Impeding the combination of astrocytic ASCT2 and NLRP3 by talniflumate alleviates neuroinflammation in experimental models of Parkinson's disease

Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP+ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.

Multi-disciplinary treatment of severe palatal radicular groove of maxillary lateral incisor: A case report and literature review / 中南大学学报(医学版)

Palatal radicular groove is a developmental malformation of maxillary incisors, lateral incisors in particular, which often causes periodontal destruction. This paper reports a case of combined periodontal-endodontic lesions induced by palatal radicular groove, which was initially misdiagnosed as a simple periapical cyst. After root canal therapy and periapical cyst curettage, the course of disease was prolonged, resulting in the absence of buccal and maxillary bone plates in the affected tooth area. After the etiology was determined, the affected tooth was extracted and guide bone tissue regeneration was performed at the same time, followed by implantation and restoration at the later stage, leading to clinical cure. The palatal radicular groove is highly occult, and the clinical symptoms are not typical. If the abscess of the maxillary lateral incisor occurs repeatedly, and the abscess of the maxillary lateral incisor has not been cured after periodontal and root canal treatment, cone-beam computed tomographic and periodontal flap surgery should be considered.

Progress of group B streptococcus meningitis in children / 国际儿科学杂志

Group B streptococcus(GBS), also known as streptococcus agalactis, is a Gram-positive conditionally causative coccus that can colonize healthy humans.GBS is a common pathogen of bacterial meningitis in infants under 3 months of age.GBS serotype Ⅲ and sequence type 17(ST 17)are the most common and virulent, and there is a significant correlation between serotype Ⅲ and ST 17, and erythromycin resistance is high.Penicillin or ampicillin is the first-line drug in China.Children with GBS meningitis are at high risk of poor prognosis.Intrapartum antibiotic prophylaxis(IAP)may be given in the presence of specific risk factors for GBS invasion in newborns. IAP reduced the incidence of early-onset GBS, but did not significantly reduce early-onset mortality and late-onset morbidity.

Pharmacodynamic mechanism study on Modified sanhuang ointment in the treatment of anal ulcers and swelling in rats / 中国药房

OBJECTIVE To explore the improvement mechanism of Modified sanhuang ointment on anal ulcers and swelling model rats. METHODS The anal ulcer model of the rat was induced by using glacial acetic acid； the effects of Modified sanhuang ointment low-dose， medium-dose and high-dose groups （185， 370， 740 mg/kg）， western medicine positive control group （Compound carraghenates cream， 1 g/kg） and TCM positive control group （Mayinglong shexiang zhichuang ointments， 1 g/kg） on body weight， area of anal ulcer， grade of anal ulcer were investigated. The other groups of rats were used to induce rectal swelling models with croton oil； the effects of Modified sanhuang ointment low-dose， medium-dose and high-dose groups （185， 370， 740 mg/kg）， western medicine positive control group （Compound carraghenates cream， 1 g/kg） and TCM positive control group （Mayinglong shexiang zhichuang ointments， 1 g/kg） on the rate of rectal and anal swelling， serum contents of inflammatory factors [interleukin 2 （IL-2）， IL-4， tumor necrosis factor （TNF-α）]， pathological morphology of rectal tissue， the expression of transient receptor potential channel V1 （TRPV1） and substance P in rectal tissue and rectal vascular permeability were investigated. RESULTS In Modified sanhuang ointment， the increase in body weight was enhanced， and the area of anal ulcers， as well as the grade of anal ulcers in rats with anal ulcer models， were reduced to varying degrees； rectal tissue damage in rectal swelling model rats was improved； the rate of rectal and anal swelling， the serum contents of inflammatory factors， the expressions of TRPV1 and substance P in rectal tissue， and rectal vascular permeability were all decreased （P＜0.05 or P＜0.01）. The effect of Modified sanhuang ointment was better than that of western medicine positive control and TCM positive control.Modified sanhuang ointment can improve anal ulcers and swelling in rats by reducing the release of inflammatory factors， inhibiting the expression of TRPV1 and substance P.

