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1.
Acta Pharmaceutica Sinica ; (12): 1-16, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1005433

RESUMO

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

2.
China Journal of Chinese Materia Medica ; (24): 1876-1884, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981406

RESUMO

To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. The experimental results showed that VFD and DS basically kept the original color of MFOEU. The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. Considering the color of MFOEU, the suitable drying methods were DS and VFD. Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas.


Assuntos
Eucommiaceae/química , Flores/química , Flavonoides/análise , Rutina/análise , Ácido Clorogênico/análise
3.
China Journal of Chinese Materia Medica ; (24): 1824-1832, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981400

RESUMO

This study aims to develop the pre-column derivatization high performance liquid chromatography(HPLC) method for the determination of 16 kinds of amino acids in Eucommia ulmoides leaves, and compare the content of amino acids in the leaves harvested at different time and under leaf-oriented cultivation mode(LCM) and arbor forest mode(AFM). The HPLC conditions are as below: phenyl isothiocyanate(PITC) as pre-column derivatization agent, Agilent ZORBAX C_(18 )column(4.6 mm×250 mm, 5 μm), mobile phase A of acetonitrile-water(80∶20), mobile phase B of 0.1 mol·L~(-1) sodium acetate solution-acetonitrile(94∶6), gradient elution, flow rate of 1.0 mL·min~(-1), injection volume of 5 μL, column temperature of 40 ℃, and detection wavelength of 254 nm. The HPLC profile indicated well separation of 16 kinds of amino acids and the amino acid content in E. ulmoides leaves was up to 16.26%. In addition, the amino acid content in leaves of E. ulmoides under LCM was higher than under AFM. The amino acid content varied with the harvesting time. Through orthogonal partial least squares discriminant analysis, the amino acids of E. ulmoides under LCM and AFM were compared, which can distinguish the leaves under LCM from those under AFM. Principal component analysis was applied to comprehensively score the amino acids of E. ulmoides leaves. The results showed that the score of leaves under LCM was higher than that under AFM. Nutritional evaluation results indicated that the proteins in E. ulmoides leaves belonged to high-quality vegetable proteins. The established method for the determination of amino acid content is reliable. With the amino acid content as index, the leaf quality of E. ulmoides under LCM is better than that under AFM. This study lays a theoretical basis for the promotion of LCM for E. ulmoides and the development of medicinal and edible products from E. ulmoides leaves.


Assuntos
Aminoácidos/metabolismo , Eucommiaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Folhas de Planta/química
4.
Chinese Journal of Epidemiology ; (12): 504-510, 2023.
Artigo em Chinês | WPRIM | ID: wpr-969935

RESUMO

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.


Assuntos
Humanos , Fissura Palatina/genética , Fenda Labial/genética , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Fatores de Risco , Polimorfismo de Nucleotídeo Único
5.
Biomedical and Environmental Sciences ; (12): 702-714, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1007843

RESUMO

OBJECTIVE@#In developed countries, midday napping and nighttime sleep duration have been linked to long-term survival; however, little is known about such effects in less developed regions. Therefore, this study aimed to assess the associations of midday napping and nocturnal sleep with mortality in middle-aged and older Chinese adults.@*METHODS@#A nationwide cohort of 15,524 adults aged ≥ 45 years was enrolled from 28 provincial regions across mainland China and followed up from 2011 to 2018, using data from the Chinese Health and Retirement Longitudinal Study. Midday napping and nighttime sleep duration were assessed using standardized questionnaires. Cox proportional hazards models with random intercepts for the surveyed provinces were used to estimate hazard ratios ( HRs) of all-cause mortality, adjusting for sociodemographic characteristics, behavioral factors, and health status.@*RESULTS@#A total of 1,745 deaths occurred during a median follow-up of 7.1 years, and the mean (standard deviation) age was 59 (10.1) years at baseline. Compared with non-nappers, over 60 min nappers had a higher risk of all-cause mortality [ HR: 1.35, 95% confidence interval ( CI): 1.17-1.56], while no significant associations were observed among < 30 min nappers. Compared with sleep duration of 6-8 h/night, both short (< 6 h) and long (≥ 8 h) sleep duration were significantly associated with increased mortality, with corresponding HR (95% CI) estimates of 1.21 (1.05-1.38) and 1.26 (1.10-1.44), respectively. We observed significant patterns for greater risks associated with longer nap duration, with a P trend value < 0.001 for all-cause mortality. No significant evidence of an additive interaction was identified between midday napping and nighttime sleep.@*CONCLUSION@#Long midday napping and inappropriate nighttime sleep were independently associated with an increased risk of all-cause mortality in middle-aged and older Chinese populations. Biological studies are needed to validate our findings and clarify the mechanisms underlying this association.


Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Idoso , Estudos Longitudinais , Estudos Prospectivos , Sono , Duração do Sono , China/epidemiologia
6.
China Journal of Chinese Materia Medica ; (24): 6676-6681, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1008865

RESUMO

Nine compounds were isolated from the 90% ethanol extract of Salacia polysperma by silica gel, Sephadex LH-20 column chromatography, together with preparative HPLC methods. Based on HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the nine compounds were identified as 28-hydroxy wilforlide B(1), wilforlide A(2), 1β,3β-dihydroxyurs-9(11),12-diene(3),(-)-epicatechin(4),(+)-catechin(5),(-)-4'-O-methyl-ent-galloepicatechin(6), 3-hydroxy-1-(4-hydroxy-3-methoxy-phenyl)propan-1-one(7),(-)-(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(8), and vanillic acid(9). Compound 1 is a new oleanane-type triterpene lactone. Compounds 1, 3, 4, 7-9 were isolated from the Salacia genus for the first time. All compounds were assayed for their α-glucosidase inhibitory activity. The results suggested that compound 8 exhibited moderate α-glucosidase inhibitory activity, with an IC_(50) value of 37.2 μmol·L~(-1), and the other compounds showed no α-glucosidase inhibitory activity.


Assuntos
Salacia/química , alfa-Glucosidases , Triterpenos/farmacologia , Espectroscopia de Ressonância Magnética , Etanol , Estrutura Molecular
7.
China Journal of Chinese Materia Medica ; (24): 5817-5821, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1008779

RESUMO

Eight compounds were isolated from ethyl acetate fraction of 80% ethanol extract of the hulls of Garcinia mangostana by silica gel, Sephadex LH-20 column chromatography, as well as prep-HPLC methods. By HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the eight compounds were identified as 16-en mangostenone E(1), α-mangostin(2), 1,7-dihydroxy-2-(3-methy-lbut-2-enyl)-3-methoxyxanthone(3), cratoxyxanthone(4), 2,6-dimethoxy-para-benzoquinone(5), methyl orselinate(6), ficusol(7), and 4-(4-carboxy-2-methoxyphenoxy)-3,5-dimethoxybenzoic acid(8). Compound 1 was a new xanthone, and compound 4 was a xanthone dimer, compound 5 was a naphthoquinone. All compounds were isolated from this plant for the first time except compounds 2 and 3. Cytotoxic bioassay suggested that compounds 1, 2 and 4 possessed moderate cytotoxicity, suppressing HeLa cell line with IC_(50) va-lues of 24.3, 35.5 and 17.1 μmol·L~(-1), respectively. Compound 4 also could suppress K562 cells with an IC_(50) value of 39.8 μmol·L~(-1).


