ABSTRACT
Purpose@#Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. @*Materials and Methods@#We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). @*Results@#Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. @*Conclusions@#These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.
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Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Subject(s)
Humans , Aged , Middle Aged , Leukemia, Myelomonocytic, Chronic/genetics , Prognosis , Splicing Factor U2AF/genetics , Mutation , Myelodysplastic Syndromes/genetics , Leukemia, Myeloid, Acute/geneticsABSTRACT
Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.
Subject(s)
Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Retrospective Studies , Translocation, Genetic , Chromosome Aberrations , KaryotypingABSTRACT
Excessive sodium/salt intake is the leading dietary risk factor for the loss of healthy life in the Chinese population. The "Healthy China 2030" Action Plan set the goal of reducing salt intake by 20% by 2030. However, salt intake in China is still at a very high level in the world, with adults reaching 11 g/d, more than twice the recommended limit of 5 g/d. The current policies and action plans of China have targeted catering workers, children, adolescents, and home chefs in salt, oil, and sugar reduction actions. However, there are still obvious deficiencies in the coordinated promotion and implementation. This study, therefore, proposed a set of comprehensive strategies (named CHRPS that is composed of communication and education, salt reduction in home cooking, salt reduction in restaurants, reducing salt content in pre-packaged food, and surveillance and evaluation) and key implementation points for further deepening the salt reduction action in China. These strategies were developed based on the main sources of dietary sodium for Chinese residents, the status of "knowledge, attitude and practice" in salt reduction, evidence of effective intervention measures, existing policies and requirements, and the salt reduction strategies of the World Health Organization and experience from some other countries. As a scientific reference, the CHRPS strategies will help the government and relevant organizations quickly implement salt reduction work and facilitate the earlier realization of China's salt reduction goal.
Subject(s)
Adult , Child , Adolescent , Humans , Sodium Chloride, Dietary , Sodium, Dietary , Diet , Food , ChinaABSTRACT
Objective: This study aimed to investigate the epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in (Hebei, Zhejiang, Shaanxi, Hunan) 4 provinces of China and the influence of demographic and economic characteristics on them. Methods: A total of 1 747 children and adolescents aged 7-17 from a Community-based Cohort Study on Nervous System Disease in 2018 were selected. High waist circumference, central obesity, elevated TG, elevated TC, elevated LDL-C, decreased HDL-C, elevated blood pressure, elevated blood glucose, and clustering of risk factors was analyzed. χ2 test was used for univariate analysis, multivariate logistic regression was used to analyze the correlation between demographic and economic factors and risk factors, and the Cochran-Armitage trend test was used for trend analysis. Results: The detection rates of high waist circumference, decreased HDL-C, elevated blood pressure, elevated TG, elevated blood glucose, central obesity, elevated TC, and elevated LDL-C were 29.08%, 15.28%, 13.17%, 13.05%, 11.79%, 7.33%, 6.53%, and 5.15%, respectively. The rate of clustering of risk factors was 18.37%. Multivariate logistic regression analysis showed that the risk of high waist circumference in girls was higher than that in boys (OR=1.67, 95%CI: 1.26-2.22), and the risk of elevated blood glucose and clustering of risk factors was lower than that in boys (OR=0.69, 95%CI: 0.49-0.99; OR=0.72, 95%CI: 0.53-0.99). The risk of high waist circumference, decreased HDL-C, and clustering of risk factors in 13-17 years old group was higher than that in the 7-year-olds group (OR=2.24, 95%CI: 1.65-3.04; OR=1.59, 95%CI: 1.20-2.11; OR=1.75, 95%CI: 1.26-2.44), but the risk of central obesity was lower (OR=0.54, 95%CI: 0.37-0.78). The risk of elevated TC, elevated TG, and decreased HDL-C in children and adolescents in southern was higher than that in northern parts of China (OR=1.88, 95%CI: 1.25-2.83; OR=1.61, 95%CI: 1.17-2.22; OR=1.55, 95%CI: 1.19-2.04), but the risk of high waist circumference and central obesity was lower than that in northern China (OR=0.57, 95%CI: 0.43-0.75; OR=0.62, 95%CI: 0.42-0.90). The risk of decreased HDL-C in rural children and adolescents was higher than in urban children and adolescents (OR=1.36, 95%CI: 1.02-1.83). The risk of multiple risk factors increased with the increase in average monthly household income per capita and BMI level. Conclusions: High waist circumference, decreased HDL-C and elevated blood pressure were prominent cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China in 2018. The region, average monthly household income per capita, and BMI were the main influencing factors of cardio-metabolic risk factors.
