerobic glycolysis and proliferation in pancreatic adenocarcinoma cells via miR-548c-3p/PDK1 axis.

Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa_circ_0002395 (circ_0002395) in both PAAD tissues and cell lines. This up-regulation of circ_0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ_0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ_0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ_0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p.

Circ_0000182 promotes cholesterol synthesis and proliferation of stomach adenocarcinoma cells by targeting miR-579-3p/SQLE axis.

BACKGROUND: Circular RNAs (circRNAs) or cholesterol metabolism have been demonstrated to participate in stomach adenocarcinoma (STAD) progression. However, the relationship between circRNAs and cholesterol metabolism in STAD and its underlined mechanism remain unclear. METHODS: RNA and protein expression levels were detected by qRT-PCR and Western blot. Cell proliferation was assessed by CCK-8, EdU incorporation and colony formation assays. Total cholesterol (TC) and free cholesterol (FC) levels were measured by the corresponding kits. The relationships between circ_0000182 and miR-579-3p or squalene epoxidase (SQLE) mRNA were investigated by bioinformatics analysis, RNA-RNA pull-down, luciferase reporter and RIP assays. RESULTS: We found that circ_0000182 expression was significantly up-regulated in both STAD tissues and cell lines, and high circ_0000182 expression was correlated with increased tumor size. Circ_0000182 promoted cell proliferation and cholesterol synthesis of STAD cells. Accordingly, cell proliferation, cholesterol synthesis and SQLE expression were significantly inhibited by circ_0000182 knockdown in STAD cells, and these effects were partly reversed by miR-579-3p inhibition or SQLE over-expression. Furthermore, we identified that circ_0000182 acted as a competing endogenous RNA (ceRNA) by sponging miR-579-3p, thereby facilitating SQLE expression, cholesterol synthesis and cell proliferation. CONCLUSION: Circ_0000182 promotes cholesterol synthesis and proliferation of STAD cells by enhancing SQLE expression via sponging miR-579-3p.

Prognostic significance of T2 mapping in evaluating myocardium alterations in patients with ST segment elevation myocardial infarction / 中华危重病急救医学

OBJECTIVE@#To investigate the value of T2 mapping in the assessment of myocardial changes and prognosis in patients with acute ST segment elevation myocardial infarction (STEMI).@*METHODS@#A retrospective study was conducted. A total of 30 patients with acute STEMI admitted to Tianjin First Central Hospital from January 2021 to March 2022 were enrolled as the experimental group. At the same time, 30 age- and sex-matched healthy volunteers and outpatients with non-specific chest pain with no abnormalities in cardiac magnetic resonance (CMR) examination were selected as the control group. CMR was performed within 2 weeks after the diagnosis of STEMI, as the initial reference. A plain CMR review was performed 6 months later (chronic myocardial infarction, CMI). Plain scanning includes film sequence (CINE), T2 weighted short tau inversion recovery (T2-STIR), native-T1 mapping, and T2 mapping. Enhanced scanning includes first-pass perfusion, late gadolinium enhancement (LGE), and post-contrast T1 mapping. Quantitative myocardial parameters were compared between the two groups, before and after STEMI myocardial infarction. The receiver operator characteristic curve (ROC curve) was used to evaluate the diagnostic efficacy of native-T1 before myocardial contrast enhancement and T2 values in differentiating STEMI and CMI after 6 months.@*RESULTS@#There were no statistically significant differences in age, gender, heart rate and body mass index (BMI) between the two groups, which were comparable. The native-T1 value, T2 value and extracellular volume (ECV) were significantly higher than those in the control group [native-T1 value (ms): 1 434.5±165.3 vs. 1 237.0±102.5, T2 value (ms): 48.3±15.6 vs. 21.8±13.1, ECV: (39.6±13.8)% vs. (22.8±5.0)%, all P < 0.05]. In the experimental group, 12 patients were re-examined by plain CMR scan 6 months later. After 6 months, the high signal intensity on T2-STIR was still visible, but the range was smaller than that in the acute phase, and the native-T1 and T2 values were significantly lower than those in the acute phase [native-T1 value (ms): 1 271.0±26.9 vs. 1 434.5±165.3, T2 value (ms): 34.2±11.2 vs. 48.3±15.6, both P < 0.05]. ROC curve analysis showed that the area under the ROC curve (AUC) of native-T1 and T2 values in differentiating acute STEMI from CMI was 0.71 and 0.80, respectively. When native-T1 cut-off value was 1 316.0 ms, the specificity was 100% and the sensitivity was 53.3%; when T2 cut-off value was 46.7 ms, the specificity was 100% and the sensitivity was 73.8%.@*CONCLUSIONS@#The T2 mapping is a non-invasive method for the diagnosis of myocardial changes in patients with acute STEMI myocardial infarction, and can be used to to evaluate the clinical prognosis of patients.

