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1.
Zhongguo Zhong Yao Za Zhi ; 49(12): 3270-3279, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39041089

RESUMO

This study established a rat model of obesity by using a high-fat diet(HFD) to explore the effect of polymethoxylated flavonoids on glucose and lipid metabolism in the model rats and decipher the role and mechanism of polymethoxylated flavonoids in mitigating obesity. Thirty normal SD rats were selected and randomized into normal, model, ezetimibe(0.1 mg·kg~(-1)), and polymethoxylated flavonoids(62.5 mg·kg~(-1) and 125 mg·kg~(-1)) groups based on the body weight. Except the normal group receiving a conventional diet, the other groups received a HFD. Rats were administrated with corresponding doses of drugs by gavage. During the administration period, the body weight of each group of rats was regularly weighed, and the serum lipid and glucose levels were measured by a fully automated biochemical analyzer. Islet homeostasis and serum levels of obesity factors were measured by ELISA. The 16S rRNA high-throughput sequencing was employed to study the gut microbiota. Hematoxylin-eosin staining was employed to observe the histomorphology of white fat, brown fat, and pancreas. After the wet weights of white fat and brown fat were measured, the organ index was calculated. Immunohistochemistry and Western blot were employed to determine the protein levels. The results showed that polymethoxylated flavonoids reduced the body weight and Lee's index and improved blood lipid levels of the model rats. Polymethoxylated flavonoids reduced blood glucose and insulin secretion, increased insulin responsiveness, and alleviated insulin resistance. In addition, polymethoxylated flavonoids regulated the serum levels of obesity factors and reduced the weights and indexes of white fat and brown fat, the diameter of white adipocytes, and the number of fat vacuoles in brown fat and pancreatic islet cells. The intervention with polymethoxylated flavonoids increased the diversity of gut microbiota in the model rats, increasing the beneficial bacteria associated with glucose and lipid metabolism and reduced the harmful bacteria at the genus level. In addition, polymethoxylated flavonoids up-regulated the protein levels of glucose transporter 4(GLUT4), phosphorylated AMP-activated protein kinase(p-AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), and uncoupling protein 1(UCP1). In summary, polymethoxylated flavonoids may increase the body utilization of glucose and lipids by regulating the homeostasis of insulin, the serum levels of obesity factors, the diversity of gut microbiota, and the expression of mitochondrial metabolism-related proteins in brown adipocytes, thereby mitigating obesity in rats.


Assuntos
Dieta Hiperlipídica , Flavonoides , Metabolismo dos Lipídeos , Obesidade , Ratos Sprague-Dawley , Animais , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ratos , Metabolismo dos Lipídeos/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Masculino , Glucose/metabolismo , Modelos Animais de Doenças , Humanos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos
2.
Int J Ophthalmol ; 17(3): 444-453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721522

RESUMO

AIM: To evaluate the role of semaphorin 7A (Sema7A) and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells (HCEs). METHODS: Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0, 125, 250, or 500 ng/mL for 24, 48, or 72h in vitro. Transepithelial electrical resistance (TEER) as well as Dextran-fluorescein isothiocyanate (FITC) permeability assays were conducted to assess barrier function. To quantify tight junctions (TJs) such as occludin and zonula occludens-1 (ZO-1) at the mRNA level, reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. Immunoblotting was used to examine the activity of the nuclear factor-kappa B (NF-κB) signaling pathway and the production of TJs proteins. Immunofluorescence analyses were employed to localize the TJs. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were utilized to observe changes in interleukin (IL)-1ß levels. To investigate the role of NF-κB signaling activation and IL-1ß in Sema7A's anti-barrier mechanism, we employed 0.1 µmol/L IκB kinase 2 (IKK2) inhibitor IV or 500 ng/mL IL-1 receptor (IL-1R) antagonist. RESULTS: Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time- and dose-dependent manner, as well as altering the localization of TJs. Furthermore, Sema7A stimulated the activation of inhibitor of kappa B alpha (IκBα) and expression of IL-1ß. The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists. CONCLUSION: Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins, as well as the expression of IL-1ß. These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.

