Bibliometrics Analysis in English and Chinese Literature on Drowning in Forensic Medicine from 1991 to 2020.

OBJECTIVES: To explore the research hotspots and development trends of the field of forensic drowning from 1991 to 2020 by bibliometrics methods. METHODS: Based on Web of Science, CNKI database, Wanfang Data knowledge service platform, python 3.9.2, CiteSpace 5.8.R3, Gephi 0.9.2, etc. were used to analyze the publishing trends, countries/regions, institutions, authors and topics of the study on drowning. RESULTS: A total of 631 English literature were obtained, including 59 articles from Chinese authors, and 386 Chinese literature were obtained. The Chinese and English journals with the largest number of related literatures were Chinese Journal of Forensic Science (80 articles) and Forensic Science International (106 articles), respectively. Japan published the most articles in English, and China ranked third. Osaka City Univ (Japan, 28 articles) published the most English articles, and Guangzhou Forens Sci Inst (China, 22 articles) ranked second. Among Chinese literature, Guangzhou Forens Sci Inst (32 articles) published the most. The topic analysis of Chinese and English literature showed that diatom examination, virtual autopsy, postmortem biochemical examination, the nature of death, and postmortem submersion interval were the hot spots of current research, but English literature had more studies on new technologies and methods, while Chinese literature was more inclined to practice, application and experience summary. CONCLUSIONS: The number of literature in forensic medicine on drowning is relatively stable. The scope of international and domestic collaborations in this field is still limited. The automated examination of diatoms, the establishment of diatom DNA barcodes and virtual autopsy will be the most important research hotspots in the coming period and are expected to achieve breakthroughs in drowning diagnosis, drowning location inference, postmortem submersion interval estimation, etc.

Forensic Analysis of 9 Poisoning Death Cases Caused by Oral Administration of Diphenidol.

OBJECTIVES: To analyze the characteristics of diphenidol poisoning cases and to provide clues and technical means for the identification of such cases. METHODS: Biological samples of 9 deaths caused by diphenidol poisoning were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the characteristics of these cases were analyzed retrospectively. RESULTS: Most of the deaths caused by diphenidol poisoning were young females. The dosage was between 60 and 300 tablets, and the mass concentration of diphenidol in the postmortem blood ranged from 0.87 to 99.00 µg/mL. There was no correlation between the dosage and the concentration of diphenidol in the blood. CONCLUSIONS: Diphenidol poisoning has the characteristics of high concealment and lethality. More attention should be paid to suicide cases, and diphenidol should be recommended as a routine detection item to avoid missing detection.

The role of HINT1 protein in morphine addiction: An animal model-based study.

Drug addiction is a recurrent, chronic brain disease. The existing treatment methods have limitations, such as poor adherence and inability to completely avoid relapse. Histidine triad nucleotide-binding protein 1 (HINT1) is involved in many neuropsychiatric diseases, such as schizophrenia, pain, and drug dependence. Studies have confirmed that there is a genetic link between HINT1 and addictions such as nicotine and cocaine. However, there is no research on the role of HINT1 protein in morphine addiction at home and abroad. Thus, we designed this project by constructing different types of morphine addiction animal models, including conditioned place preference and behavioral sensitization. We comprehensively examined the participation of HINT1 protein in key brain regions associated with addiction, including prefrontal cortex, nucleus accumbens, corpus striatum, and hippocampus, in different stages of different models. In addition, we used HINT1 knockout mice to establish the above models and physical dependence model to investigate the effect of HINT1 protein deletion on morphine addiction-related behaviors. We found that HINT1 has varying degrees of involvement in different stages of multiple addictive animal models. The absence of HINT1 can attenuate morphine-mediated addictive behavior to a certain extent and can alleviate the withdrawal symptoms of morphine.

Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex-different manner.

Pain is a complex and subjective experience. Previous studies have shown that mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a role of the D3 receptor in modulation of nociception. Given that there are sex differences in pain perception, there may be differences in responses to nociceptive stimuli between male and female D3RKO mice. In the current study, we examined the role of the D3 receptor in modulating nociception in male and female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was performed at different temperatures including 52°C, 55°C, and 58°C. The von Frey hair test was applied to evaluate mechanical pain. And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice generally exhibited longer latencies at each of the three temperatures. Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the temperature was 55°C, while for the female mice, there was a statistical difference between genotypes when the test condition was 52°C. In the von Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the formalin test, the male D3RKO mice displayed a similar nociceptive behavior as their sex-matched WT littermates, whereas significantly depressed late-phase formalin-induced nociceptive behaviors were observed in the female mutants. These findings indicated that the D3 receptor affects nociceptive behaviors in a sex-specific manner and that its absence induces more analgesic behavior in the female knockout mice. © 2016 Wiley Periodicals, Inc.

