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1.
J Dent Res ; : 22034520935788, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600097

RESUMO

During the mandibular condylar growth, the absorption of calcified cartilage matrix induced by osteoclasts is crucial for the continuous endochondral osteogenesis. Meanwhile, recent studies showed that subchondral bone resided within the low-oxygen microenvironment, and our previous study revealed that hypoxia-inducible transcription factor 1α (HIF-1α) promoted osteoclastogenesis under hypoxia. However, whether HIF-1α regulates the function of osteoclasts in the mandibular condyle cartilage remains elusive. Our study indicated that severe deformity of the mandibular condyle was displayed in 10-wk-old osteoclast-specific HIF-1α conditional knockout (CKO) mice, accompanied by shortened length of condylar process and disorganized fibrocartilage. In 1-, 2-, and 4-wk-old CKO mice, the size of the hypertrophic layer and chondrocytic layer was significantly thickened. In the chondrocytic layer, chondrocytes were atrophied, showing a form of apoptosis in 4-wk-old CKO mice. Furthermore, an increase in the thickness of the fibrous and proliferating layer was observed in 10-wk-old CKO mice, as well as a significant decrease in that of the chondrocytic and hypertrophic chondrocyte layers. Interestingly, the articular surface of the condylar process abnormally presented a horizontal concave shape, and a disk-like acellular connective tissue appeared. In addition, genetic ablation of HIF-1α blunted cartilage matrix loss by subchondral osteoclast deficiency, resulting in a high subchondral bone mass phenotype, accompanied with a decreased number of blood vessels, alkaline phosphatase staining, and vascular endothelial growth factor (VEGF) expression. Mechanistically, the number of osteoclasts in the center of the condyle in CKO mice was significantly reduced by attenuated expression of adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling. These findings reveal a novel influence of HIF-1α function in osteoclasts on maintenance of osteoclast-induced resorption of calcified cartilage matrix via AMPK signaling, as well as subchondral bone formation through VEGF-dependent angiogenesis in bone marrow.

2.
Eur Rev Med Pharmacol Sci ; 24(12): 7015-7023, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32633395

RESUMO

OBJECTIVE: Increasing evidence indicated that N6-methyl-adenosine (M6A) played a key role in a variety of pathophysiological processes. Methylases could promote the processing of mature mi-RNA in a M6A-dependent manner, thereby participating in the pathological cells' occurrence and development. However, the regulatory mechanism of M6A in atherosclerosis (AS) was still unclear. PATIENTS AND METHODS: Quantificational Real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of M6A, methyltransferase, demethylase transferase, miR-19a and other mi-RNA in atherosclerotic vascular endothelial cells (ASVEC). Cell Counting Kit (CCK8) was used to detect cell proliferation, the expression of PCNA was measured by Western Blot (WB) and qRT-PCR. Transwell assays were used to detect the invasion ability of ASVEC. Co-immunoprecipitation (Co-IP) was used to detect the binding of METTL14 to DGCR8. RNA Immunoprecipitation (RIP) was used to detect the binding of METTL14 to miR-19a. RESULTS: M6A modification levels and METTL14 methylation transferase were significantly overexpressed in ASVEC. Silencing METTL14 inhibited the proliferation and invasion of ASVEC. Low expression of METTL14 suppressed the binding of methylated RNA and RNA splicing related protein DGCR8. Moreover, silencing METTL14 significantly inhibited the expression of miR-19a while promoted the expression of primary pre-miR-19a. However, high expression of METTL14 obviously increased the expression of DGCR8 and methylated m6A. Furthermore, silencing miR-19a inhibited the proliferation and invasion of ASVEC. CONCLUSIONS: METTL14 increased the M6A modification of pri-miR-19a and promoted the processing of mature miR-19a, thus promoting the proliferation and invasion of ASVEC. These results suggested that METTL14/ M6A/ miR-19a signaling pathway may be a new target for atherosclerosis treatment.

