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1.
J Orthop Surg Res ; 19(1): 558, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261881

RESUMO

BACKGROUND: Optimal sagittal alignment of the femoral prosthesis is critical to the success of total knee arthroplasty (TKA). While robotic-assisted TKA can improve alignment accuracy, the efficacy of default femoral alignment versus individualized alignment remains under scrutiny. This study aimed to compare the differences in prosthetic alignment, anatomical restoration, and clinical outcomes between individualized femoral sagittal alignment and default sagittal alignment in robotic-assisted TKA. METHODS: In a prospective randomised controlled trial, 113 patients (120 knees) underwent robotic-assisted TKA were divided into two groups: 61 with individualized femoral flexion (individualized alignment group) and 59 with default 3-5° flexion (default alignment group). The individualized alignment was based on the distal femoral sagittal anteverted angle (DFSAA), defined as the angle between the mechanical and distal anatomical axes of the femur. The radiographic and clinical outcomes were compared. RESULTS: Despite similar postoperative femoral flexion angles between groups (P = 0.748), the individualized alignment group exhibited significantly lower incidences of femoral prosthesis extension and higher rates of optimal 0-3° prosthesis flexion (9.8% vs. 27.1%, P = 0.014,78.7% vs. 55.9%, p = 0.008, respectively). The individualized alignment group also demonstrated more favourable changes in sagittal anatomy, with higher maintenance of postoperative anterior femoral offset within 1 mm (54.1% vs. 33.9%, P = 0.026) and posterior condylar offset within 1 mm and 2 mm (44.3% vs. 25.4%, p = 0.031,73.8% vs. 50.8%, p = 0.010, respectively). Although slight improvement in the Hospital for Special Surgery Knee Score (HSS) at three months was observed (P = 0.045), it did not reach a minimal clinically important difference. CONCLUSION: Individualized tailoring of femoral sagittal alignment in robotic-assisted total knee arthroplasty (TKA) enhances prosthetic alignment and anatomical restoration, suggesting potential improvements in postoperative outcomes.


Assuntos
Artroplastia do Joelho , Fêmur , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Feminino , Masculino , Idoso , Fêmur/cirurgia , Fêmur/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Amplitude de Movimento Articular
2.
Ann Clin Lab Sci ; 54(4): 498-503, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39293848

RESUMO

OBJECTIVE: The prevalence and the clinical significance of gastric foveolar metaplasia (GFM) of duodenal mucosa in pediatric patients are undetermined. The aim was to investigate the event of GFM in duodenal biopsies and its association with gastrointestinal tract disorders in pediatric patients. METHODS: We performed a chart review of the characteristics and pathologic findings in patients with GFM described in the pathology reports during 2020 to 2022. RESULTS: Sixty-five out of 3,857 patients (1.7%) had GFM observed in a total of 70/4,778 (1.5%) cases with duodenal biopsies. The ages ranged from 3 to 19 years. The duodenal bulb with GFM was identified in 65 out of 70 cases (92.9%). 17/70 (24.3%) biopsies had coexisting chronic duodenitis, and 52/70 (74.3%) had isolated GFM in duodenum. 48/70 (68.6%) cases had pathologic findings in other parts of the gastrointestinal tract, including 20 (28.6%) inflammatory bowel disease (IBD) and four (5.7%) H. pylori gastritis. Of all 4,778 cases, 136 (2.8%) and 92 (1.9%) cases were diagnosed as IBD and H. pylori gastritis, which had an odds ratio for GFM at 15.8 and 3.2 respectively (p<0.05). CONCLUSION: Both H. pylori gastritis and IBD are associated with GFM in pediatric patients, while isolated GFM itself in the duodenal bulb has limited clinical implications.


