Tissue factor regulates autophagy in pulmonary artery endothelial cells from chronic thromboembolic pulmonary hypertension rats via the p38 MAPK-FoxO1 pathway.

AIMS: To detect the expression of autophagy components, p38 MAPK (p38) and phosphorylated forkhead box transcription factor O-1 (pFoxO1) in pulmonary vascular endothelial cells of chronic thromboembolic pulmonary hypertension (CTEPH) rats and to investigate the possible mechanism through which tissue factor (TF) regulates autophagy. METHODS: Pulmonary artery endothelial cells (PAECs) were isolated from CTEPH (CTEPH group) and healthy rats (control group (ctrl group)) which were cocultured with TF at different time points including 12 h, 24 h, 48 h and doses including 0 nM,10 nM, 100 nM, 1µM, 10µM, 100µM and cocultured with TFPI at 48 h including 0 nM, 2.5 nM, 5 nM. The expression of forkhead box transcription factor O-1 (FoxO1), pFoxO1, p38, Beclin-1 and LC3B in PAECs was measured. Coimmunoprecipitation (co-IP) assays were used to detect the interaction between FoxO1 and LC3. RESULTS: The protein expression of p-FoxO1/FoxO1 was significantly lower in the CTEPH groups (cocultured with TF from 0 nM to 100 µM) than in the ctrl group at 12 h, 24 h, and 48 h (P < 0.05) and was significantly lower in the CTEPH groups (cocultured with TFPI from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of p38 in the CTEPH groups treated with 0 nM, 10 nM, 100 nM or 1 µM TF for 48 h significantly increased than ctrl groups (P < 0.05) and was significantly increased in the CTEPH groups (cocultured with TFPI concentration from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of Beclin1 at the same concentration (cocultured with TF from 0 nM to 100 µM) was significantly lower in the CTEPH groups than ctrl groups after 24 h and 48 h (P < 0.05) and was significantly decreased in the CTEPH groups (cocultured with TFPI concentration from 2.5 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of LC3-II/LC3-I at the same concentration (cocultured with TF 0 nM, 1 µM, 10 µM, and 100 µM) was significantly lower in the CTEPH than in the ctrl groups after 12 h (P < 0.05) and was significantly lower in the CTEPH groups (cocultured with TFPI concentration from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). There were close interactions between FoxO1 and LC3 in the control and CTEPH groups at different doses and time points. CONCLUSION: The autophagic activity of PAECs from CTEPH rats was disrupted. TF, FoxO1 and p38 MAPK play key roles in the autophagic activity of PAECs. TF may regulate autophagic activity through the p38 MAPK-FoxO1 pathway.

Changes and significance of the fibrinolytic system following two pulmonary thromboembolisms in a rabbit model.

In this study, we examined the changes in the fibrinolytic system in a rabbit model of two acute pulmonary thromboembolisms (PTE). Fourteen healthy adult New Zealand white rabbits were divided into three groups: the single PTE group (five rabbits), the double PTE group (five rabbits), and the control group (four rabbits). A rabbit model of acute pulmonary embolism was established, and immunohistochemistry and polymerase chain reaction (PCR) were performed on tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) in plasma, and pulmonary embolism tissue. Plasma results: 1) t-PA levels: one hour following the initial modeling, the levels of t-PA in the modeling groups were significantly lower than those in the control group (P<0.05). In addition, the t-PA levels in the double PTE group were found to be lower after the modeling, as compared to the pre-modeling period (P<0.05). One hour after the second modeling, the double PTE group had lower t-PA levels compared to the control group (P<0.05). However, t-PA rebounded two hours after modeling in the double PTE group. One week after the second modeling, the double PTE group had higher t-PA levels compared to the other two groups (P<0.05). 2) PAI-1 results: one hour after the initial modeling, PAI-1 levels in the two modeling groups were lower compared to the pre-modeling period and control groups (P<0.05). Two hours following modeling, PAI-1 levels in both modeling groups were lower compared to the control group (P<0.05). PAI-1 levels were lower in the double PTE group one and two hours after the second modeling compared to the other two groups and pre-modeling period (P<0.05). 3) The immunohistochemistry results: the expression of PAI-1 decreased in the two modeling groups, while t-PA expression increased compared to the control group. 4) PCR results: t-PA mRNA expression did not differ among the three groups. The PAI-1 mRNA expression was lower in the two PTE groups compared to the control group. We conclude that in the early stages of PTE, the local fibrinolytic activity of the thrombus is increased, which is favorable for thrombolysis. However, as the thrombus persists, the activity of the fibrinolytic system is inhibited, contributing to the development of chronic thromboembolic pulmonary hypertension.

