TPD52 is a prognostic biomarker and potential therapeutic target for ER+/PR+/HER2+ breast cancer.

BACKGROUND: Breast cancer (BRCA) represents a significant health challenge for women globally, with refractory cases showing resistance to current therapeutic strategies. The discovery of novel molecular markers and therapeutic targets is critical for improving outcomes in these patients. The primary aim of this study is to elucidate the role of tumor protein D52 (TPD52) as a novel molecular marker and potential therapeutic target to improve outcomes for BRCA patients. METHODS: Using bioinformatics methods, we screened and evaluated the expression, prognosis, and associated mechanisms of TPD52 in BRCA. Two hundred and thirty-eight BRCA cases and 19 control cases were collected from Shanghai First Maternity and Infant Hospital, and the protein expression of TPD52 was detected by immunohistochemistry, and the correlation between TPD52 and the prognosis of BRCA was analyzed. RESULTS: The expression of TPD52 in BRCA tissues was significantly higher than that in the control (P<0.001), displaying a strong association with key clinical variables, concurrently indicating an unfavorable prognostic implication. The survival analysis revealed high TPD52 expression was an independent adverse prognostic factor for overall (P=0.008) and disease-specific survival (P=0.005). Gene set enrichment analysis showed that TPD52 negatively correlated with estradiol, AMP-activated protein kinase, and other responses. Immune infiltration analysis showed that TPD52 was associated with immune cell infiltration, Th-1/Th-2 cell balance, and immune defense cells such as dendritic and plasmacytoid dendritic cells. It is further found that high TPD52 expression is associated with progression-free and disease-free survival from the analysis of immunohistochemical data of the patients at our hospital. CONCLUSIONS: In summary, TPD52 may serve as an independent prognostic biomarker for BRCA, which may represent a promising novel therapeutic target, particularly for the refractory estrogen receptor-positive (ER+ )/progesterone receptor-positive (PR+ )/human epidermal growth factor receptor 2-positive (HER2+ ) BRCA cases that have failed endocrine therapy and targeted treatment.

Parametric analysis of craniocerebral injury mechanism in pedestrian traffic accidents based on finite element methods.

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the Total Human Model for Safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities was conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China.

Anaphylaxis is a rare but well-known cause of sudden unexpected death, although data from forensic autopsies in anaphylactic deaths are limited. Herein, a retrospective study of a series of allergic deaths from 2009 through 2019 in Shanghai, China, was conducted to investigate the demographic, medical, and forensic pathological characteristics of fatal anaphylaxis to improve medicolegal understanding on anaphylactic death. Sixty-two autopsy cases of anaphylactic death were registered in this study. Males dominated the cases (74.2%) against females (25.8%), with an average age of 38.8 years. Medications (98.4%), particularly antibiotics (72.6%), were the most frequent cause of anaphylaxis, and 44 cases (71.0%) occurred in clinics administered illegally by unlicensed clinicians. The anaphylactic symptoms began within a few minutes to less than 1 h in 53 cases, with dyspnea (56.5%) and sudden shock (46.8%) being the most common clinical signs. Thirty cases (48.4%) of anaphylaxis resulted in death within 1 h. Laryngeal edema and multiple tissue eosinophil infiltration (85.5%) were the most prevalent autopsy findings, followed by pulmonary edema and congestion (24.2%), which were considered to be non-specific but suggestive. The comorbidities were mainly cardiovascular disease (33.9%), pneumonia (8.1%) and asthma (8.1%). Serum IgE were measured in 11 of 62 cases, ranging from 43.3 to 591 IU/ml, severed as a helpful marker. Therefore, we suggested a thorough analysis of allergen exposure, clinical history and autopsy findings is required for the diagnosis of anaphylactic death currently.

Circ_0000877 accelerates proliferation and immune escape of non-small cell lung cancer cells by regulating microRNA-637/E2F2 axis.

