[QARS1 gene related glutaminyl-tRNA synthetase deficiency syndrome: report of three cases and a review of literature].

Objective: To investigate the clinical characteristics, treatment and prognosis of QARS1 gene related glutaminyl-tRNA synthetase deficiency. Methods: To summarize and analyze the clinical manifestations, imaging, laboratory examination, genetic variant characteristics and treatment of three patients from the Fujian Medical University Affiliated Union Hospital, the 900th Hospital of People's Liberation Army, the First Medical Center of People's Liberation Army General Hsopital carrying compound heterozygous variations in QARS1 gene with a long-term follow-up in China. A literature search was conducted using Wanfang, Weipu, China National Knowledge Infrastructure (CNKI) and Pubmed databases with the keywords "QARS", "QARS1" and "glutaminyl-tRNA Synthetase"(up to December 2019). Results: Case 1, a female 53 days of age, was admitted to the Fujian Medical University Affiliated Union Hospital for treatment because of the complaint of repetitive seizures for one month after birth and fever for one day. The seizure occurred within the first 2 hours of life with multiple forms and often had a status as persisted from hours to days. The seizures were resistant to many anti-epilepsy drugs (AED) and ketogenic diet but later controlled by clonazepam. However, she died at the age of seven years. Case 2 (younger brother of case 1), a one-hour-old boy, was hospitalized because of seizures after birth for 1 hour. Intrauterine growth retardation was discovered during late-pregnancy. The boy presented seizures and microcephaly immediately after birth, and his epilepsy was pharmacoresisitant. Case 3, an 8-month-old girl, was admitted due to recurrent convulsions for nearly two months. The girl had mild developmental retardation and hypotonia after birth. The infantile spasm was observed at her age of 6 months and disappeared under treatment with Vitamin B6, vigabatrin combined with adreno-cortico-tropic-hormone and magnesium sulfate. However, the seizure pattern turned to tonic seizures later. She was seizures free now with clobazam and zonisamide treatment. All of them manifested as a syndrome composed of severe global developmental retardation, progressive microcephaly, hypotonia from the very beginning, mild hypoproteinemia and diffuse brain atrophy. Genetic studies revealed compound heterozygous variations of QARS1 gene which were not reported previously. A review of the literature reported a total of 22 patients from 18 unrelated families all over the world. Except for 5 cases without epilepsy,all the patients shared very similar clinical manifestations as classic pentalogy. The recommended effective treatment for epilepsy has not been reported yet. Conclusions: Glutaminyl-tRNA synthetase deficiency caused by QARS1 gene variations manifested as a clinical syndrome's pentalogy, characterized by microcephaly, cerebral atrophy, intractable early-onset epileptic encephalopathy, global developmental retardation and severe muscle hypotonia.

Research Progress of Metabolomics in Forensic Pathology.

ABSTRACT: Metabolomics is an interdisciplinary subject that rose in the post-genomic era, which focuses on quantitative study of the response of living organisms to outside stimulation and pathophysiological changes, as well as multiple dynamic response of the level of in vivo metabolites caused by genetic mutation. It is extensively used in basic research of system biology, materia medica, clinical medicine, etc. In the forensic field, metabolomics mainly focuses on forensic toxicology, but with the generalization of certain techniques, it's foreseeable that metabolomics has a broad research prospect in forensic pathology. This article summarizes the major analysis techniques and methods of metabolomics, describes the research status of metabolomic techniques in the field of forensic pathology application research, including postmortem interval and death cause. Moreover, this article summarizes and discusses the potential applicable areas, in order to provide reference for relative research and application.

Application of Convolutional Neural Network in Identifying Different Levels of Isokinetic Exercise Efforts.