Assuntos
Duodeno , Mucosa Gástrica , Mucosa Intestinal , Metaplasia , Humanos , Metaplasia/patologia , Criança , Adolescente , Masculino , Feminino , Pré-Escolar , Duodeno/patologia , Mucosa Intestinal/patologia , Incidência , Mucosa Gástrica/patologia , Adulto Jovem , Infecções por Helicobacter/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Biópsia , Gastrite/patologia , Gastrite/epidemiologia , Gastrite/complicações , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia
3.
Front Mol Biosci ; 11: 1301099, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993839

RESUMO

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

4.
iScience ; 27(6): 109809, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38784013

RESUMO

Dysregulated innate immune signaling is linked to preleukemic conditions and myeloid malignancies. However, it is unknown whether sustained innate immune signaling contributes to malignant transformation. Here we show that cell-intrinsic innate immune signaling driven by miR-146a deletion (miR-146aKO), a commonly deleted gene in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), cooperates with mutant RUNX1 (RUNX1mut) to initially induce marrow failure and features of MDS. However, miR-146aKO hematopoietic stem and/or progenitor cells (HSPCs) expressing RUNX1mut eventually progress to a fatal AML. miR-146aKO HSPCs exhaust during serial transplantation, while expression of RUNX1mut restored their hematopoietic cell function. Thus, HSPCs exhibiting dysregulated innate immune signaling require a second hit to develop AML. Inhibiting the dysregulated innate immune pathways with a TRAF6-UBE2N inhibitor suppressed leukemic miR-146aKO/RUNX1mut HSPCs, highlighting the necessity of TRAF6-dependent cell-intrinsic innate immune signaling in initiating and maintaining AML. These findings underscore the critical role of dysregulated cell-intrinsic innate immune signaling in driving preleukemic cells toward AML progression.

5.
Chem Commun (Camb) ; 60(26): 3469-3483, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38444260

RESUMO

The unique high surface area and tunable cavity size endow metal-organic cages (MOCs) with superior performance and broad application in gas adsorption and separation. Over the past three decades, for instance, numerous MOCs have been widely explored in adsorbing diverse types of gas including energy gases, greenhouse gases, toxic gases, noble gases, etc. To gain a better understanding of the structure-performance relationships, great endeavors have been devoted to ligand design, metal node regulation, active metal site construction, cavity size adjustment, and function-oriented ligand modification, thus opening up routes toward rationally designed MOCs with enhanced capabilities. Focusing on the unveiled structure-performance relationships of MOCs towards target gas molecules, this review consists of two parts, gas adsorption and gas separation, which are discussed separately. Each part discusses the cage assembly process, gas adsorption strategies, host-guest chemistry, and adsorption properties. Finally, we briefly overviewed the challenges and future directions in the rational development of MOC-based sorbents for application in challenging gas adsorption and separation, including the development of high adsorption capacity MOCs oriented by adsorbability and the development of highly selective adsorption MOCs oriented by separation performance.

6.
J Orthop Surg Res ; 19(1): 124, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321464

RESUMO

BACKGROUND: Altered axial biomechanics of the knee are recognized as a risk factor for non-contact anterior cruciate ligament (ACL) injury. However, the relationship of knee and segmental torsion to non-contact ACL and combined anterolateral ligament (ALL) injury is unclear. This study aims to determine the relationship of knee and segmental torsion to non-contact ACL injury and to explore their relationship with ALL injuries. METHODS: We divided 122 patients with arthroscopically confirmed non-contact ACL injuries into an ACL injury group (isolated ACL injury, 63 patients) and an ACL + ALL injury group (ACL combined with ALL injury,59 patients). Additionally, 90 normal patients with similar age, gender and body mass index (BMI) were matched as a control group. The tibial tubercle-trochlear groove (TT-TG) distance, distal femoral torsion (DFT), posterior femoral condylar torsion (PFCT) and proximal tibial torsion (PTT) were measured using magnetic resonance imaging (MRI). We assessed the differences between the groups using an independent samples t test and utilized receiver operating characteristic (ROC) curves to determine the cut-off value for the increased risk of ACL injury. RESULTS: In patients with ACL injury, the measurements of the TT-TG (11.8 ± 3.1 mm), DFT (7.7° ± 3.5°) and PFCT (3.6° ± 1.3°) were significantly higher compared to the control group (9.1 ± 2.4 mm, 6.3° ± 2.7° and 2.8° ± 1.3°, respectively; P < 0.05), but the PTT did not differ between the two groups. The TT-TG, DFT and PFCT were not significantly larger in patients combined with ALL injury. ROC curve analysis revealed ACL injury is associated with TT-TG, DFT and PFCT. CONCLUSIONS: Knee torsional alignment is associated with ACL injury, predominantly in the distal femur rather than the proximal tibia. However, its correlation with ALL injury remains unclear. These findings may help identify patients at high risk for non-contact ACL injury and inform the development of targeted prevention and treatment strategies.