Fatal pulmonary bile embolism associated with acute pancreatitis - a case report and review of the literature.

A 27-year-old woman with jaundice and abdominal pain was admitted to an emergency ward. The diagnostic process showed that gallstones were causing her symptoms. The patient was treated via endoscopic retrograde cholangiopancreatography (ERCP), and during the procedure she suffered a cardiac arrest. Autopsy findings included multiple pulmonary bile emboli as well as features of disseminated intravascular coagulation. Among 22 thus far described cases of bile pulmonary embolism, 13 were associated with medical procedures involving the liver and biliary tract. We present the case report of a pulmonary bile embolism associated with acute pancreatitis treated via ERCP in a woman with gallbladder bile stones.

Predominance of M2 macrophages in organized thrombi in chronic thromboembolic pulmonary hypertension patients.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. Thrombotic lesions in CTEPH contain CD68+ macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, which are involved in wound healing and tissue repair. Currently, the phenotype of macrophages and their localization within thrombotic lesions of CTEPH are largely unknown. In our study, we subclassified thrombotic lesions of CTEPH patients into developing fresh thrombi (FT) and organized thrombi (OT), based on the degree of fibrosis and remodeling. We used multiplex immunofluorescence histology to identify immune cell infiltrates in thrombotic lesions of CPTEH patients. Utilizing software-assisted cell detection and quantification, increased proportions of macrophages were observed in immune cell infiltrates of OT lesions, compared with FT. Strikingly, the proportions with a CD206+INOS- M2 phenotype were significantly higher in OT than in FT, which mainly contained unpolarized macrophages. Taken together, we observed a shift from unpolarized macrophages in FT toward an expanded population of M2 macrophages in OT, indicating a dynamic role of macrophages during CTEPH pathogenesis.

Increase in venous thromboembolism in SARS-CoV-2 infected lung tissue: proteome analysis of lung parenchyma, isolated endothelium, and thrombi.

AIMS: COVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue. METHODS: Liquid chromatography mass spectrometry was performed on SARS-CoV-2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID-19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls. RESULTS: Compared to influenza controls, both analyses of COVID-19 whole-tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID-19 lung tissue. Analysis of isolated COVID-19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins. CONCLUSIONS: The decrease in platelet activation pathways in severe COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS-CoV-2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID-19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID-19.

Histopathological Evaluation of Pulmonary Thromboendarterectomy Specimens of Chronic Thromboembolic Pulmonary Hypertension.

AIMS: Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. Pulmonary thromboendarterectomy (PEA) is an effective treatment for CTEPH; however, the literature on its histopathological examination is lacking. This study aimed to investigate the histopathological findings and protein and gene expression in PEA specimens, establish an optimal histopathological evaluation method, and clarify the mechanisms of thrombus organization and disease progression in CTEPH. METHODS: In total, 50 patients with CTEPH who underwent PEA were analyzed. The patients were categorized according to their clinical data into two groups: good and poor postoperative courses. The relationship between their histopathological findings and the clinical course was examined. Immunohistochemical studies confirmed the expression of oxidants, antioxidants, and smooth muscle cell (SMC) differentiation markers and their changes during the progression of thrombus organization. The mRNA expression analysis of 102 samples from 27 cases included oxidants, antioxidants, and vasoconstrictor endothelin-1. RESULTS: In the PEA specimens, colander-like lesions (aggregations of recanalized blood vessels with well-differentiated SMCs) were significantly more common in the good postoperative course group than in the poor postoperative course group; analysis of proteins and genes proposed that oxidative and antioxidant mechanisms were involved. In the colander-like lesions, there was an increase in endothelin-1 mRNA and protein expression of endothelin receptor A. CONCLUSIONS: Colander-like lesions in PEA specimens must be identified. Additionally, SMC differentiation in recanalized vessels and the expression of vasoconstrictors and their receptors may contribute to the progression of CTEPH.

