摘要
OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Subject(s)
Humans , Proto-Oncogene Proteins c-akt/metabolism , Cell Proliferation , Matrix Metalloproteinase 9 , Molecular Docking Simulation , Cell Cycle , ErbB Receptors , Apoptosis , Colorectal Neoplasms/pathology , Cell Line, Tumor摘要
Objective:To investigate the clinical value of left ventricular shape index (SI) and eccentricity index (EI) in evaluating left ventricular remodeling.Methods:A retrospective analysis was performed on 324 patients (264 males, 60 females, age (62.5±11.8) years) diagnosed with myocardial infarction (MI) and 113 healthy controls (HC; 47 males, 66 females, age (57.8±10.7) years) who received gated myocardial perfusion imaging (GMPI) in First Hospital of Shanxi Medical University from January 2016 to September 2020. SI (end-diastolic SI (EDSI), end-systolic SI (ESSI)), EI and left ventricular function parameters (end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), summed motion score (SMS), summed thickening score (STS), peak ejection rate (PER) and peak filling rate (PFR)) were obtained by quantitative gated SPECT (QGS) software. Propensity score (PS) inverse probability of treatment weighting (IPTW) was used to balance the intergroup covariates. The differences and correlations of EDSI, ESSI, EI and left ventricular function parameters between patients in MI group and HC group were analyzed. ROC curve analysis was used to evaluate the values of EDV, EDSI, ESSI and EI alone and in combination in the assessment of left ventricular systolic function impairment. Data were analyzed by independent-sample t test, Pearson correlation and Spearman rank correlation analyses, and Delong test. Results:After IPTW, EDSI and ESSI in MI group ( n=319) were higher than those in HC group ( n=133; EDSI: 0.66±0.09 vs 0.60±0.06; ESSI: 0.59±0.11 vs 0.47±0.07; t values: 8.05, 14.67, both P<0.001), and EI was lower than that in HC group (0.81±0.06 vs 0.85±0.03; t=-8.93, P<0.001). In both groups, there were significant correlations between EDSI and ESSI ( r values: 0.928, 0.873), between EDSI, ESSI and EI ( r values: from -0.831 to -0.641), between EDSI, ESSI and LVEF ( r values: from -0.627 to -0.201), between ESSI and EDV, ESV and SMS ( rs values: 0.336-0.584), between ESSI and -PER, PFR ( rs values: from -0.406 to -0.402, r values: from -0.352 to -0.325) (all P<0.01). ROC curve analysis showed that EDV (AUC: 0.895) and ESSI (AUC: 0.839) had the highest efficacy in evaluating left ventricular systolic function impairment in MI group and HC group, respectively. EDV-EDSI-ESSI-(1-EI) had higher efficacy in the assessment of impaired left ventricular systolic function in MI group (AUC: 0.956), which was higher than that of EDV or EDV-EDSI or EDV-ESSI or EDV-(1-EI) ( z values: from -2.64 to -2.18, P values: 0.008-0.029); EDV-EDSI-ESSI-(1-EI) also had high efficacy in HC group (AUC: 0.911), which was higher than that of EDV or EDV-EDSI or EDV-(1-EI) ( z values: from -2.60 to -2.43, P values: 0.009-0.015). Conclusions:In MI patients, the increase of SI and the decrease of EI indicate the increase of left ventricular sphericity and the aggravation of left ventricular remodeling. SI and EI have certain clinical application values in evaluating left ventricular morphology, predicting left ventricular remodeling and left ventricular systolic function impairment.
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Objective To investigate the effects of doublecortin-like kinase 1 (DCLK1) on the malignant biological behaviors, such as proliferation, migration, and invasion, of A549 cell line and their corresponding mechanisms. Methods DCLK1-overexpressing A549 cell lines were established through lentiviral infection, and DCLK1 expression was validated by using RT-PCR and Western blot analysis. Proliferation ability was assessed with CCK-8 and plate cloning assays, and migration and invasion abilities were examined with Transwell assays. The pathway regulated by DCLK1 in lung adenocarcinoma was analyzed on the basis of the TCGA lung adenocarcinoma cohort with pathway enrichment analysis and verified through Western blot analysis. Results DCLK1 overexpression in A549 cells promoted cell proliferation, migration, and invasion. The inhibition of the FAK/PI3K/AKT/mTOR signaling pathway impaired the DCLK1-mediated malignant behavior of A549 cells. Conclusion DCLK1 promotes the malignant behavior of A549 cells through the activation of the FAK/PI3K/AKT/mTOR signaling pathway.
