Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Research on the Identification Model of Medical Damage / 法医学杂志

OBJECTIVES@#To understand the perceptions of doctors, patients and forensic examiners on the current situation of medical disputes and medical damage identification in China, and to explore the medical damage identification model that is more conducive for the resolution of medical disputes.@*METHODS@#A questionnaire was designed, and in-service clinicians, forensic examiners and inpatients in Sichuan Province and Chongqing City were randomly selected from April to November 2019. SPSS 22.0 software was used to analyze the data of various survey results.@*RESULTS@#Compared with patients (24.92%), doctors (61.72%) believed that the current doctor-patient relationship was more tense than before; both doctors and patients were more inclined to choose voluntary consultation and people's mediation to resolve medical disputes; forensic examiners have the highest level of cognition of medical and health-related laws and regulations, followed by doctors and patients; 66.72% of doctors and 78.41% of patients believed that medical damage identification was necessary, and they were more inclined to entrust forensic identification institutions; different groups all believed that forensic examiners and doctors should participate in the identification together, 80.94% of doctors believed that the appraisal institutions should be responsible for the forensic opinion, not the appraiser.@*CONCLUSIONS@#It is suggested that the Medical Association identification and forensic identification should learn from each other and formulate basic unified rules for the identification of medical damage. It is suggested to standardize the behavior of medical damage forensic identification institutions and appraisers, to improve their own appraisal level, actively invite clinical medical experts for consultation in identification, and promote the standardized, scientization of forensic identification.

Research Progress on Molecular Markers Related to Unexplained Sudden Cardiac Death and Its Forensic Application / 法医学杂志

Routine pathological examination of unexplained sudden cardiac death (USCD) lacks significant morphological characteristics. In the field of forensic medicine, molecular biology methods have been used to find the cause of death by detecting genes and research related to the mechanism of sudden cardiac death has been carried out. From the molecular pathology point of view, the application of multiple levels of biomarkers to resolve the causes of USCD has already shown potential and provides an important path for forensic identification of USCD. This article reviews the latest research progress on USCD-related genes, RNA, proteins and USCD, and summarizes forensic application.

ClC-7/Ostm1 contribute to the ability of tea polyphenols to maintain bone homeostasis in C57BL/6 mice, protecting against fluorosis.

Epidemiological investigations indicate that certain ingredients in tea bricks can antagonize the adverse effects of fluoride. Tea polyphenols (TPs), the most bioactive ingredient in tea bricks, have been demonstrated to be potent bone-supporting agents. ClC­7 is known to be crucial for osteoclast (OC) bone resorption. Thus, in this study, we investigated the potential protective effects of TPs against fluorosis using a mouse model and explored the underlying mechanisms with particular focus on ClC­7. A total of 40, healthy, 3­week­old male C57BL/6 mice were randomly divided into 4 groups (n=10/group) by weight as follows: distilled water (control group), 100 mg/l fluoridated water (F group), water containing 10 g/l TPs (TP group) and water containing 100 mg/l fluoride and 10 g/l TPs (F + TP group). After 15 weeks, and after the mice were sacrificed, the long bones were removed and bone marrow-derived macrophages were cultured ex vivo in order to perform several experiments. OCs were identified and counted by tartrate­resistant acid phosphatase (TRAP) staining. The consumption of fluoride resulted in severe fluorosis and in an impaired OC function [impaired bone resorption, and a low mRNA expression of nuclear factor of activated T-cells 1 (NFATc1), ATPase H+ transporting V0 subunit D2 (ATP6v0d2) and osteopetrosis­associated transmembrane protein 1 (Ostm1)]. In the F + TP group, fluorosis was attenuated and OC function was restored, but not the high bone fluoride content. Compared with the F group, mature OCs in the F + TP group expressed higher mRNA levels of ClC­7 and Ostm1; the transportation and retaining of Cl­ was improved, as shown by the fluorescence intensity experiment. On the whole, our findings indicate that TPs mitigate fluorosis in C57BL/6 mice by regulating OC bone resorption. Fluoride inhibits OC resorption by inhibiting ClC­7 and Ostm1, whereas TPs attenuate this inhibitory effect of fluoride.

Prolactin rs1341239 T allele may have protective role against the brick tea type skeletal fluorosis.