Preliminary Construction of Evaluation Index System for Traditional Chinese Medicine Medicated Diet based on Delphi Method and Analytic Hierarchy Process / 中医杂志

ObjectiveTo build an evaluation index system for traditional Chinese medicine （TCM） medicated diet， promoting the scientific and standardized development of medicated diet in TCM. MethodsThe framework of the evaluation index system was constructed through literature review and Delphi expert consultation method. The analytic hierarchy process was used to construct a hierarchical structure model. Pairwise comparisons between the indicators were conducted using the Saaty 1-9 scale method， and the weight of each indicator was calculated using Yaahp 10.3. ResultsThe response rates for the two rounds of expert consultation were 93.33% and 100%， respectively. The Kendall's W coefficients for the first-level and second-level indicators in the second round were 0.270 and 0.281， respectively （both P＜0.001）. Finally， an evaluation index system for TCM medicated diet therapy was constructed， consisting of 6 primary indicators and 27 secondary indicators. The weightings of the primary indicators were as follows： sensory appearance （0.1843）， health value （0.3569）， ingredient compatibility （0.1271）， packaging （0.0370）， production and preparation （0.1005）， and reliability （0.1940）. ConclusionA comprehensive and universally applicable evaluation index system for TCM medicated diet has been developed， taking into conside-rations of color， taste， appearance， efficacy， preparation， quality and others. This system can provide valuable reference for the evaluation of the value of medicated diet as well as its development.

Comparative molecular analysis of oral submucous fibrosis and other organ fibrosis based on weighted gene co-expression network analysis / 中南大学学报(医学版)

OBJECTIVES@#There is currently a lack of economic and suitable animal models that can accurately recapitulate the oral submucous fibrosis (OSF) disease state for indepth study. This is one of the primary reasons for the limited therapeutic methods available for OSF. Based on the underlying logic of pan-cancer analysis, this study systematically compares OSF and the other four types of organ fibrosis from the aspects of molecules, signaling pathways, biological processes, etc. A comprehensive analysis of the similarities and differences between OSF and other organ fibrosis is helpful for researchers to discover some general rules of fibrosis disease and may provide new ideas for studying OSF.@*METHODS@#Microarray data of the GSE64216, GSE76882, GSE171294, GSE92592, and GSE90051 datasets were downloaded from GEO. Differentially expressed mRNAs (DEmRNAs) of each type of fibrosis were identified by Limma package. Weighted gene co-expression network analysis (WGCNA) was used to identify each type of fibrosis-related module. The similarities and differences of each fibrosis-related-module genes were analyzed by function and pathway enrichment analysis.@*RESULTS@#A total of 6 057, 10 910, 27 990, 10 480, and 4 801 DEmRNAs were identified in OSF, kidney intestinal fibrosis (KIF), liver fibrosis (LF), idiopathic pulmonary fibrosis (IPF), and skin fibrosis (SF), respectively. By using WGCNA, each type of fibrosis-related module was identified. The co-expression networks for each type of fibrosis were constructed respectively. Except that KIF and LF have 5 common hub genes, other fibrotic diseases have no common hub genes with each other. The common pathways of OSF, KIF, LF, IPF, and SF mainly focus on immune-related pathways.@*CONCLUSIONS@#OSF and the other 4 types of fibrotic diseases are tissue- and organ-specific at the molecular level, but they share many common signaling pathways and biological processes, mainly in inflammation and immunity.

Advances in pediatric solid tumor immunotherapy based on chimeric antigen receptor T cell / 国际儿科学杂志

Chimeric antigen receptor T cell immunotherapy(CAR-T)has achieved a significant breakthrough in hematologic malignancies.On the contrary, the application of CAR-T in solid tumor, including pediatric solid tumor, is confronted with numerous barriers.Pre-clinical experiments and clinical trials point out that several reasons account for the consequence: rare and heterogeneous targets; limited lifetime of CAR-T in vivo as a result of T cell exhaustion; inadequate infiltration of tumor sites due to steric hindrance; side effects of treatment.Based on the above problems, this review will summarize the research progression of different targets, the choice of immune cells, inhibitory tumor microenvironment, and countermeasures for side effects, so as to provide several new explorable directions for improving the treatment effect.

