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1.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(1): 39-45, 2021 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-33448197

RESUMO

Objective: To investigate the effectiveness of treatment of locked lower cervical fracture and dislocation with anterior cervical fusion and internal fixation combined with the release of the interlocking facet through the Luschka joint and anterior lamina space. Methods: Twelve patients with lower cervical interlocking fracture and dislocation were analyzed retrospectively between January 2013 and June 2015. There were 7 males and 5 females, aged 25-59 years with an average age of 38.4 years. The disease duration was 9.6 hours to 100 days with an average of 7.3 days. There were 8 cases of unilateral locking and 4 cases of bilateral locking; 4 cases of old injury and 8 cases of fresh injury. The injured segments were 2 cases of C 3, 4, 5 cases of C 4, 5, 3 cases of C 5, 6, and 2 cases of C 6, 7. According to Meyerding classification, there were 9 cases of grade Ⅰ and 3 cases of grade Ⅱ. According to the functional classification of American Spinal Injury Association (ASIA), there were 2 cases of grade C, 6 cases of grade D, and 4 cases of grade E. The interlocking facet was released through the Luschka joint and anterior lamina space, and the anterior cervical fusion and internal fixation were used to treat the fracture and dislocation of the lower cervical spine. The recovery of spinal cord function was judged by the functional classification of ASIA; visual analogue scale (VAS) score, neck disability index (NDI) score, modified Japanese Orthopaedic Association (m-JOA) score were used to evaluate the clinical efficacy; the Cobb angle of fusion segment were observed by X-ray film. The intervertebral bone graft fusion was evaluated at 6 months after operation. Results: The average operation time was 78.30 minutes, the average intraoperative blood loss was 167.30 mL, and the average postoperative drainage volume was 58.12 mL. No blood transfusion was given during or after operation. During the operation, there was no accidental injury of large blood vessels, esophagus, and trachea; no laryngo edema, dysphagia, hoarseness, and cerebrospinal fluid leakage occurred after operation; no spinal cord injury or nerve root injury aggravated; the incision healed by first intention, and no infection occurred. All 12 cases were followed up 15-20 months, with an average of 16.5 months. The symptoms and function of the nerve injury were significantly improved when compared with that before operation. Re-examination of the cervical spine X-ray film at 6 months after operation showed that the Cage or bone graft was not displaced or broken, the screw was not loosened or detached, and the intervertebral graft fusion rate was up to 100%. At last follow-up, the ASIA grade, Cobb angle of fusion segment, neck pain VAS score, m-JOA score, and NDI score were significantly improved when compared with preoperative one ( P<0.05). Conclusion: The effectiveness of treatment of locked lower cervical fracture and dislocation with anterior cervical fusion and internal fixation combined with the release of the interlocking facet through the Luschka joint and anterior lamina space is clear, which not only can make the injured segment get satisfactory reduction, immediate stability and reconstruction, and full decompression, but also can effectively prevent the secondary injury of spinal cord.


Assuntos
Fraturas da Coluna Vertebral , Fusão Vertebral , Adulto , Vértebras Cervicais/lesões , Vértebras Cervicais/cirurgia , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento
2.
Sci Rep ; 11(1): 223, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420303

RESUMO

Soil gross nitrogen (N) transformations could be influenced by land use change, however, the differences in inherent N transformations between different land use soils are still not well understood under subtropical conditions. In this study, an 15N tracing experiment was applied to determine the influence of land uses on gross N transformations in Regosols, widely distributed soils in Southwest China. Soil samples were taken from the dominant land use types of forestland and cropland. In the cropland soils, the gross autotrophic nitrification rates (mean 14.54 ± 1.66 mg N kg-1 day-1) were significantly higher, while the gross NH4+ immobilization rates (mean 0.34 ± 0.10 mg N kg-1 day-1) were significantly lower than those in the forestland soils (mean 1.99 ± 0.56 and 6.67 ± 0.74 mg N kg-1 day-1, respectively). The gross NO3- immobilization and dissimilatory NO3- reduction to NH4+ (DNRA) rates were not significantly different between the forestland and cropland soils. In comparison to the forestland soils (mean 0.51 ± 0.24), the cropland soils had significantly lower NO3- retention capacities (mean 0.01 ± 0.01), indicating that the potential N losses in the cropland soils were higher. The correlation analysis demonstrated that soil gross autotrophic nitrification rate was negatively and gross NH4+ immobilization rate was positively related to the SOC content and C/N ratio. Therefore, effective measures should be taken to increase soil SOC content and C/N ratio to enhance soil N immobilization ability and NO3- retention capacity and thus reduce NO3- losses from the Regosols.