OBJECTIVE: Prolactin (PRL) has been reported to be associated with increased bone turnover, and increased bone turnover is also a feature of skeletal fluorosis (SF). Autocrine/paracrine production of PRL is regulated by the extrapituitary promoter and a polymorphism in the extrapituitary PRL promoter at -1149 (rs1341239) is associated with disturbances of bone metabolism in other diseases. Here, we have investigated the possibility that the rs1341239 polymorphism is associated with SF, which results from the consumption of brick tea. DESIGN: We conducted a cross-sectional study in Sinkiang, Qinghai, Inner Mongolia in China. Demography survey questionnaires were completed and physical examination and X-ray diagnoses were used to diagnose SF. Brick tea water fluoride intake (IF) and urinary fluoride (UF) were tested by an F-ion selective electrode method. A Sequenom MassARRAY system was used to determine PRL gene polymorphisms. RESULTS: Subjects who were younger than 45 years of age and carried the T allele had a significantly decreased risk of SF [OR = 0.279 (95%CI, 0.094-0.824)] compared to those carrying the homozygous G allele. This phenomenon was only observed in Kazakh subjects [OR = 0.127 (95%CI, 0.025-0.646)]. Kazakh females who carried T alleles has a decreased risk of SF [OR = 0.410 (95%CI, 0.199-0.847)]. For Kazakh subjects which IF is less than 3.5 mg/d, a decreased risk of SF was observed among the participants who carried T alleles [OR = 0.118 (95%CI, 0.029-0.472)]. Overall, subjects with 1.6-3.2 mg/L UF and carried T alleles had a significantly decreased risk of SF [OR = 0.476 (95%CI, 0.237-0.955)] compared to homozygous G allele carriers. This phenomenon was only observed in Kazakh subjects [OR = 0.324 (95%CI, 0.114-0.923)]. CONCLUSIONS: Our results suggested that the PRL rs1341239 T allele decreases the risk of brick tea SF.

Current Status of Forensic Identification for Blunt Injuries of Internal Carotid Arterial System / 法医学杂志

Internal carotid arterial system is the main source of blood supply in brain. In forensic identi-fication practice, blunt injures of internal carotid arterial system usually cause complications such as throm-bus, aneurysm and arteriovenous fistula, etc. The deaths following delayed cerebral infarction or intracra-nial haemorrhage are not rare. At present, literature of deaths caused by blunt injuries of internal carotid arterial system mainly consist of case reports in China. This paper reviews related literature and case re-ports at home and abroad, and summarizes forensic medical features and identification method of the deaths caused by such injuries. The results show that blunt injures of internal carotid arterial system are related to the direct or indirect force on head and neck, which can result in exceed physiological range traction of head and neck, incision following basicranial fracture, etc. Such injuries are common in the cases as mechanical asphyxia, cervical manipulation, traffic accident and fall, etc. The artery should be examined carefully, and the relationship among injury, disease and death should be analysed correctly when no cause of infarction and hemorrhage was found in routine examination of such cases in forensic pratice. Because of the difficulty for exposing the artery completely in autopsy, angiography can be used to infer the location when necessary for improving the scientificity and reliability of the appraisal conclusion.

Relationship between Body Height and Craniofacial Lines Measured by CT in Southwest Han Males / 法医学杂志

OBJECTIVE@#To establish regression model between craniofacial lines and body height by measuring craniofacial lines in Southwest Han males using CT and to accumulate data for the study of forensic anthropology.@*METHODS@#Head CT data of 273 Han males in Southwest were collected and 7 craniofacial lines were determined. Multiplanar reconstruction and volume rendering were performed by image post-processing software and the selected lines were measured. The relationship between each measuring indicator and body height was analyzed using SPSS 21.0 software. The regression equation of body height estimation was established and 50 samples were selected again and put into the mathematics models to verify its accuracy.@*RESULTS@#The linear regression equations of 7 lines were established (P < 0.05). The correlation coefficients of the unary linear regression equations were 0.190-0.439 and the standard errors of the estimate (SEE) were 4.597-5.023 cm. The correlation coefficients of the multiple linear regression equation were 0.494-0.524 and the SEE were 4.418-4.458 cm. The return tests showed that the highest ± 1SEE accuracy of the multiple regression equation: y = 83.959+3.589 x6+2.573 x2, were 30%; and the highest ± 2SEE accuracy of the multiple regression equation: y = 72.646+3.316 x6+1.586 x2+1.553 x4+2.211 x3, were 92%.@*CONCLUSION@#There is significant linear correlation between 7 selected lines and the stature in this study, and the plural linear regression equation established could be applied for estimating the stature of Southwest Han males.