Subject(s)
Male , Female , Humans , Child , Adolescent , Obesity, Abdominal/epidemiology , Cholesterol, LDL , Blood Glucose , Cohort Studies , Body Mass Index , Risk Factors , Obesity , Hypertension , China/epidemiology , Waist CircumferenceABSTRACT
The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.
Subject(s)
Humans , SARS-CoV-2 , COVID-19/pathology , Cause of Death , Lung/pathology , AutopsyABSTRACT
Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.
Subject(s)
Aged , Middle Aged , Humans , Feeding Behavior/psychology , Diet , Cognitive Dysfunction/epidemiology , Nutrients , Vegetables , China/epidemiologyABSTRACT
There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.
Subject(s)
Humans , Child , Rare Diseases/drug therapy , Orphan Drug Production , Pharmaceutical PreparationsABSTRACT
OBJECTIVES@#To explore the application of whole-genome sequencing (WGS) in the rapid clinical diagnosis of critically ill neonates.@*METHODS@#The critically ill neonates who admitted to the neonatal intensive care unit of Children's Hospital of Fudan University and underwent WGS from August to September, 2019 were enrolled in this prospective study. The genetic testing results and clinical outcome were analyzed with reference to the sequencing data and clinical features of the neonates.@*RESULTS@#A total of 15 neonates were tested, among whom there were 9 boys and 6 girls. The main reason for hospitalization included abnormal breathing in 7 neonates, poor response in 2 neonates, feeding difficulty in 2 neonates, fever in 1 neonate, hypothermia in 1 neonate, preterm birth in 1 neonate, and convulsion in 1 neonate. The mean turn-around time was 4.5 days for WGS. Finally a genetic diagnosis was obtained for 3 neonates, with a positive diagnostic rate of 20% (3/15). Among the 3 neonates, 2 neonates were withdrawn from the treatment due to severe conditions and 1 neonate died on the day when the sample was sent for genetic testing, whose etiology could be explained by the results of genetic testing.@*CONCLUSIONS@#WGS technique can provide a timely and effective diagnosis for critically ill neonates suspected of genetic diseases and provide genetic evidence for clinical treatment of critically ill cases.
Subject(s)
Infant, Newborn , Male , Child , Female , Humans , Critical Illness , Prospective Studies , Premature Birth , Dyspnea , FeverABSTRACT
OBJECTIVES@#To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood.@*METHODS@#Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected.@*RESULTS@#The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively.@*CONCLUSIONS@#GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.
