Comparison of catalytic functions and expression patterns of two pinene synthases from Wurfbainia villosa / 中国中药杂志

Wurfbainia villosa fruit is rich in volatile terpenoids, among which pinene is one of the main components and has anti-inflammatory, antibacterial, anti-tumor, and other pharmacological activities. This research group found that W. villosa fruits were rich in α-pinene by GC-MS, and terpene synthase(WvTPS63, formerly known as AvTPS1) with β-pinene as the main product was cloned and identified, but α-pinene synthase had not been identified. In this study, based on the genome data of W. villosa, we screened and found WvTPS66 with highly similar sequences to WvTPS63, identified enzyme functions of WvTPS66 in vitro, and performed a comparative analysis of sequence, catalytic function, expression pattern, and promoter with WvTPS63. Multiple sequence alignment showed that the amino acid sequences of WvTPS63 and WvTPS66 were highly similar and the conservative motif of terpene synthase was almost identical. In vitro enzymatic experiments on catalytic functions showed that both could produce pinene, and the main product of WvTPS63 was β-pinene, while that of WvTPS66 was α-pinene. Expression pattern analysis showed that WvTS63 was highly expressed in flowers, WvTPS66 was expressed in the whole plant, and the highest expression level was found in the pericarp, which indicated that it might be mainly responsible for the synthesis of α-pinene in fruits. In addition, promoter analysis revealed the presence of multiple regulatory elements related to stress response in the promoter regions of both genes. The findings of this study can provide a reference for the functional study of terpene synthase genes and new genetic elements for pinene biosynthesis.

Analysis of pathogen detection results of neonatal Echovirus 11 infection outbreaks in Guangdong Province in 2019 / 中华微生物学和免疫学杂志

Objective:To analyze the laboratory test results of two outbreaks of neonatal enterovirus infections in Guangdong Province in 2019 and the genetic characteristics of Echo11, aiming to provide reference for the prevention and control of neonatal enterovirus infections.Methods:The pathogenic specimens of neonatal cases suspected of enterovirus infection were collected. Fluorescence quantitative PCR and sequencing were used for enterovirus typing and identification, and virus isolation was carried out for positive specimens.The complete sequences of VP1 of Echo11 were amplified and sequenced and the phylogenetic analysis was performed using the bioinformatics software such as Danstar6, Bioedit7.09 and MEGA6.06.Results:A total of 93 specimens from 36 neonatal cases were collected. After identification, 55 specimens from 24 cases were positive for enterovirus, of which 23 cases were positive for Echo11 and one case was positive for Coxsackievirus B4(CVB4). A total of 29 enterovirus strains were isolated from the specimens of 19 cases, of which 28 were Echo11 from 18 cases, and one was CVB4. Phylogenetic analysis revealed that the nucleotide homology between the 18 strains of Echo11 in this study was 98.2%-100.0%, and the nucleotide homology between the Echo11 strains causing the two neonatal infections was 99.7%-100.0% and 99.8%-100.0%, respectively. Echo11 could be divided into six genotypes as A, B, C, D, E and F, in which genotype A and genotype C were further divided into A1-5 and C1-4, and genotype D could be divided into D1-5. The 18 strains of Echo11 in this study were all subtype D5.Conclusions:In 2019, two outbreaks of neonatal infections in medical institutions in Guangdong Province were caused by Echo11, which belonged to the genotype D5.

Study on Mechanism of Quercetin in Heart Failure Based on Network Pharmacology and Experimental Validation / 中国实验方剂学杂志