3.
J Hazard Mater ; 469: 133972, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38461665

RESUMO

Di-n-butyl phthalate (DBP) is one of the most extensively used phthalic acid esters (PAEs) and is considered to be an emerging, globally concerning pollutant. The genus Streptomyces holds promise as a degrader of various organic pollutants, but PAE biodegradation mechanisms by Streptomyces species remain unsolved. In this study, a novel PAE-degrading Streptomyces sp. FZ201 isolated from natural habitats efficiently degraded various PAEs. FZ201 had strong resilience against DBP and exhibited immediate degradation, with kinetics adhering to a first-order model. The comprehensive biodegradation of DBP involves de-esterification, ß-oxidation, trans-esterification, and aromatic ring cleavage. FZ201 contains numerous catabolic genes that potentially facilitate PAE biodegradation. The DBP metabolic pathway was reconstructed by genome annotation and intermediate identification. Streptomyces species have an open pangenome with substantial genome expansion events during the evolutionary process, enabling extensive genetic diversity and highly plastic genomes within the Streptomyces genus. FZ201 had a diverse array of highly expressed genes associated with the degradation of PAEs, potentially contributing significantly to its adaptive advantage and efficiency of PAE degradation. Thus, FZ201 is a promising candidate for remediating highly PAE-contaminated environments. These findings enhance our preliminary understanding of the molecular mechanisms employed by Streptomyces for the removal of PAEs.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Ésteres/metabolismo , Ácidos Ftálicos/metabolismo , Dibutilftalato/metabolismo , Biodegradação Ambiental , Ecossistema , Dietilexilftalato/metabolismo
4.
Appl Environ Microbiol ; 89(11): e0110623, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37902313

RESUMO

IMPORTANCE: The adenosine 5'-triphosphate (ATP) regeneration system can significantly reduce the cost of many biocatalytic processes. Numerous studies have endeavored to utilize the ATP regeneration system based on Cytophaga hutchinsonii PPK (ChPPK). However, the wild-type ChPPK enzyme possesses limitations such as low enzymatic activity, poor stability, and limited substrate tolerance, impeding its application in catalytic reactions. To enhance the performance of ChPPK, we employed a semi-rational design approach to obtain the variant ChPPK/A79G/S106C/I108F/L285P. The enzymatic kinetic parameters and the catalytic performance in the synthesis of nicotinamide mononucleotide demonstrated that the variant ChPPK/A79G/S106C/I108F/L285P exhibited superior enzymatic properties than the wild-type enzyme. All data indicated that our engineered ATP regeneration system holds inherent potential for implementation in biocatalytic processes.


Assuntos
Trifosfato de Adenosina , Escherichia coli , Análise Custo-Benefício , Cytophaga , Regeneração , Adenosina
5.
Molecules ; 28(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37894661

RESUMO

Metal-organic frameworks (MOFs) are peculiar multimodal materials that find photocatalytic applications for the decomposition of lethal molecules present in the wastewater. In this investigation, two new d10-configuration-based MOFs, [Zn2(L)(H2O)(bbi)] (1) and [Cd2(L)(bbi)] (2) (5,5-(1,4-phenylenebis(methyleneoxy)diisophthalic acid (H2L) and 1,1'-(1,4-butanediyl)bis(imidazole) (bbi)), have been synthesized and characterized. The MOF 1 displayed a (4,6)-connected (3.43.52)(32.44.52.66.7) network topology, while 2 had a (3,10)-connected network with a Schläfli symbol of (410.511.622.72)(43)2. These MOFs have been employed as photocatalysts to photodegrade nitrophenolic compounds, especially p-nitrophenol (PNP). The photocatalysis studies reveal that 1 displayed relatively better photocatalytic performance than 2. Further, the photocatalytic efficacy of 1 has been assessed by altering the initial PNP concentration and photocatalyst dosage, which suggest that at 80 ppm PNP concentration and at its 50 mg concentration the MOF 1 can photo-decompose around 90.01% of PNP in 50 min. Further, radical scavenging experiments reveal that holes present over 1 and ·OH radicals collectively catalyze the photodecomposition of PNP. In addition, utilizing density of states (DOS) calculations and Hirshfeld surface analyses, a plausible photocatalysis mechanism for nitrophenol degradation has been postulated.