Assuntos
Lesões do Ligamento Cruzado Anterior , Doenças Ósseas , Artropatias , Humanos , Estudos de Casos e Controles , Articulação do Joelho , Joelho , Tíbia , Fêmur , Imageamento por Ressonância Magnética/métodos
7.
Scand J Gastroenterol ; 59(4): 445-455, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38053282

RESUMO

BACKGROUND: Accompanied by the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the coexistence of chronic hepatitis B (CHB) and NAFLD has increased. In the context of CHB, there is limited understanding of the factors that influence the development of NASH. METHODS: We enrolled CHB combined NAFLD patients who had liver biopsy and divided them to NASH vs. non-NASH groups. A whole transcriptome chip was used to examine the expression profiles of long noncoding RNAs (lncRNAs) and mRNA in biopsied liver tissues. The function analysis of HIGD1A were performed. We knocked down or overexpressed HIGD1A in HepG2.2.15 cells by transient transfection of siRNA-HIGD1A or pcDNA-HIGD1A. In vivo investigations were conducted using hepatitis B virus (HBV) transgenic mice. RESULTS: In 65 patients with CHB and NAFLD, 28 were patients with NASH, and 37 were those without NASH. After screening 582 differentially expressed mRNAs, GO analysis revealed differentially expressed mRNAs acting on nicotinamide adenine dinucleotide phosphate (NADPH), which influenced redox enzyme activity. KEGG analysis also shown that they were involved in the NAFLD signaling pathway. The function analysis revealed that HIGD1A was associated with the mitochondrion. Then, both in vivo and in vitro CHB model, HIGD1A was significantly higher in the NASH group than in the non-NASH group. HIGD1A knockdown impaired mitochondrial transmembrane potential and induced cell apoptosis in HepG2.2.15 cells added oleic acid and palmitate. On the contrary, hepatic HIGD1A overexpression ameliorated free fatty acids-induced apoptosis and oxidative stress. Furthermore, HIGD1A reduced reactive oxygen species (ROS) level by increasing glutathione (GSH) expression, but Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) pathway was not involved. CONCLUSION: Both in vivo and in vitro CHB model, an upward trend of HIGD1A was observed in the NASH-related inflammatory response. HIGDIA played a protective role in cells against oxidative stress. Our data suggested that HIGD1A may be a positive regulator of NASH within the CHB context.


Assuntos
Hepatite B Crônica , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatite B Crônica/complicações , Fígado/patologia , Vírus da Hepatite B/genética , Espécies Reativas de Oxigênio/metabolismo
8.
Arch Biochem Biophys ; 748: 109784, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37816420

RESUMO

Bone is a preferred metastatic site of prostate cancer (PCa), and most patients with PCa metastases develop osteogenic bone metastasis, which manifests as disturbed bone structure and poor bone quality. However, the underlying mechanisms of PCa bone metastasis remain unclear. In recent years, increasing evidence has implicated extracellular vesicles, especially exosomes, in PCa bone metastasis. Exosomes are 30-150 nm in diameter, enclosing a cargo of biomolecules, such as DNA, RNA, and proteins. Exosomes play a functional role in intercellular communication, modulate the functions of recipient cells, and potentially modulate bone microenvironment changes, thereby influencing the development of PCa bone metastasis. This review summarizes the involvement of exosomes in the imbalance between bone resorption and formation, and establishing a pre-metastatic niche in bone marrow, as well as potential clinical applications of exosomes in therapeutic strategies for treating patients with advanced PCa with bone metastasis.