3.
Nat Mater ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483242

RESUMO

A topological meron features a non-coplanar structure, whose order parameters in the core region are perpendicular to those near the perimeter. A meron is half of a skyrmion, and both have potential applications for information carrying and storage. Although merons and skyrmions in ferromagnetic materials can be readily obtained via inter-spin interactions, their behaviour and even existence in ferroelectric materials are still elusive. Here we observe using electron microscopy not only the atomic morphology of merons with a topological charge of 1/2, but also a periodic meron lattice in ultrathin PbTiO3 films under tensile epitaxial strain on a SmScO3 substrate. Phase-field simulations rationalize the formation of merons for which an epitaxial strain, as a single alterable parameter, plays a critical role in the coupling of lattice and charge. This study suggests that by engineering strain at the nanoscale it should be possible to fabricate topological polar textures, which in turn could facilitate the development of nanoscale ferroelectric devices.

4.
Eur Rev Med Pharmacol Sci ; 24(10): 5714-5725, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32495907

RESUMO

OBJECTIVE: Anaerobic bacteria can enter the solid tumor in the hypoxic region to colonize and proliferate. Aggregation of nanoparticles in the tumor area can enhance molecular imaging and therapy. It is hypothesized that the combination of the two could possibly achieve better imaging and tumor treatment. This study presents a biocompatible bacteria-based system that can deliver cationic phase-change nanoparticles (CPNs) into solid tumor to achieve enhanced imaging and treatment integration. MATERIALS AND METHODS: Cationic phase-change nanoparticles (CPNs) and Bifidobacterium longum (BF) were mixed to determine the best binding rate and were placed in an agar phantom for ultrasonography. BF-CPNs complex adhesion to breast cancer cells was observed by laser confocal microscopy. In vivo, BF-CPNs and control groups were injected into tumors in breast cancer nude mouse models. Nanoparticles distribution was observed by ultrasound and in vivo fluorescence imaging. HIFU ablation was performed after injection. Gross and histological changes were compared and synergy was evaluated. RESULTS: Bifidobacterium longum (BF) and CPNs were combined by electrostatic adsorption. The BF-CPNs particles could increase the deposition of energy after liquid-gas phase-change during High Intensity Focused Ultrasound (HIFU) irradiation of tumor. CONCLUSIONS: This study shows a valid method in diagnosis and therapy integration for providing stronger imaging, longer retention time, and more effective tumor treatment.

5.
Zhonghua Zhong Liu Za Zhi ; 42(6): 456-462, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575940

RESUMO

Objective: To evaluate the incidence of early cardiac injury in patients with left-sided breast cancer receiving hypofractionated radiotherapy after breast conserving surgery, and to investigate the correlation between cardiac injury and hypofractionated radiotherapy dose. Methods: We prospectively enrolled 103 breast cancer patients who received whole breast with or without regional nodal irradiation after breast conserving surgery using either deep inspiration breath-hold (DIBH) or free breathing (FB) radiotherapy technique. Cardiac examinations that included N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and myocardial perfusion imaging were performed routinely before and after radiotherapy. The effects of heart dose, systemic therapy and individual factors (Framingham score) on the incidence of cardiac events were analyzed. Results: The median age was 48 years. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) were 4.0, 16.9, 6.3, and 4.4 Gy, respectively. With a median follow-up of 13.4 months, no patient had clinical cardiac abnormalities. The incidence rates of subclinical cardiac events at 1- 6- and 12-month were 23.5%, 31.6%, and 41.3%, respectively. The DIBH group had a lower mean dose, maximum dose, and V5-V40 in the heart, LAD, LV, and RV than the FB group (P<0.001). Univariate analysis showed an increased incidence of subclinical cardiac events with heart Dmean >4 Gy, LAD V40 > 20%, LV Dmean >6 Gy, RV Dmean >7 Gy, or cumulative doses of anthracycline or taxane > 300 mg/m(2) (All P<0.05). Anti-HER2 targeted therapy, endocrine therapy and Framingham score were not associated with the incidence of subclinical cardiac events (all P>0.05). Multivariate analysis demonstrated that Dmean of LV and RV were independently associated with the increased incidence of subclinical cardiac events. Conclusions: Early subclinical heart injury are found in patients with left-sided breast cancer after hypofractionated radiotherapy. The increased incidence of subclinical cardiac events after radiotherapy is positively associated with the cardiac radiation doses.