6.
Int J Ophthalmol ; 16(9): 1441-1449, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724268

RESUMO

AIM: To investigate the impact of 17ß-estradiol on the collagen gels contraction (CGC) and inflammation induced by transforming growth factor (TGF)-ß in human Tenon fibroblasts (HTFs). METHODS: HTFs were three-dimensionally cultivated in type I collagen-generated gels with or without TGF-ß (5 ng/mL), 17ß-estradiol (12.5 to 100 µmol/L), or progesterone (12.5 to 100 µmol/L). Then, the collagen gel diameter was determined to assess the contraction, and the development of stress fibers was analyzed using immunofluorescence staining. Immunoblot and gelatin zymography assays were used to analyze matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) being released into culture supernatants. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-PCR) were used to detect interleukin (IL)-6, monocyte chemoattractant proteins (MCP)-1, and vascular endothelial growth factor (VEGF) in HTFs at the translational and transcriptional levels. The phosphorylation levels of Sma- and Mad-related proteins (Smads), mitogen-activated protein kinases (MAPKs), and protein kinase B (AKT) were measured by immunoblotting. Statistical analysis was performed using either the Tukey-Kramer test or Student's unpaired t-test to compare the various treatments. RESULTS: The CGC caused by TGF-ß in HTFs was significantly inhibited by 17ß-estradiol (25 to 100 µmol/L), and a statistically significant difference was observed when comparing the normal control group with 17ß-estradiol concentrations exceeding 25 µmol/L (P<0.05). The suppressive impact of 17ß-estradiol became evident 24h after administration and peaked at 72h (P<0.05), whereas progesterone had no impact. Moreover, 17ß-estradiol attenuated the formation of stress fibers, and the production of MMP-3 and MMP-1 in HTFs stimulated by TGF-ß. The expression of MCP-1, IL-6, and VEGF mRNA and protein in HTFs were suppressed by 100 µmol/L 17ß-estradiol (P<0.01). Additionally, the phosphorylation of Smad2 Smad3, p38, and extracellular signal-regulated kinase (ERK) were downregulated (P <0.01). CONCLUSION: 17ß-estradiol significantly inhibits the CGC and inflammation caused by TGF-ß in HTFs. This inhibition is likely related to the suppression of stress fibers, inhibition of MMPs, and attenuation of Smads and MAPK (ERK and p38) signaling. 17ß-estradiol may have potential clinical benefits in preventing scar development and inflammation in the conjunctiva.

7.
Neoplasma ; 70(3): 361-374, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37498069

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor, which seriously threatens the life of patients. LncRNA SLC7A11-AS1 was reported to be abnormally expressed in HCC. Here, the functions and relative molecular regulatory mechanism of SLC7A11-AS1 in HCC were investigated. Nude mice and HCC cells were used as the experimental subjects. Knockdown or overexpression of exogenous genes was conducted in HCC cells. RT-qPCR, IHC, and western blot were employed to evaluate the abundance of genes and proteins. The malignant behaviors were evaluated using CCK-8, clone formation, wound-healing, and Transwell. The locations of SLC7A11-AS1 and KLF9 in cells were determined by FISH and IF assays. The total m6A level was evaluated by dot-blot assay. m6A modification of SLC7A11-AS1 was detected using RNA MeRIP. The interactions among molecules were validated by RIP, ChIP, dual luciferase reporter assay, and co-IP. SLC7A11-AS1 was elevated apparently in HCC cells and HCC tissues from mice. SLC7A11-AS1 silencing could suppress HCC progression, which was validated in in vivo and in vitro experiments. Furthermore, METTL3 mediated m6A modification of SLC7A11-AS1 to elevate its expression. In addition, SLC7A11-AS1 downregulated KLF9 expression by affecting STUB1-mediated ubiquitination degradation and KLF9 enhanced PHLPP2 expression to inactivate the AKT pathway. Eventually, rescue experiments revealed that KLF9 knockdown abolished SLC7A11-AS1 silencing-mediated suppression of HCC progression in vivo and in vitro. Our results unveiled that m6A-modified SLC7A11-AS1 promoted HCC progression by regulating the STUB1/KLF9/PHLPP2/AKT axis, indicating that targeting SLC7A11-AS1 might alleviate HCC progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Camundongos Nus , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos
8.
Sci Total Environ ; 864: 161013, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36549521

