Exploration of pathological technology training for professional postgraduates of pathology / 中华医学教育探索杂志

Combined with teaching practice, this study summarizes the teaching contents, methods and effect evaluation of pathological technology for professional postgraduates majoring in pathology. According to the basic conditions of postgraduates, the pathological technology training program has been formulated, student-centered heuristic teaching is carried out by using diversified teaching methods such as flipped classroom, interactive theoretical teaching is carried out by using the intelligent teaching platform, and practical teaching is carried out by using the problem-based learning mode, aiming to improve the theoretical literacy and practical level of pathological technology of professional postgraduates majoring in pathology, improve their clinical research thinking, and lay a foundation for clinical pathological diagnosis and scientific research in the future.

Construction of pathological sample repository and its application in experimental pathology curriculum for medical undergraduates / 中华医学教育探索杂志

The gross specimens and tissue slices used for traditional experimental pathology curriculum are fragile, and some specimens or slices are difficult to be supplemented. Besides, the classroom and schedule for experimental pathology teaching are inflexible. Therefore, the teaching effects for experimental pathology course are limited. The development of digital technology has promoted the teaching reform of medical experimental curriculum. We have digitalized the gross specimens and tissue slices to preserve and expand the samples, and constructed pathological sample repository containing both physical samples and digital samples. Furthermore, we have established a platform for remote access, and thus improved the flexibility and autonomy of study for experimental pathology curriculum. Additionally, we have integrated clinical information of the teaching samples, and interpreted the specimens with the assistance of two-dimensional code technology and voice broadcast technology, to realize human-computer interactive learning. The questionnaire shows that the application of pathological sample repository in experimental teaching has improved student learning effect and recognition.

Exploration and practice of specimen sampling teaching in standardized residency training of clinical pathology / 中华医学教育探索杂志

Pathological specimen sampling is not only the prerequisite of a good pathological diagnosis, but also the primary clinical skill that must be mastered by the standardized residency training trainees (resident trainees) in clinical pathology department. In view of the problems and difficulties encountered in the teaching of specimen sampling, through five years of exploration and attempt, this paper has gradually established a new model with five basic elements, including theory teaching, practice teaching, promoting teaching effect by examination, learning from senior students, and review teaching. The results of evaluation analysis and questionnaire survey show that the teaching mode can make the trainees master the methods of specimen sampling quickly and efficiently, learn and improve clinical skills in practice, and lay a solid foundation for the subsequent standardized training of histopathological diagnosis.

Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Emergency establishment and application of biosafety autopsy and pathology platform / 中华医学科研管理杂志

Objective:Through the establishment and application of the biosafety autopsy pathology platform in Huoshenshan Hospital, the feasibility and application effect of the biosafety autopsy pathology platform were analyzed.Methods:The feasibility and application effect of the biosafety autopsy pathology platform were analyzed by layout design, instruments and equipment preparation, testing methods examination, and effect evaluation.Results:A total number of 26 cases of systematic autopsy and 8 cases of minimally invasive autopsy (puncture) were performed on the biosafety autopsy pathology platform, and no one was infected. Some pathology original findings were identified, including COVID-19 and pathological characteristics of identification, SARS respiratory failure mechanism and treatment significance, systemic distribution and spreading mechanism of the new coronavirus, the " storm" of inflammation pathological basis, some tumor markers rise in pulmonary pathological cell source and the overcast with fibrosis characteristics, such findings play important roles in the clinical diagnosis and treatment of COVID-19.Conclusions:The study of autopsy pathology is of great significance for the prevention and control of emerging infectious disease, which calls for early intervention. To promote the standard construction of biosafety autopsy platform is the key to the pathological study of emerging infectious diseases. Pathological research and clinical diagnosis and treatment should be combined to inform each other.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTSO_LILarge-scale scRNA-seq analysis depicts the immune landscape of COVID-19 C_LIO_LILymphopenia and active T and B cell responses coexist and are shaped by age and sex C_LIO_LISARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses C_LIO_LICytokine storms with systemic S100A8/A9 are associated with COVID-19 severity C_LI

Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment

BackgroundCoronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. MethodsSixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. FindingsSixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50x109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52{middle dot}2% (24/46) had severe thrombocytopenia, compared to 6{middle dot}7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81{middle dot}3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19. InterpretationAnti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition. FundingThis investigation was supported by grants 2016CB02400 and 2017YFC1201103 from the National Major Research and Development Program of China.

Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation

An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses. One Sentence SummaryThe lectin pathway of complement activation is a promising target for the treatment of highly pathogenic coronavirus induced pneumonia.

Modularized teaching program on the clinical research training for pathological residents / 中华医学教育探索杂志

To meet the requirement of pathological practice and development, we systematically analyzed the situation of pathological residents training and the importance of initiating the clinical scientific research training. Additionally, we proposed the principle and implementation strategy for clinical scientific research training. According to features of pathological practice, we employed the modularized teaching to divide the training courses into several modules: discussion module for clinical pathology, lecture module for advanced research, and training modules for basic scientific theory, technology and writing skill. With these approaches, the systematic and structured system of standardized residents training is implemented to improve the clinical research ability of pathological residents.

Modularized teaching program on the clinical research training for pathological residents / 中华医学教育探索杂志

To meet the requirement of pathological practice and development,we systematically analyzed the situation of pathological residents training and the importance of initiating the clinical scientific research training.Additionally,we proposed the principle and implementation strategy for clinical scientific research training.According to features of pathological practice,we employed the modularized teaching to divide the training courses into several modules:discussion module for clinical pathology,lecture module for advanced research,and training modules for basic scientific theory,technology and writing skill.With these approaches,the systematic and structured system of standardized residents training is implemented to improve the clinical research ability of pathological residents.

Strategies of improving the scientific innovation ability of pathological graduate students based on modularized special training / 中华医学教育探索杂志

Pathology is a subject that studies the etiology,pathogenesis,pathological changes,progression and outcome of diseases.Pathology links the basic research and clinical practice and is an important part of translational medicine.In order to cultivate qualified pathological graduates with solid pathological theories and the abilities of proposing and addressing scientific hypotheses from pathological morphology changes,we employ modularized special training to divide the pathology training courses into morphology learning module,article searching and reading module,project design module,experiment operation module and scientific presentation module.The training contents among these modules are relatively independent but closely connected,and compose a strategy that aims to improve the scientific innovation ability of pathological graduates.

The reform of innovative talents training mode of professional master degree postgraduates in pathology / 中华医学教育探索杂志

The establishment of professional master degree in pathology is a new branch of the professional degree graduate education.It is an important measure to bring the clinical pathology into the teaching system of clinical medicine specialty in China.In response to a wave of education reform in the new century, our department has positively converted the traditional postgraduate training and teaching mode, innovated the teaching idea and content, and continued to improve the teaching method and means.On the basis of fully respecting students' subject consciousness, we have combined traditional and modern teaching means, made full use of modern education information technology, actively built and promoted pathology specialized degree graduate student research, teaching and clinical trinity management: the new training mode.Through the practice of bilingual, network, clinical problems and cases of teaching and combined with the leading edge forum of famous pathologists' research and the professional standardized training of clinical pathology, we have extensively carried out the education training, which is based on the theory, practice, research, and sub specialist guidance.

Expression of MEF2D on nasopharyngeal carcinoma tissues and its influence of prognostic / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the expression of MEF2D in NPC tissues, study the relationship between the expression and prognostic.@*METHOD@#Specimens from 101 NPC patients who were follow-up visited 1 to 7 years were analyzed for MEF2D by using immunohistochemistry.@*RESULT@#(1) The expression of MEF2D was higher in the higher clinical stage. (2) Density and Grey of MEF2D was negative correlated (|r| = 0.865, P < 0.01). (3) NPC patients' survival rate after therapies was 52.5%, the survival curve of 1th clinical stage was higher than 4th. (4) The survival curves of MEF2D stages were no statistical significance.@*CONCLUSION@#There's statistical significance of the MEF2D expression in clinical stages, but not in survival curve, which indicated that MEF2D concerned with invasion and metastatic of NPC.

