The down-regulation of STC2 mRNA may serve as a biomarker for death from mechanical asphyxia.

Death from mechanical asphyxia (DMA) is a common cause of death in forensic pathology. However, due to the lack of biomarkers, the authentication of DMA now relies on a series of non-specific signs, which may cause troubles in the judicial trials, especially when the criminal scene is not fully elucidated. To search for the potential biomarkers for DMA, brain samples of DMA and craniocerebral injury groups were screened by microarray. The obtained mRNAs were validated by animal and human samples. Primary cell culture was conducted to explore the biochemical changes under hypoxia. 415 differentially expressed mRNAs between two groups were discovered. Ten mRNAs were examined in both human and animal samples died of different causes of death. Stanniocalcin-2 (STC2) showed significant down-regulation in DMA samples compared to other groups, regardless of PMI, age, or temperature. Cellular experiments indicated that ROS level peaked after 15-min-hypoxic culture, when the expression level of STC2 was significant down-regulated simultaneously. The ER-stress-related proteins also showed potential connection with STC2. In general, it is indicated that the down-regulation of STC2 may serve as a biomarker for DMA.

Sex Estimation of Medial Aspect of the Ischiopubic Ramus in Adults Based on Deep Learning.

OBJECTIVES: To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population. METHODS: The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc. RESULTS: When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%. CONCLUSIONS: The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.

Research Progress on Molecular Changes in Pulmonary Hypoxia and Cause of Death Identification in Mechanical Asphyxia.

Lung is the largest organ of the respiratory system. During hypoxia, pulmonary cells undergo rapid damage changes and activate the self-rescue pathways, thus leading to complex biomacromolecule modification. Death from mechanical asphyxia refers to death due to acute respiratory disorder caused by mechanical violence. Because of the absence of characteristic signs in corpse, the accurate identification of mechanical asphyxia has always been the difficulty in forensic pathology. This paper reviews the biomacromolecule changes under the pulmonary hypoxia condition and discusses the possibility of application of these changes to accurate identification of death from mechanical asphyxia, aiming to provide new ideas for related research.

Distinguishing Asphyxia from Sudden Cardiac Death as the Cause of Death from the Lung Tissues of Rats and Humans Using Fourier Transform Infrared Spectroscopy.

The ability to determine asphyxia as a cause of death is important in forensic practice and helps us to judge whether a case is criminal. However, in some cases where the deceased has underlying heart disease, death by asphyxia cannot be determined by traditional autopsy and morphological observation under a microscope because there are no specific morphological features for either asphyxia or sudden cardiac death (SCD). Here, Fourier transform infrared (FTIR) spectroscopy was employed to distinguish asphyxia from SCD. A total of 40 lung tissues (collected at 0 h and 24 h postmortem) from 20 rats (10 died from asphyxia and 10 died from SCD) and 16 human lung tissues from 16 real cases were used for spectral data acquisition. After data preprocessing, 2675 spectra from rat lung tissues and 1526 spectra from human lung tissues were obtained for subsequent analysis. First, we found that there were biochemical differences in the rat lung tissues between the two causes of death by principal component analysis and partial least-squares discriminant analysis (PLS-DA), which were related to alterations in lipids, proteins, and nucleic acids. In addition, a PLS-DA classification model can be built to distinguish asphyxia from SCD. Second, based on the spectral data obtained from lung tissues allowed to decompose for 24 h, we could still distinguish asphyxia from SCD even when decomposition occurred in animal models. Nine important spectral features that contributed to the discrimination in the animal experiment were selected and further analyzed. Third, 7 of the 9 differential spectral features were also found to be significantly different in human lung tissues from 16 real cases. A support vector machine model was finally built by using the seven variables to distinguish asphyxia from SCD in the human samples. Compared with the linear PLS-DA model, its accuracy was significantly improved to 0.798, and the correct rate of determining the cause of death was 100%. This study shows the application potential of FTIR spectroscopy for exploring the subtle biochemical differences resulting from different death processes and determining the cause of death even after decomposition.

Comparison of Three Methods for Skeleton Age Estimation.