BACKGROUND: Recently, circular RNA (circRNA) has become a vital targeted therapy gene for non-small-cell lung cancer (NSCLC) cells. CircRNA_0000877 (Circ_0000877) has been researched in diffuse large B-cell lymphoma (DLBCL). However, whether circ_0000877 regulated NSCLC cell progression is still poorly investigated. The research attempted to investigate the influence of circ_0000877 in NSCLC. METHODS: Circ_0000877 levels in NSCLC tissues and cell lines were determined applying RT-qPCR. Cell functions were evaluated by CCK-8, EdU, flow cytometry, ELISA, and western blot. Gene interactions were predicted by Cirular RNA interactome database and Target Scan website and certified by dual-luciferase reporter, RIP, and RNA pull-down assays. Finally, mice experimental model was established to explore the effects of circ_0000877 on tumor growth in vivo. RESULTS: The elevated trend of circ_0000877 expression was discovered in NSCLC tissues compared to para-carcinoma tissues. The clinicopathological data uncovered that up-regulated circ_0000877 was linked to tumor size, differentiation, and TNM stages of NSCLC patients. Knockdown of circ_0000877 inhibited the proliferation, triggered apoptosis, and prohibited immune escape in NSCLC cells. It was certified that miR-637 was directly interacted with circ_0000877 and targeted by E2F2. Overexpressed E2F2 strongly overturned the functions of circ_0000877 knockdown in NSCLC cells. Mice experimental data demonstrated that circ_0000877 knockdown suppressed tumor growth in vivo. CONCLUSION: The research demonstrated that circ_0000877 exhibited the promotive effect on NSCLC cells proliferation and immune escape by regulating miR-637/E2F2 axis.

Research Progress and Forensic Application of Human Vascular Finite Element Modeling and Biomechanics.

The finite element method (FEM) is a mathematical method for obtaining approximate solutions to a wide variety of engineering problems. With the development of computer technology, it is gradually applied to the study of biomechanics of human body. The application of the combination of FEM and biomechanics in exploring the relationship between vascular injury and disease, and pathological mechanisms will be a technological innovation for traditional forensic medicine. This paper reviews the construction and development of human vascular FEM modeling, and its research progress on the vascular biomechanics. This paper also looks to the application prospects of FEM modeling in forensic pathology.

Differential Effect of ITE on the Aryl Hydrocarbon Receptor Signaling in Breast Cancer Tissue: A Histopathological Study / Efecto Diferencial de ITE en la Señalización del Receptor de Hidrocarburo de Arilo en Tejido de Cáncer de Mama: Un Estudio Histopatológico

SUMMARY: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in various types of cancers including breast cancer. However, the role of AhR with its endogenous ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the progression of breast cancer remains poorly understood. We aimed to investigate cell proliferation and migration states in breast cancer after activating AhR with the endogenous ligand ITE. Breast cancer tissue was evaluated by cell lines, immunohistochemistry, reverse transcription-polymerase chain reaction, cell proliferation, flow cytometry, migration assays and western blot techniques. We found that AhR was widely expressed in breast cancer tissues and metastasis lymph node tissues, but not in normal tissues. The expression AhR was independent between the age, grades and TNM classifications for breast cancer tissues. ITE treatment significantly induced the activation of AhR in a time-dependent manner in both MCF-7 and T47D breast cancer cell lines. Meanwhile, ITE did not affect the cell migration but significantly suppressed the cell proliferation in estrogen receptor positive (ER+) MCF-7 andT47D cells, which probably attribute to the induction of cell cycle arrest in G1 phase and shortened S phase. Further mechanism study showed that ERK1/2 and AKT signaling were required for the activation of AhR in MCF-7 cells. These data suggest that AhR is a potential new target for treating patients with breast cancer. ITE may be more potentially used for therapeutic intervention for breast cancer with the kind of ER(+).

El receptor de hidrocarburo de arilo (AhR) es un factor de transcripción activado por ligando que se expresa en gran medida en varios tipos de cáncer, incluido el cáncer de mama. Sin embargo, el papel de AhR con su ligando endógeno 2- (1'H-indol-3'-carbonil)-tiazol-4-ácido carboxílico metil éster (ITE) en la progresión del cáncer de mama sigue siendo poco conocido. Nuestro objetivo fue investigar la proliferación celular y los estados de migración en el cáncer de mama después de activar AhR con el ligando endógeno ITE. El tejido de cáncer de mama se evaluó mediante líneas celulares, inmunohistoquímica, reacción en cadena de la polimerasa con transcriptasa inversa, proliferación celular, citometría de flujo, ensayos de migración y técnicas de transferencia Western. Descubrimos que AhR se expresó ampliamente en tejidos de cáncer de mama y en linfonodos con metástasis, pero no en tejidos normales. La expresión AhR fue independiente entre la edad, grados y clasificaciones TNM para tejidos de cáncer de mama. El tratamiento con ITE indujo significativamente la activación de AhR de manera dependiente del tiempo en las líneas celulares de cancer de mama MCF-7 y T47D. Mientras tanto, ITE no afectó la migración celular, pero suprimió significativamente la proliferación celular en células MCF-7 y T47D con receptor de estrógeno positivo (ER+), lo que probablemente se atribuye a la inducción de la detención del ciclo celular en la fase G1 y la fase S acortada. Un estudio adicional del mecanismo mostró que las señales de ERK1/2 y AKT eran necesarias para la activación de AhR en las células MCF-7. Estos datos sugieren que AhR es un nuevo objetivo potencial para el tratamiento de pacientes con cáncer de mama. ITE puede ser utilizado más potencialmente en la intervención terapéutica para el cáncer de mama con el tipo de ER (+).