Assuntos
Neoplasias Ósseas , Exossomos , Vesículas Extracelulares , Neoplasias da Próstata , Masculino , Humanos , Exossomos/metabolismo , Neoplasias da Próstata/patologia , Neoplasias Ósseas/patologia , Comunicação Celular , Vesículas Extracelulares/metabolismo , Microambiente Tumoral , Metástase Neoplásica
9.
Artigo em Inglês | MEDLINE | ID: mdl-37611884

RESUMO

In photoperiod-sensitive wild animals, the secretion of melatonin (MT) is modulated by external photoperiod, and MT affects inflammation and the ageing process. The beneficial effects of MT in delaying the progress of ageing have been reported in laboratory mice and rats. However, little is known about MT in wild mammals. In the current study, we investigated energy metabolism, microbial community structure and colon homeostasis in ageing Mongolian gerbils (Meriones unguiculatus) through exogenous supplementation of MT to test the hypothesis that MT has beneficial effects on gut homeostasis in ageing gerbils. Exogenous MT supplementation had no effect on energy metabolism in Mongolian gerbils but reduced the levels of circulating tumor necrosis factor-α (TNF-α), immune globulin G (IgG) and corticosterone (CORT). The increase in the level of inflammation in ageing animals was related to changes in the structure and diversity of the gut microbiota. At the genus level, the relative abundance of Prevotella, Treponema, Corynebacterium, and Sphingomonas was increased in ageing animals and decreased significantly by the treatment of MT. Christensenella and Lactobacillus were attenuated in ageing animals, and tended to be enhanced by MT treatment. Functions related to glycosphingolipid biosynthesis-ganglio series and lipopolysaccharide biosynthesis (metabolisms of cofactors, vitamins and glycan) were increased in ageing animals and decreased significantly by the treatment of MT. Our data suggest that a supplement of MT could improve colon homeostasis through changing the composition of gut microbiota and reducing inflammation in ageing gerbils.


Assuntos
Melatonina , Camundongos , Animais , Ratos , Gerbillinae , Melatonina/farmacologia , Inflamação/tratamento farmacológico , Metabolismo Energético , Colo , Envelhecimento
10.
Front Immunol ; 14: 1213285, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37503351

RESUMO

HPV (Human papillomavirus) affects 600,000 people worldwide each year. Almost all cervical cancers are associated with a past HPV infection. In particular, the positivity to the high-risk type HPV16 is detected in most of the invasive cervical cancers. FDA has approved prophylactic vaccines that protect against new HPV16 infections, but do not induce immunity in those patients with established infections or neoplasms. To date, no therapeutic vaccine targeting HPV16-associated lesions has been authorized. We have developed an mRNA-based vaccine against the HPV16 late oncoproteins E6 and E7, which are abundantly and exclusively expressed in high-grade squamous intraepithelial lesions (HSILs), a stage of the cervical disease that precedes the progression to carcinoma. Our in vitro and in vivo studies demonstrated that the translated mRNA is functional and elicits an antigen-specific adaptive immune response. Upon immunization with the vaccine, mice with HPV16+ lesions exhibited tumor growth inhibition, extension of lifespan, and development of a protective immune memory. In light of these results and the remarkable clinical success of mRNA vaccines against SARS-CoV2, we believe that our mRNA-based therapeutic vaccine has the potential to offer a non-invasive treatment alternative to the current standard of care for HPV16+ HSILs.