OBJECTIVES: To find the appropriate method for age estimation for different ages and sexes. METHODS: The costal cartilage, sternum and pubic symphysis of 91 unknowns from 2000 to 2020 from the Forensic Department of the Criminal Investigation Team of Shanghai Public Security Bureau were collected. Costal cartilage, sternal and pubic symphysis inferences were used to estimate the age, and the consistency between the estimated results and the actual physiological age of the unknowns was tested. The accuracy of age estimation of different samples was compared, and the relationship between accuracy and age and sex was analyzed. RESULTS: Using the costal cartilage method, the inference errors of males, females and the whole population under 40 years old were (0.608±2.298) years, (0.429±1.867) years and (0.493±2.040) years, while those over 40 years old were (-1.707±3.770) years, (-3.286±4.078) years and (-2.625±4.029) years. The differences between different age groups in these three populations were statistically significant (P<0.05). Using the sternum method, the inference errors of males and females under the age of 40 were (0.921±3.019) years and (0.452±1.451) years, while those over the age of 40 were (-5.903±5.088) years and (-1.429±2.227) years. The differences between different age groups in males and females were statistically significant (P<0.05). Using the pubic symphysis method, the inference errors of males and females under 40 years old were (-0.204±1.876) years and (0.238±2.477) years, while those over 40 years old were (1.500±2.156) years and (-2.643±4.270) years. The differences between different age groups in males and females were statistically significant (P<0.05). Using the sternum method and pubic symphysis method for age estimation of over 40 years old, the difference between different sexes was statistically significant (P<0.05). CONCLUSIONS: All three methods of age estimation are stable and effective and more accurate for people under 40 years old. For age estimation of unknowns over 40 years old, the pubic symphysis method is preferred in males and the sternum method is preferred in females.

Forensic Examination of Six Homicide Injection Cases.

OBJECTIVES: To retrospectively analyze homicide cases of death after injection and provide reference for forensic identification. METHODS: Six homicide cases of death after injection which were investigated by the Criminal Investigation Team of Shanghai Public Security Bureau were collected and analyzed, including case situation, scene investigation, autopsy and other materials. RESULTS: The 6 cases were premeditated crimes, 5 cases took place in private spaces, and 5 cases involved the victims approached by suspects' decoy. There were no obvious abnormalities at the scene of the 6 cases. In 6 cases, the victim's body surface injury was mild or no, lividity color was abnormal, and the needlestick injury showed different manifestations from conventional medical measures. CONCLUSIONS: Death after injection is a highly concealed crime and easy to be ignored. For the suspected injection injury found in autopsy, it is necessary to carefully examine, identify and analyze, be alert to the situation of injecting poison (drug) and do a good job in evidence fixation and material extraction.

Pharmacokinetics, Bioequivalence, and Safety Studies of Prucalopride in Healthy Chinese Subjects.

The objectives of the present study were to evaluate the bioequivalence of 2 tablet formulations of prucalopride, generic and branded, and to investigate relevant pharmacokinetic and safety profiles. This study was designed as a randomized, open-label, fasting, single-dose, crossover, and dual-period trial. After overnight fasting, 12 subjects were given prucalopride tablets via oral administration, and blood specimens were obtained up to 96 hours after dosing. Prucalopride concentrations in plasma were measured using ultraprecision liquid chromatography-tandem mass spectrometry followed by calculation of pharmacokinetic parameters. The safety of prucalopride was assessed throughout the study. The pharmacokinetics of prucalopride can be defined as a 2-compartment model with a long elimination phase. No significant differences were observed between the pharmacokinetic profiles of the generic and branded prucalopride tablets. Bioequivalence was evaluated using 90%CIs for the ratio test/reference of log area under the concentration-time curve over 96 hours, log area under the concentration-time curve to infinity, and log peak concentration from generic and branded tablets, which were 100.06-109.94%, 100.63-110.32%, and 95.84-113.08%, respectively. During administration of the medication, there were 18 adverse events in 6 subjects in the test formulation group and 19 cases of adverse events in 6 subjects in the reference formulation group (P > .05). No severe adverse effects were detected. These results suggest that generic and branded prucalopride tablets are bioequivalent and show similar safety profiles.

Expression of Glucose-Regulated Protein 78 and miR-199a in Rat Brain After Fatal Ligature Strangulation.

The roles of endoplasmic reticulum (ER) stress and microRNA in the brain tissue after fatal mechanical asphyxia have not been clearly elucidated. We examined the expression of glucose-regulated protein 78 (GRP78), the key regulator of unfolded protein response, and miR-199a in the brain tissues of rats subjected to fatal ligature strangulation to understand the roles of ER stress and microRNA in ligature strangulation. The expressions of GRP78 and miR-199a in rat cortex, hippocampi, and midbrain were measured by immunohistochemistry and Western blot analysis in a rat model of ligature strangulation. Furthermore, the levels of miR-199a-3p and miR-199a-5p were detected by real-time fluorescent quantitative polymerase chain reaction. Glucose-regulated protein 78 was highly expressed in the cortex and midbrain in the ligature strangulation group (P < 0.01) when compared with the control group. The expression of GRP78 in the hippocampi showed no significant difference between the 2 groups. miR-199a-3p in the cortex and midbrain was significantly down-regulated in the ligature strangulation group (P < 0.01). However, miR-199a-5p in each brain region showed no significant difference between the 2 groups. In conclusion, ER stress was involved in the physiological and pathological processes of ligature strangulation. Furthermore, upstream miR-199a may play an important regulatory role in mechanical asphyxia.

