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Non-small-cell lung carcinoma (NSCLC) is a type of pernicious tumor, which owns high morbidity and mortality. TRIM34 has a stimulative role in cell apoptosis and a suppressive role in inflammation. However, no studies were focused on the regulatory impacts of TRIM34 in NSCLC. This study aimed to examine the underlying regulatory effects of TRIM34 in NSCLC. TRIM34 exhibited lower expression in NSCLC. TRIM34 facilitated mitochondrial damage and apoptosis in NSCLC. TRIM34 induced the increased activity of mTORC1 and accelerated glycolysis in NSCLC. Enhanced mitochondrial damage induced by TRIM34 overexpression was reversed after rapamycin (mTORC1 inhibitor) treatment in NSCLC. The strengthened cell apoptosis stimulated by TRIM34 overexpression was rescued after rapamycin treatment. TRIM34 activated mTORC1 to suppress NSCLC progression in vivo. TRIM34 suppressed NSCLC via inducing mTORC1-dependent glucose utilization and promoting cellular death. The results suggest that TRIM34 can be a useful therapeutic biomarker for NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Neoplasias Pulmonares/patologia , Glucose/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Apoptose , Proliferação de Células , Proteínas de Transporte/metabolismoRESUMO
BACKGROUND: The online-to-offline (O2O) teaching method is recognized as a new educational model that integrates network learning into offline classroom education, while problem-based learning (PBL) is a teaching modality that guides students to apply acquired theoretical knowledge to solve practical problems. However, implementing O2O combined with PBL has not been extensively explored in nephrology residency training. This study aims to explore the efficacy of O2O combined with PBL in the standardized residency training of nephrology by comparing it with the traditional lecture-based teaching (LBT). METHODS: Sixty residency trainees who participated in the standardized training of internal medicine in the nephrology department of the Second Affiliated Hospital of Zhejiang University School of Medicine were equally allocated into O2O combined with PBL (O2O/PBL) or the LBT group demographically matched. Examinations of theory, practice skills, clinical thinking and teaching satisfaction surveys were utilized to assess the teaching effects of the two groups. RESULTS: Participants from the O2O/PBL group outperformed those from the LBT group in the examination of theory (81.233 ± 9.156 vs. 75.800 ± 7.009, mean ± SEM), practice skills (104.433 ± 3.569 vs.100.316 ± 4.628, mean ± SEM) and clinical thinking (88.933 ± 4.473 vs. 86.667 ± 3.844, mean ± SEM). There was no significant difference in the teaching satisfaction between the two groups. CONCLUSION: The current study shows the positive impact of O2O combined with PBL approach on standardized residency training in nephrology without reducing teaching satisfaction.
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Internato e Residência , Nefrologia , Aprendizagem Baseada em Problemas , Aprendizagem Baseada em Problemas/métodos , Humanos , Nefrologia/educação , Masculino , Feminino , Competência Clínica , Avaliação Educacional , Ensino , Adulto , Instrução por Computador/métodos , Educação a DistânciaRESUMO
Military training is intense, difficult and often dangerous, so all kinds of injuries or diseases frequently occur during training. Most of the previous studies and reviews on military training-related injuries focused on musculoskeletal system, whereas there are no reviews of abdominal injuries and diseases. Although the incidence of military training-related abdominal injuries and diseases is relatively low, the patients' condition is often critical especially in the presence of abdominal organ injury, leading to multi-organ dysfunction syndrome and even death. This paper elaborates on common types of military training-related abdominal injuries and diseases as well as the prevention and treatment measures, which provides some basis for scientific and reasonable training and improvement of medical security.
