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Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients.
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Antígenos de Superfície/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Regiões 3' não Traduzidas , Animais , Apoptose/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Diferenciação Celular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Família Multigênica , Oncogenes , Prognóstico , Interferência de RNA , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Hsa-MicroRNA-124a-3p (hsa-miR-124-3p) is involved in tumor progression in certain malignant tumors. However, its function and clinical implication in hepatocellular carcinoma (HCC) have not yet been illustrated. In this study, we explored the expression and prognostic value of hsa-miR-124-3p in patients with HCC. Hsa-miR-124-3p expression in HCC was analyzed in silico, which was subsequently confirmed by quantitative PCR in 155 HCC biopsy samples. Overall survival (OS) and disease-free survival in HCC patients was evaluated by Kaplan-Meier survival analysis, and univariate and multivariate Cox proportional hazard models were used. The in silico results demonstrated that hsa-miR-124-3p was reduced in cell lines and tissues of HCC, and hsa-miR-124-3p expression was lower in HCC tumor samples than in normal liver tissues. Moreover, a decrease in hsa-miR-124-3p expression was closely correlated with tumor diameter (≥ 5 cm) and number of lesions (multiple). Lower hsa-miR-124-3p expression was shown to be correlated with a shorter OS and poor prognosis in HCC. Our findings demonstrate that hsa-miR-124-3p might be a potential target for the diagnosis and prognosis of HCC.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: The global spread of plasmid-borne carbapenem resistance is an ongoing public health challenge; however, the nature of such horizontal gene transfer events among complex bacterial communities remains poorly understood. We examined the in-situ transfer of the globally dominant New Delhi metallo-ß-lactamase (NDM)-5-positive IncX3 plasmid (denoted pX3_NDM-5) in hospital wastewater to simulate a real-world, One Health antimicrobial resistance context. METHODS: For this transmission study, we tagged pX3_NDM-5 with the green fluorescent protein gene, gfp, using a CRISPR-based method and transferred the plasmid to a donor Escherichia coli strain. Bacteria were extracted from a hospital wastewater treatment plant (Fujian Provincial Maternity and Children's Hospital, Fuzhou, China) as the bacterial recipient community. We mixed this recipient community with the E coli donor strain carrying the gfp-tagged plasmid, both with and without sodium hypochlorite (NaClO) as an environmental stressor, and conducted several culture-based and culture-independent conjugation assays. The conjugation events were observed microscopically and quantified by fluorescence-activated cell sorting. We analysed the taxonomic composition of the sorted transconjugal pool by 16S rRNA gene amplicon sequencing and assessed the stability of the plasmid in the isolated transconjugants and its ability to transfer back to E coli. FINDINGS: We show that the plasmid pX3_NDM-5 has a broad host range and can transfer across various bacterial phyla, including between Gram-negative and Gram-positive bacteria. Although environmental stress with NaClO did not affect the overall plasmid transfer frequency, it reduced the breadth of the transconjugant pool. The taxonomic composition of the transconjugal pool was distinct from that of the recipient communities, and environmental stress modulated the permissiveness of some operational taxonomic units towards the acquisition of pX3_NDM-5. Notably, pX3_NDM-5 transconjugants included the Gram-positive pathogen Enterococcus faecalis, and the plasmid could subsequently be reconjugated back to E coli. These findings suggest that E faecalis could act as a natural shuttle vector for the wide dissemination of pX3_NDM-5 plasmids. INTERPRETATION: Our culture-independent conjugation model simulates natural environmental conditions and challenges the established theory that Gram-negative and Gram-positive bacteria rarely exchange clinically important plasmids. The data show that plasmids disseminate more widely across genera and phyla than previously thought. These findings have substantial implications when considering the spread of antimicrobial resistance across One Health sectors. FUNDING: The Laboratory of Lingnan Modern Agriculture Project, the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province of China, and the Outstanding Young Research Talents Program of Fujian Agriculture and Forestry University.
