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AIM: To evaluate the efficacy and safety of foveal-sparing internal limiting membrane peeling(FSIP)or complete internal limiting membrane peeling(CMIP)for the treatment of myopic traction maculopathy(MTM)during vitrectomy.METHODS: CNKI, Wanfang, VIP, PubMed, Embase, Cochrane Library, and Web of Science were searched from January 1th 2000 to July 1th 2022, and studies that compared FSIP and CMIP for MTM were collected. The change and recovery rate of best corrected visual acuity(BCVA), incidence of full-thickness macular hole(FTMH), change of central foveal thickness(CFT)and the rate of complete reattachment.RESULTS: A total of 484 eyes from 12 literatures were included, with 203 eyes in the FSIP group and 281 eyes in the CMIP group. The results of Meta-analysis showed that FSIP group were superior to the CMIP group in the mean change of BCVA(SMD=0.52, 95%CI: 0.20~0.85, P=0.002), the improvement rate of BCVA(RR=1.50, 95%CI: 1.22~1.85, P=0.0002)and the incidence of postoperative FTMH(RR=0.23, 95%CI: 0.10~0.54, P=0.0008). There was no statistical difference between the two surgical methods in terms of mean change in CFT(SMD=0.04, 95%CI: -0.19~0.26, P=0.75)and the rate of complete reattachment(RR=1.12, 95%CI: 0.94~1.32, P=0.20).CONCLUSION: FSIP have similar anatomical outcomes compared to CMIP, but FSIP resulted in better visual acuity and lower incidence of postoperative FTMH.
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N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.
Subject(s)
Humans , Apoptosis , Mitogen-Activated Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Signal TransductionABSTRACT
OBJECTIVES@#Steroidal anti-inflammatory drugs have certain side effects in the treatment of hypertrophic scar, and the scar recurrence is easy after withdrawal of steroid anti-inflammatory drugs. Finding reliable alternative drugs is an effective means to improve this defect. Aspirin, a traditional non-steroidal anti-inflammatory drug, is safe for topical use and has anti-inflammatory effects similar to those of steroidal anti-inflammatory drugs, which may have similar effects on the treatment of hypertrophic scar. This study aims to investigate the inhibitory effect of aspirin on the proliferation of hypertrophic scar in rabbit ears and the underlying mechanism.@*METHODS@#The rabbit ear hypertrophic scar models were prepared. The rabbits were randomly divided into a normal skin group (group A), a blank control group (group B), a 0.9% NaCl group (group C), a 0.2% aspirin group (group D), a 0.5% aspirin group (group E), a 2% aspirin group (group F), and a triamcinolone acetonide group (group G). Macroscopic observation of hyperplasia was performed 8 weeks after local injection of the scar, followed by collecting the scar tissue samples for HE staining, Masson staining, and immunohistochemistry, respectively to assess the proliferation of fibroblasts and collagen fibers, and calculate the hypertrophic index, microvessel density, and immunohistochemical score.@*RESULTS@#All rabbit ear hypertrophic scar models were successfully constructed. In groups B and C, the hypertrophic scar edge was irregular, with reddish protruding epidermis, significant contracture and hard touch. In group D, E, and F, with the increase of aspirin administration concentration, the scar became thinner and gradually flat, the proliferation of fibrocytes and collagen fibers was weakened, and the hypertrophic index was gradually decreased (P<0.05). Immunohistochemistry showed that the expression of β-catenin was decreased in the group D, E and F in turn, and the immunohistochemical score was gradually decreased (P<0.05). There was no significant difference in hypertrophic index, microvessel density, and immunohistochemical score (all P>0.05).@*CONCLUSIONS@#Local injection of aspirin can reduce the generation of hypertrophic scar in a dose-dependent manner within a certain concentration range; aspirin inhibits the growth of hypertrophic scar in rabbit ears by inhibiting Wnt/β-catenin signal pathway; 2% aspirin and 40 mg/mL triamcinolone acetonide have similar curative efficacy on hypertrophic scar.