Assuntos
COVID-19 , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Animais , Camundongos , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/patologia , Papillomavirus Humano 16/genética , RNA Viral , COVID-19/complicações , SARS-CoV-2/genética , Papillomavirus Humano , RNA Mensageiro/genética
11.
Animals (Basel) ; 13(13)2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37443863

RESUMO

Pain assessment in domestic animals has gained importance in recent years due to the recognition of the physiological, behavioral, and endocrine consequences of acute pain on animal production, welfare, and animal model validity. Current approaches to identifying acute pain mainly rely on behavioral-based scales, quantifying pain-related biomarkers, and the use of devices monitoring sympathetic activity. Infrared thermography is an alternative that could be used to correlate the changes in the superficial temperature with other tools and thus be an additional or alternate acute pain assessment marker. Moreover, its non-invasiveness and the objective nature of its readout make it potentially very valuable. However, at the current time, it is not in widespread use as an assessment strategy. The present review discusses scientific evidence for infrared thermography as a tool to evaluate pain, limiting its use to monitor acute pain in pathological processes and invasive procedures, as well as its use for perioperative monitoring in domestic animals.

12.
Obes Facts ; 16(5): 427-434, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37231905

RESUMO

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-lean patients is significantly increased, and obesity significantly increases the risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference in clinical manifestations of NAFLD between overweight and obesity remains unclear. The objective of this study was to assess the clinical and histological features of NAFLD among a non-lean population. METHODS: Current study enrolled consecutive non-lean (body mass index [BMI] >23 kg/m2) patients with NAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23∼<28 kg/m2) and the obese (BMI ≥28 kg/m2). Risk factors for moderate to severe fibrosis (stage >1) were also analyzed through the logistic regression model. RESULTS: Among 184 non-lean patients with metabolic-associated fatty liver disease enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-glutamyl transpeptidase, higher levels of platelet, glucose, prothrombin time, and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group versus the overweight group (19.33% vs. 40.00%, p = 0.002). Binary logistics regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT), and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with NAFLD. Compared with the traditional fibrosis-4 (AUC = 0.77) and aminotransferase to platelet ratio index (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT, and CHOL was more accurate in predicting moderate to severe fibrosis in non-lean patients with NAFLD (AUC = 0.87). CONCLUSIONS: Clinical and histological features differed between obesity and overweight patients with NAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT, and CHOL provided a better model to predict moderate to severe fibrosis in non-lean patients with NAFLD.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Sobrepeso/complicações , Carcinoma Hepatocelular/complicações , Neoplasias Hepáticas/complicações , Obesidade/complicações , Cirrose Hepática/complicações , Fibrose , Índice de Massa Corporal
13.
Int J Clin Exp Pathol ; 16(2): 32-39, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910892

RESUMO

OBJECTIVES: Diagnosis of angiomatoid fibrous histiocytoma (AFH) can be challenging due to its variable histologic features and a lack of highly sensitive and/or specific immunohistochemical markers. The utility of TLE1 and BCOR as immunohistochemical markers for AFH is not known. METHODS: We examined the spectrum of histologic features of 36 AFHs, and studied the expression of both TLE1 and BCOR in AFH and its mimics by immunohistochemical staining. Positive nuclear expression was scored semiquantitatively. RESULTS: Both typical and unusual histologic features of AFHs were observed in this cohort. TLE1 was moderately to strongly positive in 36/36 AFHs, 4/4 synovial sarcomas, and 2/3 BCOR sarcomas; weakly positive in 4/6 inflammatory myofibroblastic tumors; negative in all dermatofibromas (n = 10), atypical fibrous histiocytomas (n = 5), myofibroma (n = 2) and juvenile xanthogranulomas (n = 5), with an overall sensitivity of 100%, and specificity of 71.4% for AFH. BCOR was moderately to strongly positive in 24/36 AFHs, 4/4 synovial sarcomas, 3/3 BCOR sarcomas, and 1/5 atypical fibrous histiocytomas; weakly positive in 10/36 AFHs; negative in the remaining tumors. The overall sensitivity and specificity of BCOR for AFH were 94.4% and 77.1%, respectively. CONCLUSIONS: TLE1 is a highly sensitive immunohistochemical marker for AFH.