Subject(s)
Animals , Male , Rats , 4-Butyrolactone/chemistry , Chromatography, Liquid , Exosomes/chemistry , Hydroxybutyrates/chemistry , Rats, Sprague-Dawley , Sodium Oxybate/analysis , Tandem Mass Spectrometry/methodsABSTRACT
Objective@#This study aimed to analyze the temporal trends and characteristics associated with waist circumference (WC) among elderly Chinese people.@*Methods@#We used data from 3,096 adults ≥ 65 years who participated in the China Health and Nutrition Survey (CHNS), an ongoing cohort study, between 1993 and 2015. We used longitudinal quantile regression models to explore the temporal trends and characteristics associated with WC.@*Results@#WC increased gradually among the elderly Chinese population during the survey. The WC curves shifted to the right with wider distributions and lower peaks in men and women. All WC percentile curves shifted upward with similar growth rates in the 25th, 50th, and 75th percentiles. The WC means increased from 78 cm to 86 cm during the 22 years of our study. WC significantly increased with age and body mass index and decreased with physical activity (PA). These associations were stronger in the higher percentiles than in the lower percentiles.@*Conclusions@#WC is rising among Chinese adults ≥ 65 years. Factors affecting WC in elderly people may have different effects on different percentiles of the WC distribution, and PA was the most important protective factor in the higher percentiles of the WC distribution. Thus, different interventional strategies are needed.
Subject(s)
Aged , Female , Humans , Male , Body Mass Index , China/epidemiology , Cohort Studies , Nutrition Surveys , Waist CircumferenceABSTRACT
Objective@#This study aimed to determine the independent and joint associations of sedentary time (ST) and physical activity (PA) with metabolic syndrome (MetS) and its components among Chinese adults.@*Methods@#The study analyzed data from 4,865 adults aged ≥ 18 years who participated in the 2009 and 2015 China Health and Nutrition Surveys (CHNS). Four types of leisure ST and three types of PA self-reported at baseline were collected. Multivariable logistic regressions were used to determine the independent and joint associations of ST and PA with the odds of MetS or its components.@*Results@#For independent effects, higher levels of television time and total leisure ST was associated with higher MetS risk [odds ratio ( @*Conclusions@#MVPA and total PA have independent preventive effects, and sedentary behavior (mainly watching TV) has an unsafe effect on MetS and its components. Strengthening the participation of MVPA and combining the LPA to replace the TV-based ST to increase the total PA may be necessary to reduce the prevalence of MetS in Chinese adults.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , China/epidemiology , Exercise/statistics & numerical data , Metabolic Syndrome/etiology , Nutrition Surveys , Risk Factors , Sedentary BehaviorABSTRACT
The mechanism of methamphetamine toxicity and addiction is the key research direction of forensic toxicology, and the development of omics technology provides a new platform for further study of this direction. METH toxic damage and addiction are reflected differently in genes, ribonucleic acid (RNA) transcription, protein and metabolism. This article summarizes the achievements and shortcomings of multi-omics technologies such as genome, transcriptome, metabolome and proteome in the study of METH damage and addiction, and discusses the strategies and advantages of multi-omics combined analysis in the study of METH toxic damage and addiction mechanism, in order to provide more useful reference information for forensic toxicology of METH.
Subject(s)
Metabolome , Metabolomics , Methamphetamine/toxicity , Proteome , ProteomicsABSTRACT
OBJECTIVES@#To study the transcriptomic changes of astrocytes in the brain of rats exposed to methamphetamine (METH) and its possible mechanism in neurotoxicity.@*METHODS@#The rats were intraperitoneally injected with METH (15 mg/kg) every 12 h for 8 times in total to establish the subacute rat model of METH. After the model was successfully established, the striatum was extracted, and astrocytes were separated by the magnetic bead method. Transcriptome sequencing was performed on selected astrocytes, and the differentially expressed genes were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.@*RESULTS@#A total of 876 differentially expressed genes were obtained by transcriptome sequencing, including 321 up-regulated genes and 555 down-regulated genes. GO analysis revealed that differentially expressed genes were mainly concentrated in cell structure, biological process regulation, extracellular matrix and organelle functions. KEGG pathway enrichment analysis showed that steroids biosynthesis, fatty acid biosynthesis, peroxisome proliferators-activated receptor (PPAR), adenosine 5'-monophosphate-activated protein kinase (AMPK) and other signaling pathways were significantly changed.@*CONCLUSIONS@#METH can cause structural changes of astrocytes through multiple targets, among which cellular structure, steroids biosynthesis and fatty acid biosynthesis may play an important role in nerve injury, providing a new idea for forensic identification of METH related death.