Objective:To predict the therapeutic targets and related signaling pathways of quercetin in the treatment of heart failure （HF） by network pharmacology and molecular docking methods，and further clarify its mechanisms through <italic>in vitro</italic> cell model. Method:The pharmacological targets of quercetin were obtained by SwissTargetPrediction and Targetnet databases； the heart failure related targets were obtained by Online Mendelian Inheritance in Man（OMIM），GeneCards and Therapeutic Target Database（TTD） databases； the protein-protein interaction（PPI） network was analyzed by STRING database（Search Tool for Recurring Instances of Neighbouring Genes），and the PPI network diagram of quercetin for heart failure target was established. Cytoscape 3.7.2 software was used for analyzing and screening the anti-heart failure network nodes of quercetin，and the obtained targets were enriched with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis by DAVID database. In order to explore the mechanism of quercetin in the treatment of heart failure，we used cell model to verify the function in heart failure treatment. Results:The predicted results showed that there were 23 targets for the treatment of heart failure，such as Matrix Metallopeptidase-9（MMP-9），androgen receptor（AR），coagulation factor 2（F2），insulin like growth factor 1 receptor（IGF1R），epidermal growth factor receptor（EGFR），janus kinase-2（JAK2），cytochrome P450 family 19 subfamily A member 1（CYP19A1），estrogen receptor-1（ESR1），tumor necrosis factor（TNF），protein tyrosine phosphatase receptor type C（PTPRC） and cytochrome P450 family 17 subfamily A member 1（CYP17A1） etc. The results suggest that quercetin may play a role in the treatment of heart failure by intervening in the physiological processes of cardiovascular cell proliferation and metabolism，regulating hypoxia-inducible factor 1 （HIF-1）signaling pathway and steroid hormone biosynthesis. Conclusion:Quercetin has the characteristics of multi-target，multi-channel and multi-channel in the treatment of heart failure. It may play a role in the treatment of heart failure by regulating MMP-9，EGFR and other key genes，participating in the biological process of cardiac and vascular cell proliferation and metabolism.

Effect of Shuangyu Tiaozhi Decoction on HNF1α/PCSK9/LDLR Signaling Pathway in Liver of Hypercholesterolemic Rats / 中国实验方剂学杂志

Objective:To observe the expression of hepatocyte nuclear factor 1<italic>α</italic> （HNF1<italic>α</italic>）， proprotein convertase subtilisin/kexin type 9 （PCSK9） and low-density lipoprotein cholesterol （LDLR） in hypercholesterolemia rat liver， and investigate the mechanism of Shuangyu Tiaozhi Decoction regulating cholesterol metabolism and attenuating hypercholesterolemia. Method:After providing a high-fat diet for 4 weeks， 40 SD rats were selected， 8 of which were randomly selected as normal group and fed a normal diet， and the remaining 32 rats were fed a high-fat diet. The rats successfully established as hypercholesterolemic model， were randomized into 4 groups： model group， low dose of Shuangyu Tiaozhi decoction group （7.8 g·kg^-1）， high dose of Shuangyu Tiaozhi decoction group （15.6 g·kg^-1）， and simvastatin group （4 mg·kg^-1）， with 8 rats in each group. The drugs were continuously given for 8 weeks. Serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C） were measured. The pathomorphological changes in liver were observed by hematoxylin and eosin （HE） staining. The immunohistochemistry was used to detect PCSK9 and LDLR expression in liver. The mRNA and protein expression levels of HNF1<italic>α</italic>， PCSK9 and LDLR were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with normal group， the TC， TG， LDL-C levels in model group were significantly increased （<italic>P</italic><0.01）， the morphology showed obvious liver steatosis. The mRNA and protein expression of HNF1<italic>α</italic> and PCSK9 were increased （<italic>P</italic><0.05）， the mRNA and protein expression of LDLR was decreased （<italic>P</italic><0.05）. Compared with model group， the serum TC， TG， LDL-C levels were significantly lowered in the Shuangyu Tiaozhi decoction high-dose group （<italic>P</italic><0.01）， the serum TC， LDL-C levels were significantly lowered in the Shuangyu Tiaozhi decoction low-dose group and simvastatin group （<italic>P</italic><0.05，<italic>P</italic><0.01）， while no significant effect was observed on the serum HDL-C levels in each treatment group. The liver steatosis decreased in each treatment group. The mRNA and protein expression of HNF1<italic>α</italic> was obviously decreased in each treatment group （<italic>P</italic><0.05，<italic>P</italic><0.01）， the mRNA and protein expression of PCSK9 was obviously decreased in Shuangyu Tiaozhi decoction low and high-dose groups （<italic>P</italic><0.05，<italic>P</italic><0.01）， the mRNA expression of PCSK9 was significantly increased in the simvastatin group （<italic>P</italic><0.01）， while the protein expression showed a downward trend. The LDLR mRNA levels were significantly increased in each treatment group （<italic>P</italic><0.01）， the LDLR protein expression was significantly increased in Shuangyu Tiaozhi high-dose group （<italic>P</italic><0.01）， and showed an upward trend in Shuangyu Tiaozhi low-dose group and simvastatin group. Results of immunohistochemistry showed PCSK9 expression was weakly positive， the expression of LDLR was strongly positive in each treatment group. The therapeutic effect of Shuangyu Tiaozhi decoction high-dose group was more remarkable than simvastatin group， while there was no obvious difference between the Shuangyu Tiaozhi decoction low-dose group and simvastatin group. Conclusion:Shuangyu Tiaozhi decoction may reduce the blood lipid levels through HNF1<italic>α</italic>/PCSK9/LDLR signaling pathway， play an active role on regulating cholesterol metabolism and alleviating high-fat diet-induced hypercholesterolemia.