3.
Theranostics ; 11(3): 1016-1030, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391518

RESUMO

Macrophages phagocytize pathogens to initiate innate immunity and products from the tumor microenvironment (TME) to mediate tumor immunity. The loss of tumor-associated macrophage (TAM)-mediated immune responses results in immune suppression. To reverse this immune disorder, the regulatory mechanism of TAMs in the TME needs to be clarified. Immune molecules (cytokines and chemokines) from TAMs and the TME have been widely accepted as mutual mediators of signal transduction in the past few decades. Recently, researchers have tried to seek the intrinsic mechanism of TAM phenotypic and functional changes through metabolic connections. Numerous metabolites derived from the TME have been identified that induce the cell-cell crosstalk with TAMs. The bulk tumor cells, immune cells, and stromal cells produce metabolites in the TME that are involved in the metabolic regulation of TAMs. Meanwhile, some products from TAMs regulate the biological functions of the tumor as well. Here, we review the recent reports demonstrating the metabolic regulation between TME and TAMs.

4.
Environ Pollut ; 270: 116301, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33360596

RESUMO

Oxygenated volatile organic compounds (OVOCs) are important precursors and intermediate products of atmospheric photochemical reactions, which can promote the formation of secondary pollutants such as ozone (O3) and secondary organic aerosol (SOA). However, there have been few studies on the sources of and long-term variation in ambient OVOCs. This study combined sensitive, near real-time measurements of VOCs by proton transfer reaction-mass spectrometry (PTR-MS) with an improved photochemical age parameterization method to quantify daytime sources of OVOCs in an urban atmosphere in China from 2014 to 2019, permitting the observation of the impacts of emission control strategies that were implemented during this period. Temporal variation in six key OVOCs (methanol, acetaldehyde, acetone, methyl ethyl ketone (MEK), formic acid, and acetic acid) were observed. The sum of concentrations of OVOCs was averagely 13% higher during the dry season (November to April), when winds transported polluted air masses to Shenzhen from the continent, than during the wet season, and peak diurnal levels occurred during the daytime year-round due to photochemical production and higher daytime anthropogenic emissions. The average dry season concentration of OVOCs declined from a peak of 30.3 ppb in 2015 to 18.7 ppb in 2019. The results of source apportionment showed that primary anthropogenic sources contributed the most to methanol, MEK, and acetic acid (32-51%); the dominant sources of acetaldehyde and formic acid were both primary and secondary anthropogenic sources; and biomass burning contributed a small fraction (5-11%) to the six OVOCs. From 2014 to 2019, contributions from primary anthropogenic sources of OVOCs decreased significantly by 50-60% due to intensive pollution control measures in Shenzhen, whereas pollution control measures had no observable impact on secondary OVOCs, indicating their formation was not limited by availability of their primary VOC precursors.