6.
Zhonghua Shao Shang Za Zhi ; 36(6): 451-457, 2020 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-32594704

RESUMO

Objective: To explore the selection and effects of flap/myocutaneous flap repair methods for the defect after perineum tumor resection. Methods: From January 2011 to February 2017, 31 patients with vulvar tumor who were admitted to Hunan Cancer Hospital underwent repair of wound after tumor resection with various flaps/myocutaneous flaps. The patients were composed of 5 males and 26 females, aged 39-76 years, with 27 vulvar cancer and 4 Paget's disease in primary diseases. The size of defects after vulvar tumor radical resection ranged from 8.0 cm×4.5 cm to 27.5 cm×24.0 cm. According to the theory of perforasome, the defects were repaired by the external pudendal artery perforator flap, deep inferior epigastric artery perforator flap, rectus abdominis myocutaneous flap, anterolateral thigh flap, internal pudendal artery perforator flap, gracilis myocutaneous flap, and profunda artery perforator flap based on the specific size and location of perineum and groin where the defect was located. According to the blood supply zone of flap, totally 17 local translocation flaps, 18 axial flaps/myocutaneous flaps, and 7 V-Y advancement flaps were resected, with an area of 7.0 cm×4.0 cm to 21.0 cm×13.0 cm. All the flaps/myocutaneous flaps were transferred in pedicled fashion, and the donor sites were closed without tension. The number of flaps/myocutaneous flaps, wound closure, flaps/myocutaneous flaps survival, and follow-up were observed and recorded. Results: Altogether 42 flaps/myocutaneous flaps were harvested in 31 patients. Two flaps/myocutaneous flaps were used in 11 cases for large circular defect repair. All the defects achieved tension-free primary closure. The blood supply of 32 flaps/myocutaneous flaps was good, while insufficient blood supply was noted in the other 10 flaps/myocutaneous flaps. Seventeen flaps/myocutaneous flaps survived smoothly. Wound dehiscence occurred in 5 flaps/myocutaneous flaps 8 to 14 days postoperatively, which was healed with dressing change. Temporary congestion was noted in 7 flaps/myocutaneous flaps 2 to 5 days postoperatively, which recovered without special treatment. Three flaps/myocutaneous flaps had infection 7 to 15 days postoperatively, two of which recovered after dressing change, while the other one had partial necrosis and received debridement and direct closure. Two flaps/myocutaneous flaps were totally necrotic 8 to 15 days postoperatively, which were repaired with pedicled rectus abdominis myocutaneous flap after debridement. Seven flaps/myocutaneous flaps had partial necrosis 7 to 20 days postoperatively and were healed after dressing change. Twenty-four patients were followed up for 9-38 months. The color of flaps/myocutaneous flaps was similar to that of the surrounding skin, the shape of vulva was natural, the movement of hip joint was not limited, the function of micturition and defecation was not affected, and tumor recurrence was noted in 3 patients. Conclusions: For the complicated large defect after perineum tumor resection, the flexible application of different forms of flaps/myocutaneous flaps to repair according to different areas regains the appearance and function. However, there are many complications, so it is necessary to further strengthen the postoperative care.