Emerging Roles of Histidine Triad Nucleotide Binding Protein 1 in Neuropsychiatric Diseases.

The histidine triad nucleotide binding protein1(HINT1),which belongs to the histidine triad(HIT) enzyme superfamily,exerts its enzymic activities as hydrolase or transferase. Its physiological functions are still unclear. HINT1 protein is expressed in various tissues and plays an important role in transcription and signal transduction. Earlier studies have identified HINT1 as a haplo-insufficient tumor suppressor. Other evidences indicate that HINT1 is involved in a wide variety of physiological processes,some of which are irrelevant with its basic enzymic activities. Investigations recently suggest that HINT1 is closely related to many peripheral and central nervous system diseases,and plays a vital role in some of neuropsychiatric diseases such as inherited peripheral neuropathies,schizophrenia,mood disorder,drug addiction,and Down's syndrome. In this review,the role of HINT1 in above-mentioned neuropsychiatric disorders was summarised,and the research findings of HINT1 in each of the above diseases were summarized and analyzed,in order to provide some guidance for further research on this protein.

Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

[Histidine triad nucleotide-binding protein 1 and human diseases].

Histidine triad nucleotide-binding protein 1 (HINT1) is a member of a superfamily of histidine triad proteins named by the conserved nucleotide-binding motif histidine-x-histidine-x-histidine-xx, in which x represents hydrophobic amino acid. HINT1 is implicated in pathological progress of many human diseases including cancer and schizophrenia; however, little is known about the essential role and pathological consequences of HINT1 in cellular physiology and diseases. Therefore, we summarize the structure, distribution, and physiological function of HINT1 in cells and tissues as well as the correlation between HINT1 and human diseases.

HINT1 deficiency in aged mice reduces anxiety-like and depression-like behaviours and enhances cognitive performances.

Histidine triad nucleotide-binding protein 1 (HINT1) is regarded as a haplo-insufficient tumour suppressor and is closely associated with many neuropsychiatric disorders, including major depressive disorders. In addition, HINT1 knockout (KO) mice exhibit anxiolytic-like behaviour, antidepression-like behaviour, and enhanced cognitive performance in several studies. However, it is still unclear whether aging contributes to these changes in the emotion and cognition of HINT1 KO mice. This study examined the role of aging in anxiety-like and depression-like behaviours and cognition behaviours in aged HINT1 KO mice compared with young HINT1 KO mice and their wild-type littermates, along with a number of molecular biological methods. In a battery of behavioural tests, aged wild-type mice showed increased anxiety-like and depression-like behaviours and decreased cognitive performance, along with lower expression levels of glutathione peroxidase, enhanced amount of malondialdehyde, and decreased expression levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus and PFC compared to young wild-type mice. HINT1 KO mice showed reduced anxiety-like and depression-like behaviours and enhanced cognitive performance compared to age-matched wild-type mice. In addition, HINT1 KO mice also showed increased GSH-Px and superoxide dismutase, and decreased malondialdehyde, together with enhanced BDNF and Trk-B expression in the hippocampus and PFC. However, when compared with young HINT1 KO mice, aged HINT1 KO mice did not show increased anxiety-like and depression-like behaviours. And there are no differences in the expression level of superoxide dismutase, malondialdehyde, BDNF, and Trk-B between aged and young HINT1 KO mice. In summary, HINT1 deficiency can counteract age-related emotion and cognition dysfunction.

Differentiation of AFS cells derived from the EGFP gene transgenic porcine fetuses.

We have obtained the EGFP (enhanced green fluorescence protein) gene transgenic porcine fetuses before. The aims of this study were (i) to determine whether stem cells could be isolated from amniotic fluid of the transgenic porcine fetuses, and (ii) to determine if these stem cells could express EGFP and differentiate in vitro. The results demonstrated that stem cells could be isolated from amniotic fluid of the EGFP gene transgenic porcine fetuses and could express EGFP and differentiate in vitro. Undifferentiated AFSs (amniotic fluid-derived stem cells) expressed POU5F1, THY1 and SOX2, while the following differentiation cells expressed markers for chondrogenic (COL2A1), osteogenic (osteocalcin and osteonectin) and neurogenic cells such as astrocyte (GFAP), oligodendrocyte (GALC) and neuron (NF, ENO2 and MAP).