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Traumatismos Abdominais , Militares , Sistema Musculoesquelético , Ferimentos e Lesões , Traumatismos Abdominais/etiologia , Traumatismos Abdominais/prevenção & controle , Humanos , Incidência , Militares/educação , Sistema Musculoesquelético/lesõesRESUMO
BACKGROUND: There are few studies reporting the use of atlantoaxial pedicle screws and the long-term effects of C1-C2 posterior fusion in children. Our study is to investigate the initial results of C1-C2 pedicle screw fixation for pediatric atlantoaxial dislocation (AAD) and assessed spontaneous change of postoperative radiography after a long-term follow-up period. METHODS: Posterior pedicle screw fixations were performed in 21 pediatric patients with AAD. All the patients underwent implant removal 1 year after their initial surgery and had regular follow-up with an average duration of 76.4 months (range, 52 to 117 mo). Clinical and radiographic data were then collected and compared. RESULTS: Frankel Grade was significantly improved at 3 months follow-up compared with pretreatment values. All patients had good bony fusion at a mean of 4.2±0.9 months (range, 3 to 6 mo) after treatment. None of the patients experienced worsening neurological symptoms or injury to the vertebral artery. However, 2 cases experienced minor complications. Following removal of the implants, no spinal deformities or subaxial instabilities were found. The mean angle of sagittal curvature increased from 12.1±2.4 degrees (range, 0 to 22 degrees) immediately postoperatively to 19.1±2.7 degrees (range, 6 to 31 degrees) at the final follow-up (P>0.05). CONCLUSIONS: The results demonstrated that C1-C2 pedicle screw fixation could achieve satisfactory initial results for the management of the pediatric AAD. Moreover, removal of the metal implant after bony fusion did not increase the risk of spinal deformity or subaxial instability at long-term follow-up.
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Articulação Atlantoaxial/cirurgia , Luxações Articulares/cirurgia , Parafusos Pediculares , Implantação de Prótese , Fusão Vertebral/métodos , Vértebra Cervical Áxis/cirurgia , Atlas Cervical/cirurgia , Criança , Pré-Escolar , Remoção de Dispositivo , Feminino , Seguimentos , Humanos , Masculino , Parafusos Pediculares/efeitos adversos , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/instrumentaçãoRESUMO
Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested that CSCs give rise to tumor recurrence and metastasis. Theasaponin E1 (TSE1), which was isolated from green tea (Camellia sinensis) seeds, has been proposed to be an effective compound for tumor treatment. However, studies on whether TSE1 takes effect through CSCs have rarely been reported. In this paper, ALDH-positive (ALDH+) ovarian cancer stem-like cells from two platinum-resistant ovarian cancer cell lines A2780/CP70 and OVCAR-3 were used to study the anti-proliferation effect of TSE1 on CSCs. The ALDH+ cells showed significantly stronger sphere forming vitality and stronger cell migration capability. In addition, the stemness marker proteins CD44, Oct-4, Nanog, as well as Bcl-2 and MMP-9 expression levels of ALDH+ cells were upregulated compared with the original tumor cells, indicating that they have certain stem cell characteristics. At the same time, the results showed that TSE1 could inhibit cell proliferation and suspension sphere formation in ALDH+ cells. Our data suggests that TSE1 as a natural compound has the potential to reduce human ovarian cancer mortality. However, more research is still needed to find out the molecular mechanism of TSE1-mediated inhibition of ALDH+ cells and possible drug applications on the disease.