Subject(s)
Animals , Rabbits , Anti-Inflammatory Agents/therapeutic use , Aspirin/therapeutic use , Cicatrix, Hypertrophic/pathology , Collagen , Signal Transduction , Triamcinolone Acetonide/therapeutic use , beta Catenin/metabolismABSTRACT
Objective:To explore the expression of microRNA-4695-5p in the serum of colorectal cancer patients and its effect on the proliferation and invasion of colorectal cancer CACO-2 cells.Methods:A total of 43 serum samples of colorectal cancer patients who were admitted to the Department of Gastrointestinal Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University from March 2018 to November 2021 were selected, and serum samples of 43 healthy people who underwent outpatient physical examination were used as controls. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels in the serum of colorectal cancer patients and those of healthy individuals. The miR-4695-5p overexpression plasmid or the negative control plasmid were transfected into CACO-2 cells, namely the miR-4695-5p group and the control group, and the transfection efficiency was verified by qRT-PCR. CCK8 method and Transwell experiment were used to detect the effect of overexpression of miR-4695-5p on the proliferation and invasion of CACO-2 cells. The dual luciferase reporter gene experiment was used to verify the targeted binding relationship between miR-4695-5p and Ras-related C3 botulinum toxin substrate 1 (RAC1). qRT-PCR and Western blot were used to detect the effect of overexpression of miR-4695-5p on the expression of RAC1 gene and Wnt/β-Catenin signaling pathway protein.The software of SPSS28.0 was used to conduct data analysis. The measurement data of normal distribution were espressed by Mean±SD. The t-test was used to compare the means between two groups, and the one-way analysis of variance was used to compare the means of multiple groups. Results:The expression level of miR-4695-5p in the serum of patients with colorectal cancer was significantly lower than that of healthy individuals ( P<0.01). The relative expression levels of miR-4695-5p in the control group and miR-4695-5p group were 1.09 ± 0.65 and 8.83±2.03, respectively. The expression level of miR-4695-5p in CACO-2 cells in the miR-4695-5p group was 8.10 times that of the control group, and CACO-2 cells overexpressing miR-4695-5p were successfully constructed ( P<0.01). Compared with the control group, the proliferation ability of CACO-2 cells in the miR-4695-5p group was significantly reduced ( P<0.05), and the invasion ability of CACO-2 cells was significantly reduced ( P<0.01). Bioinformatics tools and dual luciferase reporter gene experiments confirmed that miR-4695-5p can target and bind RAC1 ( P<0.01). Compared with the control group, the expression of RAC1 gene in the miR-4695-5p group was significantly decreased ( P<0.01), and the expression of Wnt/β-Catenin signaling pathway proteins Wnt3a, β-catenin, and c-MYC decreased significantly. Conclusions:miR-4695-5p is lowly expressed in the serum of colorectal cancer patients. miR-4695-5p inhibits the proliferation and invasion of colorectal cancer CACO-2 cells by targeting the inhibition of RAC1 gene expression and down-regulating the activity of the Wnt/β-Catenin signaling pathway.
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Asthma is a common chronic airway inflammatory disease, which is characterized by airway stenosis, airway wall thickening and increased mucus secretion followed by reversible airflow restriction.At present, asthma is considered to be a complex and heterogeneous disease, and its pathogenesis remains elusive.There are diverse immune cells involved in the formation of asthma, including T lymphocytes, eosinophils, neutrophils, etc.Due to the continuous renewal of classification and function of T lymphocytes subsets, their role in asthma has attracted more attention.Here, this review aims to summarize the immunological characteristics and roles of different T cell subsets in asthma, and highlight the new findings of T cell subsets in the pathogenesis of severe asthma, leading to provide inspiration and help for the study of the immunology pathogenesis, clinical diagnosis, treatment and prognosis in asthma.
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This study aims to compare the prevalence of sexually transmitted infections (STIs) with semen quality in men from couples with primary and secondary infertility. Semen samples were collected from 133 men who requested fertility evaluation. Seminal tract infection with Ureaplasma spp. (UU), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus-2 (HSV-2) was assessed by PCR-based diagnostic assays. Among all patients, the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility (39.7% vs 21.7%, P = 0.03). The prevalence of UU was 28.8% and 13.3% in men from couples with primary and secondary infertility, respectively. Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility (P = 0.04). Regarding the UU subtype, the prevalence of Ureaplasma urealyticum (Uuu) and Ureaplasma parvum (Uup; including Uup1, Uup3, Uup6, and Uup14) did not differ between the two groups. No associations between the prevalence rates of MH, MG, and CT were found in men from either infertility group. A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model (P = 0.04). The crude and adjusted models showed that semen volume (both P = 0.03) and semen leukocyte count (both P = 0.02) were independently associated with secondary infertility. These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.