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ObjectiveTo observe the clinical course and explore the risk factors for SARS-CoV-2 RNA negative conversion duration （NCD） in asymptomatic and mild-symptomatic patients infected with the SARS-CoV-2 Omicron variant. MethodsClinical data were collected from 244 confirmed cases of corona virus disease （COVID-19） with Omicron variant infection admitted to a temporal makeshift hospital in Shanghai from April 9， 2022 to May 20， 2022. Demographic and clinical data were analyzed， with a primary focus on the time of COVID-19 nucleic acid conversion. Univariate and multivariate Cox regression analysis were used to determine identify risk factors associated with NCD. ResultsThe median duration of negative RNA conversion was 9 days （ranged 7‒12 days）. The percentage of patients with positive nucleic acid results on the 5th， 7th， 10th， and 14th days after confirmed infection was 68.4%， 47.1%， 20.1%， and 5.7%， respectively. Kaplan-Meier curves indicated a median nucleic acid conversion time of 12 days （ranged 10‒14 days） for patients with hypertension， 9 days （ranged 7‒11 days） in patients without hypertension， and 11 days （ranged 9‒13 days） for patients aged ≥60 years， and 9 days （ranged 7‒11 days） for patients aged <60 years. Multivariate Cox regression analysis showed that only hypertension was an independent risk factor of NCD （RR=1.60； 95% CI： 1.03‒2.49， P=0.036）. ConclusionIn asymptomatic or mildly symptomatic patients infected with the Omicron variant， 20.1% patients continue to exhibit positive viral nucleic acid on the 10th days of infection. The independent risk factor associated with the conversion of SARS-CoV-2 nucleic acid to negative is hypertension.
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Abstract@#Vaccine-hypervariable poliovirus type Ⅲ was detected in an acute flaccid paralysis infant at age of 6 months in Zhejiang Province in June, 2021, and the isolated and incubated virus had six nucleotide variations in the VP1 region as compared to the poliovirus Sabin vaccine strain. The infant had a history of three-dose poliovirus vaccination, and grade 2 muscle strength of the left upper limb upon onset. He was clinically diagnosed with cellulitis of the left shoulder, and recovered to normal following treatment. No abnormality was detected in the nervous system, and the infant was cured and discharged from hospital. No vaccine-hypervariable poliovirus was detected in subsequent infant' clinical samples or in close contacts, and no similar cases were identified during the active case detection by county/district medical institutions and among community populations. Since the infant did not present poliomyelitis-related clinical symptoms caused by vaccine-hypervariable poliovirus, poliomyelitis was excluded. The vaccine-hypervariable poliovirus was not spread because of timely identification and effective responses, suggesting the urgent need to maintain the sensitivity of the acute flaccid paralysis surveillance system and improve the coverage of poliovirus vaccination, so as to inhibit the transmission of poliovirus.
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OBJECTIVES@#To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG).@*METHODS@#A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups.@*RESULTS@#After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05).@*CONCLUSIONS@#For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.
Subject(s)
Humans , Child , Prednisone/adverse effects , Tacrolimus/adverse effects , Retrospective Studies , Activities of Daily Living , Immunosuppressive Agents/adverse effects , Myasthenia Gravis/drug therapy , Glucocorticoids/therapeutic use , Mycophenolic Acid/adverse effects摘要
Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.