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Aldeído Desidrogenase/metabolismo , Células-Tronco Neoplásicas/metabolismo , Ácido Oleanólico/análogos & derivados , Neoplasias Ovarianas/metabolismo , Saponinas/farmacologia , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estrutura Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Saponinas/química , Chá/químicaRESUMO
The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been implicated in podocyte injury and glomerular sclerosis during hyperhomocysteinemia (hHcys). However, it remains unclear whether the NLRP3 inflammasome can be a therapeutic target for treatment of hHcys-induced kidney injury. Given that DHA metabolites-resolvins have potent anti-inflammatory effects, the present study tested whether the prototype, resolvin D1 (RvD1), and 17S-hydroxy DHA (17S-HDHA), an intermediate product, abrogate hHcys-induced podocyte injury by targeting the NLRP3 inflammasome. In vitro, confocal microscopy demonstrated that 17S-HDHA (100 nM) and RvD1 (60 nM) prevented Hcys-induced formation of NLRP3 inflammasomes, as shown by reduced colocalization of NLRP3 with apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) or caspase-1. Both DHA metabolites inhibited Hcys-induced caspase-1 activation and interleukin-1ß production. However, DHA had no significant effect on these Hcys-induced changes in podocytes. In vivo, DHA lipoxygenase metabolites substantially inhibited podocyte NLRP3 inflammasome formation and activation and consequent glomerular sclerosis in mice with hHcys. Mechanistically, RvD1 and 17S-HDHA were shown to suppress Hcys-induced formation of lipid raft redox signaling platforms and subsequent O2·- production in podocytes. It is concluded that inhibition of NLRP3 inflammasome activation is one of the important mechanisms mediating the beneficial action of RvD1 and 17S-HDHA on Hcys-induced podocyte injury and glomerular sclerosis.
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Ácidos Docosa-Hexaenoicos/metabolismo , Inflamassomos/metabolismo , Glomérulos Renais/lesões , Glomérulos Renais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Hiper-Homocisteinemia/metabolismo , Hiper-Homocisteinemia/patologia , Glomérulos Renais/patologia , Lipoxigenases/metabolismo , Masculino , Microdomínios da Membrana/metabolismo , Camundongos , Oxirredução , Podócitos/metabolismo , Transdução de SinaisRESUMO
Necrostatin-1 (Nec-1) has been shown to inhibit necroptosis and convey a significant protective effect after spinal cord injury (SCI). This small molecule inhibitor may reduce tissue damage and restore neurological function by lessening mitochondrial injury after SCI and preserving energy homeostasis. However, the effects of Nec-1 on endoplasmic reticulum stress (ERS)-an important pathological consequence of SCI-are still not clear. The present study investigates the relationship between necroptosis and ERS in a rat model of SCI. Electron microscopy was employed to observe ultra-structural changes in the endoplasmic reticulum and mitochondria after lesioning. Real-time quantitative PCR was used to measure the mRNA levels of ERS-related pro-apoptotic molecules such as C/EBP homologous protein (CHOP), immunoglobulin-binding protein (BiP/GRP78) and X box-binding protein-1 (XBP-1). Western blot and immunofluorescence were conducted to analyze CHOP, GRP78 and XBP-1 protein expression after lesioning. Results demonstrated that applying Nec-1 in SCI reduces ultra-structural damage to the endoplasmic reticulum and mitochondria and inhibits expression of ERS-related genes and proteins after lesioning. Immunofluorescence also shows ERS-related proteins mainly expressed in the cytoplasm of nerve cells. Taken together, these results demonstrate that Nec-1 has protective effect on the endoplasmic reticulum and mitochondria and alleviates ERS after SCI.
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Estresse do Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Imidazóis/farmacologia , Indóis/farmacologia , Traumatismos da Medula Espinal/metabolismo , Animais , Apoptose/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Masculino , Mitocôndrias/metabolismo , Necrose/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Fator de Transcrição CHOP/metabolismoRESUMO
The posterior (P), antero-posterior (AP), and anterior approaches (A) with a new complex locking rod system (D-rod system) were performed on 64 patients with lumbosacral tuberculosis respectively and the efficacies of the three approaches were compared in our study. Related data were then collected and compared with an average of 27.0 months follow up. The lumbosacral angles, VAS, ODI, ESR, and Frankel Grade were significantly improved at the post-operation or final follow-up when compared to preoperative scores. The average surgical time, blood loss, and hospital stay following anterior and posterior approaches were markedly less than those following antero-posterior approach. Moreover, there was no tuberculosis recurrence in AP and A group. However, P group had a recurrence rate of 11.1% (2/18). None of the patients in P and A group developed intraoperative or postoperative complications, while two cases were found in AP group. Taken together, anterior approach with the D-rod system is an appropriate method for lumbosacral tuberculosis treatment.