5.
J Clin Invest ; 131(1)2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-32960814

RESUMO

Estrogen receptor-negative (ER-negative) breast cancer is thought to be more malignant and devastating than ER-positive breast cancer. ER-negative breast cancer exhibits elevated NF-κB activity, but how this abnormally high NF-κB activity is maintained is poorly understood. The importance of linear ubiquitination, which is generated by the linear ubiquitin chain assembly complex (LUBAC), is increasingly appreciated in NF-κB signaling, which regulates cell activation and death. Here, we showed that epsin proteins, a family of ubiquitin-binding endocytic adaptors, interacted with LUBAC via its ubiquitin-interacting motif and bound LUBAC's bona fide substrate NEMO via its N-terminal homolog (ENTH) domain. Furthermore, epsins promoted NF-κB essential modulator (NEMO) linear ubiquitination and served as scaffolds for recruiting other components of the IκB kinase (IKK) complex, resulting in the heightened IKK activation and sustained NF-κB signaling essential for the development of ER-negative breast cancer. Heightened epsin levels in ER-negative human breast cancer are associated with poor relapse-free survival. We showed that transgenic and pharmacological approaches eliminating epsins potently impeded breast cancer development in both spontaneous and patient-derived xenograft breast cancer mouse models. Our findings established the pivotal role epsins played in promoting breast cancer. Thus, targeting epsins may represent a strategy to restrain NF-κB signaling and provide an important perspective into ER-negative breast cancer treatment.

6.
Sci Total Environ ; 754: 142253, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254874

RESUMO

Allelopathy is regarded as an economic and eco-friendly approach for the control of harmful algal blooms (HABs) because allelochemicals degrade easily and cause less pollution than traditional algicides. We first surveyed the inhibitory effect of the traditional medicinal plant Cerbera manghas L. on the notorious dinoflagellates Alexandrium tamarense, Scrippsiella trochoidea, and Karenia mikimotoi. Then, we identified and quantified the potential algicidal compounds by UPLC-MS and determined their activity. The aqueous extract inhibited algae with EC50-120 h at 0.986, 1.567 and 1.827 g L-1 for A. tamarense, S. trochoidea, and K. mikimotoi, respectively. Three potential allelochemicals were quantified in the stock solution: quinic acid (QA) (28.81 mg L-1), protocatechuic acid (PA) (53.91 mg L-1), and phloridzin (PD) (26.17 mg L-1). Our results illustrated that 1) QA did not have an inhibitory effect, 2) PA had medium toxicity to algae (EC50-120h: 0.22, 0.28, and 0.35 mM for A. tamarense, S. trochoidea, and K. mikimotoi), and 3) PD had low toxicity (EC50-120h > 0.66 mM). These findings suggested that PA might be the main allelopathic compound in the aqueous extract of the studied algae. In addition, PA could have a negative effect on the photosynthesis of S. trochoidea by impeding the reduction of quinone electrons and destroying electron transfer in PSII. In summary, this was the first study to quantify allelochemicals in C. manghas fruit. Moreover, C. manghas and protocatechuic have the potential to be algicides to control and mitigate the HABs caused by dinoflagellates.


Assuntos
Apocynaceae , Dinoflagelados , Alelopatia , Animais , Cromatografia Líquida , Proliferação Nociva de Algas , Espectrometria de Massas em Tandem
7.
Cancer Lett ; 498: 121-129, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129956

RESUMO

Cancer immunotherapy holds tremendous promise as a strategy for eradicating solid tumors, and its therapeutic effect highly relies on sufficient CD8+ T cells infiltration. Here, we demonstrate that ultrasound stimulated microbubble cavitation (USMC) promotes tumor perfusion, thereby increasing CD8+ T cells infiltration and anti-PD-L1 antibody delivery, then further enhancing the PD-L1 blockade of MC38 colon cancer in mice. Firstly, we optimized the mechanic index (MI) of ultrasound, and found that USMC with MI of 0.4 (equal to peak negative pressure of 0.8 MPa) significantly improved the peak intensity and area under curve of tumor contrast-enhanced ultrasound. Also, flow cytometry exhibited higher percentage of infiltrating CD8+ T cells in the USMC (MI = 0.4)-treated tumors than that of the control. We further explored the combination therapy of optimized USMC with anti-PD-L1 antibody. The combination therapy enhanced tumor perfusion and even led to the tumor vascular normalization. More importantly, flow cytometry showed that the combination not only increased the percentage and absolute number of tumor infiltrating CD8+ T cells, but also promoted the expression of Ki67 as well as the secretions of IFN γ and granzyme B, therefore, the combination therapy achieved greater tumor growth inhibition and longer survival than that of the monotherapies. These suggest that USMC is a promising therapeutic modality for combining immune checkpoint blockade against solid tumors.