Primary pulmonary artery tumors easily misdiagnosed as pulmonary embolism: A review.

Primary pulmonary artery tumors (PPATs), originating from the pulmonary artery intima, are rare tumors characterized by pulmonary artery luminal occlusion and pulmonary hypertension. Diagnosis of this rare entity is a challenging dilemma with the need for a high expertise in the radiological and pathological identification of PPATs. computed tomographic pulmonary angiography of PPATs may show filling defects, which are easily misdiagnosed. The radionuclide scan, along with other imaging examinations, can assist with the diagnosis, but the pathological diagnosis requires a puncture or surgical resection. Most primary pulmonary artery tumors are malignant, with poor prognosis and lack of specificity in clinical manifestations. However, there is no unified understanding and standard for diagnosis and treatment. In this review, we discuss the status, diagnosis, and treatment of primary pulmonary artery tumors, as well as how clinicians can better understand and treat the disease.

Pulmonary thromboembolism and obesity in forensic pathologic case work.

328 autopsy cases of fatal pulmonary thromboembolism (PE) were compared to 984 age- and sex-matched controls to evaluate the association between obesity and PE in a forensic context. Both PE and control cases had a mean age of 67,8 years (male 62,9 years, females 71,7 years). The percentage of morbidly obese persons with a body mass index (BMI) of above 40 or abdominal subcutaneous adipose tissue of above 4 cm was higher in the PE group (8,39% vs. 4,67% and 29.45% vs. 23.40%, respectively). On the other side, that of very slim persons (BMI below 18.5 or adipose tissue below 3 cm) was significantly smaller (4,27% vs. 7,52% and 47.55% vs. 56,60%). We thus found a strong association between being overweight and death from PE, while slim persons seem to be at an advantage. As the group of underweight persons includes those suffering from chronic diseases with reduced mobility or hypercoagulability (e.g. tumor kachexia or sarkopenia due to immobilisation), this finding is to some extent unexpected.

Pulmonary artery sarcoma masquerading as pulmonary embolism: an under-recognised entity.

Pulmonary artery sarcoma is a rare disease with only a handful of cases reported. It is histologically classified as leiomyosarcoma, spindle cell sarcoma, fibrous histiocytoma or undifferentiated sarcoma. The disease is mostly misdiagnosed as pulmonary thromboembolism and carries a grim prognosis with an average survival of only a few months. Misdiagnosis often results in patients being treated inappropriately and diagnosed in later stages of the disease. This delay in diagnosis can be associated with significant mortality in the setting of an already poor prognosis. Early aggressive surgery targeting complete surgical resection is the standard treatment. Chemotherapy and radiation therapy have been tried with variable outcomes. Given the aggressive nature of pulmonary artery sarcoma, regular post-surgery follow-up is indicated.

Forensic Pathological Analysis of Death Due to Pulmonary Thromboembolism: A Retrospective Study Based on 145 Cases.