Assuntos
Humanos , Garcinia mangostana/química , Células HeLa , Antineoplásicos , Espectroscopia de Ressonância Magnética , Xantonas/farmacologia , Garcinia/química , Extratos Vegetais/química , Estrutura Molecular
8.
Chinese Journal of School Health ; (12): 203-206, 2022.
Artigo em Chinês | WPRIM | ID: wpr-920590

RESUMO

Objective@#To explore the prevalence of sexting among secondary vocational school students and to examine the correlation between sexting and mental health, so as to provide evidence for prevention and intervention on adolescents mental health.@*Methods@#In April 2021, three secondary vocational schools from central urban area, outskirts and outer suburbs in Shanghai, among 1 580 students were selected by cluster sampling.@*Results@#The proportions of students who received and who forwarded others private photos or videos were 11.96% and 2.78%, respectively. The proportion of students who sent others personal photos or videos was 2.54%. And the proportions of boys were higher than those of girls ( χ 2=45.89, 24.09, 6.66, P <0.01). The results of multivariable Logistic analysis showed that compared with those who had never sexted, students who had ever had any sexting were at higher risk of anxiety ( OR=2.40, 95%CI =1.59-3.61), depression( OR=1.86, 95%CI =1.25-2.75), non suicidal self injury intention ( OR=2.34, 95%CI =1.48-3.69) and suicidal intention ( OR=2.96, 95%CI =1.83-4.79)( P < 0.05 ).@*Conclusion@#There is a significant correlation between sexting and mental health among secondary vocational school students. The latent risks of sexting should be included in the curriculum of comprehensive sex education for teenagers to enhance their media literacy and decision making capability, so as to prevent sexual assault or abuse caused by sexting and promote sexual and reproductive health and as well as mental health of adolescents.

9.
China Journal of Chinese Materia Medica ; (24): 1618-1624, 2022.
Artigo em Chinês | WPRIM | ID: wpr-928092

RESUMO

Aconiti Kusnezoffii Radix Cocta is one of the most commonly used medicinal materials in Mongolian medicine. Due to the strong toxicity of Aconiti Kusnezoffii Radix Cocta, Mongolian medicine often uses Chebulae Fructus, Glycyrrhizae Radix et Rhizoma to reduce the toxicity, so as to ensure the curative effect of Aconiti Kusnezoffii Radix Cocta while ensuring its clinical curative effect, but the mechanism is not clear. The aim of this study was to investigate the effects of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Aconiti Kusnezoffii Radix Cocta on the mRNA transcription and protein translation of cytochrome P450(CYP450) in the liver of normal rats. Male SD rats were randomly divided into negative control(NC) group, phenobarbital(PB) group(0.08 g·kg~(-1)·d~(-1)), Chebulae Fructus group(0.254 2 g·kg~(-1)·d~(-1)), Glycyrrhizae Radix et Rhizoma group(0.254 2 g·kg~(-1)·d~(-1)), Aconiti Kusnezoffii Radix Cocta group(0.254 2 g·kg~(-1)·d~(-1))and compatibility group(0.254 2 g·kg~(-1)·d~(-1),taking Aconiti Kusnezoffii Radix Cocta as the standard). After continuous administration for 8 days, the activities of total bile acid(TBA), alkaline phosphatase(ALP), amino-transferase(ALT) and aspartate aminotransferase(AST)in serum were detected, the pathological changes of liver tissue were observed, and the mRNA and protein expression levels of CYP1 A2, CYP2 C11 and CYP3 A1 were observed. Compared with the NC group, the serum ALP, ALT and AST activities in the Aconiti Kusnezoffii Radix Cocta group were significantly increased, and the ALP, ALT and AST activities were decreased after compatibility. At the same time, compatibility could reduce the liver injury caused by Aconiti Kusnezoffii Radix Cocta. The results showed that Aconiti Kusnezoffii Radix Cocta could inhibit the expression of CYP1 A2, CYP2 C11 and CYP3 A1, and could up-regulate the expression of CYP1 A2, CYP2 C11 and CYP3 A1 when combined with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma. The level of translation was consistent with that of transcription. The compatibility of Chebulae Fructus and Glycyrrhizae Radix et Rhizoma with Aconiti Kusnezoffii Radix Cocta could up-regulate the expression of CYP450 enzyme, reduce the accumulation time of aconitine in vivo, and play a role in reducing toxicity, and this effect may start from gene transcription.