Recurrence factors for myelin oligodendrocyte glycoprotein antibody disease in children and the effect of recurrence prevention regimens / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens.@*METHODS@#A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group (@*RESULTS@#For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% @*CONCLUSIONS@#More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.

Preparation and application of a PDGFRβ-targeted near-infrared fluorescent probe for molecular optical imaging of lung cancer / 中国胸心血管外科临床杂志

@#Objective    To prepare platelet-derived growth factor receptor β (PDGFRβ)-targeted near-infrared molecular probe and evaluate its potential in optical molecular imaging of lung cancer. Methods    PDGFRβ-specific affibody Z-tri was recombinantly expressed in Escherichia coli (E. coli) and purified using affinity chromatography. In vitro cell-binding of Z-tri was analyzed by flow cytometry. Cellular distribution of Z-tri in tumor grafts was determined by protein-tracing. The molecular probe CF750-Z-tri was prepared by conjugating near-infrared fluorescent dye CF750 to Z-tri. The optical images of xenografts of lung cancer were obtained by using CF750-Z-tri combined with optical imaging system. Results    PDGFRβ-specific affibody Z-tri was highly expressed in E. coli and purified to homogeneity. Z-tri could bind PDGFRβ-positive cells but not PDGFRβ-negative cells cultured in vitro. In the tumor xenografts of human lung cancer, intravenously injected Z-tri was predominantly distributed on cells overexpressing PDGFRβ. The near infrared fluorescent dye CF750 was efficiently conjugated to Z-tri. Optical images with high contrast of lung cancer xenografts were produced by using the near-infrared fluorescent probe CF750-Z-tri combined with optical imaging system. Conclusion    The near-infrared fluorescent probe CF750-Z-tri can be used for optical imaging of human lung cancer, which takes great potential in optical imaging-guided surgery of lung cancer.

Effect of interaction between sleep and occupational stress on the prevalence of hypertension in petroleum workers / 中国职业医学

OBJECTIVE: To explore the influence of the interaction among occupational stress, sleep duration and sleep quality on the prevalence of hypertension in petroleum workers. METHODS: A total of 3 040 workers from six oil field bases in Karamay City were selected as study subjects by multi-stage random cluster sampling method. The Chinese version of Pittsburgh Sleep Quality Scale and the revised version of Occupational Stress Scale were used to evaluate their sleep quality and occupational stress status. Binary logistic regression was used to analyze the effect of interaction of occupational stress, sleep duration and sleep quality on hypertension. RESULTS: The prevalence of hypertension in the study subjects was 15.3%(466/3 040), and the detection rates of sleep deprivation, poor sleep quality and high occupational stress were 26.5%, 78.3% and 19.6% respectively. After adjusting for confounding factors such as gender, ethnicity, age, marital status, education level, length of service, professional title, shift work, smoking, alcohol consumption and body mass index, the interaction analysis results showed that the risk of hypertension was higher in the poor sleep quality groups with normal sleep duration, sleep deprivation or longer sleep duration than that in good sleep quality group with normal sleep duration(all P<0.05), respectively. The risk of hypertension was higher in the group with sleep deprivation and high occupational stress than that in the group with normal sleep duration and low occupational stress(P<0.01). In the group with poor sleep quality and high occupational stress the risk of hypertension was higher than that in the group with good sleep quality and low occupational stress(P<0.05). CONCLUSION: The interaction among occupational stress, sleep duration and sleep quality may increase the risk of hypertension in petroleum workers.