Subject(s)
Animals , Rats , Astrocytes , Brain , Gene Expression Profiling , Methamphetamine/pharmacology , Signal Transduction , TranscriptomeABSTRACT
Objective: To isolate indoleamine 2,3-dioxygenase (IDO) inhibitory constituents from Rabdosia japonica based on bioactivity tracking separation. Methods: The overground part of R. japonica was extracted with boiling water and precipitated by ethanol, the precipitation was collected and lyophilized to obtain XPS, then successively separated by DEAE Sepharose Fast Flow anion-exchange and Superdex-75 gel permeation chromatographic steps to give XPS10-1. A combination of HPGPC, monosaccharide and amino acid composition analysis and IDO inhibitory studies was performed to investigate the structure and bioactivity of XPS10-1. Results: A IDO inhibitory glycoprotein, XPS10-1, was obtained from R. japonica based on activity tracking, its average molecular weight was estimated to 8 852, monosaccharide composition analysis showed the glycosyl part of XPS10-1 was mainly composed of rhamnose and glucose with the ratio of 10.0:2.2, and the protein part was mainly composed of glutamic acid, serine and glycine with mass ratio of 37.3:16.9:45.8. XPS10-1 showed potent IDO inhibitory effect with IC50 of (46.6 ± 3.4) μg/mL, and IC50 of IDO inhibitory effect of XPS10-1 on HeLa cells was (139.0 ± 8.7) μg/mL. Conclusion: In this study, a glycoprotein with IDO inhibitory effect was isolated from R. japonica, which could lay the foundation for the substance basis study of R. japonica.
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This study aimed to examine the association between famine exposure in different stages of life and the risk of overweight/obesity and abdominal obesity in laterlife. A total of 12,458 participants were categorized into non-exposure and four direct exposures, including fetal, childhood, adolescence, and adult exposure. Only risk of being overweight or obesity in adolescence exposure [odds ratio ( ), 1.45; 95% confidence interval ( ), 1.08-1.94] was significantly higher than in non-exposure. Childhood ( , 1.27; 95% , 1.05-1.54) and adolescence ( , 1.53; 95% , 1.15-2.05) exposures had significantly an increased risk of abdominal obesity compared with non-exposure. Additionally, different famine severity exposures had different influences on the development of overweight/obesity and abdominal obesity. Famine exposure in adolescence, which was a behavior formative period, can increase the risk of overweight/obesity and abdominal obesity in adulthood, specifically in famine severely affect area.
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This article reports the clinical and genetic features of two cases of cerebral creatine deficiency syndrome I (CCDSI) caused by SLC6A8 gene mutations. Both children were boys. Boy 1 (aged 2 years and 10 months) and Boy 2 (aged 8 years and 11 months) had the clinical manifestations of delayed mental and motor development, and convulsion. Their older brothers had the same symptoms. The mother of the boy 1 had mild intellectual disability. The genetic analysis showed two novel homozygous mutations, c.200G>A(p.Gly67Asp) and c.626_627delCT(p.Pro209Argfs*87), in the SLC6A8 gene on the X chromosome, both of which came from their mothers. These two novel mutations were rated as possible pathogenic mutations and were not reported in the literature before. This study expands the mutation spectrum of the SLC6A8 gene and has great significance in the diagnosis of boys with delayed development, and epilepsy.