7.
Zhonghua Shao Shang Za Zhi ; 36(5): 363-369, 2020 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-32456373

RESUMO

Objective: To explore the clinical effect of pre-expanded deltopectoral flap in the repair of faciocervical lesion and defect. Methods: From July 2004 to August 2018, 355 patients with faciocervical lesion and defect were admitted to the First Affiliated Hospital of Air Force Medical University, including 200 males and 155 females aged 4 to 48 years with major conditions including thermal burn scars, and type Ⅲ and Ⅳ facial-cervical deformities. During the stage Ⅰ skin soft tissue expander implantation surgery, according to the size and location of lesion and defect, expanders with appropriate volume were placed to expand the deltopectoral area. During the stage Ⅱ flap pedicled transposition surgery, after the expander was expanded to the desired volume, the impairment tissue was removed, the flap was designed according to the size of the defect (the unilateral defect area was 7 cm×5 cm to 17 cm×16 cm) and pedicled transposition was carried out. The incision in the chest donor area was directly sutured and closed. After the flap survived, stage Ⅲ flap delay and pedicle division surgery was carried out. The area of one single flap was 8 cm×5 cm to 20 cm×18 cm. The numbers of flaps and expanders, rated volume and expansion of expander, the intervals between surgeries in each stage, flap survival, postoperative complications in surgeries in each stage, and follow-up were recorded and analyzed. Results: A total of 460 pre-expanded deltopectoral flaps were used, including 250 unilateral flaps and 105 bilateral flaps. Totally 460 expanders were used in this group of patients. The rated volume was mostly 500 mL (163 expanders) and 600 mL (142 expanders). The expansion multiple of the expander was (1.14±0.19) times of the rated volume. The flap expansion time of the patients was (96±30) d, the pedicle time was (32±8) d, and the delay time was (7.5±1.6) d. The postoperative complications of patients mainly included infection (29 patients), expander exposure (18 patients), and hematoma (10 patients). During the follow-up of 6 to 120 months, the elasticity, texture, and color of the flaps of patients were similar to the surrounding tissue of the recipient area, and the face and neck were symmetrical, not bloated. Conclusions: The deltopectoral flap obtained by overexpansion has a larger area and a thinner thickness, and the elasticity, texture, and color are similar to the surrounding tissue of the recipient area. After transfer, a stable appearance of the face and neck can be obtained. The main complications are infection and expander exposure, most of which occurred after stage Ⅰ skin soft tissue expander implantation surgery.

9.
Eur J Neurol ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32402117

RESUMO

BACKGROUND AND PURPOSE: The objective of the study was to investigate the relationship between IL1R2 rs34043159 and Alzheimer's disease (AD) in the Chinese population. METHODS: A total of 500 AD patients and 500 healthy controls were recruited. The SNaPshot technique was used to detect IL1R2 rs34043159. RESULTS: The dominant and recessive models of IL1R2 rs34043159 were associated with AD with or without adjustment of age, gender and education [dominant model, P = 0.019, odds ratio (OR) 1.42, 95% confidence interval (CI) 1.06-1.89, adjusted; recessive model, P = 0.011, OR 0.69, 95% CI 0.51-0.92, adjusted]. The recessive model of IL1R2 rs34043159 was associated with early-onset AD (EOAD) with or without adjustment of age, gender and education (recessive model, P = 0.038, OR 0.60, 95% CI 0.37-0.97, adjusted). The additive model was associated with late-onset AD (LOAD) (P = 0.041). The dominant model of IL1R2 rs34043159 was associated with LOAD with or without adjustment of age, gender and education (dominant model, P = 0.005, OR 1.68, 95% CI 1.17-2.44, adjusted). CONCLUSION: An association between the dominant and recessive model of IL1R2 rs34043159 and AD was found. The recessive model of IL1R2 rs34043159 was associated with EOAD. The additive and dominant models of IL1R2 rs34043159 were associated with LOAD.

10.
Mol Biol (Mosk) ; 54(2): 252-261, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32392194

RESUMO

PARP10 is an intracellular mono-ADP ribosyltransferase and recent reports suggest that it regulates proliferation of some cell types. However, its effect on the proliferation of colorectal carcinoma cells has not yet been systematically reported. We explored the influence of PARP10 on the proliferation of several colorectal carcinoma cell types and carried out initial studies on the underlying mechanisms. Inhibition of the enzymatic activity of PARP10 led to significantly decreases in proliferative ability in LoVo cells and CT26 cells in vitro and suppressed growth of CT26 tumours in the subaxilliary region in Balb/c mice in vivo. Cell-cycle arrest accompanied these observations. Expression of the nuclear transfer factor ß-catenin and it trans-location to the nucleus were also affected and the expression of its associated signal proteins Axin2 and c-Myb were increased and decreased, respectively. We demonstrate that PARP10 promotes proliferation of those colorectal carcinoma cells which express significant levels of PARP10. This promotion is suppressed when the enzymatic activity is inhibited. ß-Catenin is likely to be the mediator of the antiproliferative effect.