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Anti-Infecciosos , Escherichia coli , Feminino , Gravidez , Criança , Humanos , Escherichia coli/genética , Águas Residuárias , RNA Ribossômico 16S/genética , Plasmídeos/genética , Bactérias/genética , HospitaisRESUMO
Acetaminophen (APAP) overdose is a leading cause of acute liver injury in the USA. The chitinase 3-like-1 (Chi3l1) protein contributes to APAP-induced liver injury (AILI) by promoting hepatic platelet recruitment. Here, we report the development of a Chi3l1-targeting antibody as a potential therapy for AILI. By immunizing a rabbit successively with the human and mouse Chi3l1 proteins, we isolated cross-reactive monoclonal antibodies (mAbs) from single memory B cells. One of the human and mouse Chi3l1 cross-reactive mAbs was humanized and characterized in both in vitro and in vivo biophysical and biological assays. X-ray crystallographic analysis of the lead antibody C59 in complex with the human Chi3l1 protein revealed that the kappa light contributes to majority of the antibody-antigen interaction; and that C59 binds to the 4α-5ß loop and 4α-helix of Chi3l1, which is a functional epitope and hotspot for the development of Chi3l1 blocking antibodies. We humanized the C59 antibody by complementarity-determining region grafting and kappa chain framework region reverse mutations. The humanized C59 antibody exhibited similar efficacy as the parental rabbit antibody C59 in attenuating AILI in vivo. Our findings validate Chi3l1 as a potential drug target for AILI and provide proof of concept of developing Chi3l1 blocking antibody as a therapy for the treatment of AILI.
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BACKGROUND: The COVID-19 pandemic broke out in 2019 and rapidly spread across the globe. Most of the severe and dead cases are middle-aged and elderly patients with chronic systemic diseases. OBJECTIVE: This study aimed to assess the association between fasting blood glucose (FPG) and body mass index (BMI) levels in patients with coronavirus disease 2019 (COVID-19) under different conditions. METHODS: Experimental-related information (age, gender, BMI, and FPG on the second day of admission) from 86 COVID-19 cases (47 males and 39 females) with an average age of (39 ± 17) years was collected in April and November 2020. These cases were divided into three groups according to the most severe classification of each case determined by the clinical early warning indicators of severe-critically illness, the degree of progression, and the treatment plan shown in the diagnosis and treatment plan of COVID-19 pneumonia. Statistical models were used to analyze the differences in the levels of FPG and BMI, age, and gender among the three groups. RESULTS: 1. Experimental group: 21 patients with asymptomatic or and mild symptoms (group A), 45 patients with common non-progression (group B), and 20 patients with common progression and severe symptoms (group C). 2. The age differences among the three groups were statistically significant and elderly patients had a higher risk of severe disease (t= 4.1404, 3.3933, 9.2123, P= 0.0001, 0.0012, 0.0000). There was a higher proportion of females than males in the normal progression and severe disease cases (χ2= 5.512, P= 0.019). 3. The level of FPG was significantly higher in group C than in group A (t= 3.1655, P= 0.0030) and B (t= 2.0212, P= 0.0475). The number of diabetes or IFG in group C was significantly higher than in group A (χ2= 5.979, P= 0.014) and group B (χ2= 6.088, P= 0.014). 4. BMI was significantly higher in group C than in groups A (t= 3.8839, P= 0.0004) and B (t= 3.8188, P= 0.0003). The number of overweight or obese patients in group C was significantly higher than in groups A (χ2= 8.838, P= 0.003) and B (χ2= 10.794, P= 0.001). 5. Patients' age, gender, and FPG were independent risk factors for COVID-19 disease progression (ß= 0.380, 0.191, 0.186; P= 0.000, 0.034, 0.045). CONCLUSION: The levels of FPG and BMI were significantly increased in the population with common progressive and severe COVID-19. FPG and age are independent risk factors for the progression of COVID-19.