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Região Lombossacral/cirurgia , Fusão Vertebral/métodos , Tuberculose da Coluna Vertebral/cirurgia , Adulto , Desbridamento/métodos , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Posicionamento do Paciente , Sacro/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: A prospective cohort study was performed to evaluate the clinical and radiological outcomes following posterior lumbar interbody fusion (PLIF) in patients treated with a PEEK cage compared to those treated with an autologous cage using the lumbar spinous process and laminae (ACSP). METHODS: Sixty-nine consecutive patients with lumbar degenerative disc disease were randomly assigned to either a PEEK cage (group A, n = 34) or an ACSP (group B, n = 35). Monosegmental PLIF was performed in all patients. Mean lumbar lordosis, mean disc height, visual analog scale (VAS) scores, functional outcomes, fusion rates and complication rates were recorded and compared. The patients were followed postoperatively for a minimum of 2 years. RESULTS: Successful radiographic fusion was documented in all patients. No flexion-extension hypermobility or pedicle screw loosening or breakage occurred during the follow-up period. No significant difference existed between the 2 groups when comparing the mean lumbar lordosis, mean disc height, visual analog scale (VAS) scores, functional outcomes, fusion rates or complication rates. Overall satisfactory results were achieved in both groups. CONCLUSIONS: The results suggest that the ACSP appears to be equally as safe and effective as the PEEK cage. TRIAL REGISTRATION: ISRCTN25558534 . Retrospectively registered 16/02/2016.
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Materiais Biocompatíveis/uso terapêutico , Transplante Ósseo , Degeneração do Disco Intervertebral/cirurgia , Cetonas/uso terapêutico , Vértebras Lombares/transplante , Polietilenoglicóis/uso terapêutico , Fusão Vertebral/métodos , Adulto , Benzofenonas , Feminino , Seguimentos , Humanos , Lordose/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medição da Dor , Parafusos Pediculares , Polímeros , Estudos Prospectivos , Radiografia , Fusão Vertebral/instrumentação , Tomografia Computadorizada por Raios X , Transplante Autólogo , Resultado do TratamentoRESUMO
PURPOSE: To outline a management principle for the combined atlas (C1)-axis (C2) fractures and assess its therapeutic effects. METHODS: Forty-one patients with combined C1-C2 fractures were treated according to their C2 fracture types. Non-operative external immobilization in the form of a cervical collar or halo vest was used in 22 patients. Early posterior pedicle screw fixations were performed in 19 patients whose fractures had a combination of any of the three conditions: an atlantodens interval (ADI) ≥ 5 mm, lateral mass displacement (LMD) > 7 mm, and/or C2-C3 angulation > 11°. Thirty-nine patients were followed up regularly with an average of 19.3 months (range, 12 to 45 months). Clinical and radiographic data were then collected and compared. RESULTS: At three months following treatment, patients' visual analog scale (VAS), Neck Disability Index (NDI), American Spinal Injury Association (ASIA) scale, and Frankel grades were all significantly improved when compared to pretreatment. These results indicated that the cervical collar, halo vest, and posterior pedicle screw fixation approaches were all able to effectively treat cases of combined C1-C2 fractures. One patient in the non-surgical group developed nonunion which required late surgical treatment and one patient had pin site infection in the non-surgical group (2/22), while there were three minor complications in the surgical group. CONCLUSION: We propose a management principle that bases the treatment of a combined C1-C2 fracture on the nature of the C2 fracture. This treatment strategy has yielded promising results as a satisfactory means for the management of combined C1-C2 fractures.