Astrocytic clasmatodendrosis in the cerebral cortex of methamphetamine abusers.

Postmortem investigation of methamphetamine (MA) abuse is an important task in forensic pathology. The present study investigated morphological changes in the astrocytes in the parietal cerebral cortex of MA abusers. Glial fibrillary acidic protein immunoreactivity in the cerebral cortex was examined in forensic autopsy cases for MA-detected group and control group. Clasmatodendrotic astrocytes (including those with swollen cell bodies and disintegrating distal processes) were frequently observed in the cerebral cortex of MA abusers. Quantitative analysis using a colour image processor showed a concomitant increase in the astrocyte area and astrocyte-to-vessel area ratio (size and number of astrocytes) in the grey matter in acute MA fatality and other MA-involved cases, although the astrocyte area (size) was also increased in cases of asphyxiation. The total astrocyte area (size) in the white matter was significantly higher in MA fatalities and asphyxia than in the other groups involving MA abusers. Those indices were independent of blood MA level, age, sex, survival or postmortem time. These observations suggest the increasing number and hypertrophic changes of astrocytes in the grey matter in MA abusers can be the outcome of long-term abuse, while disintegrating distal processes may exist only in acute fatal MA intoxication.

Fatal mechanical asphyxia induces changes in energy utilization in the rat brain: An (18)F-FDG-PET study.

PURPOSE: This study was designed to evaluate changes in brain glucose metabolism in rats following ligature strangulation. MATERIALS AND METHODS: Thirteen male Wistar rats were used in the present study, divided into control (n=7) and asphyxia groups (n=6, ligature strangulation). Positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) was used to evaluate brain glucose metabolism. Rats were scanned for PET-CT, and image data co-registered with a T2WI MRI template using SPM8 software. Image J was employed to draw regions of interest (ROIs) from the MRI template and acquire ROI activity information from the PET images. RESULTS: In the asphyxia group vs. controls, (18)F-FDG uptake (FU) was decreased in the substantia nigra (25.26%, p<0.001), rhombencephalon (pons/medulla oblongata, 13.92%, p<0.01), hypothalamus (22.06%, p<0.01), ventral tegmentum (10.12%, p<0.05) and amygdala (12.74%, p<0.05); however, FU was increased in motor (18.21%, p<0.05) and visual cortices (19.2%, p<0.05). CONCLUSIONS: The glucose metabolism distribution map in the asphyxiated rat brains were substantially changed versus controls. PET with (18)F-FDG can demonstrate excitement and inhibition of different brain areas even in cases of ligature strangulation.

A case-control study of sudden unexplained nocturnal death syndrome in the southern Chinese Han population.

To study the epidemiological characteristics of sudden unexplained nocturnal death syndrome (SUNDS) in the southern Chinese Han population during 2007 to 2013, we gathered 879 SUNDS victims from Dongguan City and in the Longgang District in Shenzhen City as the case group then selected 879 all-cause death cases, adopting a 1:1 pair method, as the control group I and collected 8142 all-cause death cases from the Bao'an District in Shenzhen City as the control group II, simultaneously. Case information collected was statistically analyzed. The annual incidence of SUNDS is 1.02 and 2.23 per 100,000 person-years for Dongguan City and in the Longgang District, respectively. The number of male and female victims is drastically different, with a ratio of 13.92:1, whereas the incidence between the 2 sexes is significantly different (χ2 = 78.734, P < 0.01), with an odds ratio value of 11.32 (95% confidence interval, 5.75-22.28). The age of death of SUNDS cases ranges from 17 to 55 years with a median age of 35 years; furthermore, the difference of distribution of age of death between the SUNDS victims and the all-cause death population is significant (χ2 = 767.12, P < 0.001). The birthplace of SUNDS victims is distributed throughout 27 provinces of China, but the difference between the SUNDS victims and the all-cause death population is not significant (χ2 = 27.273, P > 0.05). The monthly incidence of SUNDS is relatively higher from March to June, whereas the difference of monthly distribution between SUNDS victims and all-cause death population is significant (χ2 = 9.869, P < 0.05), with an odds ratio value of 1.42 (95% confidence interval, 1.14-1.76). Although the majority of SUNDS occurred during midnight sleep, they were mostly discovered from 7 to 9 am once the inmates or spouses woke in the morning. A total of 97.74% of the SUNDS victims were blue-collar factory workers with a high-intensity labor and poor education background. This investigation confirmed the stability of epidemiological characteristics of SUNDS in South China and implicated that risk factors of this fatal disease still exist. The efficient strategy of early identification such as molecular diagnosis for SUNDS is extremely urgently required.