Subject(s)
Female , Humans , Male , Infertility, Male/epidemiology , Mycoplasma genitalium , Mycoplasma hominis , Prevalence , Semen , Semen Analysis , Sexually Transmitted Diseases/epidemiology , Ureaplasma urealyticumABSTRACT
@#Objective To build a competency-based special education program at the undergraduate level based on the World Health Organization Rehabilitation Competency Framework (RCF) and tailored to educational and rehabilitation needs of students with disabilities, to improve the level of special education program, and to meet the requirements of competency-based education development.Methods Using the theory and method of RCF, we analyzed the competency requirements of special education teachers in school education contexts with reference to the Professional Standards for Special Education Teachers (Trial), the Accreditation Standards for Special Education Majors, and the Professional Competency Standards for Teacher Trainees in Special Education.Results A competency framework for special education teachers based on RCF was constructed, principles for setting special education majors based on RCF and principles for building special education majors based on RCF were proposed, and a competency model applicable to special education majors at the undergraduate level was established according to the characteristics of the school education context.Conclusion As a global rehabilitation competency framework serving the health of all people, the theory and method of RCF are important for constructing a competency-based education for special education majors. The principles, methods, educational objectives, and methodological system of special education majors at the undergraduate level are constructed based on RCF to promote the implementation of the national Professional Standards for Special Education Teachers (Trial), the Standards for Accreditation of Special Education Majors, and the Professional Competency Standards for Teachers of Special Education Majors.
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OBJECTIVE@#To explore potential categories of parental social support for young parents under the coronavirus disease 2019 (COVID-19) epidemic, and to examine correlations of different types of parents' social support with parental burnout.@*METHODS@#In April 2020, we conducted an online voluntary survey among young parents across China with scales and a self-designed questionnaire. The latent profile analysis method was used to analyze parents' received social support and perceived social support. The social support categories were taken as independent variables and parental burnout as dependent variables, and multiple regression analysis was carried out to explore the relationship between received social support, perceived social support and parental burnout. Finally, the moderating effect of resilience between social support groups and parental burnout was discussed.@*RESULTS@#The results of latent profile analysis revealed three potential types of received social support, namely isolate, normal, and multi-support and the proportions of the respondents with the three profiles were 14.1%, 78.0%, and 7.9%. Four potential types of perceived social support, namely, indigent, medium, affluent and divergent and the proportions of the respondents with the four profiles were 13.7%, 29.6%, 25.3%, and 31.3%. Among them, the parents with divergent perceived social support had more perception of social support from the couple, family and relatives, but less perception of social support from net-friend, social organizations and the government. Regression analysis showed that there was no statistically significant correlation between different profiles of received social support and parental burnout, and among the groups of perceived social support, there was a statistically significant correlation between indigent and divergent types of social support and parental burnout. The divergent parents had lower levels of parental burnout compared with indigent (β=-0.120, P=0.003). Also, resilience moderated the effect of divergent perceived social support and parental burnout. Compared with the parents with low resilience, the parents with high resilience perceived divergent social support with lower parenting burnout.@*CONCLUSION@#There are prominent latent types of received social support and perceived social support under epidemic. People with divergent perceived social support (more perceived supports from partner, family and friends) are prone to have a relatively lower risk of parental burnout. Parents with higher resilience will be more sensitive to the support of close acquaintances, and can better resist parental burnout.