ABSTRACT: Objective To develop a convolutional neural network （CNN） that can identify isokinetic knee exercises moment of force-time diagrams under different levels of efforts. Methods The 200 healthy young volunteers performed concentric isokinetic right knee flexion-extension reciprocating exercises with maximal effort as well as half the effort at angular velocities of 30°/s and 60°/s twice, respectively, with an interval of 45 min. The moment of force-time diagrams were collected. The 200 subjects were randomly divided into the training set （140 subjects） and the testing set （60 subjects）. The moment of force-time diagrams from subjects in the training set were used to train CNN model, and then the fully trained model was used to predict types of curves from the testing set. Random sampling of subjects along with subsequent development of models were performed 3 times. Results Under the circumstances of isokinetic knee exercises with maximal effort and half the effort, 2 400 moment of force-time diagrams were produced, respectively. Classification accuracy rates of the CNN models after the 3 trainings were 91.11%, 90.49% and 92.08%, respectively, and the average accuracy rate was 91.23%. Conclusion The CNN models developed in this study have a good effect on differentiating isokinetic moment of force-time diagrams of maximal effort exercises from those made with half the effort, which can contribute to identifying levels of efforts exerted by subjects during isokinetic knee exercises.

Difference Analysis Based on 16S rRNA Sequencing of Different Soil Bacterial Communities.

ABSTRACT: Objective To study the structure and differences of bacterial communities in different soils, and to explore the effectiveness of 16S rRNA sequencing in identification of different soil. Methods Soil samples from 7 places in Shanghai were collected, then bacterial genomic DNA were extracted from them. The fragments of hypervariable region from 16S rRNA sequences were sequenced with high-throughput sequencing techniques. The results were quantified or visualized with bioinformatics software. The differences in diversity and abundance among the three kinds of bacterial communities in soil samples from grassland, forests and beaches were compared and analyzed. Results The statistical differences that existed among the alpha diversity indexes of bacterial communities in soil samples of grassland, forests and beaches had statistical significance. The relative abundance and diversity of bacterial communities in these three kinds of soil were significantly different. Grassland soil had higher Acidobacteria abundance, forest soil had higher Proteobacteria abundance, beach soil had higher Actinobacteria abundance. However, the differences in soil bacterial communities in artificial grasslands, natural grasslands and industrial district grasslands did not have statistical significance. Conclusion 16S rRNA sequencing can effectively distinguish different soils. This method may be able to provide clues for first crime scene inference in criminal cases.

[Research Progress of CircRNA and Its Application Prospect in Forensic Medicine].

Circular RNA （circRNA） is a type of noncoding RNA with tissue specificity and high stability, which forms a closed continuous loop and is abundantly expressed in tissue cells. According to recent research, the regulatory function of circRNA elucidating in the occurrence and development of disease shows a potential for diagnosing clinical disease and revealing disease mechanism. This paper reviews the biological characteristics, analysis methods of circRNA and its research progress in clinical application as biomarker, and outlooks its application in the field of forensic medicine.

Forensic Analysis of 24 Cases of Long-term Antipsychotics Use-Induced Sudden Unexpected Deaths.

OBJECTIVES: To analyze the forensic characteristics of 24 psychiatric patients who died of long-term use of psychotropic drugs. METHODS: Cases of sudden death of psychiatric patients from 2011 to 2016 were collected. The forensic characteristics of these sudden deaths were retrospectively analyzed by systematic investigation plus results of autopsy and toxics （drugs）. RESULTS: Among the 24 psychiatric patients who died of long-term use of psychotropic substances, the ratio of male to female was 1.7∶1, and the average age was （59.0±8.8） years. Fifteen patients had clear disease durations （14.4±8.2） years, and other the nine were known to have disease durations of over 3 years. The death time of 62.5% of patients was the daytime in working days, and 91.7% of the patients died at home. Most patients complained different degrees of physical discomfort before death. Patients with schizophrenia （20 cases） were the most common, followed by depression （4 cases）. All patients had the history of taking psychotropic drugs, with clozapine and chlorpromazine being the mostly detected ones. The causes of death were mainly circulatory diseases （15 cases）, with the most common being myocarditis （11 cases） followed by pneumonia （4 cases）. CONCLUSIONS: Critical attention should be paid to the risk of antipsychotics-induced sudden unexpected deaths for psychiatric patients, particularly for those with schizophrenia.