Comparative study on fetal ultrasonic diagnosis and pathological results of complex congenital heart diseases / 中华超声影像学杂志

Objective To probe the diagnostic efficacy of fetal eehocardiography for characterizing complex congenital heart diseases.Methods Fetal echocardiography was performed on 49 cases of fetal complex congenital heart disease, the ultrasonic diagnosis was compared retrospectively with pathological results after autopsy.Results Antenatal sonographic diagnosis was in agreement with the pathological results in 42 cases (85.71 %), 7 cases were disagreed with pathological diagnosis (antenatal sonographic diagnosis was discrepancy in 3 cases, 4 cases were partially mis-classified).Twenty-four cases were combined with extra-cardiac malformations.Nine cases had chromosomal abnormality.Conclusions Fetal echocardiography is highly accurate for antenatal diagnosis of complex congenital heart disease, but it is hard to detect some type of cardiac anomalies.

Establishment of rat model of impact spinal cord injury and pathological observations / 中华创伤杂志

Objective To establish rat model of impact spinal cord injury, observe the pathological changes of the model and assess its stability, reproducibility and consistency. Methods Moderate and severe spinal cord injury (SCI) models were established by using modified weight drop device. The pathological and functional changes after SCI were observed by means of BBB scoring, electrophysiology,immunohistochemistry and electronic microscopy so as to estimate the reproducibility of rat models and their consistency with severity of SCI. Results Locomotion and nerve impulse transduction along the spinal cord measured by motorial and sensory evoked potentials recovered gradually over time after SCI.However, the recovery rate of moderate SCI group was better than that of severe SCI group. Histological and immunohistochemical experiments showed that the glial scar as well as cavity were formed after SCI.Whereas, compared with moderate SCI group, the injury of severe SCI group was severer, with less spared tissue. Electronic microscopic observation displayed that hemorrhage, edema, neutrophilic granulocytic infiltration and chromatin margination of glia arose at day 1 after SCI. Vacuolization of mitochondria, degeneration of axon with edema could be seen at 2 weeks after injury. Degeneration of myelin and deposition of collagen fibril emerged at 8 weeks postinjury. Conclusions The rat models of impact SCI established in this study can distinguish the graded injury, and significantly correlate with the behavioral,electrophysiological and pathological outcomes, which indicates that the models possess good stability, reproducibility and consistency. Glial scar with cavity marked by GFAP or Vimentin is the pathological hallmark after SCI, and thereby GFAP or Vimentin can be used as a marker for demarcate the border of glial scar.

Detection of interleukin-8 on tissue array of non-small cell lung cancer and its clinicopathological significance / 中国肺癌杂志

<p><b>BACKGROUND</b>Interleukin-8 (IL-8) is a member of the CXC chemokine family, which involved in tumor growth, metastasis and angiogenesis. The aim of this study is to investigate the expression of IL-8 in non-small cell lung cancer (NSCLC) and its clinicopathologic significance.</p><p><b>METHODS</b>The expression of IL-8 protein and the intratumoral microvessel density (MVD) were detected in 114 cases of NSCLC on tissue array by immunohistochemical method (EnVisionTM method).</p><p><b>RESULTS</b>The positive rate of IL-8 expression was 81.6% (93/114) in 114 cases of the primary lung cancer and 79.1% (34/43) in metastatic lymph nodes respectively. And it was remarkably higher in NSCLC with lymph node metastasis (93.0%, 40/43)) than in those without lymph node metastasis (74.6%, 53/71) (P < 0.05). IL-8 protein expression in primary lung cancer tissues was positively related to TNM stages (P < 0.05), but not to histological type, differentiation degree, age and sex of patients (P > 0.05). In addition, there was significant difference in MVD between IL-8 positive NSCLC tissues (22.1±13.6) and negative ones (14.8±11.2) (P < 0.05).</p><p><b>CONCLUSIONS</b>The present study suggests that there is overexpression of IL-8 in NSCLC, which is closely related to angiogenesis, TNM stages and lymph node metastasis. Detection of IL-8 protein may be helpful to evaluate biological characteristics and therapy for NSCLC.</p>