Subject(s)
Humans , Burnout, Psychological/epidemiology , COVID-19/epidemiology , China/epidemiology , Parents , Social SupportABSTRACT
ObjectiveTo investigate the potential pharmacological mechanism of Xinmaikang tablets in the treatment of atherosclerosis cardiovascular disease by using network pharmacology and cell experimental validation. MethodThe components of Xinmaikang tablets were searched by BATMAN-TCM database and the active ingredients and potential targets were screened. The atherosclerosis related disease targets were searched in GeneCards and online mendelian inheritance in man(OMIM) disease databases. The therapeutic targets were obtained by mapping the intersection of the tablets and disease targets. Therapeutic targets were uploaded to STRING database to construct protein-protein interaction(PPI) network. Cytoscape software was used to create a "drug-active component-therapeutic target" network map, and a network topology algorithm was used to screen key action targets. David software was used for gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) function enrichment analysis. The key targets of drug therapy were validated by in vitro cell assay. ResultA total of 19 active ingredients, 132 potential targets and 4703 atherosclerotic disease-related target genes of Xinmaikang tablets were retrieved and screened, and 84 intersection targets were obtained. 3 key therapeutic targets of Xinmaikang tablets in the treatment of atherosclerotic diseases were screened, including Calmodulin 1(CALM1), voltage-dependent L-type calcium channel subunit alpha-1C(CACNA1C) and Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3CA). A total of 313 biological processes, 89 molecular functions and 53 cell components were obtained by GO enrichment. A total of 40 pathways were obtained from KEGG functional enrichment, including purine metabolism, renin secretion, CGMP/PKG signaling pathway and so on. In vitro cell experiment results verified that Xinmaikang tablets can up-regulate the expression of CALM1 and CACNA1C, down-regulate the expression of PIK3CA, so as to inhibit the activity of inflammatory response, and play a therapeutic role in atherosclerotic diseases. ConclusionXinmaikang tablets may treat atherosclerosis cardiovascular disease through betulin, methyleugenol and other compounds, through purine metabolism, renin secretion, cGMP/PKG signaling pathway and other pathways, which acts on CALM1, CACNA1C, PIK3CA and other targets.
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ObjectiveTo collect common prescriptions from multiple channels based on the mainstream guidance materials combined with ancient books to provide references for the selection principles of common prescriptions in clinical practice guidelines of traditional Chinese medicine (TCM) and western medicine. MethodWith the research on the selection of commonly used prescriptions in Clinical Practice Guidelines of Chinese and Western Medicine for Cough in Children as an example,the nation-recommended Schedule Ⅲ drugs and prescriptions for cough in children in the clinical diagnosis and treatment guidelines of TCM (TCM and western medicine)/expert consensus/clinical pathway/diagnosis and treatment protocols,three TCM pediatric textbooks, the experience of famous experts, and ancient books were searched for the establishment of a prescription database and analysis of medication regularity. ResultThe results showed that there were 71 commonly used prescriptions for the treatment of cough in children. The top 3 clinically indicated syndromes were the syndrome of phlegm-heat blocking the lung,the syndrome of wind-heat invading the lung,and the syndrome of wind-cold attacking the lung,and the top 5 efficacies corresponding to high-frequency drugs were reliving cough and dyspnea, clearing heat/resolving phlegm, dispersing wind/dissipating cold, clearing heat/purging fire, and dispersing wind/dissipating heat. The most commonly used Chinese medicines included Armeniacae Semen Amarum, Platycodonis Radix, Bolbostemmatis Rhizoma, Ephedrae Herba, Scutellariae Radix, Pinelliae Rhizoma, and Citri Reticulatae Pericarpium. Some drugs showed high internal correlations with Armeniacae Semen Amarum and Platycodonis Radix. There were 228 prescriptions for the treatment of cough in children based on the ancient books in the Chinese Medical Code. The most commonly used Chinese medicines were Pinelliae Rhizoma, Armeniacae Semen Amarum, Ginseng Radix et Rhizoma, Poria, Citri Reticulatae Pericarpium, Platycodonis Radix, Zingiberis Rhizoma Recens, and Bolbostemmatis Rhizoma. The top 5 efficacies corresponding to high-frequency drugs were dispersing wind/dissipating cold, relieving cough and dyspnea, clearing heat/resolving phlegm, warming cold/resolving phlegm, and tonifying Qi. Some drugs showed high internal correlations with Pinelliae Rhizoma and Platycodonis Radix. As revealed by the comparison of ancient and modern medication, the medication principles could be roughly classified into two categories: ventilating the lung/descending Qi and resolving phlegm. In ancient medication, the drugs for cough in children were mainly used for warming, tonifying, dissipating cold, excreting water, alleviating edema, and astringing lung and intestines, while in modern medication, the prescriptions were mainly for dispersing wind, clearing heat, tonifying yin, and moistening dampness. ConclusionThis study systematically analyzed the commonly used prescriptions for the treatment of cough in children and provided references for the selection of TCM in clinical practice guidelines.