Assuntos
Animais , Masculino , Ratos , Sistema Enzimático do Citocromo P-450/genética , Medicamentos de Ervas Chinesas , Glycyrrhiza , Fígado , Extratos Vegetais , Ratos Sprague-Dawley , Terminalia
10.
Acta Physiologica Sinica ; (6): 294-300, 2022.
Artigo em Chinês | WPRIM | ID: wpr-927605

RESUMO

How the brain perceives objects and classifies perceived objects is one of the important goals of visual cognitive neuroscience. Previous research has shown that when we see objects, the brain's ventral visual pathway recognizes and classifies them, leading to different ways of interacting with them. In this paper, we summarize the latest research progress of the ventral visual pathway related to the visual classification of objects. From the perspective of the neural representation of objects and its underlying mechanisms in the visual cortex, we summarize the current research status of the two important organizational dimensions of object animacy and real-world size, provide new insights, and point out the direction of further research.


Assuntos
Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética , Reconhecimento Visual de Modelos , Estimulação Luminosa , Córtex Visual , Vias Visuais
11.
Chinese Acupuncture & Moxibustion ; (12): 231-236, 2022.
Artigo em Chinês | WPRIM | ID: wpr-927365

RESUMO

The current clinical evidence and underlying mechanisms of acupuncture and moxibustion in the treatment of irritable bowel syndrome (IBS) were summarized, so as to better optimize clinical treatment. The relevant articles of acupuncture and moxibustion in the treatment of IBS in recent years were retrieved and summarized. We found that the clinical efficacy of acupuncture and moxibustion in the treatment of IBS was relatively reliable. However, the mutual relationships among various mechanisms of action such as abnormal gastrointestinal motility, high visceral sensitivity, intestinal microenvironment disorders, and abnormal intestinal-brain interactions need to be further explored. The authors believe that in-depth explorations of the bidirectional regulation of "gut-brain axis", the law of changes in the abundance and diversity of intestinal flora, and the establishment of a more ideal animal model of TCM syndrome differentiation are useful ideas for subsequent research.


Assuntos
Animais , Acupuntura , Terapia por Acupuntura , Microbioma Gastrointestinal , Síndrome do Intestino Irritável/terapia , Moxibustão
12.
Journal of Southern Medical University ; (12): 966-975, 2022.
Artigo em Chinês | WPRIM | ID: wpr-941029

RESUMO

OBJECTIVE@#To explore the role of vasohibin-2 (VASH2) in regulation of proliferation and metastasis of cervical cancer cells.@*METHODS@#We analyzed the differentially expressed genes between cervical cancer cells with flotillin-1 overexpression and knockdown by RNA-seq combined with analysis of public databases. The expression levels of VASH2 were examined in normal cervical epithelial cells (HcerEpic), cervical cancer cell lines (HeLa, C-33A, Ca ski, SiHa and MS751) and fresh cervical cancer tissues with different lymph node metastasis status. We further tested the effects of lentivirus-mediated overexpression and interference of VASH2 on proliferation, migration, invasion and lymphatic vessel formation of the cervical cancer cells and detected the expression levels of key epithelial-mesenchymal transition (EMT) markers and TGF-β mRNA.@*RESULTS@#RNA-seq and analysis of public databases showed that VASH2 expression was significantly upregulated in cervical cancer cells exogenously overexpressing flotillin-1 (P < 0.05) and downregulated in cells with flotillin-1 knockdown (P < 0.05), and was significantly higher in cervical cancer tissues with lymph node metastasis than in those without lymph node metastasis (P < 0.01). In cervical cancer cell lines Ca Ski, SiHa, and MS751 and cervical cancer tissue specimens with lymph node metastasis, VASH2 expression was also significantly upregulated as compared with HcerEpic cells and cervical cancer tissues without lymph node metastasis (P < 0.05). Exogenous overexpression of VASH2 significantly promoted proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells, whereas these abilities were significantly inhibited in cells with VASH2 knockdown (P < 0.05). The cervical cancer cells overexpressing VASH2 showed significant down- regulation of e-cadherin and up- regulation of N-cadherin, Vimentin and VEGF-C, while the reverse changes were detected in cells with VASH2 knockdown (P < 0.05). TGF-β mRNA expression was significantly up-regulated in cervical cancer cells overexpressing VASH2 and down-regulated in cells with VASH2 knockdown (P < 0.001).@*CONCLUSION@#Flotillin-1 may participate in TGF-β signaling pathway-mediated EMT through its down-stream target gene VASH2 to promote the proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells in vitro.