11.
J Clin Microbiol ; 58(6)2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32269102

RESUMO

We evaluated six commercial molecular tests targeting Mycoplasma pneumoniae, namely, the BioFire FilmArray respiratory panel (RP), the Meridian Alethia Mycoplasma Direct, the GenMark ePlex respiratory pathogen panel (RPP), the Luminex NxTAG RPP, the ELITech ELITe InGenius Mycoplasma MGB research use only (RUO) PCR, and the SpeeDx Resistance Plus MP assays. Laboratory-developed PCR assays at the University of Alabama at Birmingham and the Centers for Disease Control and Prevention were used as reference standards. Among 428 specimens, 212 were designated confirmed positives for M. pneumoniae The highest clinical sensitivities were found with the InGenius PCR (99.5%) and the FilmArray RP (98.1%). The Resistance Plus MP identified 93.3% of the confirmed-positive specimens, whereas 83.6, 64.6, and 55.7% were identified by the ePlex RPP, NxTAG RPP, and Mycoplasma Direct assays, respectively. There was no significant difference between the sensitivity of the reference methods and that of the FilmArray RP and InGenius assays, but the remaining four assays detected significantly fewer positive specimens (P < 0.05). Specificities of all assays were 99.5 to 100%. The Resistance Plus MP assay detected macrolide resistance in 27/33 specimens, resulting in a sensitivity of 81.8%. This study provides the first large-scale comparison of commercial molecular assays for detection of M. pneumoniae in the United States and identified clear differences among their performance. Additional studies are necessary to explore the impact of various test performances on patient outcome.

12.
Malays J Pathol ; 42(1): 59-64, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32342931

RESUMO

INTRODUCTION: Fresh frozen plasma (FFP) is a blood component containing functional quantities of all coagulation factors stored at -18°C or below. FFP has to be thawed and transfused as soon as possible to prevent the loss of certain coagulation factor activities and to minimise microbial contamination. MATERIALS AND METHODS: Thirty units of FFP kept at -20°C were thawed using a 37°C water bath and immediately sampled for baseline Factor II (FII), Factor VIII (FVIII) and fibrinogen activity levels and sterility testing. Each unit was then divided into two smaller bags (i.e. Bag I and Bag II) and kept at 4°C. At 6 hours and Day 3, representative samples were taken from Bag I for coagulation factor activity assays, while at Day 5 representative samples were taken from Bag II for coagulation factor activity assays and sterility testing. RESULTS: FII activities at the four time points were 73.43%, 73.73%, 71% and 69.8%, respectively, while FVIII activities were 177.63%, 144.37%, 80.8% and 70.97%, respectively. Fibrinogen levels at the four time points were 3.24 g/L, 3.24 g/L, 3.21 g/L and 3.20 g/L, respectively. All samples were free from microbial contamination even at Day 5. CONCLUSION: The mean reduction in FII and fibrinogen activities on Day 5 was 5% and 1%, respectively. However, FVIII activity declined significantly by approximately 60% at Day 5. Despite these reductions, thawed plasma stored for up to 5 days at 4°C is still suitable for use as the coagulation factor activity levels still exceed the minimum release criteria recommended in quality assurance regulations.

13.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(3): 283-288, 2020 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-32187933