15.
Int J Surg Case Rep ; 96: 107336, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35753231

RESUMO

Introduction: Hybrid lesions of intralobar sequestration (ILS) associated with congenital pulmonary airway malformation (CPAM) is rare and could be undetected by prenatal ultrasound. Some of the cases are discovered incidentally or following lung infection in late childhood or adulthood. Case presentation: 17-year-old female developed chest pain, non-productive cough, low grade fever, and sore throat several weeks following SARS-CoV-2 infection. CT angiogram revealed a large lobulated cystic mass with celiac arterial supply in the posterior right lower lobe that was diagnostic for pulmonary sequestration. Gradually she recovered from all respiratory symptoms after a course of multiple antibiotic treatment for symptom relief. In order to prevent recurrent infection and malignancy, she underwent right lower lung mass resection approximately 3 months later. Discussion and conclusion: Pathological examination confirmed a hybrid lesion of ILS with mixed features of CPAM type I and type II. The hallmark morphological features of SARS-CoV-2 infection were not identified except for those of superimposed acute and chronic bronchopneumonia, abscesses formation and fibrosis within the lesion. This is the first case report of a hybrid lesion of ILS associated with CPAM type I and type II, unmasked following SARS-CoV-2 infection. By using the term of hybrid lesion to report this case is to efficiently correlate the terminology and nomenclature applied in the literature currently for multidisciplinary communication between radiology, pulmonary, surgery and pathology.

16.
Int J Mol Sci ; 24(1)2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36613791

RESUMO

Skeletal muscle-based nonshivering thermogenesis (NST) plays an important role in the regulation and maintenance of body temperature in birds and large mammals, which do not contain brown adipose tissue (BAT). However, the relative contribution of muscle-based NST to thermoregulation is not clearly elucidated in wild small mammals, which have evolved an obligate thermogenic organ of BAT. In this study, we investigated whether muscle would become an important site of NST when BAT function is conditionally minimized in Brandt's voles (Lasiopodomys brandtii). We surgically removed interscapular BAT (iBAT, which constitutes 52%~56% of total BAT) and exposed the voles to prolonged cold (4 °C) for 28 days. The iBAT-ablated voles were able to maintain the same levels of NST and body temperature (~37.9 °C) during the entire period of cold acclimation as sham voles. The expression of uncoupling protein 1 (UCP1) and its transcriptional regulators at both protein and mRNA levels in the iBAT of cold-acclimated voles was higher than that in the warm group. However, no difference was observed in the protein or mRNA levels of these thermogenesis-related markers except for PGC-1α in other sites of BAT (including infrascapular region, neck, and axilla) between warm and cold groups either in sham or iBAT-ablated voles. The iBAT-ablated voles showed higher UCP1 expression in white adipose tissue (WAT) than sham voles during cold acclimation. The expression of sarcolipin (SLN) and sarcoplasmic endoplasmic reticulum Ca2+-dependent adenosine triphosphatase (SERCA) in skeletal muscles was higher in cold than in warm, but no alteration in phospholamban (PLB) and phosphorylated-PLB (P-PLB) was observed. Additionally, there was increased in iBAT-ablated voles compared to that in the sham group in cold. Moreover, these iBAT-ablated voles underwent extensive remodeling of mitochondria and genes of key components related with mitochondrial metabolism. These data collectively indicate that recruitment of skeletal muscle-based thermogenesis may compensate for BAT impairment and suggest a functional interaction between the two forms of thermogenic processes of iBAT and skeletal muscle in wild small mammals for coping cold stress.