8.
J Affect Disord ; 281: 220-227, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33333476

RESUMO

BACKGROUND: Depression have become a widespread health concern in Chinese society. METHODS: We analyzed the factors influencing the risk of depression among residents aged 16 and over using data from the 2016 China Family Panel Studies (CFPS), in which depression was measured using the Center for Epidemiologic Studies Depression (CES-D20) scale. A total of 26,464 individuals were sampled in a weighted manner to represent the entire country. Univariate and multivariate analysis were used to explore the risk factors for depression and the odds of depression in people with different characteristics. RESULTS: A total of 76.6% of adult residents were mentally healthy. Females had higher rates of depression than males (OR=1.515). There was an "inverted U-shaped" distribution between age and risk of depression. Higher levels of education and better physiological health were associated with a lower risk of depression. Self-evaluated income and social status were not linearly related to the risk of depression but rather had a "U-shaped" distribution. For social capital, better social relationships and a higher level of social trust were associated with a lower risk of depression. Nonsmokers had a lower risk of depression than smokers (OR=0.818). LIMITATIONS: All items were self-reported and some results depend on single item responses. This is a cross-sectional survey so that causative interpretations cannot be drawn. CONCLUSION: These findings suggest potential public health measures whose efficacy needs to be tested and confirmed.

9.
BMJ Open ; 10(12): e039875, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33372073

RESUMO

OBJECTIVES: Fluid management is important in ensuring haemodynamic stability in critically ill patients, but can easily lead to fluid overload (FO). However, the optimal fluid balance plot or range for critically ill patients is unknown. This study aimed to explore the dose-response relationship between FO and in-hospital mortality in critically ill patients. DESIGN: Multicentre, prospective, observational study. SETTING: Eighteen intensive care units (ICUs) of 16 tertiary hospitals in China. PARTICIPANTS: Critically ill patients in the ICU for more than 3 days. PRIMARY OUTCOME MEASURES AND ANALYSES: FO was defined as the ratio of the cumulative fluid balance (L) and initial body weight (kg) on ICU admission, expressed as a percentage. Maximum FO was defined as the peak value of FO during the first 3 days of ICU admission. Logistic regression models with restricted cubic splines were used to explore the pattern and magnitude of the association between maximum FO and risk of in-hospital mortality. Age, sex, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score on admission, main diagnosis on admission to ICU, comorbidities, time of maximum FO, mechanical ventilation, renal replacement therapy, use of vasopressors and centres were adjusted in multivariable analysis. RESULTS: A total of 3850 patients were included in the study, 929 (24.1%) of whom died in the hospital. For each 1% L/kg increase in maximum FO, the risk of in-hospital mortality increased by 4% (adjusted HR (aHR) 1.04, 95% CI 1.03 to 1.05, p<0.001). A maximum FO greater than 10% was associated with a 44% increased HR of in-hospital mortality compared with an FO less than 5% (aHR 1.44, 95% CI 1.27 to 1.67). Notably, we found a non-linear dose-response association between maximum FO and in-hospital mortality. CONCLUSIONS: Both higher and negative fluid balance levels were associated with an increased risk of in-hospital mortality in critically ill patients. TRIAL REGISTRATION NUMBER: ChiCTR-ECH-13003934.