RESUMO

Objective: To explore the effect of parental rearing patterns and their consistency on the emotional and behavioral problems of preschool children. Methods: From October to November 2017, 27 987 children aged 3 to 6 years old from 109 kindergartens in 11 cities of Hubei, Anhui and Jiangsu Provinces were selected by using the cluster sampling method. A total of 27 200 valid questionnaires which were completed by subjects' parents were collected. The emotional and behavioral problems of preschool children were collected by "strengths and difficulties questionnaire" and the parental rearing patterns were evaluated by the "Parental Behavior Scale". The differences in emotional and behavioral abnormality rates of preschool children with different characteristics were analyzed; with emotional and behavioral problems as dependent variables and parental support/participation and compulsion/hostility as independent variables, the multivariate logistic regression model was used to analyze the effect of parental rearing patterns and their consistency on the emotional and behavioral problems of preschool children. Results: The age of children was (4.35±0.96) years old, and 51.4% of children were 13 975 males. There were 24 634 (90.6%) urban children and 17 916 (65.9%) only children. Both parents with strong support/participation accounted for 14.9%, and those with poor support/participation accounted for 11.9%; both parents with strong compulsion/hostility accounted for 15.2%, and those with low compulsion/hostility accounted for 11.3%. The rates of emotional symptoms, conduct behavior, hyperactive behavior, peer interaction, total difficulty score, and abnormal prosocial behavior of preschool children were 9.5%, 9.5%, 18.2%, 24.5%, 11.2%, and 10.2%, respectively. The multivariate logistic regression model analysis showed that after adjusting for gender, only child, living area, family economic status, mother's age and education level, father's education level, and other factors, compared with fathers/mothers with strong support/participation and low compulsion/hostility and parents with strong support/participation and low compulsion/hostility, preschool children who had fathers/mothers with poor support/participation and strong compulsion/hostility or parents with poor support/participation and strong compulsion/hostility were more likely to have emotional symptoms, conduct behavior, hyperactive behavior, peer interaction, total difficulty score, and abnormal prosocial behavior (P<0.05). Conclusions: Parental rearing patterns and their consistency are related to the emotional and behavioral problems of preschool children.


Assuntos
Sintomas Afetivos , Comportamento Infantil/psicologia , Saúde Mental/estatística & dados numéricos , Relações Pais-Filho , Poder Familiar , Pais/psicologia , Comportamento Problema , Criança , Pré-Escolar , Feminino , Humanos , Modelos Logísticos , Masculino , Fatores Socioeconômicos , Inquéritos e Questionários
15.
Zhonghua Gan Zang Bing Za Zhi ; 28(2): 175-178, 2020 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-32164073

RESUMO

Although tumor immune checkpoint inhibitors therapy brings survival benefits to cancer patients, it also faces many challenges, such as the occurrence of immune-mediated hepatotoxicity. Therefore, an in-depth understanding of the conditions, possible mechanisms, and risk factors that cause liver injury during the treatment of tumor immune checkpoint inhibitors will facilitate better clinical management.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunoterapia/efeitos adversos , Fígado/patologia , Neoplasias/terapia , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Fatores de Risco
17.
Eur Rev Med Pharmacol Sci ; 24(4): 1656-1665, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32141531

RESUMO

OBJECTIVE: Osteosarcoma (OS) is one common bone malignant tumor prevailing in young adults and children. It is increasingly recognized microRNA 449a (miR 449a) as an anti-tumor factor in various tumours. However, little is known about the biological significance of miR 449a in OS. The intent of our study was to seek the prognostic values of miR-449a in OS. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the level of miR-449a expression in 48 pairs of OS tissues and para-cancerous specimens, and the relationship between miR-449a level and clinical features of OS patient prognosis was analyzed. Moreover, we measured the miR-449a expression levels in OS cells. Transwell assay was further performed to investigate whether miR-449a influenced MG63 cell migration and invasion, which was important for malignant metastases. RESULTS: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated a notable decrease of miR-449a expressions in OS. The declined miR-449a expression was relevant with the poor prognosis and malignant clinicopathologic characteristics of OS patients. Thereafter, the functional assay was performed to determine the role of miR-449a in OS progression. Results of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays indicated that miR-449a overexpression significantly repressed OS cell proliferation, invasion, and migration. Furthermore, luciferase reporter assay showed that enhancer of zeste homolog 2 (EZH2) was a downstream target of miR-449a in OS cells. Additionally, Western blot analysis demonstrated that miR-449a exerted anti-OS functions via the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and epithelial-mesenchymal transition. We also indicated that miR-449a restoration could inhibit in vivo tumor growth. CONCLUSIONS: These results manifested that miR-449a may thus be used as a therapeutic target in OS treatments.