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Parafusos Ósseos/estatística & dados numéricos , Vértebras Cervicais/lesões , Fraturas da Coluna Vertebral/terapia , Contenções/estatística & dados numéricos , Adulto , Idoso , Parafusos Ósseos/efeitos adversos , Vértebras Cervicais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Fusão Vertebral/métodos , Contenções/efeitos adversos , Adulto JovemRESUMO
PURPOSE: To introduce a surgical method of treating Eyres type IV and V coracoid fracture using the acromion osteotomy approach and to further analyse the clinical effectiveness of this surgical procedure. METHODS: Nine patients were included in this study with a mean follow-up time of 23.3 months (range, 14.0-34.0 months). Patients were evaluated with use of the Constant score, the Simple Shoulder Test (SST) score and a visual analogue scale (VAS) pain score. Moreover, the shoulder range of motion was also observed. RESULTS: The mean operation time was 91.6 min with a blood loss volume ranging from 310 to 530 ml. The fractures of eight patients had recovered between 10 and 12 weeks post operation with no signs of infection, screw loosening, plate breaking or other internal fixation failures, while one case had non-union at 34 months' follow-up. The mean Constant score increased from 75.6 points preoperatively to 91.0 points at follow-up. The mean VAS score decreased from 5.3 preoperatively to 1.0 at follow-up, while the average SST score increased from 7.1 points preoperatively to 10.0 points at follow-up. The mean abduction, forward flexion, external rotation, internal rotation and backward extension angles were 162°, 159° 50°, 55° and 47°. Five cases were classified as excellent, three cases were marked as good and one case was classified as fair. CONCLUSIONS: Treating coracoid fracture through the approach of acromion osteotomy could be an effective treatment option with minimise damages.
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Acrômio/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Osteotomia/métodos , Escápula/cirurgia , Adulto , Placas Ósseas , Parafusos Ósseos , Feminino , Seguimentos , Fixação Interna de Fraturas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Osteotomia/efeitos adversos , Complicações Pós-Operatórias , Amplitude de Movimento Articular , Estudos Retrospectivos , Escápula/lesões , Resultado do TratamentoRESUMO
Kv1.5 (also known as KCNA5) is a protein encoded by the KCNA5 gene, which belongs to the voltage-gated potassium channel, shaker-related subfamily. Recently, a number of studies have suggested that Kv1.5 is overexpressed in numerous cancers and plays crucial roles in cancer development. However, until now, the expression and functions of Kv1.5 in osteosarcoma are still unclear. To characterize the potential biological functions of Kv1.5 in osteosarcoma, herein, we examined the expression levels of Kv1.5 in osteosarcoma cells and tissues using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry assays. Four short hairpin RNAs (shRNAs) targeting Kv1.5 were designed and homologous recombination technology was used to construct pGeneSil-Kv1.5 vectors. In addition, the vectors were transfected into osteosarcoma MG63 cells and Kv1.5 mRNA level was measured by qRT-PCR and the Kv1.5 protein level was examined by western blot. We also examined the effects of Kv1.5 silencing on proliferation, cell cycle and apoptosis of the osteosarcoma cells using CCK-8, colony formation, flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. Our results showed that Kv1.5 was aberrantly expressed in osteosarcoma and that the synthesized shRNA targeting Kv1.5 reduced Kv1.5 mRNA and protein expression effectively. Silencing Kv1.5 expression in the osteosarcoma cells significantly inhibited the proliferation of osteosarcoma cells, induced cell cycle arrest at G0/G1 phase, and induced cell apoptosis through up-regulation of p21, p27, Bax, Bcl-XL and caspase-3 and down-regulation of cyclins A, cyclins D1, cyclins E, Bcl-2 and Bik. In summary, our results indicate that Kv1.5 silencing could suppress osteosarcoma progression through multiple signaling pathways and suggest that Kv1.5 may be a novel target for osteosarcoma therapeutics.