RESUMO

Phthalates (PAEs) are ubiquitous in soils and food products and thus pose a high risk to human health. Herein, genome mining revealed a great diversity of bacteria with PAEs-degrading potential. Mining of the genome of Raoultella ornithinolytica XF201, a novel strain isolated from Dongxiang wild rice rhizosphere, revealed the presence of two silenced tandem genes pcdGH (encoding protocatechuate 3,4-dioxygenase, 3,4-PCD), key aromatic ring-cleaving genes in PAEs biodegradation. Ribosome engineering was successfully utilized to activate the expression of pcdGH genes to produce 3,4-PCD in the mutant XF201-G2U5. The mutant XF201-G2U5 showed high 3,4-PCD activity and could remove 94.5 % of di-n butyl phthalate (DBP) in 72 h. The degradation kinetics obeyed the first-order kinetic model. Strain XF201-G2U5 could also degrade the other PAEs and the main intermediate metabolites, ultimately leading to tricarboxylic acid cycle. Therefore, this strategy facilitates novel bacterial resources discovery for bioremediation of PAEs and other emerging contaminants.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Humanos , Biodegradação Ambiental , Ésteres/metabolismo , Ácidos Ftálicos/metabolismo , Dibutilftalato/metabolismo
9.
BMC Surg ; 22(1): 186, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568886

RESUMO

BACKGROUNDS: High level of anion gap (AG) was associated with organic acidosis. This study aimed to explore the relationship between delta AG (ΔAG = AGmax - AGmin) during first 3 days after intensive care unit (ICU) admission and hospital mortality for patients admitted in the cardiothoracic surgery recovery unit (CSRU). METHODS: In this retrospective cohort study, we identified patients from the open access database called Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III). A logistic regression model was established to predict hospital mortality by adjusting confounding factors using a stepwise backward elimination method. We conducted receiver operating characteristic (ROC) curves to compare the diagnostic performance of acid-base variables. Cox regression model and Kaplan Meier curve were applied to predict patients' 90-day overall survival (OS). RESULTS: A total of 2,860 patients were identified. ΔAG was an independent predictive factor of hospital mortality (OR = 1.24 per 1 mEq/L increase, 95% CI: 1.11-1.39, p < 0.001). The area under curve (AUC) values of ΔAG suggested a good diagnostic accuracy (AUC = 0.769). We established the following formula to estimate patients' hospital mortality: Logit(P) = - 15.69 + 0.21ΔAG + 0.13age-0.21BE + 2.69AKF. After calculating Youden index, patients with ΔAG ≥ 7 was considered at high risk (OR = 4.23, 95% CI: 1.22-14.63, p = 0.023). Kaplan Meier curve demonstrated that patients with ΔAG ≥ 7 had a poorer 90-day OS (Adjusted HR = 3.20, 95% CI: 1.81-5.65, p < 0.001). CONCLUSION: ΔAG is a prognostic factor of hospital mortality and 90-day OS. More prospective studies are needed to verify and update our findings.