10.
J Ethnopharmacol ; 269: 113688, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33338592

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophularia ningpoensis Hemsl. (known as Xuanshen) has been used in China for centuries as a traditional medicinal plant to treat numerous diseases including inflammation, hypertension, cancer, and diabetes. AIM OF REVIEW: In this review, we provide an update on the botany, pharmacology, phytochemistry, pharmacokinetics, traditional uses, and safety of S. ningpoensis to highlight future research needs and potential uses of this plant. MATERIALS AND METHODS: All information on S. ningpoensis was obtained from scientific databases including ScienceDirect, Springer, PubMed, Sci Finder, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar, and Baidu Scholar. Additional information was collected from Chinese herbal medicine books, Ph.D. dissertations, and M.Sc. Theses. Plant taxonomy was verified by "The Plant List" database (http://www.theplantlist.org). RESULTS: S. ningpoensis displays fever reducing, detoxifying, and nourishing 'Yin' effects in traditional Chinese medicine (TCM). More than 162 compounds have been identified and isolated from S. ningpoensis, including iridoids and iridoid glycosides, phenylpropanoid glycosides, organic acids, volatile oils, terpenoids, saccharides, flavonoids, sterols, and saponins. These compounds possess a diverse variety of pharmacological properties that affect the cardiovascular, hepatic, and nervous systems, and protect the body against inflammation, oxidation, and carcinogenesis. CONCLUSIONS: Modern pharmacological studies have confirmed that S. ningpoensis is a valuable Chinese medicinal herb with many pharmacological uses in the treatment of cardiovascular, diabetic, and liver diseases. Most of the S. ningpoensis activity may be attributed to iridoid glycosides and phenylpropanoid glycosides; however, detailed information on the molecular mechanisms, metabolic activity, toxicology, and structure-function relationships of active components is limited. Further comprehensive research to evaluate the medicinal properties of S. ningpoensis is needed.

11.
FEBS Open Bio ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33278865

RESUMO

Y-box-binding protein 1 (Ybx1, YB-1), also known as Y-box transcription factor, is involved in a variety of biological processes and pathways, including embryogenesis, reproduction and development in vertebrates. Several non-coding RNAs regulate Ybx1 signaling. However, the role of long non-coding RNAs (lncRNAs) in embryogenesis remains incompletely understood. Here, we investigated the possible involvement of lncRNAs in Ybx1-mediated regulation of vertebrate development by performing systematic transcriptome analysis of RNA sequencing data derived from ybx1 homozygous mutant zebrafish on day5 (day5_ybx1-/- ) and wild type zebrafish on day5 and day6 (day5_ybx1+/+ , day6_ybx1+/+ ). We identified several lncRNAs affected by ybx1 disruption that may target redox-related genes such as duox and noxo1a. Knockdown of three selected lncRNAs led to morphological deformation of larvae, implying an involvement of these lncRNAs in zebrafish embryo development. In summary, our study provides new insights into the lncRNA-mediated mechanisms underlying development in Ybx1 deficient zebrafish larvae.

12.
Front Immunol ; 11: 586613, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329564

RESUMO

Dendritic cells (DCs) are specialized antigen-presenting cells that play a key role in immune homeostasis and the adaptive immune response. DC-induced immune tolerance or activation is strictly dependent on the distinct maturation stages and migration ability of DCs. Ubiquitination is a reversible protein post-translational modification process that has emerged as a crucial mechanism that regulates DC maturation and function. Recent studies have shown that ubiquitin enzymes, including E3 ubiquitin ligases and deubiquitinases (DUBs), are pivotal regulators of DC-mediated immune function and serve as potential targets for DC-based immunotherapy of immune-related disorders (e.g., autoimmune disease, infections, and tumors). In this review, we summarize the recent progress regarding the molecular mechanisms and function of ubiquitination in DC-mediated immune homeostasis and immune response.