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Apoptose/genética , Neoplasias Ósseas/genética , Inativação Gênica , Canal de Potássio Kv1.5/genética , Osteossarcoma/genética , Neoplasias Ósseas/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Silenciamento de Genes , Humanos , Canal de Potássio Kv1.5/metabolismo , Osteossarcoma/metabolismo , RNA Interferente Pequeno/genéticaRESUMO
Thrombospondin-2 (THBS2), a secreted extracellular matrix protein, plays a crucial role in various biological processes including angiogenesis, tissue remodeling, and inflammation. Our study focuses on its function in human gastric cancer (GC). Through bioinformatics and tumor tissue analysis, we compared THBS2 expression in GC tissues and adjacent tissues, and predicted regulatory upstream and downstream molecules. The direct regulatory effect of miR-29b-3p on THBS2 was evaluated through dual-luciferase reporter assays, showing that miR-29b-3p targets the 3'-UTR of THBS2 mRNA, reducing its expression in GC cells. The influence of THBS2 on tumorigenesis and stemness was examined on protein expression levels via Western blot. In vivo, THBS2's role was investigated through xenograft and metastasis assays in nude mice, demonstrating that downregulation of THBS2 impairs GC tumorigenesis and liver metastasis. Our study identified THBS2 as a highly expressed prognostic factor in GC patients. Functionally, THBS2 promotes GC progression through the Notch signaling pathway by regulating Notch3, NEY1, and HES1 proteins, and sustains cancer stem cell-like characteristics by Notch3, including the expression of CD44, Nanog, OCT4, and SOX2. In sum, our study reveals that THBS2 promotes GC progression and stemness, modulated negatively by miR-29b-3p. This suggests potential therapeutic targets within the THBS2/Notch signaling axis for combating gastric cancer.
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This article examined the therapeutic effect of melatonin (MT) on the lipopolysaccharide (LPS)-induced myocardial injury, and the mechanisms involved. Septic rat model was constructed by exposing to lipopolysaccharide (LPS), and treated by MT, Ferrostatin-1 (Fer-1) and Erastin (Era). Hematoxylin-eosin staining was executed to appraise myocardial injury. H9c2 cells that exposed to LPS to induce in vitro sepsis cell model were treated by MT. p53 overexpression vectors were transfected into H9c2 cells. Inflammation- and ferroptosis-related indicators were examined by enzyme-linked immunosorbent assay. Expression of p53, xCT and GPX4 was scrutinized by quantitative real-time polymerase chain reaction and Western blot. MT relieved myocardial injury in septic rats. It decreased IL-6 and TNF-α, elevated GPX4 and GSH, and reduced MDA and Fe2+ in myocardial tissues of septic rats. LPS induced p53 elevation and xCT reduction in rats' myocardial tissues. Nevertheless, MT treatment declined p53 and increased xCT in myocardial tissues of septic rats. Interestingly, the relieving effect of MT on myocardial injury in septic rats was enhanced by Fer-1, but reversed by Era. The LPS-induced H9c2 cell damage was relieved by MT treatment. Besides, MT decreased LDH, IL-6 and TNF-α, elevated xCT, GPX4 and GSH, and reduced MDA and Fe2+ in the LPS-induced H9c2 cells. Conversely, these influences of MT on the LPS-induced H9c2 cells were reversed by p53 overexpression. MT is proposed to be a promising agent for treating the LPS-induced myocardial injury, as it relieves myocardial injury by hindering the p53/xCT-mediated ferroptosis in the LPS-induced septic rats.
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Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.
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Modelos Animais de Doenças , Exossomos , Células-Tronco Mesenquimais , Muromegalovirus , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Transdução de Sinais , Animais , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Muromegalovirus/fisiologia , Camundongos Endogâmicos C57BL , Macrófagos/imunologia , Infecções por Citomegalovirus/terapia , Infecções por Citomegalovirus/virologia , Pulmão/virologia , Pulmão/patologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Infecções por Herpesviridae/terapia , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/imunologia , Pneumonia/terapia , Pneumonia/virologiaRESUMO
Objective: Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods: Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the MannâWhitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results: A total of 553 patients (86.98% male) with a median age of 36.50 (27.00-48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18-22.51) hours vs. 7.00 (3.80-15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00-21.59) hours vs. 7.07 (3.99-13.85) hours, P=0.002; preoperative time: 3.02 (2.01-5.58) hours vs. 2.81 (1.85-3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00-1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54-8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS < 16, HR: 2.78, 95% CI: 1.38-5.601, P=0.004) had a worse impact on survival. Conclusion: More patients with BAT were transferred to higher-level hospital, leading to significantly longer prehospital and preoperation time. In the subgroup of hemodynamically stable individuals, more patients with BAT experienced hollow viscus injuries. For those patients, aggressive diagnostic laparoscopic exploration may be beneficial. Patients with longer injury-regional hospital intervals, the need for ICU care, and higher injury severity scores (ISSs) suffered from worse prognoses.