Activation of SDF-1/CXCR4 axis induces proliferation,migration,and tubulogenesis of human endothelial progenitor cells / 基础医学与临床

Objective To explore the effect of chemokine SDF-1 on the proliferation,migration and in vitro of human endothelial progenitor cells(EPCs).Methods The expression of CXCR4 and SDF-1 on EPCs was detected with immunocytochemistry.Proliferation,migration and in vitro tubulogenesis of EPCs was detected by MTT,Millicell chemotaxis and three-diamensional in vitro Matrigel assays,respectively.Results SDF-1 and CXCR4 were expressed on EPCs.SDF-1 induced proliferation,migration and tubulogenesis of EPCs.However,AMD3100 abolished the effects induced by SDF-1.Conclusion The SDF-1/CXCR4 axis possibly plays a critical role in regulating vasculogenesis of EPCs.

Researching the Significance on Expression of VEGF-C in Human Breast Carcinoma by Self-Constructed Tissue Chips / 中国普外基础与临床杂志

3 cm) were 69.4%(68 /98), 69.1%(67 /97) and 52.9%(36 /68), respectively, but not in benign disease and normal mammary gland specimens. The positive rates of VEGF-C in the centre and borderline of carcinoma in lymph node metastasis group 75.0%(51/68), 76.1%(51/67) were significantly higher than that of no metastasis group 25.0%(17/68),23.9%(16/67), P

Effects of NDGA on the growth of a human malignant glioma cell line CHG-5 / 第三军医大学学报

Objective To investigate the effects of nordihydroguaiaretic acid (NDGA) on the growth of a human malignant glioma cell line CHG 5 in vitro and in vivo . Methods Colorimetric MTT assay, flow cytometry, and light microscopy were used to investigate the proliferation in vitro , cell cycles, apoptosis of CHG 5 cells, and the growth of xenografted tumor in nude mice. Results NDGA significantly inhibited the proliferation of CHG 5 cells in vitro . Cells in G 0/G 1 phase increased, but cells in S, G 2/M phases decreased, and apoptotic cells increased significantly. After treatment of NDGA (50 mg/kg, intraperitoneally) at 5 d after the inoculation of tumor cells, the xenografted tumor volume reduced remarkably without causing significant toxic and side effects. Conclusion The inhibitory effect of NDGA on the growth of CHG 5 cells may be correlated with the regulation of cell cycles and induction of apoptosis.

Clinical significance of pS2 protein expression in breast cancer / 第三军医大学学报

Objective To explore the relationship between the expression of pS2 protein and the clinicopathological parameters in breast cancer and to evaluate the value of pS2 as a prognostic factor for breast carcinoma and a predictive factor for response to endocrine therapy. Methods Expression levels of pS2 protein, estrogen receptor (ER) and progestogen receptor (PR) in tissues from 75 cases of breast cancer were detected by immunohistochemical assay. The relationship of pS2 protein expression with patient age, menopausal status, tumor size, metastasis to the axillary lymph nodes, pathological types, ER and PR was analyzed. Results pS2 protein, expressed in 33.3% of breast carcinomas, was correlated with patient age and pathological types, but was not correlated with tumor size. The positive rate of pS2 protein before menopause was higher than that after menopause, but no significant difference was found. Similarly, higher positive rate of pS2 protein was found in patients with metastasis to axillary lymph nodes than those without, but no significant difference was found. pS2 expression was correlated with ER and PR, but they were not perfectly consistent. Conclusion In breast cancer, pS2 protein expression, associated with some clinical factors and pathological features, is a good prognostic factor. pS2 expression may be a reasonable index for endocrinotherapy of breast carcinoma, but the detection of pS2 protein can not be employed in place of the detection of ER and PR.