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ObjectiveTo collect common prescriptions from multiple channels based on the mainstream guidance materials combined with ancient books to provide references for the selection principles of common prescriptions in clinical practice guidelines of traditional Chinese medicine (TCM) and western medicine. MethodWith the research on the selection of commonly used prescriptions in Clinical Practice Guidelines of Chinese and Western Medicine for Cough in Children as an example,the nation-recommended Schedule Ⅲ drugs and prescriptions for cough in children in the clinical diagnosis and treatment guidelines of TCM (TCM and western medicine)/expert consensus/clinical pathway/diagnosis and treatment protocols,three TCM pediatric textbooks, the experience of famous experts, and ancient books were searched for the establishment of a prescription database and analysis of medication regularity. ResultThe results showed that there were 71 commonly used prescriptions for the treatment of cough in children. The top 3 clinically indicated syndromes were the syndrome of phlegm-heat blocking the lung,the syndrome of wind-heat invading the lung,and the syndrome of wind-cold attacking the lung,and the top 5 efficacies corresponding to high-frequency drugs were reliving cough and dyspnea, clearing heat/resolving phlegm, dispersing wind/dissipating cold, clearing heat/purging fire, and dispersing wind/dissipating heat. The most commonly used Chinese medicines included Armeniacae Semen Amarum, Platycodonis Radix, Bolbostemmatis Rhizoma, Ephedrae Herba, Scutellariae Radix, Pinelliae Rhizoma, and Citri Reticulatae Pericarpium. Some drugs showed high internal correlations with Armeniacae Semen Amarum and Platycodonis Radix. There were 228 prescriptions for the treatment of cough in children based on the ancient books in the Chinese Medical Code. The most commonly used Chinese medicines were Pinelliae Rhizoma, Armeniacae Semen Amarum, Ginseng Radix et Rhizoma, Poria, Citri Reticulatae Pericarpium, Platycodonis Radix, Zingiberis Rhizoma Recens, and Bolbostemmatis Rhizoma. The top 5 efficacies corresponding to high-frequency drugs were dispersing wind/dissipating cold, relieving cough and dyspnea, clearing heat/resolving phlegm, warming cold/resolving phlegm, and tonifying Qi. Some drugs showed high internal correlations with Pinelliae Rhizoma and Platycodonis Radix. As revealed by the comparison of ancient and modern medication, the medication principles could be roughly classified into two categories: ventilating the lung/descending Qi and resolving phlegm. In ancient medication, the drugs for cough in children were mainly used for warming, tonifying, dissipating cold, excreting water, alleviating edema, and astringing lung and intestines, while in modern medication, the prescriptions were mainly for dispersing wind, clearing heat, tonifying yin, and moistening dampness. ConclusionThis study systematically analyzed the commonly used prescriptions for the treatment of cough in children and provided references for the selection of TCM in clinical practice guidelines.