Subject(s)
Humans , Doublecortin-Like Kinases , Hippo Signaling Pathway , Verteporfin/pharmacology , Cell Line, Tumor , Protein Serine-Threonine Kinases/metabolism , Pancreatic Neoplasms/pathology , YAP-Signaling Proteins , Transcription Factors/metabolism , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Tumor Suppressor Proteins/genetics摘要
Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26+/- mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.
Subject(s)
Animals , Mice , DNA-Binding Proteins/genetics , Cell Differentiation , Neural Stem Cells , Translocation, Genetic , Ubiquitins/genetics , Ligases/genetics摘要
Many studies have found a correlation between suicidal behavior (SB) and anhedonia, the main symptom of depression, in terms of both psychological and neurophysiological findings. The purpose of this review is to find the relationship between the two neuroimaging mechanisms, and to provide help for the future study of how the brain imaging changes can promote the mechanism of SB in depression patients with anhedonia symptoms. This review also emphasizes the necessity of intervention for the symptoms of anhedonia when preventing depression from committing suicide. The latest research results were reviewed about anhedonia in depression and magnetic resonance imaging of SB.The results showed that the default network, insula, lateral orbitofrontal gyrus, anterior cingulate gyrus, ventral striatum gyrus, ventral lateral and dorsolateral prefrontal gyrus, thalamus and habenula nucleus were dysfunction in depression with state anhedonia symptoms, affecting SB in terms of mood, execution, reward and aversion processing, especially the low lethal SB.
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Objective@#To investigate the serum levels of anti-measles antibody among residents in Zhejiang Province in 2018, so as to provide insights into measles control.@*Methods@#Permanent residents aged 0 to 59 years were recruited using the stratified multistage random sampling method in Zhejiang Province in 2018, and subjects' demographic features, medical history of measles and history of immunization with measles-containing vaccine (MCV) were collected using a questionnaire survey. The serum level of anti-measles IgG antibody was detected, and the geometric mean concentration (GMC) of anti-measles IgG antibody was estimated. The seroprevalence, protective rate and GMC of anti-measles IgG antibody were compared among residents at different age groups and regions.@*Results@#A total of 4 189 residents were enrolled, including 1 939 males and 2 250 females, with a male to female ratio of 1∶1.16. There were 3 858 residents positive for anti-measles IgG antibody, with seroprevalence of 92.10%, and there were 2 072 residents with protective antibodies against measles, with a protective rate of 49.46%. The median GMC of anti-measles IgG antibody was 798.33 (interquartile range, 1 024.06) mIU/mL, and the protective rate of anti-measles IgG antibody appeared a tendency towards a decline with age ( χ2trend=18.067, P<0.001 ). There were significant differences in the seroprevalence ( χ2=45.090, P<0.001 ), protective rate ( χ2=57.432, P<0.001 ) and GMC of anti-measles IgG antibody (χ2=88.624, P<0.001 ) among residents at different regions, with the lowest seroprevalence of anti-measles IgG antibody in Ningbo City ( 85.19% ), the lowest antibody-protective rate (38.98%) and the lowest GMC [632.89 ( 909.04 ) mIU/mL] in Zhoushan City, the highest seroprevalence ( 95.16% ), antibody-protective rate (58.48%) and GMC [1 035.84 ( 1 301.77 ) mIU/mL] in Huzhou City.@*Conclusions@# The protective rate of anti-measles antibody was low and appeared a tendency towards a decline among residents in Zhejiang Province in 2018. There was a region-specific serum level of anti-measles antibody in Zhejiang Province in 2018.