ABSTRACT: Pulmonary thromboembolism (PTE) is a common cause of sudden unexpected death in forensic and clinical practice. Although the prevention of thrombosis has been paid more attention in clinical practice in recent years, the number of deaths due to PTE remains extensive. In the present study, 145 cases of fatal PTE were collected and retrospectively analyzed from 2001 to 2020 at the School of Forensic Medicine, China Medical University in Liaoning Province, northeast of China. The demographic characteristics, risk factors of PTE, origins of thrombi, and time interval from the occurrence of main risk factors to PTE were retrospectively analyzed. The 40 to 59 age group accounted for the 51.0% of the total cases. Immobilization, trauma (especially fracture of the pelvis, femur, tibia, or fibula), surgery, cesarean section, and mental disorders were the top 5 high-risk factors. Among the involved cases, 92.9% of the PTE (130/140) occurred within 60 days and peak at 8 to 15 days after the exposure of main risk factors. According to the autopsy findings, 87.6% of the thrombi blocked the bilateral pulmonary arteries at pulmonary hilus, with a maximum diameter of 1.6 cm and a maximum length of 21.9 cm, which were mainly derived from lower limb (65.5%) or pelvic veins (10.3%). Although the embolus limited the pulmonary circulation, there is no difference on the ratio of lung-to-heart weight between PTE and the disease-free accident victims. Overall, our present retrospective study provides important information for the forensic analysis on the cause of death and potential guidance on clinical prevention of PTE.

Fat embolism after intraosseous catheters in pediatric forensic autopsies.

In our center, we performed the autopsy of a child who died from drowning and presented, at autopsy, a major pulmonary fat embolism (PFE). A cardiopulmonary resuscitation (CPR) was performed, including infusion by intraosseous catheter (IIC). No other traumatic lesions and diseases classically related to a risk of PFE were detected. According to some animal studies, we considered the IIC as the only possible cause for PFE. However, we could not find literature to confirm this hypothesis in humans, especially in a pediatric population. To verify the occurrence of PFE after IIC in a pediatric population, we retrospectively selected 20 cases of pediatric deaths autopsied in our center, in which a CPR was performed, without bone fractures or other possible causes of PFE: 13 cases with IIC (group A) and 7 cases without IIC (group B). Several exclusion criteria were considered. The histology slides of the pulmonary tissue were stained by Oil Red O. PFE was classified according to the Falzi scoring system. In group A, 8 cases showed PFE: 4 cases with a score 1 of Falzi and 4 cases with a score 2 of Falzi. In group B, no case showed PFE. The difference between the two groups was statistically significant. The results of our study seem to confirm that IIC can lead to PFE in a pediatric population and show that the PFE after IIC can be important (up to score 2 of Falzi). To the best of our knowledge, our study is the first specifically focused on the occurrence of PFE after IIC in a pediatric population by using autoptic data.

Research Status and Prospects of Non-Traumatic Fat Embolism in Forensic Medicine.

In the practice of forensic pathology, fat embolism is one of the common causes of death, which can be divided into two categories: traumatic and non-traumatic. Non-traumatic fat embolism refers to the blockage of small blood vessels by fat droplets in the circulatory blood flow caused by non-traumatic factors such as underlying diseases, stress, poisoning and lipid metabolism disorders. At present, it is believed that the production of non-traumatic fat embolism is related to the disturbance of lipid metabolism, C-reactive protein-related cascade reaction, the agglutination of chylomicron and very low-density lipoprotein. The forensic identification of the cause of death of non-traumatic fat embolism is mainly based on the case, systematic autopsy, HE staining and fat staining, but it is often missed or misdiagnosed by forensic examiners because of its unknown risk factors, hidden onset, the difficulty of HE staining observation and irregular implementation of fat staining. In view of the lack of attention to non-traumatic fat embolism in forensic identification, this paper reviews the concepts, pathophysiological mechanism, research progress, existing problems and countermeasures of non-traumatic fat embolism, providing reference for forensic scholars.

A case of fatal fulminant fat embolism syndrome following multiple fractures resulting from a fall.