Assuntos
Equilíbrio Ácido-Base , Mortalidade Hospitalar , Bases de Dados Factuais , Humanos , Unidades de Terapia Intensiva , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Centro Cirúrgico Hospitalar , Análise de Sobrevida
10.
Zhongguo Gu Shang ; 35(2): 178-85, 2022 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-35191273

RESUMO

OBJECTIVE: To establish the fixation model of anterior cervical transpedicular system (ACTPS) after subtotal resection of two segments of lower cervical spine(C3-C7) in order to provide a finite element modeling method for anterior cervical reconstruction. METHODS: The CT data of the cervical segment (C1-T1) of a 30-year-old adult healthy male volunteer was collected. Used Mimics 10.0, Rapidform XOR3, HyperMesh 10.0, CATIA5V19 and ANSYS 14.0 to establish the three-dimensional nonlinear complete model of lower cervical spine(C3-C7) as the intact group. The number of units and nodes of the complete model were recorded. After the effectiveness of the complete model was verified, the C5 and C6 vertebral subtotal resection was performed, and the ACTPS model was established as the ACTPS group. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3 in intact group and ACTPS group, the range of motion(ROM)and stress distribution in states of flexion extension, lateral flexion, rotation was compared between two groups. RESULTS: There were 85 832 elements and 23 612 nodes in the complete model of lower cervical spine(C3-C7) which was established in this experiment. The stress distribution of ACTPS internal fixation model was relatively uniform. Comparing with the intact group, the overall range of motion in ACTPS group was decreased in flexion extension, lateral flexion and rotation directions, and the corresponding compensation of adjacent C3,4 segment was increased slightly. CONCLUSION: The stress distribution of ACTPS fixation system is uniform, there is no stress concentration area at the joint of screw and titanium plate, and the fracture risk of internal fixation is low. It is suitable for stability reconstruction after anterior decompression of two or more cervical segments.


Assuntos
Vértebras Cervicais , Fusão Vertebral , Adulto , Fenômenos Biomecânicos , Parafusos Ósseos , Vértebras Cervicais/cirurgia , Análise de Elementos Finitos , Humanos , Masculino , Amplitude de Movimento Articular
11.
Cell Biol Int ; 46(2): 213-221, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34719075

RESUMO

Sorafenib is the important first-standard drug for patients with advanced hepatocellular carcinoma (HCC). A major obstacle to successful treatment is sorafenib resistance. However, the mechanism of sorafenib resistance is unclear. The present study aimed to determine the involvement of dipeptidyl peptidase-8 (DPP8) in sorafenib resistance. DPP8 expression was detected using quantitative real-time PCR (qPCR) and western blot analysis. The effect of DPP8 on sorafenib resistance was examined using terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL), colony formation, flow cytometry, luciferase reporter, immunofluorescence, and immunoprecipitation (IP) assays. We found that DPP8 mRNA and protein levels were dramatically upregulated in HCC. Gene set enrichment analysis (GSEA) illustrated that DPP8 might be involved in apoptosis regulation. Downregulation of DPP8 substantially promoted the sensitivity of HCC cells to sorafenib. Further analysis showed that DPP8 might regulate nuclear factor kappa B (NF-κB) signaling, which was confirmed using a luciferase reporter assay. Downregulation of DPP8 decreased the expression levels of downstream genes of the NF-κB pathway. IP showed that DPP8 can interact with NF-κB subunit c-Rel, an important protein of NF-κB signaling. Finally, a drug combination of sorafenib and Val-boroPro induced higher mortality of HCC cells than sorafenib alone in DPP8-upregulated cells. Our findings indicated that using the inhibitor Val-boroPro might be a promising method to enhance sorafenib sensitivity in advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , NF-kappa B/metabolismo , Sorafenibe/farmacologia
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-928291