A study to characterize the mechanical properties and material constitution of adult descending thoracic aorta based on uniaxial tensile test and digital image correlation.

The mechanical properties and material constitution of the aorta are important in forensic science and clinical medicine. Existing studies on the material constitution of the aorta do not satisfy the practical requirements of forensic and clinical medicine, as the reported failure stress and failure strain values for human aortic materials have a high dispersion. In this study, descending thoracic aortas were obtained from 50 cadavers (dead within 24 h) free of thoracic aortic disease, aged from 27 to 86 years old, which were divided into six age groups. The descending thoracic aorta was divided into proximal and distal segments. A customized 4-mm cutter was used to punch a circumferential and an axial dog-bone-shaped specimen from each segment; the aortic ostia and calcification were avoided. Instron 8,874 and digital image correlation were used to perform a uniaxial tensile test on each sample. Four samples from each descending thoracic aorta produced ideal stress-strain curves. All parameter-fitting regressions from the selected mathematical model converged, and the best-fit parameters of each sample were obtained. The elastic modulus of collagen fiber, failure stress, and the strain showed a decreasing trend with age, while the elastic modulus of elastic fiber showed an increasing trend with age. The elastic modulus of collagen fiber, failure stress, and strain of circumferential tensile were all greater than those for axial tensile. There was no statistical difference in model parameters and physiological moduli between the proximal and distal segments. The failure stress and strain in the proximal circumferential, distal circumferential, and distal axial tensile were all greater for the male group than for the female group. Finally, the Fung-type hyperelastic constitutive equations were fitted for the different segments in different age groups.

Comparison of CT Values between Thrombus and Postmortem Clot Based on Cadaveric Pulmonary Angiography.

OBJECTIVES: To explore the difference in CT values between pulmonary thromboembolism and postmortem clot in postmortem CT pulmonary angiography (CTPA) to further improve the application value of virtual autopsy. METHODS: Postmortem CTPA data with the definite cause of death from 2016 to 2019 were collected and divided into pulmonary thromboembolism group (n=4), postmortem clot group (n=5), and control group (n=5). CT values of pulmonary trunk and left and right pulmonary artery contents in each group were measured and analyzed statistically. RESULTS: The average CT value in the pulmonary thromboembolism group and postmortem clot group were (168.4±53.8) Hu and (282.7±78.0) Hu, respectively, which were lower than those of the control group (1 193.0±82.9) Hu (P<0.05). The average CT value of the postmortem clot group was higher than that of the pulmonary thromboembolism group (P<0.05). CONCLUSIONS: CT value is reliable and feasible as a relatively objective quantitative index to distinguish pulmonary thromboembolism and postmortem clot in postmortem CTPA. At the same time, it can provide a scientific basis to a certain extent for ruling out pulmonary thromboembolism deaths.

Detection of multiple biomarkers associated with satellite cell fate in the contused skeletal muscle of rats for wound age estimation.