Fat embolism syndrome is a life-threatening condition in which fatty substances enter the circulation and cause respiratory distress and neurological symptoms. It can occur following trauma and severe fat embolism occurring soon after trauma is known as fulminant fat embolism syndrome. Although fat staining of the lungs is helpful for diagnosing fat embolism syndrome at autopsy, clinical and other information is needed to determine the relationship between cause of death and the syndrome. In this report, we describe the macroscopic, microscopic, and computed tomography (CT) findings specific for fat embolism that were observed in a patient with fulminant fat embolism syndrome who died soon after the injury. An 85-year-old woman fell from a bath stretcher during assisted bathing and died 3 h later. Autopsy revealed fractures of the left femoral neck and other bones, as well as large amounts of fat-like material in the right and left pulmonary arteries. Histological examination of the lung with Oil red O staining showed extensive fat vacuoles. Based on these findings and postmortem CT images of the fractures and fatty globules in the pulmonary arteries detected prior to death, the cause of death was determined to be blunt force trauma, with fat embolism syndrome playing a significant role. This case is an example of fulminant fat embolism, which can be fatal in a short period of time, and demonstrates that CT performed postmortem but before autopsy can be useful in detecting fat embolism syndrome due to trauma.

Low skeletal muscle mass defined by thoracic CT as a prognostic marker in acute pulmonary embolism.

OBJECTIVE: Sarcopenia defined as low skeletal muscle mass (LSMM) is associated with several clinically relevant factors in people who are critically ill. The aim of the present study was to analyze the role of LSMM derived from thoracic computed tomography (CT) for prediction of mortality and prognosis of acute pulmonary embolism (PE). METHODS: The clinical database of our department was retrospectively screened for patients with acute PE between 2013 and 2017. Overall, 234 patients were included in the analysis. LSMM was assessed on axial slides at the thoracic vertebra 5 (Th5) level of contrast-enhanced pulmonary angiography thoracic CT. The skeletal muscle index (SMI) was calculated by adjusting the muscle area to height. All-cause 30-d mortality was used as a primary outcome. RESULTS: Overall, 64 participants (27.4% of the sample) died. SMI was slightly higher for survivors than non-survivors (57.7 ± 11.9 versus 55.6 ± 14.3 cm2/m2; P = 0.07). SMI was associated with 30-d mortality in univariate as well as multivariate analysis (respective hazard ratios and 95% CI: 1.06, 1.03-1.09; 1.08, 1.04-1.11). CONCLUSIONS: SMI at Th5 derived from thoracic CT has a relevant effect on 30-d mortality in people with acute PE and should be included in the clinical routine.

Beyond Clots in the Pulmonary Circulation: Pulmonary Artery Tumors Mimicking Pulmonary Embolism.

Pulmonary embolism (PE) is the most common filling defect seen on CT scan pulmonary angiography. Pulmonary artery (PA) tumors can mimic PE on imaging and clinical presentation. One classic feature of tumors is failure to improve on anticoagulation. PA tumors, particularly malignant ones, have radically different treatments and usually have a grim prognosis. Thus, it is essential that PA tumors, when suspected, receive an expedited confirmatory diagnosis followed by multidisciplinary treatment at an expert center. In this review, we present clinical, imaging, and histopathologic features of benign and malignant PA tumors, emphasizing differentiating features from PE. We also describe available diagnostic and treatment methods for PA tumors.

CT Angiography Clot Burden Score from Data Mining of Structured Reports for Pulmonary Embolism.