Research progress on anti-atherosclerosis effect and mechanism of flavonoids compounds mediated by macrophages / 中国中药杂志

Flavonoids are important active ingredients of traditional Chinese medicine, mainly with cardiovascular, anti-liver injury, antioxidant, antispasmodic, and estrogen-like effects. These compounds have obvious effects on the cardiovascular and cerebrovascular diseases. Macrophage-derived foam cells are the key medium in the process of atherosclerosis(AS). In plaque, allserum lipids, serum lipoproteins, and various pro-or anti-inflammatory stimulating factors, chemokines, and small bioactive molecules can significantly affect the macrophage phenotype and induce stronger pro-inflammatory or anti-inflammatory properties. Studies have shown that some flavonoids can be used for macrophages through different pathways and mechanisms, playing an anti-atherosclerosis effect to different degrees, including promotion of cholesterol efflux from macrophages, anti-foaming of macrophages, inhibition of secretion of inflammatory factors, and antioxidant modified low density lipoprotein(ox-LDL)-induced apoptosis of macrophages. Related gene regulation inclu-ded ATP-binding cassette transporter A1(ABCA1), ATP-binding cassette transporter G1(ABCG1), Toll-like receptor(TLR), and scavenger receptor(SR). In this article, we would review the recent research progress of flavonoids on anti-atherosclerosis effect me-diated by macrophage. It is expected to provide new treatment strategies for AS-related cardiovascular and cerebrovascular diseases, and provide research ideas and development directions for the use of related natural medicines and design of new products.

Mutations in aminoacyl-tRNA synthetase genes: an analysis of 10 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of the diseases associated with aminoacyl-tRNA synthetases (ARS) deficiency.@*METHODS@#A retrospective analysis was performed of the clinical and gene mutation data of 10 children who were diagnosed with ARS gene mutations, based on next-generation sequencing from January 2016 to October 2019.@*RESULTS@#The age of onset ranged from 0 to 9 years among the 10 children. Convulsion was the most common initial symptom (7 children). Clinical manifestations included ataxia and normal or mildly retarded intellectual development (with or without epilepsy; n=4) and onset of epilepsy in childhood with developmental regression later (n=2). Some children experienced disease onset in the neonatal period and had severe epileptic encephalopathy, with myoclonus, generalized tonic-clonic seizure, and convulsive seizure (n=4); 3 had severe delayed development, 2 had feeding difficulty, and 1 had hearing impairment. Mutations were found in five genes: 3 had novel mutations in the AARS2 gene (c.331G>C, c.2682+5G>A, c.2164C>T, and c.761G>A), 2 had known mutations in the DARS2 gene (c.228-16C>A and c.536G>A), 1 had novel mutations in the CARS2 gene (c.1036C>T and c.323T>G), 1 had novel mutations in the RARS2 gene (c.1210A>G and c.622C>T), and 3 had novel mutations in the AARS gene (c.1901T>A, c.229C>T, c.244C>T, c.961G>C, c.2248C>T, and Chr16:70298860-70316687del).@*CONCLUSIONS@#A high heterogeneity is observed in the clinical phenotypes of the diseases associated with the ARS deficiency. A total of 14 novel mutations in 5 genes are reported in this study, which enriches the clinical phenotypes and genotypes of the diseases associated with ARS deficiency.