Assuntos
Feminino , Humanos , Proteínas Angiogênicas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Metástase Linfática , RNA Mensageiro , Fator de Crescimento Transformador beta/metabolismo , Neoplasias do Colo do Útero/patologia
13.
Journal of Peking University(Health Sciences) ; (6): 394-399, 2022.
Artigo em Chinês | WPRIM | ID: wpr-940980

RESUMO

OBJECTIVE@#To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios.@*METHODS@#The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07).@*RESULTS@#After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4).@*CONCLUSION@#This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.


Assuntos
Humanos , Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Polimorfismo de Nucleotídeo Único , Via de Sinalização Wnt/genética
14.
Journal of Peking University(Health Sciences) ; (6): 387-393, 2022.
Artigo em Chinês | WPRIM | ID: wpr-940979

RESUMO

OBJECTIVE@#To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design.@*METHODS@#Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database.@*RESULTS@#A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes.@*CONCLUSION@#Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.


Assuntos
Humanos , Povo Asiático , Estudos de Casos e Controles , Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Mutação , Pais , Polimorfismo de Nucleotídeo Único , Sequenciamento do Exoma
15.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 36-42, 2022.
Artigo em Chinês | WPRIM | ID: wpr-940349

RESUMO

ObjectiveTo explore the effect and mechanism of Xiaojindan extract (XJD) on macrophage polarization. MethodLipopolysaccharide (LPS) and interleukin-4 (IL-4) were used to induce M1 and M2 polarization of RAW264.7 cells. The influence of 10-80 mg·L-1 XJD on cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. Nitric oxide (NO) and interleukin-6 (IL-6) release was explored by Griess assay and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA expression of M1 and M2 macrophage markers was measured by real-time quantitative polymerase chain reaction (Real-time PCR), and the CD206+ expression was determined by flow cytometry. The activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway was analyzed by western blot. Result10-80 mg·L-1 XJD showed no marked cytotoxicity in LPS (0.5 mg·L-1)- or IL-4 (20 μg·L-1)-induced RAW264.7 cells. Compared with the control group, LPS significantly promoted the expression of M1 macrophage markers (P<0.01), including increased NO and IL-6 release (P<0.01) and upregulated mRNA expression of interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) (P<0.01). Compared with LPS-induced group, 20-80 mg·L-1 XJD decreased the release of NO and IL-6 in a dose-dependent manner (P<0.01), and similarly 10-80 mg·L-1 XJD suppressed the mRNA expression of IL-1β, iNOS, COX-2 and TNF-α (P<0.01). Compared with the control group, IL-4 obviously increased the expression of M2 macrophage markers (P<0.01), including increased CD206+ cell population and upregulated mRNA expression of arginine-1 (Arg-1), interleukin-10 (IL-10), interleukin-13 (IL-13) and transforming growth factor-β1 (TGF-β1). Compared with IL-4-induced group, 10-80 mg·L-1 XJD dose-dependently decreased CD206+ cell population (P<0.01) and inhibited the mRNA expression of Arg-1, IL-10, IL-13 and TGF-β1 (P<0.01). Western blot showed that XJD significantly downregulated the activation of PI3K/Akt pathway as compared to LPS- and IL-4-induced groups (P<0.05, P<0.01). ConclusionXJD significantly inhibited the macrophage polarization in the LPS- and IL-4-induced RAW264.7 cells by targeting PI3K/Akt pathway.