A retrospective study of implant-abutment connections on crestal bone level.

This study compared the effects of external hex, internal octagon, and internal Morse taper implant-abutment connections on the peri-implant bone level before and after the occlusal loading of dental implants. Periapical radiographs of 103 implants (63 patients) placed between 2002 and 2010 were collected, digitized, standardized, and classified into groups based on the type of implant-abutment connection. These radiographs were then analyzed with image-processing software to measure the peri-implant crestal bone change during the healing phase (4 months after implant placement) and at loading phases 1 and 2 (3 and 6 months after occlusal loading, respectively). A generalized estimating equation method was employed for statistical analysis. The amount of peri-implant crestal bone change differed significantly among all time-phase pairs for all 3 types of implant-abutment connection, being greater in the healing phase than in loading phase 1 or 2. However, the peri-implant crestal bone change did not differ significantly among the 3 types of implant-abutment connections during the healing phase, loading phase 1, or loading phase 2. This retrospective clinical study reveals that the design of the implant-abutment connection appears to have no significant impact on short-term peri-implant crestal bone change.

Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice.

Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.

Variations in bone density at dental implant sites in different regions of the jawbone.

The survival rate of dental implants is markedly influenced by the quality of the bone into which they are placed. The purpose of this study was to determine the trabecular bone density at potential dental implant sites in different regions of the Chinese jawbone using computed tomography (CT) images. One hundred and fifty-four potential implant sites (15 in the anterior mandible, 47 in the anterior maxilla, 55 in the posterior mandible, and 37 in the posterior maxilla) were selected from the jawbones of 62 humans. The data were subjected to statistical analysis to determine any correlation between bone density (in Hounsfield units, HU) and jawbone region using the Kruskal-Wallis test. The bone densities in the four regions decreased in the following order: anterior mandible (530 +/- 161 HU, mean +/- s.d.) approximately equal anterior maxilla (516 +/- 132 HU) > posterior mandible (359 +/- 150 HU) approximately equal posterior maxilla (332 +/- 136 HU). The CT data demonstrate that trabecular bone density varies markedly with potential implant site in the anterior and posterior regions of the maxilla and mandible. These findings may provide the clinician with guidelines for dental implant surgical procedures (i.e., to determine whether a one-stage or a two-stage protocol is required).

Prevalence of androgenetic alopecia in China: a community-based study in six cities.

BACKGROUND: There are racial differences in the prevalence and types of androgenetic alopecia (AGA). The prevalence of AGA has been studied in Caucasians and in some Asian people. In China, although there have been some epidemiological studies carried out in single cities or regions, no multicentre population-based study has been reported. OBJECTIVES: To study the prevalence and types of AGA in China and to compare the results with those previously reported in Caucasians and in other Asian people. METHODS: A community-based study was carried out in six cities of China. Subjects were interviewed face-to-face and completed questionnaires. The degree of AGA was classified according to the Norwood and Ludwig classifications. RESULTS: In total 17 886 subjects were interviewed and 15 257 completed the questionnaires. In men, the overall prevalence of AGA was 21.3%, with 2.8% in men aged 18-29 years, 13.3% in those aged 30-39 years, 21.4% in those aged 40-49 years, 31.9% in those aged 50-59 years, 36.2% in those aged 60-69 years and 41.4% in those aged 70 years and over. The most common type was frontal and vertex hair loss. A small number of subjects (3.7%) showed 'female pattern' hair loss. In women, the prevalence of AGA was 6.0%, with 1.3% in women aged 18-29 years, 2.3% in those aged 30-39 years, 5.4% in those aged 40-49 years, 7.5% in those aged 50-59 years, 10.3% in those aged 60-69 years and 11.8% in those aged 70 years and over. Ludwig grade I was the most common type. The prevalence of AGA varied between cities. A positive family history was present in 29.7% of men and 19.2% of women with AGA. CONCLUSIONS: The prevalence of AGA in Chinese men and women was lower than in Caucasians and similar to that in Koreans.