Research Progress of Regulatory Effect and Mechanism of Flavonoids on Vascular Endothelial Cell Injury / 中国实验方剂学杂志

To investigate the effect of flavonoid compounds on vascular endothelial cells. Vascular endothelial cells were located between plasma and vascular tissue, and can complete the metabolic exchange of plasma and interstitial fluid, synthesize and secrete a variety of biologically active substances, so as to ensure the normal contraction and relaxation of blood vessels, and maintain the tension of blood vessels. Besides, it can regulate blood pressure and the balance of blood coagulation and anticoagulation, and maintain normal blood flow and long-term patency of blood vessels. Endothelial cell damage can cause a series of cardiovascular diseases, such as hypertension and coronary heart disease. Flavonoids are widely found in nature. Because these compounds are mostly yellow or light yellow, they contain ketone groups in the molecule, which are called flavones. Flavonoids are widely distributed, mostly in higher plants and ferns. Various flavonoid compounds, such as flavonoids, flavonols, flavanones isoflavones and flavanones, can protect vascular endothelial cells. This article reviews relevant findings published in domestic and foreign journals. It is found that flavonoids have effects in resisting inflammation, reducing blood vessel fragility, improving blood vessel permeability, lowering blood lipids and cholesterol, vasodilating and resisting hemagglutinating, with the same effect as phytoestrogens. They can reduce vascular endothelial cell damage through anti-inflammatory, anti-oxidative stress, stable mitochondrial function, and regulating nitric oxide（NO）. It can be used in clinic to treat diseases, such as insufficient cerebral blood supply, sequelae caused by cerebral hemorrhage, hyperviscosity, cerebral thrombosis, coronary heart disease and angina pectoris.

Progress of residual inflammatory cardiovascular risk / 医学研究生学报

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality in the world. Although the comprehensive control of cardiovascular disease risk factors has achieved remarkable progress in recent years, the incidence of cardiovascular events is still high after the control of traditional risk factors such as low density lipoprotein cholesterol, blood pressure and blood glucose, collectively referred to as cardiovascular residual risk. Inflammation is a central driver of atherosclerosis and the ultimate rupture of plaque, as well as an important cause of residual cardiovascular risk. Therefore, this article reviews the formation, assessment and treatment of residual inflammatory cardiovascular risk.

Oral microbiological diversity in patients with salivary adenoid cystic carcinoma / 华西口腔医学杂志

OBJECTIVE@#The aim of this study was to identify the differences in microbial diversity and community in patients with salivary adenoid cystic carcinoma (SACC).@*METHODS@#Saliva was collected from 13 patients with SACC confirmed by histopathological diagnosis and 10 healthy control subjects. Total metagenomic DNA was extracted. The DNA amplicons of the V3-V4 hypervariable regions of the 16S rRNA gene were generated and subjected to high-throughput sequencing. Microbial diversity and community structure were analyzed with Mothur software.@*RESULTS@#A total of 16 genera of dominant bacteria in the SACC group were found, including Streptococcus (36.68%), Neisseria (8.55%), Prevotella_7 (7.53%), and Veillonella (6.37%), whereas 15 dominant bacteria in the control group were found, including Streptococcus (18.41%), Neisseria (18.20%), Prevotella_7 (8.89%), Porphyromonas (6.20%), Fusobacterium (5.86%) and Veillonella (5.82%). The statistically different phyla between the two groups were Firmicutes, Proteobacteria and Fusobacterium (P<0.05). The statistically different genera between the two groups were Streptococcus, Neisseria and Porphyromonas (P<0.05), and Capnocytophaga was only detected in patients with SACC.@*CONCLUSIONS@#Significant differences were observed in the oral microorganisms between the two groups.