Assuntos
Tecido Adiposo Marrom , Temperatura Baixa , Animais , Aclimatação/fisiologia , Tecido Adiposo Marrom/metabolismo , Arvicolinae/genética , Músculo Esquelético/metabolismo , RNA Mensageiro/metabolismo , Termogênese/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
17.
Int J Lab Hematol ; 43(5): 1117-1122, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33847065

RESUMO

INTRODUCTION: Infantile leukemia encompasses a heterogeneous group which needs stratifying for treatment selection. METHODS: We collected 78 cases of infantile leukemia and retrospectively analyzed their clinicopathological data. RESULTS: Infantile leukemia featured a ratio of acute myeloid leukemia (AML) to B-lymphoblastic leukemia (B-ALL) of 1:2, with a better survival for AML than B-ALL (median survival 36 vs 24 months). When stratified by age, "early" infantile B-ALL (2-6 months) showed a high rate of KMT2A rearrangement (100%), similar to the rate seen in congenital B-ALL (1 month) (100%) and higher than seen in "late" infantile B-ALL (≥7 months) (68%). The three categories of infantile B-ALL exhibited an age-dependent increase in survival (median survival 8.5, 24, and >24 months, respectively). The age-dependent survival benefit remained after excluding the cases negative for KMT2A rearrangement. Conversely, infantile AML lacked an age-dependent pattern of survival. CONCLUSION: The clinical outcome of infantile leukemia depends on the type of leukemia. Given the age-dependent survival, infantile B-ALL can be divided into three subcategories.


Assuntos
Leucemia Mieloide Aguda/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Feminino , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Humanos , Lactente , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Masculino , Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Estudos Retrospectivos
18.
Virus Res ; 298: 198405, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33775752

RESUMO

BACKGROUND/AIMS: To identify the inflammatory damage caused by chronic hepatitis B (CHB) in patients of chronic hepatitis B virus (HBV) infection complicated with non-alcoholic fatty liver disease (NAFLD), then guiding clinicians to carry out antiviral treatment. METHODS: According to the pathological features of liver biopsy, treatment-naïve obese patients of chronic HBV infection complicated with NAFLD who had elevated alanine transaminase (ALT) were divided into CHB group and NASH group. Transcriptome chips were used to analyze the expression profiles of long non-coding RNA (lncRNA) and mRNA in liver puncture tissues from the two groups. The chip data of CHB and NASH groups were analyzed for differential expression analysis, gene function analysis, signal pathway analysis, target gene prediction and competing endogenous RNAs (ceRNA) network analysis. RESULTS: By comparing CHB group with NASH group, a total of 44 differentially expressed lncRNAs and 567 differentially expressed mRNAs were screened. GO analysis predicted that the differentially expressed mRNAs may affect monooxygenase activity and oxidoreductase activity. KEGG analysis predicted that the differentially expressed mRNAs may be related to signaling pathways involved in oxidative phosphorylation, phagosomes, and NAFLD. Differential analysis of lncRNA shown that the expression of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in CHB group was significantly upregulated. Subsequently, through target gene prediction and ceRNA network analysis, we found thioredoxin interacting protein (TXNIP), which was significantly upregulated in the CHB group and had a ceRNA relationship with MALAT1. It is predicted that there may be a ceRNA regulation relationship of MALAT1/hsa-miR- 20b-5p/TXNIP. CONCLUSION: The MALAT1/hsa-miR-20b-5p/TXNIP axis may mediate CHB-induced inflammatory damage in chronic HBV infection complicated with NAFLD, and the mechanism may be related to the activation of NLRP3 inflammatory bodies and downstream inflammatory responses.