Differentiation and characteristics of the enhanced green fluorescent protein gene transgenic goat neural stem cells cultured in attached and non-attached plates.

The aims of this study were (i) to determine whether NSCs (neural stem cells) could be isolated from the brain of embryonic day 98 fetal goat, (ii) to determine if these stem cells have the capability of multipotent differentiation following transfection with a reporter gene, EGFP (enhanced green fluorescent protein) and (iii) to study the characteristics of the stem cells cultured in attached and non-attached plates. NSCs were isolated from embryonic day 98 fetal goat brain, transfected with EGFP gene using lipofection, and subcultured in attached and non-attached plates respectively. The transgenic stem cells were induced to differentiate into osteogenic and endothelial cells in vitro respectively. Markers associated with undifferentiated NSCs and their differentiated cells were tested by RT-PCR (reverse transcription-PCR). The results demonstrated that stem cells could be isolated from embryonic day 98 fetal goat brain, and EGFP gene could be transfected into the cells. The transgenic NSCs were capable of self-renewal, a defining property of stem cells, and were grown as free-floating neurospheres in non-attached plates. When the neurospheres were transferred and cultured in attached plates, cells migrate from the neurospheres and are grown as spindle cells. The stem cells were grown as quasi-circular cells when the single stem cells were cultured in attached plates. Both the NSCs cultured in non-attached and attached plates could express Hes1 (hairy and enhancer of split 1), Oct4 (octamer-binding protein 4), Nanog, Sox2 [SRY (sex-determining region Y)-box 2] and Nestin, while following differentiation cells expressed markers for osteogenic cells (Osteocalcin+ and Osteonectin+) and endothelium (CD34+ and eNOS+). The results demonstrated that the goat EGFP gene transgenic NSCs have the capability of multipotent differentiation, which means that the transgenic NSCs may be useful in cell transplantation studies in future.

[Epigenetic mechanisms of the influence of maternal care on off spring development].

It has been demonstrated that the social environment early in life has a long lasting effect on the physical and psychological health of the human body. However, understanding of the relationship between early life experiences, such as maternal care behavior, and life-long cognitive and emotional health can only rely on the studies on animal models. In this paper, we summarized the maternal care effects on both defensive responses to stress and reproductive behavior in rat, and explored the possible underlying epigenetic mechanisms for these effects. Based on this model, we further investigated the significance of such epigenetic effects on human mental health.

[Structural plasticity associated with drugs addiction].

An essential feature of drug addiction is that an individual continues to use drug despite the threat of severely adverse physical or psychosocial consequences. Persistent changes in behavior and psychological function that occur as a function of drugs of abuse are thought to be due to the reorganization of synaptic connections (structural plasticity) in relevant brain circuits (especially the brains reward circuits). In this paper we summarized evidence that, indeed, exposure to amphetamine, cocaine, nicotine or morphine produced persistent changes in the structure of dendrites and dendritic spines on cells in relevant brain regions. We also approached the potential molecular mechanisms of these changes. It is suggested that structural plasticity associated with exposure to drugs of abuse reflects a reorganization of patterns of synaptic connectivity in these neural systems, a reorganization that alters their operation, thus contributing to some of the persistent sequela associated with drug use-including addiction.

HINT1 Is Involved in the Chronic Mild Stress Elicited Oxidative Stress and Apoptosis Through the PKC ε/ALDH-2/4HNE Pathway in Prefrontal Cortex of Rats.

