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3.
Phytochem Anal ; 2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-33977590

RESUMEN

INTRODUCTION: Citri Reticulatae Pericarpium Viride (Qing Pi in Chinese) is a clinically effective Chinese herb, which contains biologically valuable flavonoids. Qing Pi is divided into two commodity specifications, Si Hua Qing Pi (SHQP) and Ge Qing Pi (GQP), based on the harvesting time. The flavonoid contents in Qing Pi from different origins and commodity specifications may vary significantly, which will affect their therapeutic functions. Thus, it is crucial to set up a reliable and comprehensive quality evaluation method for flavonoid analysis in Qing Pi. OBJECTIVES: We aimed to establish a rapid and sensitive ultrahigh-performance liquid chromatography method coupled with diode-array detection and high-resolution mass spectrometry (UPLC-DAD-HRMS) for identification and quantification of ten flavonoids in Qing Pi. Chemometric methods were further applied to distinguish Qing Pi of different origins and specifications. METHODOLOGY: An UPLC-DAD-HRMS method was developed for the simultaneous separation and quantification of ten flavonoids in 46 batches of Qing Pi samples from different sources in China. Chemometric approaches were applied to discriminate Qing Pi from different origins and commodity specifications. RESULTS: The chemometric procedures (i.e., hierarchical clustering analysis and principal component analysis) were employed to identify the differences of Qing Pi samples with different origins and commodity specifications. The results showed that the contents of ten flavonoids in Qing Pi samples of different origins were significantly different, and the same results were found out between SHQP and GQP. CONCLUSIONS: This study provides a chemical basis for quality control of Qing Pi.

4.
Psychol Health Med ; : 1-6, 2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-33971765

RESUMEN

This study aimed to explore which age group out of the patients in quarantine wards with novel coronavirus pneumonia is the most susceptible to anxiety. The data of 32 Covid-19 patients isolated in the quarantine wards of the second Infectious Diseases Department of Baoding Hospital and 71 Covid-19 patients in Tangshan City Infectious Disease Hospital from January 24th to March 5th, 2020, a total of 103 patients, were analyzed. Among these patients, 97 isolated patients were scored with a self-rating anxiety scale (SAS) score seven days after quarantine, and the correlation between age and score was analyzed. These 97 isolated patients were then divided into three groups according to age: group A (up to 35 years old), group B (36-60 years), and group C (over 60 years). One-way analysis of variance was used to compare the scores among groups. The Q-test was used for pairwise comparison.P < 0.05 was considered statistically significant.There was a negative correlation between age and SAS score in isolated Covid-19 patients, and the differences in the score among groups were statistically significant. Patients under 35 years old were more prone to anxiety when they were isolated for seven days. Isolated patients aged up to 35 years old need more attention from quarantine medical staff, communication should be strengthened, and psychological intervention from psychotherapists should be given if necessary.

5.
Chem Biodivers ; 2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-33973702

RESUMEN

Shengxuening (SXN) is a Chinese patent medicine with main ingredients (including chlorophyll derivatives and sodium iron chlorophyllin) extracted from silkworm excrement. SXN exhibited efficacy in clinical trials of renal anemia and iron deficiency anemia; however, the specific mechanisms remain unclear. This study found that SXN increased the number of peripheral blood cells and improved the bone marrow morphology in myelosuppressed mouse model, reversed the reduction in body weight and spleen indices, and increased the serum levels of erythropoietin and granulocyte-macrophage colony-stimulating factor. Quantitative real-time PCR array and Western blot analysis showed the enhanced expression of stem cell factor (SCF), JAK2, and STAT3 in the liver. These results suggested that SXN promoted the recovery of hemopoietic function in myelosuppressed models by increasing the secretion of hematopoietic factors and activating the JAK2/STAT3 pathway. Therefore, this medicine may be applied as therapeutic pharmaceutical drug to mitigate myelosuppression.