Oral lichen planus induced by long-term use of antimicrobials for recurrent aphthous ulcer:A case report and literature review / 中南大学学报(医学版)

The precise etiology of oral lichen planus(OLP)is still unclear,but the existing evidence suggests that drug intake,virus infection,fungal infection,psychological disorders,and immunodeficiency are closely associated with the pathogenesis of OLP.We report a case of OLP accompanied with candidiasis induced by long-term use of antimicrobials for recurrent aphthous ulcer(RAU)and update the literature,to discuss the possible association between OLP and misuse of antimicrobials,and to inform general dentists and pharmacists the importance for practice with optimal antimicrobial stewardship.In this case,a 42-year-old man presented to Xiangya Stomatological Hospital with white reticular patterns spreading in the oral cavity for almost 1 year.He was diagnosed with OLP via histopathological examination.He had a 5-year history of RAU which occurred every 1-2 months,and he was given antimicrobials ingested or injected whenever the ulcers came up.Satisfactory treatment results were obtained by stopping the abuse of antimicrobials and local antifungal therapy.Meanwhile,the exacerbation and alleviation of OLP was closely related to the administration of antimicrobials.Combined with literature review,antimicrobial might contribute to the development of OLP by inducing candidiasis,a common side-effect of misuse of antimicrobials.Considering the seriousness of antimicrobial resistance and opportunistic infection,dentists should prescribe antimicrobials judiciously according to guidelines and evidence-based indications.Appropriate prescribing of antimicrobials is a professional responsibility to all dentists.

Determination of active ingredients and prediction of targetin Sanhua Decoction for cerebral ischemia based on HPLC and network pharmacology methods / 国际中医中药杂志

Objective:To determinate the active ingredients and predicte action targets in Sanhua Decoction for treating cerebral ischemia based on HPLC and network pharmacology methods. Methods:The HPLC analysis was performed on HC-C18 (250 mm × 4.6 mm, 5 μm) with the mobile phase of methanolacetonitrile-0.05% phosphoric acid with gradient elution at the flow rate of 1.0 ml/min and 0.8 ml/min. The detection wavelength was set at 254 nm, the column temperature was at 30 ℃, and the injection volume was 10 μl. TCMIP v2.0 platform was used to search the action targets of rhein, emodin, chrysophanol, hesperidin, magnolol and notopterygiol. We used Cerebral ischemia as a keyword searching the databases such as Genecards, OMIM, TTD, and Disgenet to screen six potential targets for the treatment of cerebral ischemia by active ingredients, construct a protein interaction (PPI) network and a disease-component-target-pathway integration network.Results:The literature search determined that rhein, emodin, chrysophanol, hesperidin, magnolol and qianhuol were the index components for the determination of Sanhua Decoction. Their linear ranges were 0.080 4-0.804 0 μg, 0.015 3-0.382 0 μg, 0.041 8-0.626 4 μg, 0.312 6-3.908 0 μg, 0.037 9-0.568 8 μg, 0.045 3-1.359 6 μg, respectively. The correlation coefficient R 2 is greater than 0.999 0. The content ranges of the above six components in seven samples were 0.887-0.971 mg/g, 0.094-0.101 mg/g, 0.110-0.119 mg/g, 1.494-1.669 mg/g, 0.126-0.145 mg/g and 0.153-0.167 mg/g, respectively. Network pharmacology analysis found that the targets of the six components for the treatment of cerebral ischemia may be TNF, TP53, MAPK14, JUN, IL1B, MYC, ESR1, ICAM1, PTGS2, PPARG and so on. Conclusions:A quality control method forthe six active ingredients in Sanhua Decoction treating cerebral ischemia was established. This method is simple and repeatable. The ten potential targets of the six active ingredients in Sanhua Decoction for the treatment of cerebral ischemia have been clarified, laying a foundation for further research on the action mechanism.