Major depressive disorder (MDD) is a severe, highly heterogeneous, and life-threatening psychiatric disease which affects up to 21% of the population worldwide. A new hypothesis suggests that the mitochondrial dysfunction causing oxidative stress (OS) and dysregulation of apoptosis in brain might be one of the key pathophysiological factors in MDD. Histidine triad nucleotide binding protein 1 (HINT1), which was first supposed to be protein kinase C (PKC) inhibitor, has been gradually demonstrated to be involved in diverse neuropsychiatric diseases. It still remains elusive that how HINT1 involves in depression. The present study utilized a rat model exposed to chronic mild stress (CMS) to explore the involvement of HINT1 in depression. Face validity, construct validity and predictive validity of CMS model were comprehensive evaluated in this study. Behavioral tests including sucrose preference test, open field test, and elevated plus maze and forced swimming test revealed that stressed rats displayed elevated level of anxiety and depression compared with the controls. CMS rats showed a significant decrease of superoxide dismutase, and a marked increase malondialdehyde levels in prefrontal cortex (PFC). We also found the CMS rats had elevated expression of HINT1, decreased levels of phosphorylated-PKC ε and aldehyde dehydrogenase-two (ALDH-2), and accumulated 4-hydroxynonenal (4HNE) in PFC. Moreover, CMS increased the levels of cleaved caspase-3 and Bax, and decreased the level of Bcl-2 in PFC. The alterations in behavior and molecule were prevented by antidepressant venlafaxine. These results demonstrated that HINT1 was involved in the CMS elicited OS and apoptosis in PFC, probably through the PKC ε/ALDH-2/4HNE pathway. The results suggest that the suppression of HINT1 might have potential as a novel therapeutic strategy for depression.

The role of HINT1 in methamphetamine-induced behavioral sensitization.

BACKGROUND: Drug addiction is a chronically relapsing disorder in humans yet the underlying mechanism remained unclear. Recent studies suggested that histidine triad nucleotide binding protein1 (HINT1) may play significant roles in diverse neuropsychiatric diseases including drug addiction. METHODS: In the current study, we used different batches of mice to establish different stages of methamphetamine (METH)-induced behavioral sensitization (BS) to explore the dynamic changes throughout the process of addiction in different brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), and hippocampus (Hip). In addition, we used HINT1 knockout (KO) mice to investigate the effect of HINT1 protein deletion on METH-induced BS. RESULTS: We found that in PFC of the METH group mice, the HINT1 expression level initially increased after development phase, and then dropped to the normal level during expression phase. However, there was no statistical difference in the HINT1 expression level in the other three encephalic regions (NAc, CPu, and Hip). The absence of HINT1 could promote METH-mediated addictive behavior to a certain extent, while the significant difference between genotypes only occurred in the development phase. CONCLUSIONS: Using the new technique, hip fractures were correctly predicted in 78% of cases compared with 36% when using the T-score. The accuracy of the prediction was not greatly reduced when using SSM and SAM (78% and 74% correct, respectively). Various geometric and BMD distribution traits were identified in the fractured and non-fractured groups.

Does genetic mouse model of constitutive Hint1 deficiency exhibit schizophrenia-like behaviors?

The histidine triad nucleotide binding protein 1 (HINT1) is closely related to many neuropsychiatric disorders. Clinical studies supported that mutations in the Hint1 gene correlated potentially with schizophrenia. In addition, Hint1 gene knockout (KO) mice exhibited hyperactivity induced by amphetamine and apomorphine. However, it is still unclear whether this animal model exhibits schizophrenia-like behaviors and, if so, their underlying mechanisms remain to be elucidated. Thus, our study sought to evaluate schizophrenia-like behaviors in Hint1-KO mice, and explore the associated changes in neuronal structural plasticity and schizophrenia-related molecules. A series of behavioral tests were used to compare Hint1-KO and their wild-type (WT) littermates, alongside a number of morphological and molecular biological methods. Relative to WT mice, Hint1-KO mice exhibited reduced social interaction behaviors, aggressive behavior, sensorimotor gating deficits, apathetic and self-neglect behaviors, and increased MK-801-induced hyperactivity. Hint1-KO mice also showed partly increased dendritic complexity in the hippocampus (Hip) relative to WT mice. Total glutamate was decreased in the medial prefrontal cortex, nucleus accumbens (NAc), and Hip of KO mice. Expression of NR1, NR2A, and D4R was decreased whereas that of D1R was increased in the NAc of KO relative to WT mice. The expression level of NR2B was increased whereas that of D1R was decreased in the Hip of KO mice. Hint1-KO mice exhibited schizophrenia-like behaviors. Partly increased dendritic complexity and dysfunction in both the dopaminergic and glutamatergic systems may be involved in the abnormalities in Hint1-KO mice.

Worldwide tendency and focused research in forensic anthropology: A bibliometric analysis of decade (2008-2017).