6.
J Mater Chem B ; 2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-33989375

RESUMEN

Bacteria associated infection is a critical challenge for metallic implants and devices in biomedical applications. Here, we report phosphonate/zwitterionic/quaternary amine terpolymers as a new type of antifouling and bactericidal coating for metallic substrates. Through reversible-addition fragmentation chain transfer polymerization (RAFT) and quaternization, well-controlled phosphonate/zwitterionic/cationic terpolymers with identical phosphonate segments (repeat units of 15) and varied zwitterionic and cationic components (nSBMA : nTMAEMA = 64 : 0, 54 : 18, 18 : 32, 9 : 52, and 0 : 70) were precisely prepared. The polymers can be coated on TC4 substrates based on the strong coordination between phosphonate groups and metallic substrates, as evidenced by water contact angle and XPS tests. Bactericidal evaluation revealed that the antibacterial efficiency was enhanced with the increase of cationic content in the coating polymers. TC4 substrates coated with the polymer coating with a cationic segment of 70 repeat units were able to kill 97.5 and 94.0% of S. aureus and E. coli, respectively. By virtue of the antifouling ability of the zwitterionic component and the bactericidal ability of the cationic component, the antibacterial efficiency was increased to 99.5% without significant compromising of the cytocompatibility. Meanwhile, the dual functional terpolymers could be easily applied on other metallic substrates, such as titanium, stainless steel, and Ni/Cr alloy, which were able to kill up to 97.9% of S. aureus and 99.9% of E. coli, respectively, endowing the excellent antibacterial properties to general bio-metals. The high-efficiency antibacterial modification strategy demonstrated here may find many applications on metallic implants and devices to combat bacterial associated infections.

7.
BMC Cancer ; 21(1): 534, 2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-33975558

RESUMEN

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignancy predominantly associated with infection by the Epstein-Barr virus (EBV). Approximately 12,900 new cases of NPC occur each year, with more than 70% of cases occurring in the east and southeast Asia. NPC is different from ordinary head and neck squamous cell carcinoma due to its particular biological properties and it is highly sensitive to radiotherapy. With the development of RT technology, the 3-year local control rate and survival rates of non-metastatic NPC reached 80-90% in the intensity-modulated RT (IMRT) era. However, whether distant metastatic NPC (de novo mNPC, dmNPC) should receive locoregional RT (LRRT) needs to be clarified. RESULTS: Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, all patients were successfully divided into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-LRRT groups, statistical differences were found in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference was found in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT can improve OS of low- and intermediate-risk subgroups. CONCLUSIONS: The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.

8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(5): 425-429, 2021 May 10.
Artículo en Chino | MEDLINE | ID: mdl-33974248

RESUMEN

OBJECTIVE: To summarize the result of genetic testing and therapeutic prospect of 2042 unrelated Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD) from a single center from 2005 to 2019. METHODS: Peripheral blood samples of the pedigrees were collected for the detection of DMD gene variants with combined multiple ligation-dependent probe amplification (MLPA), next generation sequencing (NGS) and Sanger sequencing. RESULTS: DMD and BMD have respectively accounted for 78.60% and 21.40% of the pedigrees, which included 33 female probands. Variants of the DMD gene were detected in 1986 pedigrees (97.26%). Large deletions, duplications and small-scale mutations have respectively accounted for 71.85%, 8.76% and 19.39%. Common deletions and duplications have included deletion of exons 45-50 and duplications of exon 2, while no hot spot was found with small-scale mutations. For 1595 pedigrees affected with DMD, 935 (58.62%) were hereditary and 660 (41.38%) were de novo in origin. 34.28% (700/2042) of the patients had symptoms which could be relieved by gene therapy. CONCLUSION: This has been the largest single-center study of DMD pedigrees, which has attained definite diagnosis in 97.26% of the patients. The results have enabled genetic counseling and prenatal diagnosis for the affected families upon their subsequent pregnancies, enriched the spectrum of DMD gene variants, as well as facilitated study of the mechanism of DMD gene mutations and exploration of clinical treatment.