16.
Chinese Journal of Epidemiology ; (12): 241-247, 2022.
Artigo em Chinês | WPRIM | ID: wpr-935377

RESUMO

Objective: To explore the immunogenicity and influencing factors of hepatitis B vaccination based on different vaccination schedules among chronic kidney disease (CKD) patients. Methods: CKD patients who participated in randomized controlled trials in four hospitals in Shanxi province and completed three doses of 20 µg vaccination (at months 0, 1 and 6) and four doses of 20 µg or 60 µg vaccination (at months 0, 1, 2, and 6) were surveyed from May 2019 to July 2020.According to the ratio of 1∶1∶1, 273 CKD patients were divided into 3 groups randomly. Quantification of the anti-hepatitis B surface antigen-antibody (anti-HBs) in serum samples was performed using chemiluminescent microparticle immunoassay at months 1 and 6 after the entire course of the vaccinations. The positive rate, high-level positive rate, geometric mean concentration (GMC) of anti-HBs, and the influencing factors were analyzed by χ2 tests, analysis of variance, unconditional logistic regression analysis. Results: A total of 273 CKD patitents were participants.The positive rates in the CKD patients with four doses of 20 µg vaccination (92.96%,66/71) or 60 µg vaccination (93.15%, 68/73) were higher than that in the CKD patients with three doses of 20 µg vaccination (81.69%, 58/71) at month one after the full course of the vaccinations (P<0.05). The GMCs of anti-HBs showed similar results (2 091.11 mIU/ml and 2 441.50 mIU/ml vs. 1 675.21 mIU/ml) (P<0.05). The positive rate was higher in the CKD patients with four doses of 60 µg vaccination (94.83%,55/58) than in those with three doses of 20 µg vaccination (78.79%,52/66) (P<0.05) at month six after the full course of the vaccinations. And the GMC of anti-HBs in the patients with four doses of 60 µg vaccination (824.28 mIU/ml) was significantly higher than those in the patients with 3 or 4 doses of 20 µg vaccination (639.74 mIU/ml and 755.53 mIU/ml) (P<0.05). After controlling the confounding factors, the positive rate in the CKD patients with four doses of 60 µg vaccination were 3.19 (95%CI: 1.02-9.96) and 5.32 (95%CI: 1.27-22.19) times higher than those in the patients with three doses of 20 µg vaccination at months 1 and 6 after the full course of the vaccinations, respectively. The positive rate in CKD patients without immune suppression or hormone therapy was 3.33 (95%CI: 1.26-8.80) and 4.78 (95%CI: 1.47-15.57) times higher than those in the patients with such therapy, respectively. Conclusions: Four doses of 20 µg or 60 µg hepatitis B vaccination could improve the immunogenicity in patients with CKD. And four doses of 60 µg vaccination might play a positive role in maintaining anti-HBs in this population. The immunogenicity in the CKD patients with immune suppression or hormone therapy was poor.


Assuntos
Animais , Cricetinae , Humanos , Células CHO , Cricetulus , Seguimentos , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B , Imunização Secundária , Insuficiência Renal Crônica , Vacinação
17.
Chinese Journal of Contemporary Pediatrics ; (12): 33-40, 2022.
Artigo em Inglês | WPRIM | ID: wpr-928563

RESUMO

OBJECTIVES@#To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.@*METHODS@#A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.@*RESULTS@#Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).@*CONCLUSIONS@#There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.