18.
Eur Rev Med Pharmacol Sci ; 24(4): 1939-1947, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32141563

RESUMO

OBJECTIVE: Increasing evidence has shown that HSF1 is involved in glycemia regulation, and SIRPα plays a pivotal role in islet ß-cell viability. However, it is still unknown whether SIRPα is associated with HSF1 in regulating the cell viability and cell death of islet ß-cells. MATERIALS AND METHODS: Western blot and qPCR were applied to determine protein and mRNA levels of HSF1 and SIRPα. Cell viability and death were investigated by cell counting kit-8 and trypan blue exclusion assay. Meanwhile, cell apoptosis was analyzed by detecting caspase3 activity. Moreover, luciferase reporter assay was applied to explore the mechanism by which HSF1 transcriptionally upregulated SIRPα expression. RESULTS: Our study reveals that HSF1 expression was lower in islets from T1DM compared to normal mice. We found that overexpression of HSF1 decreased the apoptosis of islet ß-cell lines. Moreover, we demonstrated that overexpression of HSF1 decreased the apoptosis of islet ß-cells through increasing the expression of SIRPα. In terms of mechanism, luciferase reporter assays showed that HSF1 upregulated SIRPα expression by activating its gene promoter region. The binding site (-1809 to -1795) was required for HSF1-induced increase of SIRPα gene promoter activity. CONCLUSIONS: These results indicate that the low expression of HSF1/SIRPα may be one of the mechanisms of islet ß-cell death and targeting HSF1/SIRPα may be a novel strategy for the treatment of T1DM.

19.
Int J Obstet Anesth ; 42: 87-98, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32173221

RESUMO

BACKGROUND: Quadratus lumborum block (QLB) can reduce pain and opioid consumption after cesarean delivery. This systematic review investigated the effectiveness of QLB in reducing postoperative opioid use and its effect on pain scores compared with other analgesic methods after cesarean delivery. METHODS: Six medical databases were searched from their inception to August 2019. Trials were eligible if parturients underwent cesarean delivery under spinal anesthesia (not epidural or general anesthesia). The primary outcome was postoperative opioid consumption during the first 24 and 48 h. Secondary outcomes included pain scores, patient satisfaction, and side effects. The risk of bias was assessed using the Cochrane tool. Where possible, meta-analytic techniques were used to synthesize data, presented as mean difference with 95% confidence interval (CI). RESULTS: Twelve studies involving 904 patients were identified and analyzed. Opioid (intravenous morphine) consumption was significantly reduced with QLB when compared with placebo or no block during the first 24 h by 14.1 mg, (95% CI -20.8 to -7.5 mg) and 48 h by 20.8 mg, (95% CI -33.1 to -8.5 mg). Additionally, QLB significantly reduced 12-h pain scores at rest and during movement. However, this difference disappeared at 24 and 48 h. There was insufficient evidence regarding postoperative opioid use or pain scores with the use of QLB compared to intrathecal morphine. CONCLUSIONS: The review findings show the superior analgesic effect of QLB when compared with systemic opioids in reducing postoperative opioid consumption, when intrathecal morphine is not administered.

20.
Zhonghua Zhong Liu Za Zhi ; 42(1): 50-54, 2020 Jan 23.
Artigo em Chinês | MEDLINE | ID: mdl-32023769

RESUMO

Objective: To explore the clinical features and risk factors of hepatic injury due to immune checkpoint inhibitors (CPI) therapy in malignant tumor. Methods: Data of 112 patients (64 men and 48 women) who received CPI between January 2016 and March 2019 in Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen Hospital, and Huazhong University of Science and Techology Union Shenzhen Hospital were retrospectively collected. The median age of these patients was 60 years. Results: Hepatic adverse events were observed in 30 patients out of 112 patients (26.8%). Among them, the incidence of grade 3-5 hepatic adverse events were 7.14% (8/112). The median time of hepatic adverse event occurrence was 3 weeks (2-30) after undergoing therapy. The results of univariate and multivariate analyses showed that liver cancer was attributed to the CPI induced hepatitis (P<0.05). Patients with severe hepatic injury got almost complete resolution after receiving methlprednisolone for 4 to 6 weeks. Conclusion: Live cancer is the risk factor of CPI-related hepatic adverse events.


Assuntos
Imunoterapia , Hepatopatias , Neoplasias , Feminino , Humanos , Imunoterapia/efeitos adversos , Fígado , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Estudos Retrospectivos , Fatores de Risco
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