Asunto(s)
Distrofia Muscular de Duchenne , China , Distrofina/genética , Exones/genética , Femenino , Eliminación de Gen , Pruebas Genéticas , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Mutación , Linaje , Embarazo
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(5): 435-438, 2021 May 10.
Artículo en Chino | MEDLINE | ID: mdl-33974250

RESUMEN

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for 29 Chinese pedigrees affected with tuberous sclerosis complex (TSC) and assess efficacy of combined next generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) for the diagnosis. METHODS: NGS and MLPA were used in conjunct to detect variants of TSC1 and TSC2 genes among the probands of the pedigrees. Paternity test was carried out to exclude maternal DNA contamination. Prenatal diagnosis was provided to 14 couples based on the discoveries in the probands. RESULTS: Twenty-seven variants were identified in the TSC1 and TSC2 genes among the 29 pedigrees, which yielded a detection rate of 93.1%. Respectively, 5 (18.5%) and 22 (81.5%) variants were identified in the TSC1 and TSC2 genes. Twelve variants were unreported previously. Prenatal diagnosis showed that five fetuses were affected with TSC, whilst the remaining nine were unaffected. CONCLUSION: Above finding has expanded the spectrum of TSC1 and TSC2 gene variants. Combined NGS and MLPA has enabled diagnosis of TSC with efficiency and accuracy.


Asunto(s)
Esclerosis Tuberosa , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Humanos , Mutación , Embarazo , Diagnóstico Prenatal , Esclerosis Tuberosa/diagnóstico , Esclerosis Tuberosa/genética , Proteína 1 del Complejo de la Esclerosis Tuberosa/genética , Proteína 2 del Complejo de la Esclerosis Tuberosa/genética
10.
BMJ ; 373: n1038, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33975825

RESUMEN

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

11.
Radiother Oncol ; 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33984350

RESUMEN

PURPOSE: This study aimed to evaluate the prognostic value of paranasal sinus involvement (PSI) in NPC and to explore its appropriate position in the current AJCC staging system. MATERIALS AND METHODS: Pretreatment MRI of 1317 patients with NPC treated with intensity-modulated radiotherapy (IMRT) between January 2010, and January 2013, were reviewed retrospectively. Survival was compared between patients with PSI-slight (sinus bone wall erosion only) and PSI-severe (tumor penetrated into sinus cavity). Multivariable analysis was performed to identify the independent predictors of survival. RESULTS: The study included 1317 patients (median age 46 years; range, 11-78 years). PSI-slight was present in 15.2% (200/1317) patients and PSI-severe in 20.0% (263/1317) patients. Overall survival (OS), distant metastasis-free survival (DMFS), loco-regional recurrence-free survival (LRFS), and progression-free survival (PFS) were significantly lower in patients with PSI-severe (all P < .05). In multivariable analysis, PSI-severe was an independent prognostic factor for OS, DMFS, LRFS, and PFS (all P < .05). 96 AJCC T3 category patients with PSI-severe were reclassified as T4 category. The revised T category had significantly better predictive value (higher C-index) than that the AJCC system for survival (OS, .661 vs. .652; DMFS, .655 vs. .650; and PFS, .625 vs. .625; P < .05 for all). CONCLUSION: PSI-severe is an independent negative prognostic factor in nasopharyngeal carcinoma, which is recommended to be classified as T4 category in the 8th AJCC staging system for NPC.

12.
Eur J Clin Nutr ; 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33931771

RESUMEN

BACKGROUND: Wholegrains contribute a range of beneficial nutrients, such as dietary fiber and several minerals and vitamins, that are beneficial to depressive symptoms. However, there are a few studies aimed at exploring whether a wholegrain diet is related to depressive symptoms. We conducted this study to investigate the relationship between wholegrains consumption and depressive symptoms. METHODS: This cross-sectional study included a total of 24,776 (mean age: 39.9 years, age range: 18.1-91.3 years; males, 54.1%) inhabitants living in Tianjin, China. Wholegrains consumption was assessed using a valid self-administered food frequency questionnaire. Depressive symptoms were evaluated using the Chinese version of Zung Self-Rating Depression Scale (SDS) and the cutoff point was set at 45. Multiple logistic regression analysis was used to estimate the relationship between wholegrains consumption and depressive symptoms. RESULTS: The prevalence of depressive symptoms was 19.1% and 22.4% in males and females, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence intervals) of depressive symptoms across wholegrains consumption were 0.77 (0.65-0.91) for <1 time/week, 0.73 (0.62-0.86) for 1 time/week and 0.68 (0.59-0.79) for ≥2 time/week in males compared with the control group (almost never). In females, the odds ratios (95% confidence intervals) were 0.86 (0.71-1.04) for <1 time/week, 0.94 (0.78-1.13) for 1 time/week, and 0.76 (0.65-0.91) for ≥2 time/week. Similar results were observed when we use other cut-offs (SDS ≥ 40 and 50) to define depressive symptoms. CONCLUSION: This study first demonstrated that the higher consumption of wholegrains might have effects on the prevention and improvement of depressive symptoms. Prospective or intervention studies are needed to confirm these findings.