DNA-based personal identification in disaster / 法医学杂志

The disaster is a sudden unexpected event that causes serious human injuries and deaths as well as missing persons. The main tasks of forensic DNA laboratories are to identify victim in the disaster. After reviewed the previous disasters and related studies, we proposed a new procedure of DNA identification for the use of disaster in the future, which includes preparation works, samples collection, samples storage, DNA extraction, typing, data analysis and interpretation of results. Some experiences and problems about the DNA identification are also discussed.

Analysis of Y-chromosomal biallelic polymorphisms in Sichuan Han of Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the forensic utility of Y-single nucleotide polymorphisms (SNPs) markers.</p><p><b>METHODS</b>Allele-specific PCR, restriction enzyme digestion or direct PCR were performed to examine 10 different SNP loci on Y chromosome, namely M9, M15, M45, M89, M95, M122, M134, M145, M173 and P25 in 161 Chinese Han males.</p><p><b>RESULTS</b>A total of 8 of the 10 SNPs are reported to be polymorphic in Chinese. The gene diversity for the loci showing polymorphism ranged from 0.988/0.012-0.752/0.248, with a power of discrimination 0.094-0.373. Loci M122 and M134 were the most polymorphic markers in Chinese Hans. Nine different haplogroups with frequencies from 1.2% to 51.6% were observed and 3 of the haplogroups-K*(x O2a, O3, P), O3*(x O3e) and O3e were found in 75.2% of Chinese Hans.</p><p><b>CONCLUSION</b>A comprehensive gene diversity data of Y chromosome and haplogroups were obtained in Sichuan Han population, which will be served as the base for using these Y-SNP markers in forensic medicine and individual identification in Sichuan Hans.</p>

Identification of sarcosaphagous flies by analyses the sequence of 16S rDNA / 法医学杂志

OBJECTIVE@#To solve the difficulties of identification of Sarcosaphagous flies such as Lucilia sericata (Meigen) and Lucilia cuprina (Wiedemann) which could not be identified by analyzing the 278bp and 635 bp regions of the gene encoding for cytochrome oxidase subunit I and II (CO I and CO II) in mtDNA.@*METHODS@#Specimens were collected from the corpses of rabbits on the grassland in Huhhot and Chengdu, the sequences of 551 bp region of 16S rDNA of their mtDNA were analyzed, the multiple-alignment program DNAMAN(version 4.0) and MEGA 2.1 sofeware were employed for sequence alignments neighbour-joining tree construction.@*RESULTS@#Lucilia sericata (Meigen) and Lucilia cuprina (Wiedemann) were distinguished successfully by sequence analysis of The 551 bp region of the gene of 16S rDNA.@*CONCLUSION@#The 551 bp region of the gene of 16S rDNA of sarcosaphagous flies can be used for identifying them on species level effectively. It is likely to be a successful compliment to identify the sarcosaphagous flies by sequence analysis of CO I and CO II in mtDNA.

Genetic polymorphisms of four STR loci on chromosome X and their forensic applications in a Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To add DXS7133, GATA198A10, DXS9896 and DXS6797 to the panel of forensically validated X chromosome markers, and apply the multiplex amplification system to a population study and forensic analysis on the Hans of Chengdu.</p><p><b>METHODS</b>The PCR products were detected by the polyacrylamide gel electrophoresis and silver staining method. Hardy-Weinberg equilibrium of females was tested and every forensically interested value was calculated.</p><p><b>RESULTS</b>Sequencing revealed that their common sequence motifs were tetranucleotide repeats. Population genetic data were obtained by analyzing 120 unrelated females and 100 males from Chengdu Han ethnic group. In this population, DXS7133, GATA198A10, DXS9896 and DXS6797 exhibited 6, 6, 11, 8 distinguishable alleles respectively. Chi-square test demonstrated that genotype frequencies in females did not depart from Hardy-Weinberg equilibrium. Power of discrimination for female samples for the four loci were 0.7962, 0.8021, 0.9675, and 0.9444. The parentage testing in 32 cases revealed a typical X-linked inheritance and no mutations.</p><p><b>CONCLUSION</b>DXS7133, GATA198A10, DXS9896 and DXS6797, which are highly polymorphic in Chengdu Han population, are appropriate for individual identification and paternity testing involving a female child.</p>