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Objective@#To establish an optimized path for health management of HBV infections among pregnant and lying-in women based on a Delphi method, so as to provide the evidence for intensifying the interruption of the mother-to-child transmission of HBV.@*Methods@#Based on literature review and previous studies, the preliminary framework and contents of the optimized path for health management of HBV infections were constructed. Experts from epidemiology, clinical medicine and maternal and children healthcare were invited to participate in two-round Delphi consultations, and the preliminarily designed indicators were screened and revised. The score for feasibility of each indicator was calculated, and the weight of each indicator was estimated using a proportional distribution method.@*Results@#Sixteen experts participated in the consultation, including 13 women. The participants had a mean age of (45.69±5.71) years, and a mean employment duration of (23.06±7.05) years. All participants had a degree of bachelor and above, and there were 14 experts with vice senior professional titles. The mean positive coefficient was 96.88% and the mean authority coefficient was 0.790 during the two-round expert consultations. There were significant differences in the coordination coefficient of importance, necessity and feasibility of indicators at all levels (P<0.05), and the coefficient of variation of the feasibility was all less than 0.250. The final optimized path for health management of HBV infections among pregnant and lying-in women included 6 primary indicators, 17 secondary indictors and 73 tertiary indicators. Among the primary indicators, delivery management (0.173 4), screening and evaluation (0.172 8) and pregnancy management (0.172 7) had a high weight.@*Conclusion@#A scientific and reliable optimized path is created for health management of HBV infections among pregnant and lying-in women, which has a potential value for improving the interruption of mother-to-child transmission of HBV.
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Objective: To analyze the epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019. Methods: The data of hepatitis A incidence in Zhejiang Province from 2010 to 2019 were collected from the infectious disease surveillance system of China Information System for Disease Control and Prevention. ArcGIS 10.7 software was used for spatial autocorrelation analysis. SaTScan 9.6 software was used for spatiotemporal scanning analysis. SPSS 25.0 software was used for additional analysis. Results: Zhejiang Province has reported 5 465 cases of hepatitis A in 2010-2019 years, with an average annual incidence rate of 1.00/100 000, and periodicity and seasonality are not obvious. The incidence of male was higher than that of female (P=0.023), and the highest incidence rate was 50-59 years old. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the incidence of hepatitis A in Zhejiang Province from 2010 to 2017, with the weakest correlation in 2010 (Moran's I =0.103, Z=1.769, P=0.049), and the strongest correlation in 2016 (Moran's I=0.328, Z=4.979, P=0.001). Spatiotemporal scanning analysis showed that there was spatial aggregation of hepatitis A in Zhejiang Province from 2010 to 2019, with a total of three aggregation areas identified. Among them, the mostly aggregation area was concentrated in Xiangshan county of Ningbo city, which covered 10 counties (cities and districts), including Ninghai county and Yinzhou district, and appeared from January 1 to June 30, 2012. Conclusion: The incidence level of hepatitis A in Zhejiang Province shows a stable fluctuation trend from 2010 to 2019, and the seasonal regularity is not obvious. The population group aged 50-59 years old is the key population. There is spatial aggregation in the epidemic situation of hepatitis A. Targeted prevention and control measures of hepatitis A should be done based on the law of spatiotemporal aggregation and local incidence.
Subject(s)
Female , Humans , Male , Middle Aged , China/epidemiology , Cluster Analysis , Hepatitis A/epidemiology , Incidence , Spatial Analysis摘要
Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.
Subject(s)
Humans , Encephalitis Virus, Japanese , Encephalitis, Japanese/prevention & control , Immunization , Japanese Encephalitis Vaccines , Vaccination , Vaccines, Inactivated摘要
Estimating the actual real-world effectiveness of the vaccine is an essential part of the post-marketing evaluation. This regression discontinuity design (RDD) using observational data is designed to quantify the effect of an intervention when eligibility for the intervention is based on a defined cutoff as age, making it suited to estimate vaccine effects. This approach can avoid the high cost and ethical issues; overcome difficulties in the organization and practice process in randomized controlled trials, which leads to a higher level of causal inference evidence and more realistic results. Here, we describe key features of RDD in general, and then specific scenarios, with examples, to illustrate that RDD are an essential tool for advancing our understanding of vaccine effects.