From the perspective of forensic wound age estimation, experiments related to skeletal muscle regeneration after injury have rarely been reported. Here, we examined the time-dependent expression patterns of multiple biomarkers associated with satellite cell fate, including the transcription factor paired box 7 (Pax7), myoblast determination protein (MyoD), myogenin, and insulin-like growth factor (IGF-1), using immunohistochemistry, western blotting, and quantitative real-time PCR in contused skeletal muscle. An animal model of skeletal muscle contusion was established in 30 Sprague-Dawley male rats, and another five rats were employed as non-contused controls. Morphometrically, the data obtained from the numbers of Pax7 + , MyoD + , and myogenin + cells were highly correlated with the wound age. Pax7, MyoD, myogenin, and IGF-1 expression patterns were upregulated after injury at both the mRNA and protein levels. Pax7, MyoD, and myogenin protein expression levels confirmed the results of the morphometrical analysis. Additionally, the relative quantity of IGF-1 protein > 0.92 suggested a wound age of 3 to 7 days. The relative quantity of Pax7 mRNA > 2.44 also suggested a wound age of 3 to 7 days. Relative quantities of Myod1, Myog, and Igf1 mRNA expression > 2.78, > 7.80, or > 3.13, respectively, indicated a wound age of approximately 3 days. In conclusion, the expression levels of Pax7, MyoD, myogenin, and IGF-1 were upregulated in a time-dependent manner during skeletal muscle wound healing, suggesting the potential for using them as candidate biomarkers for wound age estimation in skeletal muscle.

The value of PMCTA in the diagnosis of coronary atherosclerosis in isolated human hearts.

Postmortem computed tomography (PMCT) has a limited value in investigating coronary artery disease, despite several obvious advantages over the conventional autopsy. To address this issue, postmortem computed tomography angiography (PMCTA) has been introduced into various studies, where it has been used to investigate natural and unnatural deaths involving vascular damage, occlusion, or other pathologies of the vascular system. To investigate the application value of PMCTA in the diagnosis of coronary artery stenosis in ex situ hearts, the water-based contrast media were injected into isolated hearts, scaned, and finally compared with gold standards (autopsy and histology findings of the coronary artery). This study involved 16 subjects from the Academy of Forensic Science who were suspected to have died of sudden death without traumatic injuries. Unenhanced PMCT was performed first, followed by PMCTA using a water-based contrast agent, injected into the coronary arteries of isolated hearts using a self-designed angiography device. The image data were reconstructed into three-dimensional (3D) angiography images using software in the angiography facility. The 3D images were recorded and evaluated by two radiologists and then statistically analysed. The results of PMCTA were consistent with the gold standards for the diagnosis of coronary artery stenosis (P > 0.05). However, water-based contrast media can only be used to examine the pathological changes of blood vessels, which may have limitations in the diagnosis of causes of death such as myocardial oedema. PMCTA can be used as a new method to evaluate the degree of coronary atherosclerosis in addition to traditional autopsy. The 3D reconstruction technique reveals the coronary artery lesions more objectively and vividly and provides the opportunity to re-read the data at any time. Key points: The methods and parameters for coronary angiography in isolated human hearts were standardized based on the previous researcher.PMCTA in isolated human hearts is including the 3D reconstruction technique that reveals the coronary artery lesions more objectively and vividly, and provides the opportunity to re-read the data at anytime.PMCTA could only be used to examine the pathological changes of blood vessels, which might have limitations for the diagnosis of causes of death.PMCTA in isolated human hearts can be viewed as an auxiliary method for establishing the cause of death, which can provide an assessment of degree and extent of arterial stenosis and accurately help determine the abnormal location.

Analysis of forensic autopsy cases associated with epilepsy: Comparison between sudden unexpected death in epilepsy (SUDEP) and not-SUDEP groups.

Background and aims: Epilepsy is a common and chronic neurological disorder characterized by seizures that increase the risk of mortality. SUDEP is the most common seizure-related category of death. The study aimed to evaluate the key characteristics between SUDEP and not-SUDEP death cases. Methods: A retrospective study of forensic autopsy cases from 2002 to 2021, performed by the Academy of Forensic Science (Ministry of Justice, China), identified a total of 31 deaths associated with epilepsy. We compared the different characteristics between individuals who died of SUDEP (SUDEP group) and individuals with epilepsy died suddenly due to unrelated causes (not-SUDEP group). Results and conclusions: 13 cases met the general accepted definition of SUDEP; and 18 cases were classified as not-SUDEP. The mean age of the not-SUDEP group was significantly higher than that of the SUDEP groups (p < 0.05) and there were more cases without a clear cause of epilepsy in the SUDEP group than in the not-SUDEP group (p < 0.05). Death position differed significantly between the two groups, with more cases dying in the prone position in the SUDEP group (p < 0.05). Complete autopsies were performed in 24 of the 31 cases. There were no significant differences in heart, lungs and brain weights, or in ventricular thickness (p > 0.05) between the SUDEP and not-SUDEP groups. In addition, compared to the not-SUDEP group, the SUDEP group featured a significantly more cases with coronary lesions (grades 1-3, p < 0.05). Neuropathological lesions were identified in 12 of the 13 SUDEP cases (92.3%), cardiac lesions were present in 10 cases (76.9%) and pulmonary edema and pulmonary congestion were present in all cases. The primary cause of death in 13 of the 31 cases was seizure disorder or epilepsy. The primary mechanism of death in SUDEP group was mainly asphyxia while that in the not-SUDEP group was cardiopulmonary failure (p < 0.05). Patients in the prone position had a significantly higher risk of asphyxia than those who were not. Here, we investigated the key characteristics between SUDEP and not-SUDEP death cases, which may help to facilitate forensic diagnosis in presumed SUDEP cases.