RESUMO

OBJECTIVE@#To establish the fixation model of anterior cervical transpedicular system (ACTPS) after subtotal resection of two segments of lower cervical spine(C3-C7) in order to provide a finite element modeling method for anterior cervical reconstruction.@*METHODS@#The CT data of the cervical segment (C1-T1) of a 30-year-old adult healthy male volunteer was collected. Used Mimics 10.0, Rapidform XOR3, HyperMesh 10.0, CATIA5V19 and ANSYS 14.0 to establish the three-dimensional nonlinear complete model of lower cervical spine(C3-C7) as the intact group. The number of units and nodes of the complete model were recorded. After the effectiveness of the complete model was verified, the C5 and C6 vertebral subtotal resection was performed, and the ACTPS model was established as the ACTPS group. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3 in intact group and ACTPS group, the range of motion(ROM)and stress distribution in states of flexion extension, lateral flexion, rotation was compared between two groups.@*RESULTS@#There were 85 832 elements and 23 612 nodes in the complete model of lower cervical spine(C3-C7) which was established in this experiment. The stress distribution of ACTPS internal fixation model was relatively uniform. Comparing with the intact group, the overall range of motion in ACTPS group was decreased in flexion extension, lateral flexion and rotation directions, and the corresponding compensation of adjacent C3,4 segment was increased slightly.@*CONCLUSION@#The stress distribution of ACTPS fixation system is uniform, there is no stress concentration area at the joint of screw and titanium plate, and the fracture risk of internal fixation is low. It is suitable for stability reconstruction after anterior decompression of two or more cervical segments.


Assuntos
Adulto , Humanos , Masculino , Fenômenos Biomecânicos , Parafusos Ósseos , Vértebras Cervicais/cirurgia , Análise de Elementos Finitos , Amplitude de Movimento Articular , Fusão Vertebral
13.
Curr Med Sci ; 41(4): 777-781, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403103

RESUMO

OBJECTIVE: Supracondylar humerus fractures are the most frequent fractures of the paediatric elbow. The present study introduced a modified surgical procedure for treatment of supracondylar humerus fractures in children. METHODS: From February 2015 to August 2019, 73 patients with Gartland's type II and III supracondylar fractures were treated with this modified method. Totally, 68 of all patients were followed up for 3-12 months (mean 8.25 months). The evaluation results included fracture nonunion, ulnar nerve injury, pin track infection, carrying angle and elbow joint Flynn score. RESULTS: The results showed that bone union was observed in all children, one case had an iatrogenic ulnar nerve injury, and the symptoms were completely relieved in 4 months after removing of the medial-side pin. All children had no cubitus varus deformity and no pin track infection, and the rate of satisfactory results according to Flynn's criteria score was 100%. CONCLUSION: The modified closed reduction and Kirschner wires internal fixation could effectively reduce the rate of open reduction, the risk of iatrogenic ulnar nerve injury, and the incidence of cubitus varus deformity in treatment of supracondylar humerus fractures in children.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Úmero/cirurgia , Procedimentos de Cirurgia Plástica , Fios Ortopédicos , Criança , Pré-Escolar , Feminino , Humanos , Fraturas do Úmero/fisiopatologia , Úmero/fisiopatologia , Masculino , Pediatria
14.
Zhongguo Gu Shang ; 34(7): 650-4, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34318642

RESUMO

OBJECTIVE: To study the changes of anterior soft tissue swelling after anterior cervical subtotal corpectomy, titanium mesh fusion and internal fixation. METHODS: From November 2015 to July 2018, 151 patients with cervical spondylotic myelopathy were treated with anterior single corpectomy, titanium mesh fusion and internal fixation, including 109 males and 42 females, aged 44 to 81 (59.77±8.34) years. Through postoperative follow up observation, the C2-C7 level of anterior intervertebral space distance was measured to evaluate the changes of anterior soft tissue swelling. RESULTS: All patients were followed up for 15 to 40(28.00±3.52) months. One week after the operation, the swelling of anterior soft tissue reached the peak, and then decreased. At 8 months after the operation, the swelling of anterior soft tissue on C5, C6 and C7 plane returned to normal. At 12 months after the operation, the swelling of anterior soft tissue on C2, C3 and C4 plane returned to normal. CONCLUSION: Anterior subtotal cervical corpectomy, titanium mesh bone graft fusion and internal fixation can cause swelling of the anterior soft tissue. One week after operation, we should pay more attention to the aggravation of the swelling of the anterior soft tissue to avoid the occurrence of dysphagia, respiratory obstruction, asphyxia and other complications.