Development and Validation of a Diagnostic Nomogram to Predict the Anthracycline-Induced Early Cardiotoxicity in Children with Hematological Tumors.

This study aimed to establish and validate an effective nomogram to predict the risk of cardiotoxicity in children after each anthracycline treatment. According to the inclusion and exclusion criteria, the eligible children were randomly divided into the training cohort (75%) and the validation cohort (25%). Least absolute shrinkage and selection operator (LASSO) regression was used to select the predictors and a nomogram was developed. Then, concordance index (C-index), the area under the curve (AUC), Hosmer-Lemeshow (H-L) test, and decision curve analysis (DCA) were employed to evaluate the performance and clinical utility of nomogram. Internal validation was processed to inspect the stability of the model. A total of 796 eligible children were included in this study and divided into a training set (n = 597) and a validation set (n = 199). LASSO regression analysis revealed that cumulative anthracycline dose, ejection fractions, NT-proBNP, and diastolic dysfunction were effective predictors of cardiotoxicity. The nomogram was established based on these variables. The C-index and the AUC of the predicting nomogram were 0.818 in the training cohort and 0.773 in the validation cohort, suggesting that the nomogram had good discrimination. The calibration curve of the nomogram presented no significant deviation from the reference line, and the P-value of the H-L test was 0.283, implying a preferable degree of calibration. The threshold of DCA also reflects that the nomogram is clinically useful. A nomogram was developed to predict anthracycline chemotherapy-induced cardiotoxicity in children with hematological tumors. The nomogram has a good prediction effect and can provide a reference for clinicians' diagnosis and treatment.

Circ_0000705 facilitates proline metabolism of esophageal squamous cell carcinoma cells by targeting miR-621/PYCR1 axis.

CircRNAs have been found to play crucial roles in the metabolism and progression of cancers, but their roles and mechanisms in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. This work is aimed to explore the role and mechanism of hsa_circ_0000705 (circ_0000705) in ESCC. Circ_0000705 expression was up-regulated in ESCC tissues and cell lines, and high circ_0000705 expression was correlated with poor survival. Circ_0000705 facilitated cell proliferation, invasion, migration and proline metabolism of ESCC cells. The inhibitory effects of circ_0000705 knockdown on cell invasion, migration and proline metabolism were partly rescued by miR-621 inhibition or PYCR1 over-expression. Furthermore, circ_0000705 expression is negatively correlated with miR-621 expression, and positively correlated with PYCR1 in ESCC tissues. Mechanistically, circ_0000705 acted as a ceRNA by sponging miR-621, thereby facilitating PYCR1 expression in ESCC cells. In conclusion, circ_0000705 promoted proline metabolism and malignant progression of ESCC by regulating the miR­621/PYCR1 axis.

Circ_0001093 promotes glutamine metabolism and cancer progression of esophageal squamous cell carcinoma by targeting miR-579-3p/glutaminase axis.

Increasing studies indicate that circular RNAs (circRNAs) play critical roles in tumor metabolism of multiple cancers. However, the contribution of circRNAs in glutamine metabolism of esophageal squamous cell carcinoma (ESCC) remains elusive. The objective of this research was to investigate the role and mechanism of circRNA hsa_circ_0001093 (circ_0001093) in the glutamine metabolism and tumorigenesis of ESCC. Circ_0001093, microRNA-579-3p (miR-579-3p) and glutaminase (GLS) expressions in ESCC tissues and cell lines were measured by qRT-PCR, tissue array or Western blot. Cell proliferation, invasion and migration were assessed by CCK-8 or transwell assays. Glutamine consumption, glutamate and ATP production were detected by indicated assay kits. The relationships between circ_0001093 and miR-579-3p or GLS mRNA were investigated by bioinformatics analysis, RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays. Here, we found that circ_0001093 expression was up-regulated in ESCC tissues and cell lines. Increased circ_0001093 expression predicted an unfavourable prognosis, and was associated with the lymph node metastasis, TNM staging and tumor size in ESCC tissues. Circ_0001093 knockdown suppressed cell proliferation, invasion, migration and glutamine metabolism of ESCC cells, while circ_0001093 over-expression showed the opposite effects. Mechanistically, circ_0001093 acted as a competing endogenous RNA (ceRNA) by sponging miR-579-3p, thereby increasing GLS expression. Furthermore, the inhibitory effects of circ_0001093 knockdown on the invasion, migration and glutamine metabolism were partly rescued by miR-579-3p inhibition or GLS over-expression in ESCC cells. Additionally, miR-579-3p expression was down-regulated in ESCC tissues, while GLS expression was up-regulated. In conclusion, this study first provides evidence that the circ_0001093/miR-579-3p/GLS regulatory network can affect glutamine metabolism and malignant phenotype of ESCC, which can further impact ESCC progression.