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Background Occupational aluminum exposure is closely related to cognitive impairment, and alcohol consumption is also closely related to cognitive dysfunction. Objective To explore the effects of types of alcohol consumption on cognitive function of occupational aluminum exposed workers. Methods A total of 181 workers aged from 23 to 56 years were selected by cluster sampling method in an electrolytic aluminum workshop of an aluminum plant in a region and in a maintenance workshop of another plant in the same region from July to August, 2019. Venous blood was collected, and plasma aluminum concentration was determined by inductively coupled plasma mass spectrometry. The study subjects were divided into low and high exposure groups based on the median blood aluminum level and type of work. Their basic information was collected by occupational health examination. Workers' cognitive function was assessed using the Montreal Cognitive Assessment Scale-Beijing Edition. Logistic regression was used to analyze the association between plasma aluminum concentration and cognitive impairment, and between the types of alcohol consumption (including Baijiu, red wine, and beer) and cognitive impairment, Unconditional logistic regression was used to fit multiplicative interaction model as well as additive interaction model of plasma aluminum concentration and the types of alcohol consumption, and to calculate the relative excess relative risk due to interaction (RERI) and attributable proportion due to interaction (AP). Results The M (P25, P75) concentrations of plasma aluminum were 40.01 (25.05, 60.56) µg·L−1 in the total study subjects, 25.16 (17.13, 34.78) µg·L−1 in the low exposure group and 60.56 (47.40, 68.53) µg·L−1 in the high exposure group. After adjusting the type of alcohol consumption, drinking, age, duration of exposure to aluminum, education, marital status, and smoking, the odds ratios for impairments of attention, language expression, and overall cognitive function in the high exposure group were 4.295 (95%CI: 1.912-9.648), 5.687 (95%CI: 1.355-23.867), and 2.720 (95%CI: 1.225-6.040) times of the low exposure group respectively. Besides, after adjusting blood aluminum concentration, total alcohol consumption, age, duration of exposure to aluminum, education, marital status, and smoking, the risk of attention impairment of the Baijiu drinkers was 2.613 (95%CI: 1.054 to 6.837) times of the non-Baijiu drinkers; the risks of impairment of visuospatial abilities and execution functions, language expression, delayed recall, and overall cognitive function of the beer drinkers were 3.165 (95%CI: 1.285-7.797), 17.898 (95%CI: 1.590-201.480), 3.118 (95%CI: 1.215-8.003), and 3.824 (95%CI: 1.736-8.423) times of the non-beer drinkers. There were both additive [RERI (95%CI): 1.745 (1.394-2.097), AP (95%CI): 0.415 (0.201-0.630)] and multiplicative (OR=3.591, 95%CI: 1.393-9.255) interactions between Baijiu intake and plasma aluminum concentration levels on the attention domain. The cognitive impairment attributed to the interactive effects of drinking Baijiu and plasma aluminum concentration in individuals with attention impairment accounted for 41.5%. There were both additive [RERI (95%CI): 5.955 (0.562-11.328), AP (95%CI): 0.829 (0.577-1.081)] and multiplicative (OR=42.174, 95%CI: 5.469-325.252) interactions between beer drinking and plasma aluminum concentration on the overall cognitive function. Among the individuals with overall cognitive impairment, the cognitive impairment caused by the interaction of beer drinking and plasma aluminum concentration accounted for 82.9%. Conclusion Occupation aluminum exposed workers' attention, language expression, and overall cognitive function are closely related to their plasma aluminum concentration. Plasma aluminum concentrations have interactions with Baijiu and beer consumption on cognitive impairment of workers.
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Outer membrane vesicles (OMVs) are nano-sized spherical vehicles, with a size range between 20-250 nm. OMVs are spontaneously secreted from Gram-negative bacteria and formed by lipid bilayer membranes, comprising multiple parent bacteria-derived components including bacterial antigens, pathogen-associated molecular patterns, proteins and lipids. OMVs have shown multiple potentials for the treatment of various diseases, including cancer therapy and bacterial infection. In this review, the structure, composition and methods for isolating and characterizing of OMVs were introduced. The applications of OMVs for diseases therapy were summarized and future perspectives were discussed.
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Purpose@#This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. @*Materials and Methods@#Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). @*Results@#Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05). @*Conclusion@#Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.