Subject(s)
Humans , Causality , Vaccine Efficacy , Vaccines摘要
Objective:To investigate the regulatory effect of miR-26a in radiation-induced heart disease (RIHD) mice.Methods:C57/BL6 mice were used to establish RIHD models. The cardiac function, fibrosis, the expression levels of collagen 1 (COL1) and connective tissue growth factor (CTGF), and miR-26a were detected in RIHD mice. Whether CTGF was the target gene of miR-26a was verified by dual luciferase kit. Moreover, cardiac fibroblasts were transfected with miR-26a up and miR-26a down lentivirus vectors to construct the miR-26a overexpression and underexpression cell models. The expression of CTGF, proliferation, and apoptosis of cardiac fibroblasts were detected.Results:In the RIHD mice, heart function was decreased, myocardial fibrosis was remodeled, the expression levels of COL1 and CTGF were up-regulated, and the expression level of miR-26a was down-regulated. Dual luciferase reporter assay confirmed that CTGF was the target gene regulated by miR-26a. Overexpression of miR-26a could inhibit the expression of CTGF, suppress the proliferation of cardiac fibroblasts, promote cell apoptosis and secrete collagen. Underexpression of miR-26a yielded the opposite results.Conclusion:MiR-26a affects the function of cardiac fibroblasts by targeting CTGF and probably mediates the process of radiation-induced myocardial fibrosis, which may become a new regulatory target of RIHD.
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Balance impairment significantly correlates with falls in the elderly.The timed up and go test(TUGT)is a common and simple assessment tool to evaluate balance and gait function and widely used to screen for the risk of falls in the elderly.In this review, we explore the following issues on TUGT: the development, the association with computerized dynamic posturography, and the validity and reference value for fall risk prediction.This may further improve the applicability and prediction accuracy of the screening tool for falls in the elderly.
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Objective@#To investigate the willingness to receive measles-containing vaccine (MCV) and its influencing factors among healthcare workers in the Yangtze River Delta region, so as to provide the evidence for improving the measles-containing vaccination rate@*Methods@#Healthcare workers were sampled from 19 medical institutions in each of Shanghai Municipality, Jiangsu Province, Zhejiang Province and Anhui Province for questionnaire surveys using a multi-stage stratified convenience sampling methods from July 2020 to March 2021. Participants' gender, age, educational level, professional title, measles-containing vaccination, awareness of MCV and willingness to receive MCV were collected, and the factors affecting the willingness to receive MCV were identified among healthcare workers using a multivariable logistic regression model. @*Results@#Totally 1 403 questionnaires were allocated, and 1 394 valid questionnaires were recovered, with an effective recovery rate of 99.36%. The respondents included 327 men and 1 067 women, with a male to female ratio of 1∶3.26, and 64.35% (897) were at ages of 31 to 50 years. There were 1 005 respondents with a bachelor degree (72.09%), 765 with middle and senior professional titles (54.88%), 676 with a history of measles-containing vaccination (48.49%), 1 176 with willingness to receive MCV (84.36%) and 218 without willingness to receive MCV due to convenience of vaccination (30.73%) and cost (19.27%). Multivariable logistic regression analysis showed that region (Zhejiang, OR=1.613, 95%CI: 1.054-2.470; Anhui, OR=2.058, 95%CI: 1.259-3.363), and no history of measles (OR=2.219, 95%CI: 1.302-3.781) were factors improving the willingness to receive MCV among healthcare workers, and hospital level (secondary, OR=0.483, 95%CI: 0.306-0.763; tertiary, OR=0.251, 95%CI: 0.160-0.394), history of measles-containing vaccination (no, OR=0.262, 95%CI: 0.172-0.399; unknown, OR=0.386, 95%CI: 0.266-0.559), and unawareness of MCV knowledge (OR=0.208, 95%CI: 0.081-0.536) were factors inhibiting the willingness to receive MCV among healthcare workers.@*Conclusions@#The willingness to receive MCV correlates with region, history of measles, hospital level, history of measles-containing vaccination and awareness of MCV knowledge among healthcare workers in the Yangtze River Delta region.