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10.1002/advs.202203058 Adv. Sci. 2022, 9, 2203058 The above article from Advanced Science, published online on 21 July 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202203058), has been retracted by agreement between the authors, the Editor-in-Chief, Kirsten Severing, and Wiley-VCH GmbH. The retraction has been agreed as the article is based on research results and data that the authors were not authorized to use. Moreover, the majority of co-authors have been listed despite insufficient qualification for contributorship.
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10.1002/advs.202202550 Adv. Sci.2022, 9, 2202550 The above article from Advanced Science, published online on 5 June 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202202550), has been retracted by agreement between the authors, the Editor-in-Chief, Kirsten Severing, and Wiley-VCH GmbH. The retraction has been agreed as the article is based on research results and data that the authors were not authorized to use. Moreover, the majority of co-authors have been listed despite insufficient qualification for contributorship.
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Background: Jianghua Kucha (JHKC) is a special tea germplasm with enriched specialized secondary metabolites, including theacrine, non-epimeric flavanols and methylated flavanols. Moreover, primary metabolites provide precursors and energy for the production of secondary metabolites. However, the accumulation patterns of primary and secondary metabolites in different tissues of JHKC are unclear. Methods: The changes of primary and secondary metabolites and related metabolic pathways (primary and secondary metabolism) in different JHKC tissues (the bud, 1st-4th leaves, and new stem) were investigated via metabolomics analysis with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Results: Significant differences were observed in 68 primary and 51 secondary metabolites mainly related with the pathways of starch and sucrose, amino acids, caffeine, and flavanols metabolism and TCA cycle. The bud exhibited higher levels of glucose-6-phosphate, citric acid, most amino acids, theobromine, catechin-gallate, epicatechin-gallate, procyanidins, and theasinensins; the 1st leaf showed higher levels of caffeine and epigallocatechin-3-gallate; and the 4th leaf contained higher levels of most monosaccharides, theacrine, and epigallocatechin-3-O-(3"-O-methyl)-gallate. In addition, primary metabolites and important secondary metabolites had certain correlations. Conclusion: This study provides comprehensive insight into primary and secondary metabolites in JHKC and offers guidelines for efficiently utilizing specialized metabolites of JHKC in the future.
RESUMO
BACKGROUND: Eosinophilic granuloma (EG) is a proliferative condition that affects the cells of bone tissue. There are no specific clinical signs or imaging manifestations in the early stages of the disease, making it simple to overlook and misdiagnose. Because of the disease's rarity, there is presently no standardized treatment principle. There are few accounts of such occurrences affecting the axis among children. We discovered a case of a child whose EG resulted in atlantoaxial joint dislocation and destruction of the axial bone. CASE SUMMARY: After having pharyngeal discomfort for more than six months without a clear explanation, a 6-year-old boy was brought to our hospital. Following a careful evaluation, the pathology indicated a strong likelihood of an axial EG. Ultimately, we decided to treat the boy with posterior pedicle screw fixation and local steroid injections. CONCLUSION: EGs of the upper cervical spine are quite uncommon in children, and they are exceedingly easy to overlook or misdiagnose. Posterior pedicle screw fixation and local steroid injections are effective treatments for patients with axial EGs affecting the atlantoaxial junction.