Multiobjective optimization algorithm for accurate MADYMO reconstruction of vehicle-pedestrian accidents.

In vehicle-pedestrian accidents, the preimpact conditions of pedestrians and vehicles are frequently uncertain. The incident data for a crash, such as vehicle deformation, injury of the victim, distance of initial position and rest position of accident participants, are useful for verification in MAthematical DYnamic MOdels (MADYMO) simulations. The purpose of this study is to explore the use of an improved optimization algorithm combined with MADYMO multibody simulations and crash data to conduct accurate reconstructions of vehicle-pedestrian accidents. The objective function of the optimization problem was defined as the Euclidean distance between the known vehicle, human and ground contact points, and multiobjective optimization algorithms were employed to obtain the local minima of the objective function. Three common multiobjective optimization algorithms-nondominated sorting genetic algorithm-II (NSGA-II), neighbourhood cultivation genetic algorithm (NCGA), and multiobjective particle swarm optimization (MOPSO)-were compared. The effect of the number of objective functions, the choice of different objective functions and the optimal number of iterations were also considered. The final reconstructed results were compared with the process of a real accident. Based on the results of the reconstruction of a real-world accident, the present study indicated that NSGA-II had better convergence and generated more noninferior solutions and better final solutions than NCGA and MOPSO. In addition, when all vehicle-pedestrian-ground contacts were considered, the results showed a better match in terms of kinematic response. NSGA-II converged within 100 generations. This study indicated that multibody simulations coupled with optimization algorithms can be used to accurately reconstruct vehicle-pedestrian collisions.

Preliminary study on the mechanisms of ankle injuries under falling and impact conditions based on the THUMS model.

Ankle injuries are common in forensic practice, which are mainly caused by falling and traffic accidents. Determining the mechanisms and manners of ankle injuries is a critical and challenging problem for forensic experts. The identification of the injury mechanism is still experience-based and strongly subjective. There also lacks systematic research in current practice. In our study, based on the widely used Total Human Model of Safety 4.0 (THUMS 4.0), we utilized the finite element (FE) method to simulate ankle injuries caused by falls from different heights (5 m, 10 m and 20 m) with different landing postures (natural posture, inversion, eversion, plantar-flexion and dorsi-flexion) and injuries caused by impacts from different directions (anterior-posterior, lateral-medial and posterior-anterior) with different speeds (10 m/s, 15 m/s and 20 m/s) at different sites (ankle and lower, middle and upper sections of leg). We compared the injury morphology and analyzed the mechanisms of ankle injuries. The results showed that falling causes a specific compression fracture of the distal tibia, while fractures of the tibia and fibula diaphysis and ligament injuries caused by falling from a lower height or inversion, planter flexion or dorsiflexion at a large angle are not distinguishable from the similar injury patterns caused by impact on the middle and upper segments of the leg. No obvious compression fracture of the tibia distal was caused by the impacts, whereas ligament injuries and avulsion fractures of the medial or lateral condyle and fractures of the diaphysis of the tibia and fibula were observed. Systematic studies will be helpful in reconstructing the ankle injury processes and analyzing the mechanisms in forensic practice, providing a deeper understanding of ankle injury mechanisms for forensic experts.

Cerebral hemorrhage caused by shaking adult syndrome? Evidence from biomechanical analysis using 3D motion capture and finite element models.