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Objective:To explore the difference of gray matter volume between anxious depression(AD)and non anxious depression(NAD) patients, and its correlation with clinical characteristics.Methods:One hundred and fifty patients with depression were included from September 2014 to October 2018, meanwhile 62 healthy controls with matching demographic characteristic were recruited. The severity of the patients was assessed by Hamilton depression scale-17(HAMD-17). Patients were divided into anxious depression group(AD group, n=80)and non-anxious depression group (NAD group, n=70) according to whether anxiety/somatization factor scored 7. All subjects were scanned with 3.0 T underwent structural MRI scan. The structural magnetic resonance data were preprocessed by voxel-based morphometry (VBM). The rest toolkit was used to calculate the difference of gray matter volume among the three groups. By SPSS 19.0, post-hoc t test was used for pairwise comparison and Pearson correlation analysis was performed between gray matter volume and clinical factors in patients with anxious depression. Results:Compared to the NAD group, the gray matter volume of the right middle frontal gyrus(MNI: x=28.5, y=21.0, z=48.0, t=-4.83, Bonferroni multiple comparison adjustment, P<0.05/3) and left dorsolateral superior frontal gyrus(MNI: x=-18.0, y=27.0, z=43.5, t=-6.08, Bonferroni multiple comparison correction, P<0.05/3)were significantly decreased in AD group. Correlation analysis found that the gray matter volume of the right middle frontal gyrus in patients with anxious depression was negatively correlated with the insight of anxiety/somatization factor score ( r=-0.36, P=0.001). Conclusion:The volume of prefrontal lobe in patients with anxiety depression is lower than that in patients with non anxiety depression, which may be related to the serious clinical symptoms in patients with anxiety depression.The decrease of right middle frontal gyrus volume can be used as a potential biological marker for the severity of impaired insight.
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Non-suicidal self-injury is common in adolescents. At present, the pathological mechanism of non-suicidal self-injury is still unclear, and there is a lack of objective biological markers in diagnosis and treatment, which is an urgent problem to be solved in clinical diagnosis and treatment. The magnetic resonance imaging is an important technique to explore the imaging mechanism of non-suicidal self-injury. The purpose of this review is to systematic evaluation of the latest research results of magnetic resonance imaging of non-suicidal self-injury. It was found that non-suicidal self-injury in people without other mental disorders showed abnormal damage in the orbitofrontal, the dorsolateral prefrontal lobe, the medial prefrontal lobe, the ventrolateral prefrontal lobe, the amygdala, the cingulate gyrus, the supramarginal gyrus, the amygdala, the hippocampus, the insular, the corpus callosum, the thalamus, the putamen, the dorsal striatum, the cuneate prefrontal lobe and the right temporal lobe. These areas are the core areas related to emotional processing, decision-making, cognition and movement. Non-suicidal self-injury with other mental disorders such as borderline personality disorder and depression may be affected by underlying diseases and exhibit different damage patterns, which showing abnormal brain regions related to emotional network, decision-making, social cognition and exercise.The results of this review can be helpful for the future study of the magnetic resonance imaging mechanism of non-suicidal self-injury.
摘要
As occupational health work enters a new era, the diagnosis and identification of occupational diseases, that are closely related to the protection of workers′ health rights, require higher and newer standards. In 2021, the National Health Commission of the People′s Republic of China revised and issued the Administrative Measures for the Diagnosis and Verification of Occupational Diseases to improve and perfect the original diagnosis and verification system of occupational diseases. These measures clarify the time limit for diagnosis of occupational diseases and shorten the time limit for identification of occupational diseases; and strengthen the main responsibility of the employer. This new system design is more operable. It embodies the management idea of Streamline administration, delegate power, combine decentralization, and optimize services. The language expression is more accurate and standardized. The revision of the Administrative Measures for Diagnosis and Verification of Occupational Disease is conducive to improving the efficiency of occupational disease diagnosis and protecting the rights and interests of workers. It is conducive to strengthening the supervision and management of occupational disease diagnosis institutions and occupational disease verification offices by administrative supervision and management departments. It is conducive to strengthening the responsibilities of employers. However, there are some problems: Article No. 28 sets up obstacles to the realization of legal value, which does not clearly stipulate the concept of new evidence. The effective time of this regulation has caused difficulties for occupational disease diagnosis institutions and occupational disease verification offices. It is recommended that this regulation can be further improved in the future revisions.