13.
Psychother Psychosom ; : 1-10, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33152729

RESUMO

BACKGROUND: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load. OBJECTIVE: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load. METHODS: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed. RESULTS: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18-1.31; p < 0.01), depression (OR = 1.23; 95% CI 1.17-1.29; p < 0.01), somatization (OR = 1.20; 95% CI 1.14-1.25; p < 0.01), hostility (OR = 1.24; 95% CI 1.18-1.30; p < 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34-1.66; p < 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78-0.89; p < 0.01), subjective support (OR = 0.84; 95% CI 0.80-0.88; p < 0.01), utilization of support (OR = 0.80; 95% CI 0.72-0.88; p < 0.01), social support (OR = 0.90; 95% CI 0.87-0.93; p < 0.01), and global well-being (OR = 0.30; 95% CI 0.22-0.41; p < 0.01) were negatively associated. CONCLUSIONS: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it.

14.
Biomed Res Int ; 2020: 2514207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204689

RESUMO

The purpose of this study was to investigate the efficacy of tranexamic acid (TXA) in patients undergoing open-wedge high tibial osteotomy (OWHTO). Patients from August 2018 to May 2020 were retrospectively studied. Clinical data were obtained including gender, age, height, weight, body mass index (BMI), smoking, alcohol consumption, hypertension, diabetes, history of aspirin, prepostoperative hematocrit (Hct) and hemoglobin (Hb), thrombotic events, blood transfusion requirement, hospital length of stay, size of osteotomy gap, and wound complications such as wound hematoma and infection. 52 patients were enrolled in the tranexamic acid group (TA group), and 48 patients were enrolled in the nontranexamic acid group (NTA group); there were no significant differences between both groups in terms of gender, age, BMI, preoperative Hb, size of osteotomy gap, incidence of smoking, alcohol consumption, hypertension, diabetes, history of aspirin, thrombotic events, blood transfusion requirement, and wound hematoma and infection. The mean hospital length of stay was 9.4 ± 1.0 days in the TA group and 11.0 ± 1.2 days in the NTA group (P < 0.001), the blood loss was 296.0 ± 128.7 ml in the TA group and 383.3 ± 181.3 ml in the NTA group (P < 0.05), and the postoperative Hb level was 120.8 ± 15.0 g/l in the TA group and 109.5 ± 13.8 g/l in the NTA group (P < 0.001). In conclusion, the administration of TXA is beneficial to patients undergoing OWHTO via decreasing hospital length of stay, reducing blood loss, and maintaining higher postoperative Hb levels.

15.
J Cell Physiol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230843

RESUMO

Intestinal mucosal injury is one of the most significant complications of burns. In our previous study, it was found that autophagy could alleviate burn-induced intestinal injury, but the underlying mechanisms are still unclear. Irregular expression of long noncoding RNAs (lncRNAs) is present in many diseases, including burns. However, the relationship between lncRNAs and intestinal mucosal injury requires further elucidation. In this study, we established a burn mice model and detected the expression level of autophagy-related proteins. Then, H19 content after autophagy intervention was tested in vitro and in vivo. The interaction of H19 with Let-7g and that of Let-7g with epidermal growth factor (EGF) were verified by dual-luciferase reporter assays. We found that the expression of the autophagy-associated proteins LC3-II and Beclin-1 was raised in the intestinal tract of the burn mice model. Similarly, the transfection of H19 raised autophagy levels. H19 was elevated after autophagy intervention in vitro and in vivo. H19 overexpression was able to promote IEC-6 cell migration and proliferation. Let-7g was suppressed by the overexpression of H19 and the combination of Let-7g mimic was able to abolish the physiological effect of H19. Moreover, the suppression of Let-7g increased the expression of EGF protein, which heightened IEC-6 cell migration and proliferation. Besides this, dual-luciferase assays revealed that Let-7g was a direct target of H19 as well as the EGF gene. Taken together, autophagy-mediated H19 increases in mouse intestinal tract after severe burn and functions as a sponge to Let-7g to regulate EGF, which suggests that H19 serves as a potential therapeutic target and biomarker for intestinal mucosal injury after burns.