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COVID-19 , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Índice de Massa Corporal , COVID-19/epidemiologia , Glicemia , Estudos Retrospectivos , Jejum , PandemiasRESUMO
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high rates of morbidity and mortality. Currently, several surfactant or anti-inflammatory drugs are under test as treatments for ALI. Sodium aescinate (SA) has been shown to exert anti-inflammatory and antiedematous effects. In the present work, the authors explored the effects of SA and the possible mechanisms of SA action in rats with ALI induced by oleic acid (OA) administration. Eight groups of rats received infusions of normal saline (NS) or OA. Rats exposed to OA were pretreated with 1 mg/kg of SA, or posttreated with SA at low (1 mg/kg), medium (2 mg/kg), or high (6 mg/kg) dose; a positive-control group received methylprednisolone. The pressure of oxygen in arterial blood (P(O(2))) levels, the pulmonary wet/dry weight (W/D) ratios, and indices of quantitative assessment (IQA) of histological lung injury were obtained 2 or 6 hours after OA injection (0.1 mL/kg, intravenously). The levels of superoxide dismutase (SOD), malondialdehyde (MDA), matrix metalloproteinase gelatinase B (MMP-9), and tissue inhibitor of metalloproteinase (TIMP-1) in both plasma and lung tissue were also determined. Both pre- and posttreatment with SA improved OA-induced pulmonary injury, increased P(O(2)) and SOD values, lowered IQA scores, and decreased the lung W/D ratio and MDA and MMP-9 levels in plasma and lung tissue. SA appeared to abrogate OA-induced ALI by modulating the levels of SOD, MDA, and MMP-9 in plasma and lung tissue.
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Lesão Pulmonar Aguda/tratamento farmacológico , Escina/farmacologia , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Artérias/efeitos dos fármacos , Artérias/metabolismo , Gasometria/métodos , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/metabolismo , Ácido Oleico , Oxigênio/sangue , Oxigênio/metabolismo , Ratos , Ratos Sprague-Dawley , Compostos de Sódio/farmacologia , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
OBJECTIVE: To explore the efficacy of Yishen Huoxue Tongluo() decoction containing serum on the apoptosis of human disc nucleus pulposus cells under the overload static pressure stress and its related mechanism. METHODS: Human nucleus pulposus cells were divided into three groups. The blank group had no intervention. The model group and traditional Chinese medicine serum intervention group were treated with 3 MPa compressive stress in vitro for 2, 4 and 6 hours. The changes and differences of morphology, growth status and ultrastructure of intervertebral disc nucleus pulposus cells were observed. The apoptosis rate of nucleus pulposus cells and nuclear factor kappa-B p65 (NF-κB p65), SRY-related high mobility group box 9 (SOX9), C/EBP-homologous protein (CHOP), matrix metalloprotein-13 (MMP-13) and corresponding gene expression were detected. RESULTS: At the same time, compared with the blank group, the nucleus pulposus cells in the model group were smaller in volume, less in cytoplasm and worse in growth; the nucleus pulposus cells in the traditional Chinese medicine serum intervention group were slightly larger in volume, more complete in morphology, richer in cytoplasm and better in growth. Under the same action time, the ultrastructure of nucleus pulposus cells in blank group was complete, and the structures of primary and secondary processes were not broken;and the ultrastructure of model group and traditional Chinese medicine serum intervention group were damaged, the main and secondary processes were broken to varying degrees, and there was no significant difference between the two groups. At the same time, the apoptosis rate of nucleus pulposus cells in model group was higher than that in blank group, while the apoptosis rate of nucleus pulposus cells in the traditional Chinese medicine serum intervention group was lower than that inmodel group, the difference was statistically significant (P<0.05); with the increase of action time, there was no significant difference in the apoptosis rate of nucleus pulposus cells between blank group and traditional Chinese medicine serum intervention group, and the apoptosis rate of nucleus pulposus cells in model group was increased. Compared with model group, the expression of NF-κB p65, CHOP, MMP-13 were decreased and SOX9 was increased in traditional Chinese medicine serum intervention group at the same time (P<0.05);with the increase of action time, the expression of NF-κB p65, CHOP and MMP-13 were increased, and the expression of SOX9 was decreased in blank group and model group(P<0.05), and the expression level of model group was higher than that of blank group(P<0.05). Overall observation by gene expression, under the same action time, the relative quantifications of NF-κB p65, CHOP and MMP-13 in traditional Chinese medicine serum intervention group were lower than that in model group, while SOX9 was increased (P<0.05);compared with model group, the relative quantifications of NF-κB p65, CHOP and MMP-13 in blank group were decreased(P<0.05), and the relative quantification of SOX9 was increased(P<0.05);with the increase of action time, the relative quantifications of NF-κB p65, CHOP and MMP-13 of nucleus pulposus cells in blank group and model group were increased and SOX9 was decreased(P<0.05). CONCLUSION: Yishen Huoxue Tongluo() decoction can reduce the apoptosis of nucleus pulposus cells under overload and static pressure, and has the effect of delaying the degeneration of nucleus pulposus cells. Its mechanism may be related to the decrease of CHOP, MMP-13 expression and the increase of SOX9 expression by inhibiting NF-κB p65 signal pathway of nucleus pulposus cells.