Expression patterns of ectodysplasin and ectodysplasin receptor during early dental development in zebrafish / 华西口腔医学杂志

OBJECTIVE@#This study aims to study the expression patterns of ectodysplasin (EDA) and ectodysplasin receptor (EDAR) during the early development of zebrafish and provide a foundation for further research of the Eda signaling pathway in tooth development.@*METHODS@#Total RNA was extracted from zebrafish embryos at 48 hours postfertilization (hpf) and then reverse transcribed for cDNA library generation. The corresponding RNA polymerase was selected for the synthesis of the digoxin-labeled antisense mRNA probe of zebrafish pharyngeal tooth specific marker dlx2b and Eda signaling-associated genes eda and edar in vitro. The three sequences were ligated into a pGEMT vector with a TA cloning kit, and polymerase chain reaction (PCR) was applied to linearize the plasmid. The resultant PCR sequences were used as templates for synthesizing Dig-labeled mRNA probe dlx2b, eda, and edar. Zebrafish embryos were collected at 36, 48, 56, 60, 72, and 84 hpf, then whole mount in situ hybridization was performed for the detection of eda and edar expression patterns. Then, their expression patterns at 72 hpf were compared with the expression pattern of dlx2b.@*RESULTS@#The mRNA antisense probes of dlx2b, eda, and edar were successfully obtained. The positive signals of eda and edar were observed in zebrafish pharyngeal tooth region at 48-72 hpf and thus conform to the signals of dlx2b in the positive regions.@*CONCLUSIONS@#The ligand eda and edar, which are associated with the Eda signaling pathway, are strongly expressed only at the pharyngeal tooth region in zebrafish from tooth initiation to the morphogenesis stage. Thus, the Eda signaling pathway may be involved in the regulation of the early development of zebrafish pharyngeal teeth.

Diagnosis of intellectual disability/global developmental delay via genetic analysis in a central region of China / 中华医学杂志(英文版)

BACKGROUND@#Advanced technology has become a valuable tool in etiological studies of intellectual disability/global developmental delay (ID/GDD). The present study investigated the role of genetic analysis to confirm the etiology in ID/GDD patients where the cause of the disease was uncertain in central China.@*METHODS@#We evaluated 1051 ID/GDD children aged 6 months to 18 years from March 2009 to April 2017. Data concerning basic clinical manifestations were collected, and the method of etiology confirmation was recorded. Genome-wide copy number variations (CNVs) detection and high-throughput sequencing of exons in the targeted regions was performed to identify genetically-based etiologies. We compared the incidence of different methods used to confirm ID/GDD etiology among groups with differing degrees of ID/GDD using the Chi-square or Fisher exact probability test.@*RESULTS@#We recruited 1051 children with mild (367, 34.9%), moderate (301, 28.6%), severe (310, 29.5%), and profoundly severe (73, 6.9%) ID/GDD. The main causes of ID/GDD in the children assessed were perinatal factors, such as acquired brain injury, as well as single gene imbalance and chromosomal gene mutation. We identified karyotype and/or CNVs variation in 46/96 (47.9%) of cases in severe ID/GDD patients, which was significantly higher than those with mild and moderate ID/GDD of 34/96 (35.4%) and 15/96 (15.6%), respectively. A total of 331/536 (61.8%) patients with clear etiology have undergone genetic analysis while 262/515 (50.9%) patients with unclear etiology have undergone genetic analysis (χ = 12.645, P < 0.001). Gene structure variation via karyotype analysis and CNV detection increased the proportion of children with confirmed etiology from 51.0% to 56.3%, and second-generation high-throughput sequencing dramatically increased this to 78.9%. Ten novel mutations were detected, recessive mutations in X-linked genes (ATPase copper transporting alpha and bromodomain and WD repeat domain containing 3) and dominant de novo heterozygous mutations in X-linked genes (cyclin-dependent kinase like 5, protocadherin 19, IQ motif and Sec7 domain 2, and methyl-CpG binding protein 2) were reported in the study.@*CONCLUSIONS@#The present study indicates that genetic analysis is an effective method to increase the proportion of confirmed etiology in ID/GDD children and is highly recommended, especially in ID/GDD children with uncertain etiology.