13.
Bone ; : 115997, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33964467

RESUMEN

BACKGROUND: Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The clinical manifestations and radiographic features of KBD were similar to that of osteoarthritis (OA). METHODS: We first performed a genetic association scan of 32 OA susceptibility genes with KBD in 898 Han Chinese subjects. The MassARRAY genotyping system (Agena) was used for SNP genotyping. PLINK 1.9 was used for quality control and association testing. Using articular cartilage specimens from 7 adult KBD patients and 4 healthy control subjects, lentivirus-mediated RNA interference (RNAi), qRT-PCR, Western blot and immunohistochemistry were employed to validate the functional relevance of TP63 in KBD chondrocyte. RESULTS: SNP genotyping and association analysis identified TP63 (rs12107036, OR = 0.7133, P = 0.005) and OARD1 (rs11280, OR = 1.512, P = 0.004) were significantly associated with KBD. We found that TP63 was significantly up-regulated in KBD articular cartilage in both mRNA and protein level compared to healthy controls (P < 0.05). Lentivirus-mediated RNAi of TP63 suppression notably decreased the abundance of Caspase3 and SOX9 in chondrocytes. Most importantly, compared to the untransfected chondrocytes, the TP63 inhibition increased the production of ACAN. The mRNA expression of chondrocyte marker genes (COL2A1 and ACAN) was partly stable by TP63 knockdown relative to control group. CONCLUSION: Our study identifies TP63 as a novel susceptibility gene for KBD, and demonstrates that inhibition of TP63 suppress chondrocyte apoptosis and partly facilitates chondrogenesis. The combination of SNP genotyping and genetic manipulation techniques provides a useful tool for understanding the biological mechanism and differential diagnosis studies of KBD and OA.

14.
Chem Commun (Camb) ; 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33970180

RESUMEN

Herein, we report a 54-nuclei copper nanocluster, [Cu54S13O6(tBuS)20(tBuSO3)12] (Cu54), which is the largest atom-precise CuI/CuII mix-valent cluster reported. The Cu54 nanoclusters supported by TiO2 exhibit decent photocatalytic activity for phenol degradation under visible light. This work provides a platform to explore the catalytic behaviors of CuI/CuII nanosystems.

15.
PLoS One ; 16(5): e0251258, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33974657

RESUMEN

Our computational developments and analyses on experimental images are designed to evaluate the effectiveness of chemical spraying via unmanned aerial vehicle (UAV). Our evaluations are in accord with the two perspectives of color-complexity: color variety within a color system and color distributional geometry on an image. First, by working within RGB and HSV color systems, we develop a new color-identification algorithm relying on highly associative relations among three color-coordinates to lead us to exhaustively identify all targeted color-pixels. A color-dot is then identified as one isolated network of connected color-pixel. All identified color-dots vary in shapes and sizes within each image. Such a pixel-based computing algorithm is shown robustly and efficiently accommodating heterogeneity due to shaded regions and lighting conditions. Secondly, all color-dots with varying sizes are categorized into three categories. Since the number of small color-dot is rather large, we spatially divide the entire image into a 2D lattice of rectangular. As such, each rectangle becomes a collective of color-dots of various sizes and is classified with respect to its color-dots intensity. We progressively construct a series of minimum spanning trees (MST) as multiscale 2D distributional spatial geometries in a decreasing-intensity fashion. We extract the distributions of distances among connected rectangle-nodes in the observed MST and simulated MSTs generated under the spatial uniformness assumption. We devise a new algorithm for testing 2D spatial uniformness based on a Hierarchical clustering tree upon all involving MSTs. This new tree-based p-value evaluation has the capacity to become exact.