Assuntos
Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Displasia Broncopulmonar/epidemiologia , Idade Gestacional , Lactente Extremamente Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
18.
Journal of Peking University(Health Sciences) ; (6): 467-472, 2021.
Artigo em Chinês | WPRIM | ID: wpr-942203

RESUMO

OBJECTIVE@#To explore the relationship between nutrients intake during pregnancy and the glycemic control effect in pregnant women with gestational diabetes mellitus (GDM).@*METHODS@#Pregnant women for 25-35 gestational weeks who underwent prenatal examination and completed GDM diagnostic test in two third-class hospitals in Beijing from October 2015 to October 2017 were recruited to participate in the cohort study, and were investigated at enrollment, 2 weeks after enrollment, and delivery. The cross-sectional survey data 2 weeks after enrollment was used for this study. Among them, dietary survey used the 24 h dietary records to collect the food intake of the subjects for the past day, and the intake of energy, macronutrients and micronutrients, was calculated according to the Chinese Food Composition Table. Using the data of fasting blood glucose (FBG) collected by clinical information system and referring to the Chinese Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes (2014), the GDM patients with FBG ≤5.3 mmol/L were divided into the well-control group, those with FBG >5.3 mmol/L were divided into poorly-control group, and pregnant women with normal glucose tolerance were consi-dered as the normal group. Binary Logistic regression was used to analyze the association between the nutrients intake and glycemic control effect in pregnant women with GDM.@*RESULTS@#A total of 227 pregnant women were enrolled, including 104 GDM patients and 123 normal pregnancy women. Among them, 76 subjects in the well-control group (73.1%, 76/104) and 28 subjects in the poorly-control group (26.9%, 28/104). Compared with the well-control group and the normal group, the protein intake and its energy ratio of the poorly-control group were significantly higher, while carbohydrate energy ratio was significantly lower. In terms of micronutrients, there was no significant difference between the well-control group and the poorly-control group. After adjusting for age, gestational age and physical activity level, with the well-control group as the control group, binary Logistic regression model showed that higher protein energy ratio was positively correlated with poorly glycemic control effect in pregnant women with GDM (OR=6.12, 95%CI: 1.44-25.98), while higher carbohydrate energy ratio was negatively correlated with poorly glycemic control (OR=0.54, 95%CI: 0.32-0.91).@*CONCLUSION@#Reduced protein intake and increased carbohydrate intake were associated with better glycemic control in pregnant women with GDM. It is suggested that GDM patients should adjust their dietary pattern further to achieve good glycemic control effect.


Assuntos
Feminino , Humanos , Gravidez , Glicemia , Estudos de Coortes , Estudos Transversais , Diabetes Gestacional , Ingestão de Alimentos , Controle Glicêmico , Nutrientes , Gestantes
19.
China Journal of Chinese Materia Medica ; (24): 1205-1210, 2021.
Artigo em Chinês | WPRIM | ID: wpr-879023

RESUMO

To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.


Assuntos
Animais , Ratos , Depressão/tratamento farmacológico , Hipocampo , Plasticidade Neuronal , Ratos Sprague-Dawley , Sinapses
20.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 172-180, 2021.
Artigo em Chinês | WPRIM | ID: wpr-905942

RESUMO

In this paper, through the collection and collation of ancient materia medica, medical books and medical formulary, combining with modern literature, the historical changes of the name, origin, position, harvesting time, medicinal parts, toxicity, functions and indications, processing methods of Rhododendri Mollis Flos (RMF) were systematically combed and verified, so as to provide reference for clinical application, processing standard and basic research of RMF. According to textual research, RMF is the dried flower of Rhododendron molle. In each historical period, there are many aliases and local names, being with phenomenon of homonyms and synonyms. RMF is mostly wild and planted in a small amount, harvesting time is mostly in March to April. However, the harvesting flowering period is differently described as initial bloom, full bloom and extensive bloom. RMF was first recorded in Shennong Bencaojing (《神农本草经》), but it did not mention its medicinal parts. Then the flowers, fruits, roots are be used as medicine, but flowers are still the main medicinal parts. RMF had a long processing history, included fried, vinegar-fried, wine-fried, steamed, wine-steamed, vinegar-steamed, and many other processing methods in ancient times. However, at present, only raw products are used in clinical practice, and only a few modern books retain the methods of stir-fried and wine-steamed, believing that the processing can reduce toxicity of RMF.

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