Assuntos
Proteínas de Transporte , Hepatite B Crônica , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , RNA Longo não Codificante , Proteínas de Transporte/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/genética , Humanos , Inflamação , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Longo não Codificante/genética , RNA Mensageiro/genética
19.
Sci Rep ; 11(1): 2183, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500467

RESUMO

Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of intermediate malignancy. Treatment options for unresectable and/or metastatic tumors are very limited. Immunotherapy with PD-1/PD-L1 inhibitors may be worth exploring. The aim of this study was to evaluate the expression of PD-L1 in AFHs. PD-L1 expression was assessed on 36 AFHs from 36 pediatric patients by immunohistochemical staining of PD-L1 (clone 22C3). Positivity was defined as membranous expression in ≥ 1% of either tumor or immune cells. The correlations between PD-L1 expression and clinicopathologic features were assessed. Two patients had lymph node metastasis. All patients underwent surgical resection; three of them also had systemic chemotherapy. Three patients had recurrence after initial resection; all patients were alive with a median follow-up of 2.5 years. Overall, twenty-two (61%) tumors were positively stained for PD-L1 and positivity was seen on both tumor and immune cells in eighteen of the 22 tumors. A positive correlation was found between tumor cell PD-L1 expression and CD8+ T-cell infiltration. There were no statistically significant differences between the status of PD-L1 expression and the clinicopathological features assessed. PD-L1 expression was identified in 61% of AFHs with a predominantly adaptive pattern. Our findings provide a rationale for future studies evaluating the potential of checkpoint immunotherapy for patients with unresectable and/or metastatic tumor.


Assuntos
Antígeno B7-H1/metabolismo , Histiocitoma Fibroso Maligno/metabolismo , Adolescente , Linfócitos T CD8-Positivos/imunologia , Criança , Pré-Escolar , Feminino , Histiocitoma Fibroso Maligno/imunologia , Histiocitoma Fibroso Maligno/patologia , Humanos , Leucócitos/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Masculino
20.
World J Clin Cases ; 9(35): 10909-10918, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-35047601

RESUMO

BACKGROUND: Thumb polydactyly is one of the most common congenital hand deformities, and the Bilhaut-Cloquet procedure or a modified one is often used. However, controversy remains over the rare instances in which both thumbs are not of similar length or far apart in distance. AIM: To evaluate the clinical outcomes of pedicle complex tissue flap transfer in the treatment of duplicated thumbs with unequal size. METHODS: From January 2014 to December 2020, 15 patients underwent duplicated thumb reconstruction by pedicle complex tissue flap transfer at our hand surgery center. The technique was used when it was necessary to combine different tissues from both severed and preserved thumbs that were not of similar length or far apart in distance. Subjective parents' evaluations and functional outcomes (ALURRA and TATA criteria) were obtained. The alignment deviation, instability, range of motion (percent of opposite thumb) of the interphalangeal and metacarpophalangeal joints, and the aesthetic aspects, including circumference, length, nail size, and nail deformity, were used to assess the clinical outcomes. RESULTS: The average age of patients at the time of surgery was 13 mo, and the mean final follow-up occurred at 42 mo. An appropriate volume with a stable joint and good appearance was obtained in 14 reconstructed thumbs. An unstable interphalangeal joint occurred in one thumb. The flexion-extension arc at the metacarpophalangeal joint was good, while that at the interphalangeal joint was poor. Most of the parents were satisfied with the cosmetic and functional results of the reconstructed thumbs. The mean ALURRA score was 21.8 (range: 20-24), and the Tada score was 6.9 (range: 5-8). Compared with the non-operated side, the length of the operated thumb was approximately 95%, the girth was 89%, and the nail width was 82.9%. The mean ranges of motion were 62.1% of that of the unaffected thumb in the interphalangeal joint and 78.3% in the metacarpophalangeal joint. CONCLUSION: Harvesting a pedicle flap from a severed thumb is a safe and reliable procedure. Defects of the preserved thumb, such as the skin, nail, and bone, can be effectively restored using the complex tissue flap.

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