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Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Apoptose , Medicamentos de Ervas Chinesas , HumanosRESUMO
Functional elimination of p53 is a common feature of a large percentage of human malignancies. Here, we report the development of a pharmacological strategy aimed at restoring p53 function and its use for targeted therapy in p53-deficient mice. Specific inhibition of deubiquitinases ubiquitin-specific peptidase 14 (USP14) resulted in durable tumor regressions of autochthonous lymphomas and sarcomas in p53-deficient mice without affecting normal tissues, and therapeutic response was correlated with an increase in the ubiquitination of constitutive photomorphogenesis 9 (COP9) signalosome subunit 5 (COPS5), a key negative regulatory effector for p53. Inhibition of USP14 resulted in durable tumor regression through COPS5 deubiquitilation and a p53-dependent and -independent regulation mechanism by USP14. This series highlights the utility of proteasome deubiquitinating activity inhibition as a novel treatment paradigm for p53-deficient cancers. In addition, it provides preliminary evidence that inhibition of USP14 resulted in durable tumor regression through COPS5 deubiquitilation and p53-dependent and -independent regulation mechanism by USP14. These findings suggest that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target for patients with p53 deficiency.
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Glioblastoma is the most common primary malignant tumor of brain in adults.Although great efforts have been made to improve prognosis in recent years,the median survival is still less than 20 months,and less than 5%of patients survive longer than 20 months.The standard treatment is maximum surgical excision combined with radiotherapy and temozolomide chemotherapy.Single cell RNA sequencing(scRNA-seq)technology accurately analyzes each unique cell,enabling us to better understand the heterogeneity of tumors,the evolution process of tumor cells,the special functions of various types of cells in the immune microenvironment,and the interactions between cells,thus providing new ideas for personalized clinical therapy.This review focuses on the application of scRNA-seq in the study of glioblastoma heterogeneity,tumor immune microenvironment,cell communication and treatment.
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Colorectal cancer (CRC) is the third most common cancer worldwide, and liver metastasis presents a major cause of CRC-associated death. Extensive genomic analysis has provided valuable insight into the pathogenesis and progression of CRC; however, a comprehensive proteogenomic characterization of CRC liver metastasis (CLM) has yet to be reported. Here, we analyzed the proteomes of 44 paired normal colorectal tissues and CRC tissues with or without liver metastasis, as well as analyzed genomics of CRC characterized previously by The Cancer Genome Atlas (TCGA) to conduct integrated proteogenomic analyses. We identified a total of 2,170 significantly deregulated proteins associated with CLM, 14.88% of which were involved in metabolic pathways. The mutated peptide number was found to have potential prognosis value, and somatic variants revealed two metabolism-related genes UQCR5 and FDFT1 that frequently mutated only in the liver metastatic cohort and displayed dysregulated protein abundance with biological function and clinical significance in CLM. Proteogenomic characterization and integrative and comparative genomic analysis provides functional context and prognostic value to annotate genomic abnormalities and affords a new paradigm for understanding human colon and rectal cancer liver metastasis.
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OBJECTIVE@#To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-β1 (TGF-β1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs).@*METHODS@#The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-β1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016.@*RESULTS@#LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-II (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of -8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1.@*CONCLUSION@#RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.