16.
J Environ Manage ; 291: 112716, 2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-33957418

RESUMEN

The increase of unpalatable Stellera chamaejasme plants has become commonplace in degraded grasslands of China, which can hinder the establishment and growth of palatable plants and have an impact on sustainable development of livestock production. Controlling S. chamaejasme is thus a necessary, yet usually problematic step towards the degraded grassland. Various measures have been implemented to control S. chamaejasme but relatively little is known about the growth and development of S. chamaejasme in degraded grassland. Therefore, focusing on the life history traits of S. chamaejasme can provide theoretical support underpinning its management. In this study, different age classes of S. chamaejasme plants were surveyed and studied from a degraded typical steppe in China, and the variation of the phenotypic traits, biomass increasement, biomass allocation, reserves and nutrient content were described. These analyses could be of great importance in identifying the management practices of S. chamaejasme that are most consistent with the development of S. chamaejasme in degraded grasslands. We found that most of the phenotypic traits and biomass of all organs increased by different patterns with age class. Like many other species, there has been three developmental phases in S. chamaejasme, however, previous researches only focus on the S. chamaejasme in the adult reproductive phase, therefore leading to a delay between the time of S. chamaejasme's seedling and the time when it begins to establish. Our findings demonstrate that S. chamaejasme mainly distributes the biomass to belowground part (RMF and SMF), which is conducive to the survival of S. chamaejasme on degraded grasslands, making mowing fail to eradicate S. chamaejasme in practice. Partial least squares path modeling suggested that nutrient content (N) played a key role in flowering of S. chamaejasme, but the indirect effect was greater than direct effect. The results from this study highlight that control efforts and the management of S. chamaejasme should not only focus on the S. chamaejasme individual in unreproductive phase, but also on the belowground part of plant in reproductive phase.

17.
Front Immunol ; 12: 609762, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33968014

RESUMEN

Cancer is one of the leading causes of death and a major public health problem all over the world. Immunotherapy is becoming a revolutionary clinical management for various cancer types. Restoration of aberrant immune surveillance on cancers has achieved markable progress in the past years by either in vivo or ex vivo engineering of the immune cells. Here, we summarized the central roles of immune cells in tumor progression and regression, and the existing and emerging strategies for different immune cell-based immunotherapies. In addition, the current challenges and the potential solutions in translating the immunotherapies into the clinic are also discussed.

18.
BMC Psychiatry ; 21(1): 232, 2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33947370

RESUMEN

BACKGROUND: This study investigated cognitive and emotional functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and disruptive, impulse-control, and conduct disorders (DICCD). METHODS: Thirty patients with ADHD, 26 with DICCD, 22 with ADHD+DICCD were recruited from the outpatient department of Shanghai Changning Mental Health Center, plus 20 healthy controls (HC). Differences between the groups in cognitive and emotional functioning were examined using Golden's Stroop and Emotional Stroop tests. For Emotional Stroop Mean reaction time (RT) of positive word (POS) and negative word (NEG) with color congruence (C) or incongruence (I) were recorded as POS-C, POS-I, NEG-C and NEG-I, respectively. RESULTS: For Golden's interference scores (IGs), both errors and RTs in the ADHD group were higher than in the other groups. Longer mean RTs of POS-C, POS-I, NEG-C and neural word (NEU) of the ADHD group, and NEG-I of ADHD+DICCD and DICCD groups were observed compared to HC. After 12 weeks of methylphenidate treatment, differences between ADHD subgroups and HC on Golden's Stroop RT disappeared, but differences in Golden's Stroop errors and Emotional Stroop mean RTs remained. The ADHD+DICCD group showed longer mean RTs in NEG-C, NEG-I and NEU of the Emotional Stroop test than the ADHD group. CONCLUSIONS: Our study shows that regardless of emotional responding, deficit in cognitive control is the core symptom of ADHD. However, emotionally biased stimuli may cause response inhibitory dysfunction among DICCD with callous-unemotional traits, and the comorbidity of ADHD and DICCD tends to account for the negative emotional response characteristic of DICCD. These deficits may be eliminated by medication treatment in ADHD, but not the ADHD with comorbid DICCD. Our results support the notion that ADHD with comorbid DICCD is more closely related to DICCD than to ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno de la Conducta , Adolescente , Atención , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Niño , China/epidemiología , Cognición , Comorbilidad , Trastorno de la Conducta/complicaciones , Trastorno de la Conducta/epidemiología , Emociones , Humanos , Pruebas Neuropsicológicas
19.
Bioengineered ; 12(1): 1627-1641, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33949293