Study on epidemic factors of varicella outbreak under high varicella vaccine coverage / 中华疾病控制杂志

Objective To explore the epidemic factors of varicella transmission under high varicella vacince coverage, assess the vaccine effectineness of one dose of varicella vaccine, so as to provide scientific basis for controlling the varicella outbreak and optimizing the varicella immunization strategy. Methods A 1 ∶〗2 paired case-control study of a varicella outbreak was conducted in a primary school in central region of Jiangsu Province in 2018. Analysis of varicella epidemic factors was performed using conditional logistic stepwise regression. Results This outbreak lasted for 14 days. A total of 45 students were infected with varicella, of which 71.1% were breakthrough cases. The fever, rash degree and disease course of breakthrough cases were all relatively mild compared with those without immune history (all P5 years and the initial immunization age <15 months were potential risk factors for breakthrough cases. The overall vaccine effectiveness of one dose of varicella vaccine was 77.9%(95% CI: 53.3%-92.1%). The fever, severity of the rash and the course of the disease were all milder than those without the history of immunization (all P<0.05). Conclusions The clinical symptoms of the breakthrough cases are relatively mild, and one dose of varicella vaccine is insufficient to control the outbreak of varicella with limited vaccine effectiveness. Two doses of varicella immunization strategy is recommended.

Diagnosis of intellectual disability/global developmental delay via genetic analysis in a central region of China / 中华医学杂志(英文版)

Background@#Advanced technology has become a valuable tool in etiological studies of intellectual disability/global developmental delay (ID/GDD). The present study investigated the role of genetic analysis to confirm the etiology in ID/GDD patients where the cause of the disease was uncertain in central China.@*Methods@#We evaluated 1051 ID/GDD children aged 6 months to 18 years from March 2009 to April 2017. Data concerning basic clinical manifestations were collected, and the method of etiology confirmation was recorded. Genome-wide copy number variations (CNVs) detection and high-throughput sequencing of exons in the targeted regions was performed to identify genetically-based etiologies. We compared the incidence of different methods used to confirm ID/GDD etiology among groups with differing degrees of ID/GDD using the Chi-square or Fisher exact probability test.@*Results@#We recruited 1051 children with mild (367, 34.9%), moderate (301, 28.6%), severe (310, 29.5%), and profoundly severe (73, 6.9%) ID/GDD. The main causes of ID/GDD in the children assessed were perinatal factors, such as acquired brain injury, as well as single gene imbalance and chromosomal gene mutation. We identified karyotype and/or CNVs variation in 46/96 (47.9%) of cases in severe ID/GDD patients, which was significantly higher than those with mild and moderate ID/GDD of 34/96 (35.4%) and 15/96 (15.6%), respectively. A total of 331/536 (61.8%) patients with clear etiology have undergone genetic analysis while 262/515 (50.9%) patients with unclear etiology have undergone genetic analysis (χ2 = 12.645, P < 0.001). Gene structure variation via karyotype analysis and CNV detection increased the proportion of children with confirmed etiology from 51.0% to 56.3%, and second-generation high-throughput sequencing dramatically increased this to 78.9%. Ten novel mutations were detected, recessive mutations in X-linked genes (ATPase copper transporting alpha and bromodomain and WD repeat domain containing 3) and dominant de novo heterozygous mutations in X-linked genes (cyclin-dependent kinase like 5, protocadherin 19, IQ motif and Sec7 domain 2, and methyl-CpG binding protein 2) were reported in the study.@*Conclusions@#The present study indicates that genetic analysis is an effective method to increase the proportion of confirmed etiology in ID/GDD children and is highly recommended, especially in ID/GDD children with uncertain etiology.

Protective Effect of Ferulic Acid on PC12 Cells with H2O2-induced Oxidative Damage / 中国实验方剂学杂志

Objective:To investigate the protective effect of ferulic acid on PC12 cells injured by H2O2 and the molecular mechanisms. Method:The oxidative stress model was established by treating PC12 cells with H2O2, and then different dosages of ferulic acid (1, 10, 100 μmol·L-1) were used for intervention. Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the cell viability,lactate dehydrogenase (LDH) and malondialdelyde (MDA) in cell supernatant, and superoxidedismutase (SOD) in cells was tested by biochemical method respectively. Insulin-like growth factors-1 (IGF-1) mRNA and protein expressions were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result:The 24 h intervention with different dosages of ferulic acid (1, 10, 100 μmol·L-1) could significantly improve the oxidative damage of PC12 cells induced by H2O2, compared with the model group, ferulic acid at 1,10,100 μmol·L-1 significantly increased PC12 cells viability,significantly decreased LDH and MDA content in cell supernatant (PPPPPConclusion:Ferulic acid exerts a protective effect on H2O2-inducing PC12 cells injury,which might be related to insulin signaling pathways.