16.
J Nanobiotechnology ; 18(1): 163, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167997

RESUMO

BACKGROUND: Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-ß that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported. RESULTS: We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-ß. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy. CONCLUSIONS: C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

17.
Lung Cancer ; 150: 240-246, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33249379

RESUMO

BACKGROUND: Patients with anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC) treated with crizotinib inevitably relapse, with brain as common site of progression. PATIENTS AND METHODS: ASCEND-6, a phase 1/2, single-arm study, included adult Chinese patients with stage IIIB or IV ALK+ NSCLC pretreated with crizotinib as the last therapy (irrespective of prior chemotherapies [≤2]). Primary endpoints were pharmacokinetics (PK), safety, and tolerability. Key secondary endpoint was overall response rate (ORR; investigator assessed). RESULTS: Of the 103 enrolled patients, all received prior crizotinib, 70 % received ≥1 prior chemotherapy regimen, and 63.1 % had brain metastases at baseline. In the phase 1 component, 20 patients completed a 5-day PK run-in period. Median Tmax (n = 16) was ∼6 h; geometric means of AUC0-24 h (n = 16) and Cmax (n = 16) at steady state were 22,000 ng*h/mL and 1080 ng/mL, respectively. In the final analysis, median follow-up time was 34 months (range: 27.8-40.6). The ORR was 41.7 % (95 % confidence interval [CI]: 32.1-51.9), and median progression-free survival was 7.2 months (95 % CI: 4.1-7.5). Median overall survival was 17.5 months (95 % CI: 10.8-24.3). Most frequent adverse events, regardless of study drug relationship (mostly grade 1/2), were diarrhea (74.8 %), vomiting (62.1 %), alanine transaminase increased (59.2 %), aspartate transaminase increased (58.3 %), and nausea (58.3 %). CONCLUSIONS: Ceritinib PK in Chinese patients is consistent with those observed in the global ASCEND-1 study. Ceritinib was well tolerated and showed durable responses in Chinese patients with ALK+ NSCLC who progressed after crizotinib and ≤2 prior lines of chemotherapy.

18.
Front Oncol ; 10: 1568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042801

RESUMO

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

19.
Front Oncol ; 10: 1785, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042827

RESUMO

Immune checkpoint inhibitors (ICIs) have been applied to clinical practice and achieved significant therapeutic benefit in a variety of human malignancies. These drugs not only enhance the body's antitumor immune response but also produce side effects called immune-related adverse events (irAEs). Although checkpoint inhibitor pneumonitis (CIP) has a low clinical incidence, it is likely to cause the delay or termination of immunotherapy and treatment-related death in some severe cases. An increasing number of CIP cases have been reported since 2015, which are attributed to the augmentation of approvals and uses of ICIs, but a comprehensive understanding of CIP is still lacking. This review focuses on the epidemiology, clinical characteristics, treatment strategies, and underlying mechanisms of CIP to strengthen the recognition of pulmonary toxicity among clinicians and researchers.

20.
Front Hum Neurosci ; 14: 551470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093828

RESUMO

Objective: Osteonecrosis of the femoral head (ONFH) is a common condition that is encountered in clinical practice, and yet, little is known about its characteristics and manifestations in the brain. Therefore, in this study, we aimed to use resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the spatial patterns of spontaneous brain activity in the brain of ONFH patients. Methods: The study included ONFH patients and healthy controls. The pattern of intrinsic brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) of blood oxygen level-dependent signals using rs-fMRI. Meanwhile, we also used Harris hip scores to evaluate the functional performance of ONFH patients and healthy controls. Result: Ten ONFH patients and 10 health controls were investigated. We found global ALFF differences between the two groups throughout the occipital, parietal, frontal, prefrontal, and temporal cortices. In the ONFH patients, altered brain activity was found in the brain regions in the sensorimotor network, pain-related network, and emotion and cognition network. The results of the correlation investigations also demonstrated that the regions with ALFF changes had significant correlations with the functional performance of the patients evaluated by Harris hip scores. Conclusions: Our study has revealed the abnormal pattern of brain activity in ONFH patients, and our findings could be used to aid in understanding the mechanisms behind the gait abnormality and intractable pain associated with ONFH at the central level.

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