Progress of immunotherapy in pediatric lymphocyte malignancies / 国际儿科学杂志

In the last half-century, the multi-cooperation of conventional therapies including chemotherapy, radiotherapy and bone marrow hematopoietic stem cell transplantation has saved a lot of children with lymphocyte malignancies, but the outcomes of relapsed and/or refractory diseases remain dismal.Thus, it is in urgent need of novel approaches to improve clinical efficiency.After decades of rapid development, immunotherapy has achieved remarkable results from the treatment of pediatric lymphocyte malignancies, especially chimeric antigen receptors T(CAR-T), bi-specific T cell engager(BiTE), and immune checkpoint blockader(ICB). However, a part of patients is still resistant to immunotherapy.The review will focus on CAR-T, BiTE and ICB to elucidate the pre-clinical studies and clinical trials that have been intensively conducted in pediatric leukemia and lymphoma, as well as the brief introduction of their limitations and probably optimal strategies.

Application of Nuclear Imaging Probes in PD-L1 Immunotherapy of Tumor / 肿瘤防治研究

Immunotherapy strategies of targeting PD-1 and its ligand PD-L1 are widely administered in varied types of cancer. Patient benefitting from PD-L1 targeted immunotherapy mainly depends on the expression level of PD-L1 in tumor tissues. Currently, the expression level of PD-L1 is primarily detected through the invasive method of biopsy in clinic, which is severely limited by the temporal and spatial heterogeneity of PD-L1 expression. Nuclear medicine probe can realize the noninvasive as well as in vivo detection of PD-L1 at the molecular level, which has important clinical significance for the guidance of patient screening and the prediction of patient's response to immunotherapy. This article reviews PD-L1 targeting nuclear imaging probes and their applications in tumor PD-L1 imaging.

Audio-visual Emotion Regulation System Based on TGAM Module / 中国医疗器械杂志

OBJECTIVE@#Based on the TGAM PCB module, a system of emotion control using audio-visual feedback is designed.@*METHODS@#TGAM collects EEG information through the electrode in contact with the forehead skin. The system analyzes the user's emotion through the STM32F103ZET6 of the main control chip, and finally controls the control end of the system to regulate the user's emotion.@*RESULTS@#It can be seen from the test results that the system can precisely recognize the user's emotions, and at the same time effectively adjust the user's emotions from both audio-visual aspects.@*CONCLUSIONS@#The system has high recognition accuracy and good adjustment effect.

Efficacy of Nicorandil in the treatment of unstable angina pectoris in 30 patients / 中国基层医药

Objective:To investigate the efficacy of Nicorandil in the treatment of unstable angina pectoris.Methods:Sixty patients with unstable angina pectoris who received treatment in Department of Cardiovascular Disease, Suixi Hospital of Traditional Chinese Medicine, China during January-July 2020 were included in this study. They were randomly assigned to receive either conventional treatment including antiplatelet, increasing coronal blood flow velocity, lipid-lowering treatment and stabilization of atherosclerotic plaque (control group, n = 30) or Nicorandil treatment and conventional treatment (observation group, n = 30). Clinical efficacy was compared between the two groups. Angina attack, electrocardiogram changes and adverse reactions in each group were analyzed before and after treatment. Results:Total effective rate in the observation group was significantly higher than that in the control group [88.67% (26/30) vs. 53.33% (16/30), χ2 = 7.937, P = 0.005]. The frequency and duration of angina pectoris in the observation group were (1.53 ± 0.62) times/week, (1.93 ± 0.78) minutes, which were significantly lower or shorter than those in the control group [(1.97 ± 0.71) times /week, (2.60 ± 1.00) minutes, t = -2.359, -3.162, P = 0.025, 0.004). The total effective rate of electrocardiogram in the observation group was significantly higher than that in the control group [70.00% (22/30) vs. 43.34% (13/30), χ2 = 5.554, P = 0.018]. There was no significant difference in the incidence of adverse drug reactions such as nausea, dizziness and palpitation between the two groups (all P > 0.05). Conclusion:Based on conventional treatment, Nicorandil treatment for unstable angina pectoris can improve the clinical symptoms and electrocardiogram changes, exhibit remarkable efficacy, and therefore deserve clinical promotion.