The diagnostic value of quantitative imaging for acute myocardial infarction / 中华危重病急救医学

Objective:To explore the diagnostic performance of cardiac magnetic resonance imaging (CMR) with T1 mapping and T2 mapping for detection of acute phase of ischemic cardiomyopathy.Methods:Twenty-four patients with acute myocardial infarction (AMI) detected by coronary angiography from May 2020 to April 2021 in Tianjin First Center Hospital were selected. All patients underwent CMR (Philips Ingenia 3.0-T) at (9±4) days after definite diagnosis, which was defined as the first diagnosis. After 3 months and 6 months of chronic myocardial infarction (CMI) phase, one CMR was performed. On the same period with age and sex matching, a total of 26 cases of healthy volunteers and outpatient with non-specific chest pain and CMR examination without abnormality as control group. Plain scan included Cine, T2-weighted (STIR), and native T1/T2 mapping. The enhanced scan included perfusion, late gadolinium enhancement, post-T1 mapping. The changes of myocardial quantitative parameters before and after myocardial infarction were compared. Receiver operator characteristic curves (ROC curve) were developed to evaluate, compare, and distinguish the changes in the AMI group and the CMI group after 6 months.Results:Pre-enhanced T1 value, T2 value and extracellular volume (ECV) of AMI group were significantly higher than those of control group [pre-enhanced T1 value (ms): 1 438.7±173.4 vs. 1 269.2±42.3, pre-enhanced T2 value (ms): 49.8±9.3 vs. 21.7±4.0 , ECV (%): 33.2±10.2 vs. 27.2±2.1, all P < 0.05]. ECV was significantly higher in AMI (%: 33.2±10.2 vs. 27.2±2.1), but stabilized after 3 months (%: 33.2±10.2 vs. 32.4±5.1), and after 6 months later (%: 27.7±4.9 vs. 32.4±5.1), there were no significant difference (all P > 0.05). Pre-enhanced T1 and T2 values were significantly higher in AMI, lower after 3 months, but significantly decreased after 6 months [pre-enhanced T1 values (ms): 1 438.7±173.4 vs. 1 272.1±25.2, pre-enhanced T2 values (ms): 49.8±9.3 vs. 29.0±4.0, all P < 0.05]. The ROC curve showed that the specificity of pre-enhanced T1 and T2 values between AMI and CMI were 100%, and the sensitivity were 72.7%, 100%, respectively, pre-enhanced T1 and T2 value could be better distinguish between AMI and CMI diagnosis method. Conclusion:T1 mapping and T2 mapping with ECV can clearly diagnosis ischemic cardiomyopathy, especially pre-enhanced myocardial T1 and T2 values which is non-invasive diagnosis method of AMI, and can distinguish AMI or CMI, has a great significance to the patient's clinical treatment and follow-up.

Changes of arterial blood gas indexes of free-field primary blast lung injury of pigs and its application value / 中华危重病急救医学