Effects of implant surface roughness and stiffness of grafted bone on an immediately loaded maxillary implant: a 3D numerical analysis.

This study investigated the effects of the stiffness of a maxillary sinus graft and the surface roughness of an immediately loaded implant using a non-linear three-dimensional finite element (FE) analysis (3D). Six FE models were created, including two stiffness values of grafted bone (345 and 3450 MPa of elastic modulus) and three conditions of implant-bone interfaces (Frictional coefficient of 0.3 for machined surface, 0.45 for rough implant surface and a bonded implant-bone interface for an osseointegrated implant). Computer tomographic images of a human skull were used to construct a posterior maxillary model. All implants were designed via the computer aided design software with a spiral threaded configuration. Three loading scenarios were investigated for each of the six models; axial loading and lateral loadings at 30 degrees and 60 degrees . The results showed that a 60 degrees lateral loading has scored the highest level of bone stresses among the three loading conditions. Immediately loaded implants with 0.3 frictional coefficient have suffered the highest bone stresses which were higher than those with bonded interface by about 57%. Increasing the frictional coeffecient to 0.45, however, did not show any benefits in reducing the peak bone stress. Raising the stiffness of grafted bone diminished the bone stress by about 10% in both the immediately loaded and the osseointegrated implants. It was also noted that increasing graft stiffness and implant surface roughness reduced the sliding at the implant-bone interface which may improve the implant stability and long-term survival.

[Experimental study of mechanism and measures of prevention and treatment of hypothermal vasoconstriction].

OBJECTIVE: To investigate the mechanism and to explore the measures of prevention and treatment of hypothermal vasoconstriction. METHODS: By the techniques of endothelial cell culture and scanning electron microscopy, and vasomotor functional test of isolated vascular vessels, the relation of hypothermal vasoconstriction and the release of endothelium-derived contractile and vasodilative factors were observed. RESULTS: Hypothermia obviously induced vasoconstriction of isolated vascular vessels, whether endothelium was intact or removed, the lower the temperature, the higher the vascular tension. Removal of endothelium could decrease the effect of vasoconstriction by hypothermia. The conditioned medium of bovine aortic endothelial cell could induce significantly vasoconstriction of isolated rat common neck arterial ring in hypothermia. It indicated that the bovine aortic endothelial cells secreted contractile factors into the medium. Reheating to 37 degrees C or vasodilator or reheating plus vasodilator did not obviously influence the hypothermia-induced vasoconstriction within 2 hours. When reheating to 50 degrees C, vascular tension was decreased, but only changed in range of 28% to 42%. CONCLUSION: Hypothermia vasoconstriction is relative to vasoconstrictor factors secreted by endothelium. Reheating to 37 degrees C or vasodilator does not antagonize the constriction of vascular vessels. Reheating to 50 degrees C only partially eliminates the constrict effect of blood vessels, so the prevention of hypothermia vasoconstriction should be emphasized.

[The foundation of the injury model on cultured human fetal lung fibroblasts and its immunohistochemistry research].

Cultured human fetal lung Fbs was first used to study the relationship between wound age and the change of cFn synthesized by Fbs in Vitro. A sterilized injector was applied to scrap the cultured confluent Fbs and a "wound" was obtained. Fbs around the wound was seen to change from a stationary stage to an active stage. Using the method of immunochemistry and image analysis system (IAS), cFn synthesized by Fbs around the wound was observed at once, 30 min, 1 h, 3 h and 6 h after injury. It was found that cFn began to change 1 h after injury and increased continually within 6 h. It suggests that the change of cFn synthesized by Fbs is time-dependent after injury and this approach breaks a new path in the study on estimation of wound age.