Background Many studies emphasize the role of structured reports (SRs) because they are readily accessible for further automated analyses. However, using SR data obtained in clinical routine for research purposes is not yet well represented in literature. Purpose To compare the performance of the Qanadli scoring system with a clot burden score mined from structured pulmonary embolism (PE) reports from CT angiography. Materials and Methods In this retrospective study, a rule-based text mining pipeline was developed to extract descriptors of PE and right heart strain from SR of patients with suspected PE between March 2017 and February 2020. From standardized PE reporting, a pulmonary artery obstruction index (PAOI) clot burden score (PAOICBS) was derived and compared with the Qanadli score (PAOIQ). Scoring time and confidence from two independent readings were compared. Interobserver and interscore agreement was tested by using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. To assess conformity and diagnostic performance of both scores, areas under the receiver operating characteristic curve (AUCs) were calculated to predict right heart strain incidence, as were optimal cutoff values for maximum sensitivity and specificity. Results SR content authored by 67 residents and signed off by 32 consultants from 1248 patients (mean age, 63 years ± 17 [standard deviation]; 639 men) was extracted accurately and allowed for PAOICBS calculation in 304 of 357 (85.2%) PE-positive reports. The PAOICBS strongly correlated with the PAOIQ (r = 0.94; P < .001). Use of PAOICBS yielded overall time savings (1.3 minutes ± 0.5 vs 3.0 minutes ± 1.7), higher confidence levels (4.2 ± 0.6 vs 3.6 ± 1.0), and a higher ICC (ICC, 0.99 vs 0.95), respectively, compared with PAOIQ (each, P < .001). AUCs were similar for PAOICBS (AUC, 0.75; 95% CI: 0.70, 0.81) and PAOIQ (AUC, 0.77; 95% CI: 0.72, 0.83; P = .68), with cutoff values of 27.5% for both scores. Conclusion Data mining of structured reports enabled the development of a CT angiography scoring system that simplified the Qanadli score as a semiquantitative estimate of thrombus burden in patients with pulmonary embolism. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Hunsaker in this issue.

Fatal pulmonary thromboembolism in asymptomatic COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has claimed the lives of millions of people globally. AIMS: This study aims to identify the pathological findings at autopsy of asymptomatic COVID-19 death, to compare the incidence of acute bilateral pulmonary thromboembolism (ABPTE) in asymptomatic COVID-19 deaths versus non-COVID-19 deaths and to explore the possible pathogenesis of thrombosis in COVID-19. We also consider the place of COVID-19 in the death certification of 4 cases who died from ABPTE. METHODS: This study primarily reviewed post-mortem reports of 6 asymptomatic COVID-19 deaths. Post-mortem reports for the years 2019 and 2020 were also reviewed to establish the incidence of ABPTE. Each post-mortem report was reviewed for gross examination, histology and toxicology findings. A literature review on COVID-19 autopsy findings, COVID-19 pathogenesis, thrombosis in COVID-19 and asymptomatic SARS-CoV-2 infection was also conducted using PubMed. RESULTS: Of the 6 asymptomatic COVID-19 deaths, 4 died as a result of ABPTE, 1 died of ischaemic and hypertensive cardiac disease caused by coronary artery disease and ventricular hypertrophy and the remaining case died of heart failure due to dilated cardiomyopathy caused by subendocardial fibrosis. There were 2 cases of bilateral pulmonary thromboembolism (BPTE) in 2019 out of 140 post-mortems. Excluding the 4 cases of ABPTE described already, there was 1 case of ABPTE in 2020 out of 156 post-mortems. A literature review on the pathogenesis of thrombosis in COVID-19 highlighted the significant role that the endothelium plays. CONCLUSIONS: Massive pulmonary thromboembolism may be a significant cause of death in asymptomatic COVID-19 infection.

MiR-34a-3p suppresses pulmonary vascular proliferation in acute pulmonary embolism rat by targeting DUSP1.