Clinical analysis of solitary fibrous tumors of the abdomen and pelvis / 中华普通外科杂志

Objective:To investigate the pathogeny, diagnosis and treatment of solitary fibrous tumors of the abdomen and pelvis.Methods:Retrospective analysis was made on the clinical data of 12 SFT patients undergoing surgical resection in Peking University International Hospital from Jul 2015 to Jul 2019.Results:All patients underwent radical resection. After operation, complications in clued pelvic hemorrhage in 1 case and ureteral fistula in 1 case, all improved after conservative treatment.According to pathological and immunohistochemical results, 7 cases were MSFT and 5 cases were SFT. All patients were followed up for 2-53 months. 5 cases were recurrent, among which 1 case died of intestinal obstruction caused by tumor compression.Conclusion:The clinical manifestations of solitary fibrous tumors are mostly nonspecific.Imaging examination and puncture pathology are of great significance for preoperative diagnosis. Radical resection is an important means to improve the prognosis of patients.

Analysis of the clinicopathological features and surgical treatment of primary retroperitoneal paragangliomas in 24 patients / 中华普通外科杂志

Objective:To evaluate the clinicopathological features of primary retroperitoneal paragangliomas.Methods:Data of 24 patients with retroperitoneal paragangliomas who underwent surgical treatment in our hospital from Jan 2015 to Dec 2018 was collected and analyzed.Results:Hypertension, abdominal pain/discomfort and headache were the most common complaints while 10 patients were asymptomatic and were diagnosed accidently in routine body examination. Tumor size ranged from 3.4-13.0 cm (6.9±2.5) cm, and all the tumors were located in the vicinity of abdominal aorta and inferior vena cava. All the patients received surgical treatment. Intraoperative blood pressure fluctuations were significantly correlated with prolonged operation time, more blood loss, more blood transfusion and prolonged length of stay (all P<0.05). The median follow-up time was 29 months and 1 patient died from tumor recurrence and progression. The other patients have had a tumor free survival. Conclusions:Surgical resection was the principal treatment of primary paraganglioma. Preoperative assessment was very important for perioperative safety.

Diagnostic value of microRNA-29b for left ventricular hypertrophy in elderly patients with coronary heart disease / 中华老年医学杂志

Objective:To investigate the diagnostic value of microRNA-29b(miR-29b)for left ventricular hypertrophy(LVH)in elderly patients with coronary heart disease(CHD).Methods:From January 2015 to December 2018, 140 elderly patients with CHD admitted in our hospital were enrolled, including 70 CHD patients without LVH(the NLVH group)and 70 CHD patients with LVH(the LVH group). Seventy healthy elderly adults without CHD who underwent heart examination at our hospital during the same period were included as the control group.The interventricular septum thickness(IVSD), left ventricular posterior wall thickness(LVPWD) and the relative expression level of microRNA-29b were detected and compared among the three groups.The correlation of microRNA-29b with IVSD and LVPWD was analyzed, and the diagnostic value of microRNA-29b for LVH in elderly CHD patients was analyzed.Results:There were significant differences in IVSD, LVPWD and the relative expression level of microRNA-29b among the three groups( F=22.838, 22.147 and 114.096, all P=0.000). The IVSD, LVPWD and the relative expression level of microRNA-29b were higher in the LVH group than in the NLVH group( t=3.479, 3.206 and 9.852, all P=0.000)and than in the control group( t=3.904, 3.553 and 10.792, all P=0.000). The relative expression level of microRNA-29b was higher in the NLVH group than in the control group( t=2.306, P=0.420). The receiver-operating characteristics(ROC)curve analysis of microRNA-29b for the diagnosis of LVH in elderly CHD patients showed that the maximum entry point of Youden index was 0.80, the optimal critical value was 3.52, the sensitivity and specificity for the diagnosis of LVH was 91.73% and 88.27%.Pearson correlation analysis showed that the expression level of microRNA-29b was positively correlated with IVSD and LVPWD( r=0.63 and 0.61, P=0.000). Conclusions:The expression level of microRNA-29b is significantly increased in elderly CHD patients with LVH, and positively correlated with IVSD and LVPWD.The expression level of microRNA-29b has high sensitivity and specificity in the diagnosis of LVH in elderly CHD patients.