RESUMEN

Hepatocellular carcinoma (HCC) is a leading cause of mortality in cancer patients, but the association between miR-125b-2-3p and the onset and prognosis of HCC has not been reported in previous studies; thus, the clinicopathological implications of miR-125b-2-3p in HCC require elaboration. To examine the expression of miR-125b-2-3p in HCC, both in-house RT-qPCR and public datasets were used to calculate the standard mean difference (SMD) and the summary receiver operating characteristic (sROC). MiR-125b-2-3p was markedly lower in HCC than in non-tumor tissue as assessed by the in-house RT-qPCR which was confirmed by the integrative analysis showing the SMD being -0.69 and the area under the curve (AUC) being 0.84 based on 1,233 cases of HCC and 630 cases of non-HCC controls. To gain a overview of the clinical value of miR-125b-2-3p in HCC, all possible datasets were integrated, and lower miR-125b-2-3p levels could lead to poorer differentiation and a more advanced clinical stage of HCC. The hazard ratio (HR) of miR-125b-2-3p was also calculated using a Cox proportional hazards model, and the miR-125b-2-3p level could act as an protective indication for the survival with the HR being 0.74 based on 586 cases of HCC. Furthermore, the effect of nitidine chloride (NC), a natural bioactive phytochemical alkaloid, on the regulation of miR-125b-2-3p and its potential targets was also investigated. The miR-125b-2-3p level was increased after NC treatment, while the expression of its potential target PRKCA was reduced. Above all, a low-expressed level of miR-125b-2-3p plays a tumor suppressive role in HCC.

20.
Hum Mol Genet ; 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33949662

RESUMEN

Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintains the structural integrity of tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly in an autosomal dominant manner. Here, we identified a homozygous stop-gain mutations in DSG2 (c.C355T, p.R119X) that led to complete desmoglein-2 deficiency in a patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition of desmosome proteins, disrupted intercalated disc structures in the myocardium. Induced pluripotent stem cells were generated from the patient (R119X-iPSC), and the mutated DSG2 gene locus was heterozygously corrected to a normal allele via homology-directed repair (HDR-iPSC). Both isogenic iPSCs were differentiated into cardiomyocytes (iPSC-CMs). Multielectrode array analysis detected abnormal excitation in R119X-iPSC-CMs but not HDR-iPSC-CMs. Micro force testing of 3-dimensional self-organized tissue rings (SOTRs) revealed tissue fragility and a weak maximum force in SOTRs from R119X-iPSC-CMs. Notably, these phenotypes were significantly recovered in HDR-iPSC-CMs. Myocardial fiber structures in R119X-iPSC-CMs were severely aberrant, and electron microscopic analysis confirmed that desmosomes were disrupted in these cells. Unexpectedly, the absence of desmoglein-2 in R119X-iPSC-CMs led to decreased expression of desmocollin-2 but no other desmosome proteins. Adeno-associated virus-mediated replacement of DSG2 significantly recovered the contraction force in SOTRs generated from R119X-iPSC-CMs. Our findings confirm the presence of a desmoglein-2-deficient cardiomyopathy among clinically diagnosed dilated cardiomyopathies. Recapitulation and correction of the disease phenotype using iPSC-CMs provides evidence to support the development of precision medicine and the proof of concept for gene replacement therapy for this cardiomyopathy.

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