Objective:To observe the changes of arterial blood gas indexes in pigs with the free-field primary blast lung injury (PBLI) model, and to explore the value of arterial blood gas indexes in predicting moderate to severe PBLI.Methods:Nine adult healthy Landrace pigs were selected to construct the pig free-field PBLI model. Arterial blood samples were taken 15 minutes before the explosion (before injury) and 10, 30, 60, 120, and 180 minutes after the explosion (after injury). Arterial blood gas indexes and pulse oxygen saturation (SpO 2) were measured, compare the changes of blood gas analysis indexes and SpO 2 levels at different time points, and observe the changes of gross injury scores and pathological injury scores of lung tissue. Analyze the correlation between the blood gas indicators. Results:As time prolonged, at each time point, pH, arterial partial pressure of oxygen (PaO 2), and SpO 2 were lower than those before the injury, and blood lactic acid (Lac) and arterial partial pressure of carbon dioxide (PaCO 2) were higher than those before the injury. Compared with that before the injury, the pH value in the blood decreased significantly 10 minutes after the injury (7.39±0.06 vs. 7.46±0.02, P < 0.05), and the Lac increased significantly (mmol/L: 3.61±2.89 vs. 1.10±0.28, P < 0.05), and lasts until 180 minutes after injury (pH value: 7.37±0.07 vs. 7.46±0.02, Lac (mmol/L): 2.40±0.79 vs. 1.10±0.28, both P < 0.05); while PaO 2 and SpO 2 decreased significantly at 180 minutes after injury [PaO 2 (mmHg, 1 mmHg = 0.133 kPa): 59.40±10.94 vs. 74.81±9.39, P < 0.05; SpO 2: 0.75±0.11 vs. 0.89±0.08, P < 0.05], PaCO 2 increased significantly (mmHg: 56.17±5.38 vs. 48.42±4.93, P < 0.05). Correlation analysis showed that the gross injury score of lung blast injury animals was positively correlated with the pathological injury score ( r = 0.866, P = 0.005); PaO 2 and SpO 2 were positively correlated ( r = 0.703, P = 0.000); pH value and Lac were negative Correlation ( r = -0.400, P = 0.006); pH value is negatively correlated with PaCO 2 ( r = -0.844, P = 0.000). Conclusion:This study successfully established a large mammalian free-field PBLI model, arterial blood gas analysis is helpful for the early diagnosis of PBLI, whether SpO 2 can be used to evaluate the severity of lung injury remains to be further verified.

Imaging features of Brucella spondylitis in non-pasture areas / 中华地方病学杂志

Objective:To understand the X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) imaging features of Brucella spondylitis (BS) in non-pasture areas. Methods:The medical records of 21 patients with BS diagnosed and treated in the Second Affiliated Hospital, Dalian Medical University from December 2013 to November 2020 were collected. There were 14 males and 7 females. The age was (52.4 ± 15.8) years old, ranging from 21 to 77 years old. They all came from non-pasture areas. The diagnostic criteria refered to the "Diagnosis for Brucellosis" (WS 269-2019). The results of imaging examinations (including X-ray, CT and MRI, 19, 16 and 21 cases respectively) were retrospectively analyzed.Results:In 21 patients with BS, the main lesion site was lumbar vertebrae (16 cases, 76.2%). In 19 cases of X-ray examination, 9 cases (47.4%) showed "Bird's Beak" hyperostosis, and 7 cases (36.8%) had vertebral bone destruction. Among the 16 cases of CT examination, 10 cases (62.5%) had hyperosteosclerosis and 8 cases (50.0%) had vertebral bone destruction, they had been showed the characteristic change of "Lace Like" sign. There were 7 cases (43.8%) of intervertebral disc lesions, 1 case (6.2%) of paravertebral abscess and 1 case (6.2%) of psoas major abscess. In 21 patients with MRI examination, 10 cases (47.6%) showed hyperostosis and 11 cases (52.4%) showed bone destruction; 13 cases (61.9%) had signal changes of intervertebral disc. There were 1 case (4.8%) of prevertebral abscess, 1 case (4.8%) of paravertebral abscess and 1 case (4.8%) of psoas major abscess. Sixteen patients underwent CT and MRI examinations at the same time, MRI was superior to CT in detecting intervertebral disc lesions (13 vs 7 cases, χ 2 = 4.800, P < 0.05). Conclusion:The X-ray, CT and MRI imaging features of BS patients in non-pasture areas are varied, and the lesion site mainly involves the lumbar vertebrae, and MRI is superior to CT in detecting intervertebral disc lesions.

Status quo of education of foreign geriatric nurse practitioners / 中华医学教育探索杂志

With the acceleration of the aging in China, the demand of health care for the elderly is increasing, which puts forward higher requirements for the education of geriatric nurses. There is no education system yet to develop geriatric nurse practitioners in China. Therefore, this paper introduces the length of schooling, curriculum contents, cultivation goals, the practice time, sites and main contents, the types and forms of teaching methods, the contents and requirements of course and graduation assessment of the training programs for master's and doctoral students abroad, so as to provide reference for the training of geriatric nurse practitioners in China.