BACKGROUND: Acute pulmonary embolism (APE) is a prevalent reason of cardiovascular morbidity and mortality. Recent studies have underscored the positive effects of microRNAs (miRNAs) on many diseases. The present study aimed to identify the critical miRNA with differential expressions and explore its role in APE. METHODS: The critical miRNA with its target gene was screened by bioinformatics analysis. Their binding relationship was analyzed by TargetScan, Dual-luciferase reporter and RNA pull-down assays. A rat model of APE was established by self-blood coagulum. Human pulmonary artery smooth muscle cells (PASMCs) were exposed to platelet-derived growth factor (PDGF-BB) for excessive proliferation, and transfected with miR-34a-3p mimic. Mean pulmonary arterial pressure (mPAP) of rat was measured, and the pulmonary tissues were used for the pathological observation by Hematoxylin-Eosin (H&E) staining. Cell viability and proliferation were detected by Cell Counting Kit-8 (CCK-8) and EdU assays. The expressions of miR-34a-3p with its target genes (including dual-specificity phosphatase-1 (DUSP1)), neuron-derived orphan receptor-1 (NOR-1) and proliferating cell nuclear antigen (PCNA) were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR) or/and Western blot. RESULTS: MiR-34a-3p expression was down-regulated in APE patients, which attenuated the increment of mPAP and thickening of the pulmonary arterial walls in APE rats, accompanied with regulation of NOR-1 and PCNA levels. MiR-34a-3p suppressed DUSP1 expression by directly binding to its 3'-untranslated region (UTR), and attenuated cell viability, proliferation, and the expressions of NOR-1 and PCNA in PDGF-BB-induced PASMCs by inhibiting DUSP1 expression. CONCLUSION: Up-regulated miR-34a-3p negatively regulates DUSP1 expression to inhibit PASMC proliferation, which, thus, may act on APE treatment by negatively regulating pulmonary vascular proliferation.

Research Status and Prospects of Non-Traumatic Fat Embolism in Forensic Medicine / 法医学杂志

In the practice of forensic pathology, fat embolism is one of the common causes of death, which can be divided into two categories: traumatic and non-traumatic. Non-traumatic fat embolism refers to the blockage of small blood vessels by fat droplets in the circulatory blood flow caused by non-traumatic factors such as underlying diseases, stress, poisoning and lipid metabolism disorders. At present, it is believed that the production of non-traumatic fat embolism is related to the disturbance of lipid metabolism, C-reactive protein-related cascade reaction, the agglutination of chylomicron and very low-density lipoprotein. The forensic identification of the cause of death of non-traumatic fat embolism is mainly based on the case, systematic autopsy, HE staining and fat staining, but it is often missed or misdiagnosed by forensic examiners because of its unknown risk factors, hidden onset, the difficulty of HE staining observation and irregular implementation of fat staining. In view of the lack of attention to non-traumatic fat embolism in forensic identification, this paper reviews the concepts, pathophysiological mechanism, research progress, existing problems and countermeasures of non-traumatic fat embolism, providing reference for forensic scholars.

Time efficiency and reliability of established computed tomographic obstruction scores in patients with acute pulmonary embolism.

OBJECTIVE: Acute pulmonary embolism (PE) is a life-threatening disease with a high mortality. Computed tomographic pulmonary angiography (CTPA) is used in clinical routine for diagnosis of PE. Many pulmonary obstruction scores were proposed to aid in stratifying clinical course of PE. The purpose of the present study was to compare common pulmonary obstruction scores in PE in regard of time efficiency and interreader agreement based upon a representative patient sample. METHODS: Overall, 50 patients with acute PE were included in this single center, retrospective analysis. Two readers scored the CT images blinded to each other and assessed the scores proposed by Mastora et al., Qanadli et al., Ghanima et al. and Kirchner et al. The required time was assessed of each reading for scoring. RESULTS: For reader 1, Mastora score took the longest time duration, followed by Kirchner score, Qanadli score and finally Ghanima score (every test, p<0.0001). The interreader variability was excellent for all scores with no significant differences between them. In the Spearman's correlation analysis strong correlations were identified between the scores of Mastora, Qanadli and Kirchner, whereas Ghanima score was only moderately correlated with the other scores. There was a weak correlation between time duration and Mastora score (r = 0.35, p = 0.014). For the Ghanima score, a significant inverse correlation was found (r = -0.67, p<0.0001). CONCLUSION: For the investigated obstruction scores, there are significant differences in regard of time consumption with no relevant differences in regard of interreader variability in patients with acute pulmonary embolism. Mastora score requires the most time effort, whereas the score by Ghanima the least time.