Regulatory Effect and Mechanism of Araliaceae Traditional Chinese Medicine on Cholesterol / 中国实验方剂学杂志

Araliaceae plant Notoginseng Radix et Rhizoma, Ginseng Radix et Rhizoma and Panacix Quinquefolii Radix are famous Chinese herbal medicines, with anti-inflammatory and anti-aging effect, as well as obvious effect on cardiovascular and cerebrovascular systems. Studies have found that the metabolism and transport of cholesterol may affect the function of the cardiovascular system. Cholesterol can be divided into high-density cholesterol and low-density cholesterol. Cholesterol has many physiological regulating effect. High-density cholesterol has a protective effect on cardiovascular disease. When the cholesterol metabolism in the body is disordered, low-density cholesterol is increased, and will cause the increase in the risk of cardiovascular and cerebrovascular diseases. By consulting relevant Chinese and foreign documents and materials, we found that traditional Chinese medicine Araliaceae has a significant regulatory effect on cholesterol. It can directly regulate the cholesterol level of experimental hyperlipidemia rats, reduce total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) in rats, and partially increase high-density lipoprotein cholesterol(HDL-C) level in rats. It can inhibit cholesterol synthesis by inhibiting cholesterol synthesis-regulating genes liver X receptor-α(LXR-α), peroxisome proliferator-activated receptor γ(PPARγ), cytochrome P450 7A1(CYP7A1); and up-regulate cholesterol metabolism genes peroxisome proliferator-activated receptor-α(PPARα), PPARγ, CYP8B1, CYP7A1, LXR) and body ATP-binding cassette transporter, ABC transporter(ABCA1, ABCG5/8)to promote cholesterol metabolism in the body. Araliaceae plants may play a neuroprotective role by regulating cholesterol metabolism and transport in the brain, and improve neurodegenerative diseases. Studies on the effect of Araliaceae plants on the metabolism and transport of cholesterol in brain will become a hot research topic in the future. The above review is expected to provide a reference for further research on the lipid-lowering effect and mechanism of Araliaceae plants.

A new meroterpenoid from Ganoderma resinaceum / 中草药

Objective: For the purpose of finding new agents, the chemical study on Ganoderma resinaceum was carried out. Methods: The chemical constituents from the dried fruiting bodies of G. resinaceum were isolated by column chromatographic methods of silica gel, MCI-Gel resin, and high performance liquid chromatography. The structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Results: Four compounds including one new meroterpenoid were isolated from this fungus. Their structures were identified as ganoresinains F (1), 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (2), ganoderic acid XL2 (3) and 2,3-dihydro-4(1H)-quinolone (4). Conclusion: Compound 1 is a new compound and named as ganoresinains F (1).

On the necessity of an integrative approach to understand protein structural dynamics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Proteins are dynamic, fluctuating between multiple conformational states. Protein dynamics, spanning orders of magnitude in time and space, allow proteins to perform specific functions. Moreover, under certain conditions, proteins can morph into a different set of conformations. Thus, a complete understanding of protein structural dynamics can provide mechanistic insights into protein function. Here, we review the latest developments in methods used to determine protein ensemble structures and to characterize protein dynamics. Techniques including X-ray crystallography, cryogenic electron microscopy, and small angle scattering can provide structural information on specific conformational states or on the averaged shape of the protein, whereas techniques including nuclear magnetic resonance, fluorescence resonance energy transfer (FRET), and chemical cross-linking coupled with mass spectrometry provide information on the fluctuation of the distances between protein domains, residues, and atoms for the multiple conformational states of the protein. In particular, FRET measurements at the single-molecule level allow rapid resolution of protein conformational states, where information is otherwise obscured in bulk measurements. Taken together, the different techniques complement each other and their integrated use can offer a clear picture of protein structure and dynamics.