LncRNA MAFG-AS1 Accelerates Cell Migration, Invasion and Aerobic Glycolysis of Esophageal Squamous Cell Carcinoma Cells via miR-765/PDX1 Axis.

BACKGROUND: LncRNA dysregulation is implicated in esophageal squamous cell carcinoma (ESCC) progression; However, the precise role and function of lncRNA MAFG-AS1 in ESCC remains unknown. MATERIALS AND METHODS: Expressions of MAFG-AS1, miR-765, PDX1, GLUT1 and LDH-A were detected via qRT-PCR or/and Western blot in ESCC tissues and cell lines. CCK-8, transwell and glycolysis assays were used to investigate the effects of MAFG-AS1 on ESCC cell proliferation, migration, invasion and aerobic glycolysis after knockdown or overexpression of MAFG-AS1, and bioinformatics analyses, RNA pull-down and dual luciferase reporter systems were applied to investigate the interaction between MAFG-AS1, miR-765 and PDX1. RESULTS: MAFG-AS1 was significantly up-modulated in ESCC tissues and cell lines. MAFG-AS1 significantly accelerated ESCC cell proliferation, migration, invasion and aerobic glycolysis. MAFG-AS1 competitively adsorbed miR-765, while miR-765 negatively modulated the expression of PDX1. miR-765 and PDX1 participated in the promotive effects of MAFG-AS1 on cell migration, invasion and aerobic glycolysis in ESCC cells. CONCLUSION: Our research indicates that the MAFG-AS1/miR-765/PDX1 axis accelerates ESCC cell proliferation, migration, invasion and aerobic glycolysis.

Study on anti-inflammatory active components and mechanism of Corydalis Bungeanae Herba / 中国中药杂志

Corydalis Bungeanae Herba is often used to treat a variety of inflammatory diseases in traditional Chinese medicine. In order to determine its chemical material basis, the components of Corydalis Bungeanae Herba were isolated by automated purification system. Flavonoids and alkaloids were prepared, and all such components were identified by mass spectrometry. The effects of the components on the production of inflammatory mediators and pharmacological mechanisms in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model were examined. Mouse macrophages(RAW264.7) were first treated with LPS. The relationship between cell viability and LPS concentration was observed. Then, the effects of flavonoids components and alkaloid components with different administration concentrations on cell viability were detected to determine the maximum administration concentration. Secondly, 2.5, 5, 10 and 20 μg·mL~(-1) flavonoids components and alkaloid components were added respectively to observe the effects and mechanism of different concentrations of flavonoids components and alkaloid components on LPS-induced inflammation of RAW264.7 macrophages. Griess reagent assay was used to detect NO content in cell supernatant. The inflammatory cytokines(TNF-α, IL-1β and IL-6) in cell supernatant were determined by ELISA method. Western blot method was used to detect the intracellular nuclear factor(NF-κB) IκBα phosphorylation(p-IκBα), p65 phosphorylation(p-p65) and protein expression of TLR4, TLR2. The results showed that the alkaloid components inhibited the production of NO, TNF-α, IL-1β and IL-6 in a dose-dependent mannerin the concentration range of 2.5-20 μg·mL~(-1). In inflammation upstream pathways, the inhibitory effect of the alkaloid components on the TLR2 expression level was weaker than that of TLR4. In inflammation downstream, alkaloid components significantly inhibited phosphorylation of IκBα and p65 in a dose-dependent manner. These data suggested that the alkaloid components were the material basis components of Corydalis Bungeanae Herba, and its anti-inflammatory mechanism might be related to inhibiting the transmission of inflammatory signals in TLRs/NF-κB signaling pathways dominated by TLR4, interfering with the activation of inflammatory genes and inhibiting their over expression, and down-regulating the secretion level of inflammatory factors.

The research progress of cardiac magnetic resonance in diagnosis of myocardial amyloidosis / 中国中西医结合急救杂志

Cardiac involvement in amyloidosis has a relatively poor prognosis, and early diagnosis and treatment is very important to the prognosis of such involved patients. "One stop type" cardiac examination can be carried out by the cardiac magnetic resonance imaging (CMRI) and the evaluation of cardiac morphology and function can be complete. "One stop type" CMRI may show the thickness of myocardium in left ventricle, cardiac diastolic dysfunction, sub-endocardial enhancement (patch, diffuse and transmural types), rising of T1 value, too fast clarifying rate of contrast agent in blood pool, pericardial and/or pleural cavity effusion, that may help to elevate the efficiency of diagnosis. The CMRI presents myocardial tissue characteristics quite well, that may help for early diagnosis of myocardial amyloidosis, and clearly demonstrate the situation of heart involvement; to follow-up patients with repeat CMRI examinations can monitor drug therapeutic effect, direct and regulate treatment, judge prognosis, etc. so that CMRI possesses very high clinical application value.