[Clinical significance of changes in ophthalmic arterial flow in pregnancy induced hypertension monitored by color Doppler imaging].

Ophthalmic arterial flow parameters were measured by color doppler imaging in 30 cases of healthy non-pregnant women, 30 cases of normal pregnancy and 37 cases of pregnancy induced hypertension (PIH), together with left ventricular output determination. An elevation of 2nd peak, B/A ratio and all parameters but RI was recognized as the characteristics of ophthalmic arterial flow spectrum in PIH. A positive correlation was observed between these changes and severity of PIH. All parameters returned to normal as PIH was controlled either after treatment or after delivery. Ophthalmic arterial flow monitoring might be useful in diagnosis of PIH (sensitivity 82%, specificity 98%). and for prognosis of PIH.

A new family of fucose-containing gangliosides isolated from human senile cataracts.

Gangliosides were isolated from human cataracts by solvent extraction, silicic acid chromatography, thin-layer chromatography and gas-liquid chromatography. A total of 11 resorcinol-positive bands were revealed by thin-layer chromatography. Bands 1, 5 and 7 were partially identified as hematoside. GM1 ganglioside and disialoganglioside by gas-liquid chromatography as the O-trimethylsilylated methylglycosides. In addition to galactose and glucose, fucose was found to be present in seven ganglioside fractions (bands 3, 4, 6 and 8-11). All these fucolipids contained N-acetylglucosamine in addition to sialic acid. Fucogangliosides G-3, G-4 and G-6 contained a 2:1 molar ratio of galactose to glucose, while G-8 had a galactose/glucose molar ratio of 1:1. Long-chain fatty acids constituted 60-77% of the total normal fatty acids in N-acetylgalactosamine-containing gangliosides, whereas the fucogangliosides contained primarily palmitate, although significant amounts of long-chain acids were also detected. The major long-chain base of the fucoganglioside was sphinganine (dihydrosphinogosine). The role of fucose-containing gangliosides in maintaining adhesions between lens membranes in cataracts is discussed with reference to glycosphingolipids in other tissues.

The presence of ceramide hydrolase and synthetase in pig lens epithelium.

An enzyme that catalyzes the synthesis of ceramide and its degradation to sphingosine and fatty acid has been found in pig lens epithelium. The enzyme has been partially purified fivefold by subcellular fractionation. It is activated by Triton X-100 and sodium cholate. The pH optimum for both hydrolase and synthetase has occurred at alkaline range. The enzymatic hydrolysis of ceramide has an apparent Km of 1.0 x 10(-4) M, and its reverse reaction (via the free-acid pathway) has an apparent Km of 8.2 X 10(-5) M and 2.45 X 10(-4) M for palmitic acid and sphingosine, respectively. The hydrolysis of ceramide by this enzyme was stimulated approximately 75% in the presence of fatty acid-free bovine serum albumin at the concentration of 3.33 X 10(-5) M.

Isolation and partial characterization of fucose- and N-acetylglucosamine-containing neutral glycosphingolipids from human senile cataracts.

Five neutral glycosphingolipids were isolated from human cataracts using silicic acid column chromatography and preparative thin-layer chromatography. Three of these glycolipids were partially identified by gas-liquid chromatography as glucosylceramide, lactosylceramide, and trihexosylceramide. Two glucosamine-containing glycosphingolipids (one of which contained fucose) were also detected. One of these two lipids contained galactose, glucose, N-acetylglucosamine in the molar ratio of 2:1:1, while the other contained fucose, galactose, glucose, and N-acetylglucosamine with the molar ratio of 1:2:1:1. Dihydrosphingosine (sphinganine) was the major long-chain base detected in all these fractions. The fatty acids of these neutral glycosphingolipids were variable in chain length, although the majority of them were greater than 20 carbons. This represents the first time whereby a family of neutral glycosphingolipids has been detected in human cataracts. This is also the first demonstration of the existence of a neutral fucolipid in the lenses of any species.