Assuntos
Doenças da Medula Espinal , Fusão Vertebral , Espondilose , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
15.
World J Clin Cases ; 9(20): 5737-5743, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34307633

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignant epithelial tumor originating from adrenocortical cells that carries a very poor prognosis. Metastatic or inoperable diseases are often considered incurable, and treatment remains a challenge. Especially for advanced cases such as ACC complicated with renal venous cancer thrombus, there are few cumulative cases in the literature. CASE SUMMARY: The patient in this case was a 39-year-old middle-aged male who was admitted to the hospital for more than half a month due to dizziness and chest tightness. Computed tomography (CT) findings after admission revealed a left retroperitoneal malignant space-occupying lesion, but the origin of the formation of the left renal vein cancer thrombus remained to be determined. It was speculated that it originated from the left adrenal gland, perhaps a retroperitoneal source, and left adrenal mass + left nephrectomy + left renal vein tumor thrombus removal + angioplasty were performed under general anesthesia. Postoperative pathology results indicated a diagnosis of ACC. Postoperative steroid therapy was administered. At 3 mo after surgery, abdominal CT reexamination revealed multiple enlarged retroperitoneal lymph nodes and multiple low-density shadows in the liver, and palliative radiotherapy and mitotane were administered, considering the possibility of metastasis. The patient is currently being followed up. CONCLUSION: ACC is a highly malignant tumor. Even if the tumor is removed surgically, there is still the possibility of recurrence. Postoperative mitotane and adjuvant chemoradiotherapy have certain benefits for patients, but they cannot fully offset the poor prognosis of this disease.

16.
Zhongguo Gu Shang ; 34(6): 530-3, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34180172

RESUMO

OBJECTIVE: To investigate the feasibility and clinical effect of hemi-resection of posterior arch of atlas in the upper cervical spinal dumbbell-shaped schwannomas. METHODS: A retrospective analysis was performed on 13 patients with high level cervical dumbbell schwannomas from January 2005 to December 2018, including 10 males and 3 females, aged 19 to 67 years old. The occipital foramen to the C1 were 4 cases and 9 cases of C1,2. Tumors were removed by posterior arch of the atlas resection without internal fixation. The clinical efficacy was evaluated by visual analogue pain scale (VAS), Japanese Orthopaedic Association (JOA) scores, and American Spinal Injury Association(ASIA) ratings. RESULTS: The operation was successfully completed in 13 cases of this group. No vertebral artery injury or spinal cord injury occurred during the operation. All 13 patients were followed up for more than 12 months. No local recurrence was found. Both the VAS and the JOA score were significantly improved compared with those before surgery. The ASIA classification before operation was:1 case of grade C, 6 cases of grade D, 6 cases of grade E;the latest follow up was 3 cases of ASIA grade D and 10 cases of E. CONCLUSION: The posterior arch of the atlas hemisection can remove the upper cervical dumbbell schwannoma in one stage. The short-term clinical effect is good, and there are no complications such as cervical instability.


Assuntos
Vértebras Cervicais , Neurilemoma , Adulto , Idoso , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Cell Biol Int ; 45(9): 1906-1916, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33969575