Diagnostic value of cardiac magnetic resonance for acute heart failure with unknown cause / 中国中西医结合急救杂志

Objective To evaluate the diagnostic value of cardiac magnetic resonance (MR) for acute heart failure (AHF) with unknown cause. Methods A retrospective study was conducted, eleven patients with AHF with unknown cause admitted to Tianjin First Center Hospital from September 2017 to August 2018 were enrolled, and all the patients underwent complete cardiac MR imaging (plain MR and delayed enhancement imaging) with satisfactory image quality fulfilled the diagnostic requirement. Additionally, all of them had no history of heart disease and lack of diagnostic laboratory tests (routine blood test, blood biochemistry and myocardial enzyme), electrocardiogram (ECG) changes and echocardiography abnormality. Besides, 10 patients had completed invasive coronary angiography or coronary CT angiography (CCTA); the results of laboratory tests, ECG abnormality, echocardiography and cardiac MR were recorded, and the values of echocardiography and cardiac MR examination in the diagnosis and exploring the cause of patients with AHF with unknown cause were analyzed. Results Nine of 11 patients with AHF with unknown cause had positive finding on cardiac MR examination; there were 3 patients with chronic myocardial infarction, 3 with dilated cardiomyopathy, 2 with cardiac involvement of amyloidosis and 1 with myocarditis. The left ventricular end systolic volume (LVESV) measured on cardial MR was significantly higher than that on echocardiography (mL: 120.68±57.47 vs. 108.84±50.49, P < 0.05), the left ventricular ejection fraction (LVEF) and myocardial valvular regurgitation measured on MR were less than those on echocardiography (LVEF: 0.36±0.09 vs. 0.43±0.10; regurgitation: 11 vs. 22, both P < 0.05); while, the differences of the end diastolic volume (LVEDV) and the number of patients with pericardial effusions between MR and echocardiography had no statistical significant differences [LVEDV (mL): 183.37±65.26 vs. 182.26±70.44; pericardial effusion: 6 cases vs. 6 cases, all P > 0.05]. Conclusion Cardiac MR could synthetically evaluate the heart by its morphology, function as well as accompanied sign (pericardial effusion) and cardiac tissue characteristics; eventually, it may provide valuable information concerning the selection of proper clinical therapeutic strategies and improvement of AHF patients' prognose.

Late gadolinium enhancement and T1 mapping for the diagnosis of cardiac amyloidosis / 中华危重病急救医学

Objective@#To explore the role of late gadolinium enhancement (LGE) and T1 mapping for detection of cardiac amyloidosis.@*Methods@#Nine cases of cardiac amyloidosis who had diagnosed by renal biopsy diagnosed type light-chain (AL) amyloidosis and acute heart failure suspected involvement of the heart in Tianjin First Central Hospital from May 2018 to March 2019 were enrolled, and at the same time 14 cases of non-obstructive hypertrophic cardiomyopathy patients, 12 cases of healthy physical examination at the same period were enrolled as the control. All patients underwent Philips 3.0-T including plain scan as cine, T2WI, native T1 mapping and enhanced scan as perfusion, LGE imaging, post T1 mapping. For LGE cardiac magnetic resonance imaging (CMRI), a bolus of 0.1 mL/kg of gadolinium-based contrast followed by a 20 mL saline flush was administered. After a 7-minutes delay, ECG-gated images were acquired in 3 long-axis and a stack of short-axis slices identical to those of cine images using a breath-hold gradient recalled echo phase-sensitive or magnitude only inversion recovery sequence. LGE and T1 mapping CMRI observation, including cardiac function index [left ventricle end-diastolic volume (LVEDV), left ventricle end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), valvular regurgitation], cardiac morphological index [including left ventricular wall thickness, left ventricular weight (LVM)], myocardial histological characteristics and markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and accompanying signs (including pericardial effusion, pleural effusion) were performed.@*Results@#The predominant LGE pattern in amyloidosis was diffuse left ventricular sub endocardial enhancement (3/9), diffuse in left ventricular wall enhancement (3/9), and transmural delayed enhancement in left ventricular (2/9) and non-typical delayed enhancement (1/9). Myocardial T1 was significantly elevated in cardiac AL amyloidosis patients compared to normal subjects and hypertrophic cardiomyopathy (ms: 1 497.3±22.0 vs. 1 273.3±30.1, 1 329.3±42.6, both P < 0.05). Myocardial T1 was increased in AL amyloid before LGE. A post-contrast myocardial T1 was significantly elevated in cardiac AL amyloidosis patients compared to normal subjects and hypertrophic cardiomyopathy (ms: 476.7±44.2 vs. 516.1±41.5, 569.9±12.3, both P > 0.05). Three of 9 amyloidosis patients with review images showing T1 value and cardiac function was no significantly different with the first check (ms: 1 484.8±6.5 vs. 1 497.3±22.0, P = 0.11).@*Conclusions@#One-stop CMRI can improve the diagnosis of cardiac amyloidosis, LGE can display the myocardial scarring and fibrosis, and T1 mapping is sensitive to myocardial edema and diffuse fibrosis. LGE and T1 mapping can improve the diagnostic accuracy, which is very meaningful for diagnosis and follow-up of patients.