PURPOSE: The objective of this study was to illustrate the global research productivity and tendency of forensic anthropology in recent ten years (2008-2017) by bibliometric analysis. METHODS: "Forensic anthropology" was used as the Medical Subject Headings term and topic in PubMed and Web of Science Core Collection. RESULTS: As 5130 articles retrieved, two independent investigators evaluated all of them respectively. After restricting the published year, excluding duplicated and irrelevant articles, 1663 articles were available. The total of 219 countries and regions contributed to this research and the United States was the most productive country. There were 201 peer-reviewed journals including all of articles and two of them were identified as core journals according to Bradford's law. Eight of the top 10 productive authors were from developed countries. The top 10 cited articles were published by authors from developed countries with half in the United States. Sex estimation and age estimation were the most popular topics. CONCLUSIONS: With the basic and recognized methodology administered in this study, it provided a relative broad view to evaluate the scientific research capacity of forensic anthropology and reveal the worldwide tendency in this field.

A bibliometric analysis of forensic entomology trends and perspectives worldwide over the last two decades (1998-2017).

Through bibliometric analysis, this study aimed to reveal worldwide research productivity and trends in forensic entomology over the last two decades (1998-2017). As "forensic entomology" is yet to be established as a Medical Subject Headings term, we used "forensic entomology" and "legal entomology" as topics in Web of Science Core Collection, Medline, and PubMed searches. Two independent investigators retrieved and evaluated 3165 articles. After determining the cutoff for publication year and excluding repeated or irrelevant articles, 1087 articles remained for analysis. In terms of papers published, the United States was the most productive among the 136 countries (and disputed regions) that contributed to forensic entomological research. Among the 179 journals that published all articles, two were considered core journals based on Bradford's Law (i.e., the two journals published the majority of relevant articles). Most studies focused on the order Diptera and family Calliphoridae. The most common topics were estimation of postmortem interval and species identification.

[The role of epigenetic regulation in etiology of major depressive disorder].

Epigenetics refers to the heritable, but reversible, regulation of various biological functions mediated principally through changes in DNA methylation and chromatin structure derived from histone modification. Recent research indicated that epigenetic mechanisms may play vital role in etiology of major psychosis, such as schizophrenia, bipolar disorder and drug addiction. With brief introduction of epigenetic molecular mechanisms and relevance of epigenetics to human common diseases, this review focuses on epigenetic hypothesis and some supporting evidence which are recently emerged in major depressive disorder (MDD).

[Sequence polymorphism of mtDNA HVR Iand HVR II of Oroqen ethnic group in Inner Mongolia].

Venous blood samples from 50 unrelated Oroqen individuals living in Inner Mongolia were collected and their mtDNA HVR I and HVR II sequences were detected by using ABI PRISM377 sequencers. The number of polymorphic loci, haplotype, haplotype frequence, average nucleotide variability and other polymorphic parameters were calculated. Based on Oroqen mtDNA sequence data obtained in our experiments and published data, genetic distance between Oroqen ethnic group and other populations were computered by Nei's measure. Phylogenetic tree was constructed by Neighbor Joining method. Comparing with Anderson sequence, 52 polymorphic loci in HVR I and 24 loci in HVR II were found in Oroqen mtDNA sequence, 38 and 27 haplotypes were defined herewith. Haplotype diversity and average nucleotide variability were 0.964+/-0.018 and 7.379 in HVR I, 0.929+/-0.019 and 2.408 in HVR II respectively. Fst and dA genetic distance between 12 populations were calculated based on HVR I sequence, and their relative coefficients were 0.993(P < 0.01). A phylogenetic tree was constructed based on genetic distances and included Oroqen, Taiwan and South Han population in a clade, which indicated near genetic relation between them, and far relation with northern Han, Mongolian and other foreign populations. The genetic polymorphism of mtDNA HVR I and HVR II in Oroqen ethnic group has some specificities compared with that of other populations. These data provide a useful tool in forensic identification, population genetic study and other research fields.

[Gene expression profiling in drug addicted brain].

Drug addiction, a chronic brain disease caused by interaction of in vitro drug toxification and in vivo gene susceptibility, has been widely studied but its underlining mechanism is so far been elucidated. A major goal in this field is to identify drug-induced molecular changes and their effects on brain function. By the advance of high throughput technologies in genomics and transcriptomics, the whole gene expression profile in addicted brain could be obtained and proved to be a very powerful tool to unclose the molecular mechanism underlying the addiction biology context. Here, we summarized the progress of serial analysis of gene expression (SAGE) and microarray, as well as their application in drug addiction.