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Animais , Ratos , Lipopolissacarídeos/farmacologia , Células Mesangiais , Resveratrol/farmacologia , Fator de Transcrição AP-1 , Fator de Crescimento Transformador beta1 , Peptídeos e Proteínas de Sinalização Intercelular , Proliferação de Células , DNA , Células CultivadasRESUMO
Sleep is a highly conserved phenomenon in endotherms, and has a universal physiological function across all species. In mammals, sleep can be divided into two stages: rapid eye movement (REM) sleep and non-REM (NREM) sleep, which alternate in a cyclic manner. Humans spend about one-third of their lives asleep. Sufficient sleep is necessary for humans to sustain everyday functioning. Sleep plays an important role in regulating energy metabolism, immune defense, endocrine function, and the consolidation of memory process. With the development of social economy and the change of life style, sleep duration of the residents has gradually decreased and the incidence of sleep disturbances has increased. Sleep disturbances can lead to severe mental disorders, such as depression, anxiety disorders, dementia, and other mental diseases, and may increase the risk of physical diseases, such as chronic inflammation, heart disease, diabetes, hypertension, atherosclerosis and others. Maintaining good sleep is of great significance for developing social productive forces, promoting sustainable development of economic society, and is a necessary condition for carrying out the "Healthy China Strategy". The sleep research in China started in 1950s. After decades of development, researchers have made great progress in the molecular mechanisms of sleep and wakefulness, the pathogenesis of sleep disorders and the development of new therapies. With the advancement of science and technology and the public's attention to sleep, the level of clinical diagnosis and therapy of sleep disorders in China is gradually brought in line with international standards. The publication of diagnosis and treatment guidelines in the field of sleep medicine will promote the standardization of the construction. In the future, it is still necessary to promote the development of sleep medicine in the following aspects: Strengthening the professional training and discipline construction, improving the cooperation of sleep research, promoting the intelligent diagnosis and treatment of sleep disorders, and developing the new intervention strategies. Therefore, this review will comprehensively summarize the origin, current situation, and future expectations of sleep medicine in China, including discipline construction of sleep medicine, the number of sleep project grants, research findings, the status and progress of diagnosis and treatment of sleep disorders, and the development direction of sleep medicine.
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Animais , Humanos , Sono , Transtornos do Sono-Vigília/terapia , Aterosclerose , China/epidemiologia , Nível de Saúde , MamíferosRESUMO
We employed bibliometrics to comprehensively study the hotspots and frontiers of gut microbiota research involving traditional Chinese medicine(TCM), aiming to provide new ideas for the subsequent research in this field. The studies of gut microbiota with TCM published from January 1, 2002 to December 31, 2021 were retrieved from CNKI, Wanfang, VIP and Web of Science(WoS). After data screening and cleaning, CiteSpace 5.8.R3 was used to visualize and analyze the authors, journals, and keywords. A total of 1 119 Chinese articles and 815 English articles were included in the study. The period of 2019-2021 witnessed the surge in the number of articles published in this field, being the peak research period. TAN Zhou-jin and DUAN Jin-ao were the authors publishing the most articles in Chinese and English, respectively. The two authors ranked top in both Chinese and English articles, playing a central role in this research field. The top five Chinese and English journals in this field had a large influence in the international research field. High-frequency keywords and keyword clustering showed that the research hotspots in this field were concentrated in four areas: trial and clinical research on the regulation of gut microbiota in disease treatment by TCM, metabolic transformation of Chinese medicines by gut microbiota, and the effect of TCM added to feed on the gut microbiota and growth performance of animals. The study of gut microbiota structure in patients with different TCM syndromes, as well as that of TCM combined with probiotics/flora transplantation in the treatment of diseases, can provide new ideas for clinical diagnosis and traditional drug treatment of diseases and has great research space and research value in the future.
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Animais , Medicina Tradicional Chinesa , Microbioma Gastrointestinal , Publicações , BibliometriaRESUMO
Objective:To explore any effect of transcranial direct current stimulation (tDCS) on neurons, behavior, cerebral blood flow (CBF), vascular regeneration, and the expression of vascular endothelial growth factor (VEGF) and CD34 protein in rats modeling cerebral infarction.Methods:Thirty-two adult male Sprague-Dawley rats were randomly divided into a sham surgery group (Sham group), a model group (modeled with middle cerebral artery occlusion, MCAO group), an anode transcranial direct current stimulation group (A-tDCS group), and a cathode transcranial direct current stimulation group (C-tDCS group), each of 8. MCAO models were established in the rats of the MCAO, A-tDCS and C-tDCS groups using thread fixation. Twenty-four hours after successful modeling, both the Sham and MCAO groups were connected with electrodes without current stimulation, while the A-tDCS and C-tDCS groups were given 20 minutes of 200μA anodic or cathodic electrical stimulation daily, 5 days a week for 12 days. Before and 24 hours after the modeling, and then after the 12 days of treatment, the four groups received Longa neurobehavioral scoring. Moreover, three days after the modeling as well as after the 12 days of treatment, changes in CBF were observed using MRI. Any blood vessel regeneration was observed using immunofluorescence methods, and the expression of VEGF and CD34 proteins were detected using western blotting.Results:The rats in the MCAO, A-tDCS and C-tDCS groups exhibited various degrees of neurological deficit after the modeling. After the 12 days of treatment the average neurobehavioral scores of the A-tDCS and C-tDCS groups were significantly lower than that of the MCAO group, with the A-tDCS group′s average significantly lower than that of the C-tDCS group. Three days after the modeling, 3D-arterial spin labeling scanning showed a significant decrease in CBF around the ischemic lesion in the MCAO, A-tDCS and C-tDCS groups, but that had increased to varying degrees after 12 days of treatment. The changes in the A-tDCS and C-tDCS groups were significantly larger than in the MCAO group on average, with the former group improving significantly more than the latter. After the 12 days of treatment, new vascularization and the expression of VEGF and CD34 proteins were significantly higher in the A-tDCS and C-tDCS groups than in the MCAO group, with the change in the former group again significantly greater than in the latter.Conclusions:tDCS can relieve the symptoms of neurological deficits in rats with cerebral infarction, promote vascular regeneration, CBF, and expression of VEGF and CD34 proteins. Anodic is superior to cathodic stimulation.