RESUMO

Sorafenib was the first systemic therapy approved by the Food and Drug Administration to treat advanced hepatocellular carcinoma (HCC). However, sorafenib therapy is frequently accompanied by drug resistance. We aimed to explore the mechanisms of sorafenib resistance and provide feasible solutions to increase the response to sorafenib in patients with advanced HCC. The expression profile of discoidin domain receptor 2 (DDR2) in HCC tissues and cells was detected using quantitative real-time PCR (qPCR) and western blotting assays. The effects of DDR2 on sorafenib resistance were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, TdT-mediated dUTP nick end labeling, and flow cytometry assays. The effect of DDR2 on the nuclear factor kappa B (NF-κB) signaling pathway was evaluated by luciferase reporter, immunofluorescence, qPCR and flow cytometry assays. We demonstrated that DDR2 expression was dramatically upregulated in sorafenib-resistant HCC tissues relative to sensitive tissues. Downregulation of DDR2 sensitized HCC cell lines to sorafenib cytotoxicity. Further analysis showed that DDR2 could increase the nuclear location of REL proto-oncogene, a NF-κB subunit, to mediate NF-κB signaling. Blocking NF-κB signaling using the NF-κB signaling inhibitor, bardoxolone methyl, increased the response of HCC cells to sorafenib. Further analysis showed that DNA amplification of DDR2 is an important mechanism leading to DDR2 overexpression in HCC. Our results demonstrated that DDR2 is a potential therapeutic target in patients with HCC, and targeting DDR2 represents a promising approach to increase sorafenib sensitivity in patients with HCC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Receptor com Domínio Discoidina 2/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Zhongguo Gu Shang ; 34(4): 349-53, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33896135

RESUMO

OBJECTIVE: To explore the diagnosis, treatment, cause and prevention of nerve compression by bone fragment after lumbar spine surgery. METHODS: The clinical data of 23 patients with nerve compression by bone fragment after lumbar spine surgery from February 2012 to March 2019 were collected retrospectively, including 9 males and 14 females, aged 42 to 81 years with an average of (62.60±5.70) years. The surgical methods included lumbar interbody fusion in 20 cases and spinal endoscopy in 3 cases. All 23 patients experienced radiating pain on the decompression side or the contralateral limb after operation. The time of occurrence was from immediately after operation to 2 weeks after operation, with an average of (3.2±1.7) days. All patients underwent postoperative examination of lumbar spine CT or MRI to confirm residual ectopic bone fragments, and at the same time, bilateral lower extremity color Doppler ultrasound excluded thrombosis. Sources of ectopic bone fragments:14 cases of residual bone fragments caused by intervertebral fusion bone graft loss or fenestration fusion, 6 cases of fractured upper articular process head, and 3 cases of upper articular process bone remaining during spinal endoscopic surgery. RESULTS: The patient's hospital stay was 10 to 37 (23.4±6.2) days. All patients were followed up for 6 to 25 (13.6±3.4) months. Three patients underwent posterior open nerve root exploration for removing bone fragments on the same day or the second day after surgery, and the symptoms were relieved. Twenty patients underwent conservative treatment firstly, and 13 patients were discharged after pain relieved by conservative treatment, 7 patients failed conservative treatment, the 2 cases of failed 7 cases had undergone nerve root block surgery during conservative treatment. Two patients underwent spinal endoscopy nerve root exploration and bone mass removal, and five patients underwent posterior open nerve root exploration and bone fragmentation removal. All postoperative pain symptoms were relieved. Preoperative CT, MRI and intraoperative bone fragment removal confirmed the shape and location of the bone fragments. The most likely source of bone fragments was the loss of intervertebral fusion bone grafts or residual bone fragments resulting from fenestration fusion (14 cases), fractured upper articular process head (6 cases), and upper articular process bones remaining in endoscopic surgery (3 cases). According to the Macnab criteria in evaluating clinical outcome, 20 cases got excellent results and 3 good. CONCLUSION: After the lumbar spine surgery, the nerve compression by bone fragments is treated with appropriate treatments, and good clinical results can be obtained. Timely removal of residual bone fragments during operation and careful exploration of nerve roots before closing incision can avoid such complications.


Assuntos
Vértebras Lombares , Fusão Vertebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Descompressão Cirúrgica , Endoscopia , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
19.
Acta Pharmacol Sin ; 42(5): 832-842, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33824461

RESUMO

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/uso terapêutico , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Resinas Acrílicas/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Trióxido de Arsênio/farmacocinética , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Cetrimônio/química , Cetrimônio/toxicidade , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Camundongos Endogâmicos ICR , Nanopartículas/toxicidade , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Oligopeptídeos/toxicidade , Paclitaxel/química , Paclitaxel/farmacocinética , Porosidade , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Dióxido de Silício/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
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