Late gadolinium enhancement and T1 mapping for the diagnosis of cardiac amyloidosis / 中华危重病急救医学

Objective To explore the role of late gadolinium enhancement (LGE) and T1 mapping for detection of cardiac amyloidosis. Methods Nine cases of cardiac amyloidosis who had diagnosed by renal biopsy diagnosed type light-chain (AL) amyloidosis and acute heart failure suspected involvement of the heart in Tianjin First Central Hospital from May 2018 to March 2019 were enrolled, and at the same time 14 cases of non-obstructive hypertrophic cardiomyopathy patients, 12 cases of healthy physical examination at the same period were enrolled as the control. All patients underwent Philips 3.0-T including plain scan as cine, T2WI, native T1 mapping and enhanced scan as perfusion, LGE imaging, post T1 mapping. For LGE cardiac magnetic resonance imaging (CMRI), a bolus of 0.1 mL/kg of gadolinium-based contrast followed by a 20 mL saline flush was administered. After a 7-minutes delay, ECG-gated images were acquired in 3 long-axis and a stack of short-axis slices identical to those of cine images using a breath-hold gradient recalled echo phase-sensitive or magnitude only inversion recovery sequence. LGE and T1 mapping CMRI observation, including cardiac function index [left ventricle end-diastolic volume (LVEDV), left ventricle end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), valvular regurgitation], cardiac morphological index [including left ventricular wall thickness, left ventricular weight (LVM)], myocardial histological characteristics and markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and accompanying signs (including pericardial effusion, pleural effusion) were performed. Results The predominant LGE pattern in amyloidosis was diffuse left ventricular sub endocardial enhancement (3/9), diffuse in left ventricular wall enhancement (3/9), and transmural delayed enhancement in left ventricular (2/9) and non-typical delayed enhancement (1/9). Myocardial T1 was significantly elevated in cardiac AL amyloidosis patients compared to normal subjects and hypertrophic cardiomyopathy (ms: 1497.3±22.0 vs. 1273.3±30.1, 1329.3±42.6, both P < 0.05). Myocardial T1 was increased in AL amyloid before LGE. A post-contrast myocardial T1 was significantly elevated in cardiac AL amyloidosis patients compared to normal subjects and hypertrophic cardiomyopathy (ms: 476.7±44.2 vs. 516.1±41.5, 569.9±12.3, both P > 0.05). Three of 9 amyloidosis patients with review images showing T1 value and cardiac function was no significantly different with the first check (ms: 1484.8±6.5 vs. 1497.3±22.0, P = 0.11). Conclusions One-stop CMRI can improve the diagnosis of cardiac amyloidosis, LGE can display the myocardial scarring and fibrosis, and T1 mapping is sensitive to myocardial edema and diffuse fibrosis. LGE and T1 mapping can improve the diagnostic accuracy, which is very meaningful for diagnosis and follow-up of patients.

Mitogen-activated protein kinase inhibition enhances the antitumor effects of sporamin in human pancreatic cancer cells.