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OBJECTIVE@#To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment.@*METHODS@#The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence.@*RESULTS@#A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias.@*CONCLUSION@#Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.
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Criança , Humanos , Terapia por Acupuntura/métodos , Transtorno Autístico , Moxibustão/métodos , Viés de Publicação , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
Background Formaldehyde and benzene homologues are common environmental pollutants, and their neurotoxicity has aroused widespread concern. Objective To investigate the effect of taurine on cognitive impairment after exposure to formaldehyde and benzene analogues in young rats. Methods Twenty four-week old SD rats were randomly divided into four groups, with six rats in each group: control group (clean air), model group (5 mg·m−3 formaldehyde + 5 mg·m−3 benzene + 10 mg·m−3 toluene + 10 mg·m−3 xylene), low-dose taurine intervention group (5 g·L−1 taurine + mixture of formaldehyde and benzene analogues), and high-dose taurine intervention group (10 g·L−1 taurine + formaldehyde and mixture of benzene analogues), and the exposure was administered by oral and nasal aerosol inhalation for 28 d. At the end of exposure, the learning and memory ability of rats in each group was measured by Morris water maze test. After the behavioral test, the rats were anesthetized and neutralized, and the brain tissue was harvested for histopathological and molecular biological tests. The apoptosis rate of neurons in hippocampal CA1 area was detected by Tunel assay, and the expression levels of apoptosis-related proteins such as caspase 3, bax, and bcl-2 in hippocampal tissue were detected by Western blotting. Results The growth and development of rats in each group were good during inhalation. During the Morris water maze experiment, the escape latencies of rats in the taurine intervention groups were not different from that in the control group (P>0.05) from day 3 to day 5 of training, while the escape latency of rats in the model group was significantly higher than that in the control group (P <0.05). The number of crossing platform and the target quadrant residence time in the high-dose taurine intervention group were not different from those in the control group (P>0.05), while the two variables in the model group and low-dose taurine intervention group were significantly lower than those in the control group (P <0.05). The apoptotic rates of neurons in the hippocampal CA1 area of rats in the control group, model group, and low-dose and high-dose taurine intervention groups were 5.11%, 18.87%, 9.39%, and 4.63%, respectively. The apoptotic rate in the model group was higher than those in the control group and low-dose and high-dose taurine intervention groups (P<0.05). The expression levels of caspase 3, bax, and bcl-2 in the hippocampus of rats in the low-dose and high-dose taurine intervention groups showed no difference compared with the control group (P>0.05). The expression levels of caspase 3 and bax in the model group were higher than those in the control group and low-dose or high-dose taurine intervention groups (P<0.05), and the expression levels of bcl-2 was lower (P<0.05). Conclusion The mixed exposure to formaldehyde and benzene analogues can damage the learning and memory ability of young rats, and increase the apoptosis of neurons in hippocampal CA1 region. Taurine can reverse the damage induced by formaldehyde and benzene analogues.