Subject(s)
Child , Child, Preschool , Humans , Male , Creatine , Epilepsy , Genetic Testing , Mutation , Nerve Tissue Proteins , Genetics , Plasma Membrane Neurotransmitter Transport Proteins , Genetics , SyndromeABSTRACT
Since 2003, coronavirus has caused multiple major public health events that resulted in global epidemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and corona virus disease 2019 (COVID-19). Especially since COVID-19 outbroke in Wuhan, Hubei, in December 2019, coronavirus has had a significant impact on people's health and lives. But so far, the pathological diagnosis of COVID-19 has been relatively deficient: it is still confined to the pathological findings of punctured organs, and the majority of medical workers have poor awareness of its pathological characteristics. The COVID-19, as same as SARS and MERS, is caused by coronaviruses and can cause viral pneumonia. They have certain similarities. This article comprehensively reviews the pathological features observed in the autopsies of the aforementioned three diseases, in order to provide reference to the analysis of pathological changes of COVID-19.
Subject(s)
Humans , Betacoronavirus , COVID-19 , Coronavirus Infections , Pandemics , Pneumonia, Viral , SARS-CoV-2ABSTRACT
Objective To establish an analysis method for simultaneous determination of 13 sedative substances and their metabolites in blood by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology and to apply the method to actual cases. Methods The samples were extracted with ethyl acetate after an internal standard was added. The extract was condensed until it was nearly dry and then its residues were dissolved with methanol, filtered through 0.22 μm filter and finally determined. The 13 sedative substances and their metabolites were separated through the C18 chromatographic column, then gradient elution was performed on them with methanol and 20 mmol/L ammonium formate (containing 0.1% formic acid) solution. After that, they were determined in the electrospray positive ion mode and quantified by internal standard method. Results The 13 sedative substances and their metabolites in blood showed good linearity in the range of 5-200 μg/L with correlation coefficients ranging from 0.990 3 to 0.999 8. The detection limits were 0.1-1.0 μg/L. Recovery rates of sedative substances were in the range of 71.2%-93.4% when solutions with concentrations of 10, 50 and 200 μg/L were added. The deviations of intra-day and inter-day relative standard deviations (RSD) were not more than 8.6%. Accuracies (bias) were within ±9.8%. Conclusion This method is rapid, simple, effective and sensitive, and can be applied to analysis of 13 sedative substances and their metabolites in blood in forensic toxicology.
Subject(s)
Chromatography, High Pressure Liquid , Chromatography, Liquid , Forensic Toxicology , Hypnotics and Sedatives , Tandem Mass SpectrometryABSTRACT
Objective To retrospectively analyze the forensic pathological postmortem examination and clinical data of children who died of viral pneumonia in identification of cause of death cases and to discuss the clinical characteristics and pathological features of viral pneumonia in children, in order to provide reference to pathological diagnosis of viral pneumonia in children caused by 2019 novel coronavirus (2019-nCoV) infection. Methods Postmortem examination data from 61 cases of children whose causes of death were identified as viral pneumonia in recent years were collected from the Center of Forensic Identification, Southern Medical University. The gender, age, clinical symptoms and pathological features were comparatively analyzed. Results Among the 61 cases of children who died of viral pneumonia, most were within 2 years old (83.61%), and a large proportion died within 2 weeks after the onset of the disease (91.80%). Gross changes in postmortem examination included respiratory mucosal hyperemia, pleural effusion, pulmonary swelling, variegated pulmonary pleura and serosa, as well as focal pulmonary hemorrhage and pulmonary edema. A large proportion of sick children had enlarged mesenteric lymph nodes (83.61%) and thymic dysplasia (21.31%). Histopathological changes included edema of alveoli and interstitial substance, pneumorrhagia,shedding of alveolar epithelial cells, serous and (or) fibrous exudation in the alveoli, formation of viral inclusions, formation of transparent membranes, infiltration of inflammatory cells that mainly consisted of macrophages and lymphocytes in interstitial substance and alveoli. Viral infections often affected the heart and gastrointestinal tract. Conclusion The clinical symptoms of children with viral pneumonia are difficult to notice, and because the immune systems of children are not fully developed and they have poor immunity, they can easily become severely ill and even die. Analyzing the forensic autopsies and the histopathological characteristics could provide reference for pathological diagnosis of viral pneumonia.