Design of Remote Multi-part Personal Radiation Dose System Based on Bluetooth Communication Module / 中国医疗器械杂志

OBJECTIVE@#A remote multi-part personal radiation dose detection system is designed with ATmega32A single chip microcomputer as the control core.@*METHODS@#First of all, the geiger counter tube module collects the radiation signal of the surrouding environment. Secondly, using ATmega32A Microprocessor of Slave computer to calculate the collected signal. Finally, it is sent to the host receiving device or mobile APP through Bluetooth module,so as to realize real-time detection of radiation data, remote transmission and security alarm.@*RESULTS@#The system is measured in the same environment as the RG1100 radiometer, with a maximum difference of 0.03 μSv/h.This shows that it can stably realize the functions of radiation measurement, monitoring, alarm, remote connection and multimodal display.@*CONCLUSIONS@#The system has the advantages of good portability (easy to carry), low power consumption, accurate measurement and so on. It has certain reference value and practicability.

Comparative research on brain networks of children with attention deficit hyperactivity disorder and normal children based on visual cognitive tasks / 生物医学工程学杂志

Aiming at the difference between the brain networks of children with attention deficit hyperactivity disorder (ADHD) and normal children in the task-executing state, this paper conducted a comparative study using the network features of the visual function area. Functional magnetic resonance imaging (fMRI) data of 23 children with ADHD ［age: (8.27 ± 2.77) years］ and 23 normal children ［age: (8.70 ± 2.58) years］ were obtained by the visual capture paradigm when the subjects were performing the guessing task. First, fMRI data were used to build a visual area brain function network. Then, the visual area brain function network characteristic indicators including degree distribution, average shortest path, network density, aggregation coefficient, intermediary, etc. were obtained and compared with the traditional whole brain network. Finally, support vector machines (SVM) and other classifiers in the machine learning algorithm were used to classify the feature indicators to distinguish ADHD children from normal children. In this study, visual brain function network features were used for classification, with a classification accuracy of up to 96%. Compared with the traditional method of constructing a whole brain network, the accuracy was improved by about 10%. The test results show that the use of visual area brain function network analysis can better distinguish ADHD children from normal children. This method has certain help to distinguish the brain network between ADHD children and normal children, and is helpful for the auxiliary diagnosis of ADHD children.

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome / 基因组蛋白质组与生物信息学报·英文版

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

A classic case with maple syrup urine disease caused by compound heterozygous mutations of BCKDHB gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic etiology of a patient with classic maple syrup urine disease (MSUD).</p><p><b>METHODS</b>Next-generation sequencing (NGS) was used to screen the exons of BCKDHA, BCKDHB, DBT and DLD genes. Suspected mutations were verified by Sanger sequencing. Bioinformatic analysis was carried out to predict the influence of mutations on the protein structure and function.</p><p><b>RESULTS</b>NGS and Sanger sequencing have detected a c.550delT mutation in exon 5 of the BCKDHB gene in the mother and a c.1046G>A mutation in exon 10 of the BCKDHB gene in the father, while no mutation was found with BCKDHA, DBT and DLD genes. Among these, the c.550delT is a novel mutation. Bioinformatic analysis suggested that the two mutations both located in a highly conserved region and may decrease the activity of branched-chain α-ketoacid dehydrogenase complex through alternation of its structure.</p><p><b>CONCLUSION</b>The compound heterozygous mutations c.550delT and c.1046G>A of the BCKDHB gene probably underlie the clinical manifestations of the patient with classic MSUD.</p>