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Objective:To investigate the development and maturation process of intestinal organoids in neonatal mice so as to provide a new model for research on perinatal/neonatal intestinal epithelial development and related diseases.Methods:Intestinal tissue of 3-day-old C57BL/6 mice were collected and cultured for mouse intestinal organoids (MIOs) under standard conditions down to the fifth generation. The morphological changes of MIOs were observed and recorded using inverted phase contrast microscope. Real-time fluorescent quantitative polymerase chain reaction and immunofluorescence technique were used to detect the expression and location of markers of intestinal stem cells and differentiated cells of intestinal epithelium among different generations of MIOs (Selected marker genes: Lgr5 for intestinal stem cells, Tpm2 and Gja1 for fetal intestinal progenitor cells, Villin for intestinal epithelial cells, Lyz1 for Paneth cells, Muc2 for goblet cells, Chga for endocrine cells; Selected marker proteins: villin for intestinal epithelial cells, mucin 2 for goblet cells, chromaffin A for endocrine cells, lysozyme for Paneth cells). One-way analysis of variance and Bonferroni test were adopted for statistical analysis. Results:Two types of MIOs were observed, immature spheroid and mature organoids with crypt-villus structure. Spheroid was the main form in the primary culture. From primary to the second generation, the proportion of spheroids decreased from (96.61±1.36)% to (8.93±1.50)%, and so did the size ( F=12.88, P<0.001). During the second to the fifth generation, mature organoid, as the main form, increased from (91.07±1.50)% to (95.56±2.14)%. The expression of intestinal stem cell marker Lgr5 in the second generation decreased to 0.40±0.06 times of the primary one ( F=76.75, P<0.001) and then increased after this period. The expression of fetal intestinal progenitor markers Tpm2 decreased significantly during the passage (primary generation: 1.00±0.11, the fifth generation: 0.003±0.001, F=148.00, P<0.001); And the expression of Gja1 decreased from primary generation (1.00±0.14) to the second generation (0.06±0.04) ( F=197.10, P<0.001), but kept stable from the second to fifth genetation ( F=2.20, P=0.13). The expressions of gene markers of differentiated cells in intestinal epithelium, including enterocytes, goblet cells, endocrine cells, and Paneth cells, increased after the second generation (the second generation: Villin: 0.46±0.11; Muc2: 0.68±0.29; Chga: 2.53±0.16; Lyz1: 0.98±0.21; the fifth generation: Villin: 1.02±0.05; Muc2: 8.79±0.61; Chga: 4.32±0.45; Lyz1:3.81±0.36; all P<0.05). Immunofluorescence showed that villin, the intestinal epithelial cell marker protein, was distributed along the villus-side of MIOs in primary and the fifth generation culture. Mucin 2 from goblet cell and chromaffin A from endocrine cell expressed at a very low level in the primary generation, while higher in the fifth generation. In the primary culture, lysozyme from Paneth cell was evenly distributed in organoid cells, and high fluorescent dot-shaped expression was observed in the fifth generation. Conclusions:The development and maturation of immature intestinal epithelium can be simulated by continuous culture of neonatal MIOs. MIOs between the primary and second generation could be used as a research model for development of perinatal intestinal epithelium, and the second to the fifth generation as a model for neonatal intestinal diseases studies.
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Transporters have a great influence on the transportation and distribution of drugs in the body. On the one hand, solute carrier transporters could transport drugs into tissues and organs, which may improve the oral bioavailability or change the tissue-distribution of the drugs. On the other hand, the ATP-binding cassette could pump some drugs out of the cell, which decreases the intracellular drug concentrations and leads to drug resistance. This paper summarizes the distribution, substrate characteristics and drug design strategies of several important drug transporters, such as improving bioavailability by prodrug design, introducing acid group to improve hepatic selectivity and adjusting the polarity of compounds to decrease efflux ratio.
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In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.
Subject(s)
Humans , Amyloid Precursor Protein Secretases , Aspartic Acid Endopeptidases , Drugs, Chinese Herbal/pharmacology , Metabolomics , SimaroubaceaeABSTRACT
The present study evaluated the curative efficacy of Chinese herbal injection on unstable angina pectoris( UAP) by network Meta-analysis. The databases,including Pub Med,Cochrane Library,Web of Science,CNKI,CBM,VIP and Wanfang were searched for randomized controlled trial( RCT) of Chinese herbal injection in the treatment of UAP. All researchers independently screened the articles,extracted the data and evaluated the quality. Open BUGS and Stata were employed for the analysis of the trials that met the quality standards. Fifty-eight studies were finally included in this study,involving 20 intervention measures. In terms of the effective rate,16 injections such as Dengzhan Xixin Injection,Xuesaitong Injection and Danshen Injection combined with western medicine exhibited significant efficacy. In terms of ECG,Puerarin Injection,Ginkgo Leaf Extract and Dipyridamole Injection( GDI),Breviscapine Injection combined with western medicine were superior to western medicine. In terms of the reduction of the angina attack times,Sodium Tanshinone ⅡASulfonate Injection,GDI and Dazhu Hongjingtian Injection combined with western medicine showed better effects than western medicine. In terms of shortening the angina duration,Shenmai Injection combined with western medicine was superior to western medicine. As revealed by the results,Dengzhan Xixin Injection,Xuesaitong Injection,Danshen Injection,Breviscapine Injection,Danshen Ligustrazine Injection combined with western medicine displayed prominent curative efficacy,which were recommended for clinical application. Meanwhile,appropriate intervention measures should be selected according to individual conditions. Limited by the quality of the included trials,the conclusions still need to be further verified.