The present study combined three-dimensional (3D) motion capture with finite element simulation to reconstruct a real shaking adult syndrome (SAS) case and further explore the injury biomechanics of SAS. The frequency at which an adult male can shake the head of another person, head-shaking amplitude, and displacement curves was captured by the VICON 3D motion capture system. The captured shaking frequency and shaking curve were loaded on the total human model for safety (THUMS) head to simulate the biomechanical response of brain injury when a head was shaken in anterior-posterior, left-right, and left anterior-right posterior directions at frequencies of 4 Hz (Hz), 5 Hz, 6 Hz, and 7 Hz. The biomechanical response of the head on impact in the anterior, posterior, left, left anterior, and right posterior directions at the equivalent velocity of 6 Hz shaking was simulated. The violent shaking frequency of the adult male was 3.2-6.8 Hz; head shaking at these frequencies could result in serious cerebral injuries. SAS-related injuries have obvious directionality, and sagittal shaking can easily cause brain injuries. There was no significant difference between the brain injuries caused by shaking in the simulated frequency range (4-7 Hz). Impact and shaking at an equivalent velocity could cause brain injuries, though SAS more commonly occurred due to the cumulative deformation of brain tissue. Biomechanical studies of SAS should play a positive role in improving the accuracy of forensic identification and reducing this form of abuse and torture in detention or places of imprisonment.

Reconstruction of a real-world car-to-pedestrian collision using geomatics techniques and numerical simulations.

The aim of this study is to provide an improved method for traffic accident reconstruction based on geomatics techniques and numerical simulations. A combination of various techniques was used. First, an unmanned aerial vehicle (UAV), laser scanner and structured-light scanner were used to obtain information on the accident scene, vehicle and victim. The collected traces provided detailed initial impact conditions for subsequent numerical simulations. Then, multi-body system (MBS) simulations were conducted to reconstruct the kinematics of the car-to-pedestrian collision. Finally, a finite element (FE) simulation using the THUMS model was performed to predict injuries. A real-life vehicle-pedestrian collision was used to verify the feasibility and effectiveness of this method. The reconstruction result revealed that the kinematic and injury predictions of the numerical simulations effectively conformed to the surveillance video and investigation of the actual accident. UAV photogrammetry was demonstrated to be more efficient in accident data collection than hand sketch and measurement, and 3D laser scanning enabled an easier and more accurate modeling process of vehicle. The present study shows the feasibility of this method for use in traffic accident reconstruction.

Current Status and Perspectives of Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Hematological Malignancies.

Single-targeted chimeric antigen receptor (CAR) T cells tremendously improve outcomes for patients with relapsed/refractory hematological malignancies and are considered a breakthrough therapy. However, over half of treated patients experience relapse or refractory disease, with antigen escape being one of the main contributing mechanisms. Dual-targeting CAR T-cell therapy is being developed to minimize the risk of relapse or refractory disease. Preclinical and clinical data on five categories of dual-targeting CAR T-cell therapies and approximately fifty studies were summarized to offer insights and support the development of dual-targeting CAR T-cell therapy for hematological malignancies. The clinical efficacy (durability and survival) is validated and the safety profiles of dual-targeting CAR T-cell therapy are acceptable, although there is still room for improvement in the bispecific CAR structure. It is one of the best approaches to optimize the bispecific CAR structure by boosting T-cell transduction efficiency and leveraging evidence from preclinical activity and clinical efficacy.

SM03, an Anti-CD22 Antibody, Converts Cis-to-Trans Ligand Binding of CD22 against α2,6-Linked Sialic Acid Glycans and Immunomodulates Systemic Autoimmune Diseases.

SM03, an anti-CD22 recombinant IgG1 mAb, is currently in a phase III clinical trial for the treatment of rheumatoid arthritis (NCT04312815). SM03 showed good safety and efficacy in phase I systemic lupus erythematosus and phase II moderate to severe rheumatoid arthritis clinical trials. We propose the success of SM03 as a therapeutic to systemic autoimmune diseases is through the utilization of a novel mechanism of action unique to SM03. CD22, an inhibitory coreceptor of the BCR, is a potential immunotherapeutic target against autoimmune diseases. SM03 could disturb the CD22 homomultimeric configuration through disrupting cis binding to α2,6-linked sialic acids, induce rapid internalization of CD22 from the cell surface of human B cells, and facilitate trans binding between CD22 to human autologous cells. This in turn increased the activity of the downstream immunomodulatory molecule Src homology region 2 domain-containing phosphatase 1 (SHP-1) and decreased BCR-induced NF-κB activation in human B cells and B cell proliferation. This mechanism of action gives rationale to support the significant amelioration of disease and good safety profile in clinical trials, as by enabling the "self" recognition mechanism of CD22 via trans binding to α2,6 sialic acid ligands on autologous cells, SM03 specifically restores immune tolerance of B cells to host tissues without affecting the normal B cell immune response to pathogens.