Sporamin, a sweet potato tuber storage protein, is a Kunitz-type trypsin inhibitor (TI) that has exhibited antitumor activity through poorly defined mechanisms in a number of types of tumor cells. The present study aimed to analyze the combined effects of sporamin and three mitogen-activated protein kinase (MAPK) inhibitors, PD98059, SP600125 and SB203580, on the pancreatic cancer cell line, PANC-1. Cell proliferation activity was assessed using a 3H-thymidine incorporation assay, and cell viability was analyzed using an MTT assay. Apoptosis was assayed by flow cytometry and fluorescence microscopy. Protein expression levels in PANC-1 cells were determined by western blotting. The results of this analysis demonstrated that sporamin induced a temporary increase in the phosphorylation of MAPKs, including phosphorylated extracellular signal regulated-kinase 1/2, phosphorylated c-Jun amino-terminal protein kinase 1/2 and phosphorylated p38-MAPK, in a concentration-dependent manner. However, treatment with MAPK inhibitors promoted the inhibition of cell proliferation and viability, and the induction of apoptosis in sporamin-treated PANC-1 cells. In conclusion, the present study demonstrated that MAPK inhibition enhanced the antitumor activity of sporamin in PANC-1 cells.

Detection and application of bcl-2/IgH gene translocation and immunoglobulin gene rearrangement in follicular lymphoma / 中华病理学杂志

Objective@#To evaluate the application of FISH testing of bcl-2/IgH gene translocation and IgH/L gene rearrangement in different stages of follicular lymphoma.@*Methods@#In 32 follicular lymphoma cases, which were collected at Guangdong General Hospital from September 2014 to December 2016, the bcl-2/IgH gene ectopic state was detected by FISH while the IgH/L gene rearrangement was tested using PCR-GeneScan to analyze the relationship between bcl-2/IgH gene translocation, different stages of follicular lymphoma and clonal immunoglobulin (IgH/L) gene rearrangements.@*Results@#From the paraffin sections of all 32 follicular lymphomas, 17 cases showed bcl-2/IgH gene translocation, and the percentages of FL1, FL2 and FL3 translocation were 12/13, 3/5 and 2/14, respectively. Among the 24 cases of IgH/L gene arrangements identified from the total sample, the occurrence rates of FL1, FL2 and FL3 gene arrangement were 7/13, 4/5 and 13/14, respectively. Spearman′s rank correlation analysis and χ2 analysis showed that bcl-2/IgH gene translocation was negatively correlated with follicular lymphoma stage and the association was statistically significant. In more advanced stages of follicular lymphoma, the occurrence of bcl-2/IgH gene translocation tended to decrease with distinct FL1, FL2 and Fl3 gene expression (P<0.05). As IgH/L gene rearrangement in FL3 was higher than that in FL1 and FL2, its detection may be complimentary to FISH test for bcl-2/IgH gene translocation in diagnosing follicular lymphoma.@*Conclusions@#The combined use of FISH and PCR-GeneScan increases the positive rate of follicular lymphoma diagnosis, and this combination is more sensitive than FISH or clonal analysis only to detect the chromosomal abnormality or the gene rearrangement.

Sporamin suppresses growth of human esophageal squamous cell carcinoma cells by inhibition of NF­κB via an AKT­independent pathway.

The aim of the present study was to determine whether sporamin, a trypsin inhibitor, suppresses the growth of human esophageal squamous cell carcinoma (ESCC) cells in vitro. Sporamin treatment led to the suppression of viability and proliferation of human ESCC cell lines, EC9706 and EC109, as determined by MTT and [3H] thymidine incorporation assays, respectively. Flow cytometry and fluorescence microscopy demonstrated that sporamin significantly induced apoptosis in EC9706 and EC109 cells. Western blotting demonstrated that sporamin downregulated the expression of Bcl­2 and Bcl­2 like 1, and upregulated the expression of Bcl­2­associated X in EC9706 and EC109 cells. In addition, marked inhibition of nuclear factor (NF)­κB activation was observed in sporamin­treated EC9706 and EC109 cells by an electrophoretic mobility shift assay. Sporamin treatment also resulted in reduced expression levels of phosphorylated (p)­NF­κB inhibitor α and nuclear NF­κB p65. However, the expression levels of p­protein inase (AKT) and its downstream target, p­p70 S6 kinase, were not markedly altered following sporamin treatment. In conclusion, sporamin may suppress the growth of human ESCC cells via NF­κB­dependent and AKT­independent mechanisms and may act as a promising natural therapeutic agent for the treatment of human ESCC.