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AIM: To investigate the relationship between the levels of chemokine receptor 2(CXCR2)and basic fibroblast growth factor(bFGF)in aqueous humor and the prognosis of trabeculectomy in patients with acute primary angle-closure glaucoma(APACG).METHODS: A total of 80 cases(80 eyes)APACG patients who underwent trabeculectomy in our hospital from June 2020 to January 2022 were collected in the case group. According to the postoperative efficacy, they were grouped into a success group of 60 cases(60 eyes)and a failure group of 20 cases(20 eyes). Another 86 cataract patients(86 eyes)who underwent phacoemulsification with normal intraocular pressure in our hospital during the same period were included in the control group. Enzyme linked immunosorbent assay was applied to detect the levels of CXCR2 and bFGF in aqueous humor. ROC curve was applied to analyze the value of predicting trabeculectomy failure in APACG patients by the levels of CXCR2 and bFGF in aqueous humor. Furthermore, multivariate Logistic regression was applied to analyze the influencing factors of trabeculectomy failure in APACG patients.RESULTS: The levels of CXCR2 and bFGF in the aqueous humor of the case group were significantly higher than those of the control group(P<0.05). The levels of CXCR2 and bFGF in the aqueous humor of the failed group and the proportion of patients with postoperative shallow anterior chamber were significantly higher than those of the successful group(P<0.05). The AUC for predicting trabeculectomy failure in APACG patients using CXCR2 and bFGF levels alone and in combination was 0.885, 0.883 and 0.953, respectively. CXCR2 and bFGF were independent risk factors for trabeculectomy failure in APACG patients(P<0.05).CONCLUSION: The levels of CXCR2 and bFGF in the aqueous humor of APACG patients are obviously elevated, and both are risk factors for trabeculectomy failure.
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Objective: To explore the impact of health management measures for entry personnel (entry management measures) against COVID-19 on the epidemiological characteristics of imported Dengue fever in Guangdong Province from 2020 to 2022. Methods: Data of imported Dengue fever from January 1, 2016 to August 31, 2022, mosquito density surveillance from 2016 to 2021, and international airline passengers and Dengue fever annual reported cases from 2011 to 2021 in Guangdong were collected. Comparative analysis was conducted to explore changes in the epidemic characteristics of imported Dengue fever before the implementation of entry management measures (from January 1, 2016 to March 20, 2020) and after the implementation (from March 21, 2020 to August 31, 2022). Results: From March 21, 2020, to August 31, 2022, a total of 52 cases of imported Dengue fever cases were reported, with an imported risk intensity of 0.12, which were lower than those before implementation of entry management measures (1 828, 5.29). No significant differences were found in the characteristics of imported cases before and after implementation of entry management measures, including seasonality, sex, age, career, and imported countries (all P>0.05). 59.62% (31/52) of cases were found at the centralized isolation sites and 38.46% (20/52) at the entry ports. However, before implementation of entry management measures, 95.08% (1 738/1 828) of cases were found in hospitals. Among 51 cases who had provided entry dates, 82.35% (42/51) and 98.04% (50/51) of cases were found within seven days and fourteen days after entry, slightly higher than before implementation [(72.69%(362/498) and 97.59% (486/498)]. There was significant difference between the monthly mean values of Aedes mosquito larval density (Bretto index) from 2020 to 2021 and those from 2016 to 2019 (Z=2.83, P=0.005). There is a strong positive correlation between the annual international airline passengers volume in Guangdong from 2011 to 2021 and the annual imported Dengue fever cases (r=0.94, P<0.001), and a positive correlation also existed between the international passenger volume and the annual indigenous Dengue fever cases (r=0.72, P=0.013). Conclusions: In Guangdong, the entry management measures of centralized isolation for fourteen days after entry from abroad had been implemented, and most imported Dengue fever cases were found within fourteen days after entry. The risk of local transmission caused by imported cases has reduced significantly.
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Animais , Humanos , COVID-19 , Aedes , Epidemias , China/epidemiologia , Dengue/epidemiologiaRESUMO
BACKGROUND@#Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis.@*METHODS@#Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists.@*RESULTS@#A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%).@*CONCLUSION@#The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.
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Humanos , Feminino , Masculino , Artrite Psoriásica/epidemiologia , Reumatologistas , Prevalência , População do Leste Asiático , Psoríase/epidemiologiaRESUMO
OBJECTIVE@#To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats.@*METHODS@#A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures.@*RESULTS@#Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion.@*CONCLUSION@#The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.