Subject(s)
Humans , Angina Pectoris , Angina, Unstable/drug therapy , China , Drugs, Chinese Herbal , Network Meta-Analysis , Treatment OutcomeABSTRACT
Objective:To analyze the effect of glucocorticoid on the biological function of lens epithelial cells (LECs) by bioinformatics and predict related microRNA (miRNA).Methods:GSE3040 database was downloaded and the human LECs line (HLE-B3) cells in the experimental group were treated with 1 μmol/L dexamethasone, and HLE-B3 cells in the control group were treated with 1 μmol/L dimethyl sulfoxide(DMSO).GEO2R was used to analyze the differentially expressed genes between the two groups.Metascape website was employed to analyze the functional enrichment of differentially expressed genes, and EdU cell proliferation assay was performed to detect the difference in cell proliferation between the two groups.STRING website and cytoscape software were used to construct protein-protein interaction network.Hub genes were calculated by cytohubba app, and quantitative real-time PCR was performed to detect the expression levels of hub genes between the two groups.MirCode website was used to predict the related miRNAs.Results:A total of 341 differentially expressed genes were detected between the experimental group and the control group, among which there were 300 up-regulated genes and 41 down-regulated genes. SLC12A1, MED13L, ALDH5A1, SLC15A3 and WWC1 were the top five down-regulated genes and SCNN1A, ANKRD36, FKBP5, PYY and ADH1B were the top five up-regulated genes.The top 20 terms of functional enrichment were listed, and the negative regulation of HLE-B3 cells proliferation showed the most enrichment.Cell proliferation rate in the experimental group was (8.09±0.20)%, which was significantly lower than (39.63±0.80)% in the control group ( t=38.43, P<0.01).The top ten hub genes were SST, CXCL8, GRM1, GNRH1, CXCL5, PPBP, CX3CR1, PYY, EDNRA and GRK5, and quantitative real time PCR confirmed that the expression levels of SST, CXCL8, GRM1, PYY, EDNRA and GRK5 mRNA were statistically different (all at P<0.05).The top six miRNAs which might be associated with hub genes were miR-15abc, miR-214, miR-23abc, miR-129-5p, miR-132 and miR-24. Conclusions:The 1 μmol/L glucocorticoid can negatively regulate the proliferation of HLE-B3 cells. SST, CXCL8, GRM1, PYY, EDNRA and GRK5 may be hub genes and miR-15abc, miR-214, miR-23abc, miR-129-5p, miR-132, miR-24 are most likely to relate to them.
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OBJECTIVE@#To investigate the effects of acupuncture on ovary morphology and function in dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) model rats.@*METHODS@#A total of 40 adult female Wistar rats were randomly allocated to 4 groups by a random number table, including control, model, metformin and acupuncture groups, 10 rats in each group. PCOS rat model was developed by injecting with DHEA (6 mg/100 g body weight) in 0.2 mL of oil subcutaneously. Electrical stimulation (2 Hz, 3 mA) was applied to Guanyuan (CV 4), Zigong (EX-CA1) and Qihai (CV 6) acupoints for 30 min daily in the acupuncture group, and metformin (200 mg/kg) was given to rats in the metformin group, both once per day for 21 consecutive days, and rats in the normal group was fed with normal saline and fed regularly. After 21 days of administration, the rat blood samples were collected for detecting the reproductive hormonal levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E@*RESULTS@#Compared with the model group, rats in the acupuncture and metformin groups were significantly lower in weight gain, FSH, LH and T levels, and E@*CONCLUSION@#Acupuncture might improve ovary morphology and its function in DHEA-induced PCOS model rats.