Virtual Autopsy Morphological Features of Drowning.

OBJECTIVES: To explore the application value of virtual autopsy to obtain key evidence information on drowned corpses and its application value of virtual autopsy in the diagnosis of drowning. METHODS: In this study, 7 corpses were selected as the research objects. The image data of corpses were collected by computed tomography (CT) before conventional autopsy. The characteristics of corpses were observed through image reading, combined with virtual measurement indexes, and compared with 15 non-drowned corpses. RESULTS: The postmortem CT of drowning showed the more fluid in respiratory tract than the non-drowning, and ground-glass opacities in the lung. The statistical volume of fluid in the sinus (maxillary sinus and sphenoid sinus) was (10.24±4.70) mL in drowning cases and (2.02±2.45) mL in non-drowning cases. The average CT value of fluid in the sinus, left atrial blood and gastric contents in drowning cases were (15.91±17.20), (52.57±9.24) and (10.33±12.81) HU, respectively, which were lower than those in non-drowning cases (P<0.05). CONCLUSIONS: The comprehensive consideration of multiple characteristic image manifestations and the virtual measurement indexes are helpful to the forensic pathological diagnosis of drowning. Virtual autopsy can be used as an auxiliary method in the forensic diagnosis of drowning.

Detection of traumatic internal carotid artery pseudoaneurysm by postmortem imaging: A case report.

RATIONALE: Postmortem imaging (PMI), including computed tomography (PMCT), postmortem computed tomography angiography (PMCTA), and postmortem magnetic resonance imaging (PMMRI), is rapidly becoming effective and a practical method in forensic medicine. This study aimed to present a specific forensic case in which the PMI approach and its applications were used. PATIENT CONCERNS: A 40-year-old male patient had moderate unilateral nose bleeding constantly 10 times after suffering from a head injury induced by a car accident. After a bilateral massive nose bleeding for the last time, he died from hemorrhagic shock. Traumatic internal carotid artery pseudoaneurysm (TICAP) was suspected in this patient. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: A whole-body scanning was performed using PMCT and PMMRI. Then, PMCTA using left ventricular cardiac puncture was also implemented. A water-soluble contrast agent was injected into the left ventricle and pumped toward the intracranial, followed by a repeated whole-body PMCT scan. The PMCT/PMMRI detected a high-density/signal mass inside the left sphenoid sinus. The PMCTA detected a distinct leakage of the contrast agent into the left sphenoid sinus from an adjacent aneurysm of the C3 section of the left internal carotid artery. Autopsy and histology confirmed a TICAP inside the sphenoid sinus. LESSONS: This case showed that the PMI was of great value for identifying the cause of death in special cases. When vascular lesions are suspected in the body, PMI and especially the PMCTA approach may be an effective detection method.

LncRNA KCNQ1OT1 promotes the development of diabetic nephropathy by regulating miR-93-5p/ROCK2 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to play vital roles in diabetic nephropathy (DN). The aim of this study was to explore the function of mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in DN. METHODS: DN cell models were established using high glucose (HG) treatment in human glomerular mesangial cells (HGMC) and human renal glomerular endothelial cells (HRGEC). The expression levels of KCNQ1OT1, microRNA-93-5p (miR-93-5p), and Rho associated coiled-coil containing protein kinase 2 (ROCK2) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. ROCK2 and apoptosis/fibrosis-related protein levels were examined by western blot. The predicted interaction between miR-93-5p and KCNQ1OT1 or ROCK2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: KCNQ1OT1 was upregulated in DN patients and DN cell models. KCNQ1OT1 knockdown inhibited cell proliferation and fibrosis and induced apoptosis in DN cell models. MiR-93-5p was a direct target of KCNQ1OT1, and miR-93-5p inhibition restored the KCNQ1OT1 knockdown-mediated effects on cell proliferation, fibrosis and apoptosis in DN cell models. In addition, ROCK2 was identified as a target of miR-93-5p, and miR-93-5p overexpression suppressed cell proliferation and fibrosis and accelerated apoptosis by targeting ROCK2 in DN cell models. Moreover, KCNQ1OT1 regulated ROCK2 expression by binding to miR-93-5p. CONCLUSION: KCNQ1OT1 knockdown inhibited cell proliferation and fibrosis and induced apoptosis in DN by regulating miR-93-5p/ROCK2 axis, providing potential value for the treatment of DN.