RESUMO
OBJECTIVE: Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra-articular chitosan injection for KOA in patients with abnormal body weight. METHODS: Patients with stage II-III KOA (Kellgren-Lawrence rating, K-L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra-articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low-weight-non-injection (Lw-N, BMI <18.5); low-weight-chitosan injection (Lw-CS, BMI <18.5); overweight-non-injection (Ow-N, BMI ≥25); overweight-chitosan injection (Ow-CS, BMI ≥25). A 2-year follow-up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non-parametric tests. RESULTS: In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2-year follow-up period was significantly higher in the Ow-CS group (20/35) than in the Lw-CS group (12/39) (p < 0.05). The K-L rating showed an overall increasing trend over time, with the K-L rating in the Ow-N and Ow-CS groups significantly higher than that in the Lw-CS group at the final follow-up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post-arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra-articular chitosan injection groups (Lw-CS and Ow-CS) compared with the non-injection groups (Lw-N and Ow-N). VAS was lower in the Ow-CS group than in the Lw-CS group (p < 0.05). There was no significant difference in WOMAC between the intra-articular chitosan injection and non-injection groups at each time point (Lw-N vs. Lw-CS, Ow-N vs. Ow-CS, p > 0.05). CONCLUSION: Arthroscopic surgery combined with intra-articular chitosan injection shows short-term positive effects in treating KOA. Intra-articular chitosan injection appears to have a greater short-term pain relief effect in obese patients.
Assuntos
Artroscopia , Quitosana , Osteoartrite do Joelho , Humanos , Quitosana/administração & dosagem , Osteoartrite do Joelho/cirurgia , Artroscopia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Injeções Intra-Articulares , Idoso , Medição da Dor , Índice de Massa Corporal , Terapia CombinadaRESUMO
BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: 60 patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), VAS, WOMAC scoring, and AKS scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the pre-surgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced a slightly more pronounced decline in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.
RESUMO
Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts individuals and healthcare systems worldwide. However, the exploration of N6-methyladenosine (m6A)-related aging genes in OA pathogenesis remains largely underexplored. This study aimed to elucidate the role of m6A-related aging genes in OA and to develop a robust diagnostic model based on their expression profiles. Leveraging publicly available gene expression datasets, we conducted consensus clustering to categorize OA into distinct subtypes, guided by the expression patterns of m6A-related aging genes. Utilizing XGBoost, a cutting-edge machine learning approach, we identified key diagnostic genes and constructed a predictive model. Our investigation extended to the immune functions of these genes, shedding light on potential therapeutic targets and underlying regulatory mechanisms. Our analysis unveiled specific OA subtypes, each marked by unique expression profiles of m6A-related aging genes. We pinpointed a set of pivotal diagnostic genes, offering potential therapeutic avenues. The developed diagnostic model exhibited exceptional capability in distinguishing OA patients from healthy controls. To corroborate our computational findings, we performed quantitative real-time polymerase chain reaction analyses on two cell lines: HC-OA (representing adult osteoarthritis cells) and C-28/I2 (representative of normal human chondrocytes). The gene expression patterns observed were consistent with our bioinformatics predictions, further validating our initial results. In conclusion, this study underscores the significance of m6A-related aging genes as promising biomarkers for diagnosis and prognosis, as well as potential therapeutic targets in OA. Although these findings are encouraging, further validation and functional analyses are crucial for their clinical application.
Assuntos
Neoplasias , Osteoartrite , Adulto , Humanos , Adenina , Envelhecimento/genética , Osteoartrite/diagnóstico , Osteoartrite/genéticaRESUMO
BACKGROUND: Polycystic kidney disease is the most common hereditary kidney disorder with early and frequent hypertension symptoms. The mechanisms of cyst progression in polycystic kidney disease remain incompletely understood. METHODS: Bsg (basigin) heterozygous and homozygous knockout mice were generated using cas9 system, and Bsg overexpression was achieved by adeno-associated virus serotype 9 injection. Renal morphology was investigated through histological and imaging analysis. Molecular analysis was performed through transcriptomic profiling and biochemical approaches. RESULTS: Bsg-deficient mice exhibited significantly elevated arterial blood pressure. Further investigation demonstrated that Bsg deficiency triggers spontaneous cystic formation in mouse kidneys, which shares similar cyst pathological features and common transcriptional regulatory pathways with human polycystic kidney disease. Moreover, Bsg disruption promoted polycystin-1 ubiquitination and degradation, leading to activation of polycystic kidney disease associated cAMP and AMPK signaling pathways in Bsg knockout mouse kidneys. Finally, adeno-associated virus serotype 9 mediated Bsg reexpression reversed cystic progression in Bsg knockout mice in vivo, and Bsg overexpression inhibited the expansion of Madin-Darby canine kidney cysts in vitro. CONCLUSIONS: Our findings show that Bsg deficiency leads to an early-onset spontaneous polycystic kidney phenotype, suggesting that dysregulated Bsg signaling may be a contributing factor in cystogenesis.
Assuntos
Cistos , Doenças Renais Policísticas , Animais , Cães , Humanos , Camundongos , Basigina/genética , Basigina/metabolismo , Cistos/metabolismo , Cistos/patologia , Rim/metabolismo , Camundongos Knockout , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/metabolismoRESUMO
Background: Acute myocardial infarction (AMI) poses a significant threat to cardiovascular diseases (CVDs), leading to a high risk of heart failure (HF) and cardiovascular death. Growing evidence has unveiled the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors to improve cardiovascular outcomes in patients with CVD regardless of diabetes, but there is limited evidence in AMI patients. Furthermore, it is controversial whether the effects can be ascribed to the amelioration of left ventricular (LV) function, which further complicates the understanding of their underlying mechanism. Methods: This study is a prospective, phase IV, open-label, parallel group, single-center trial conducted in a large tertiary teaching hospital in China. A total of 120 patients with AMI and type 2 diabetes mellitus (T2DM) will be included. Those who received SGLT2 inhibitors are considered as the experimental group, and those taking other antidiabetic agents are considered as the control group. The primary outcome is change in LV end-systolic volume index (LVESVi) measured by cardiac magnetic resonance (CMR) imaging from baseline during 1-year follow-up period. Secondary outcomes include other LV parameters such as LV mass, LV volume, and LV ejection fraction (EF); quality of life and functional capacity such as Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) and EuroQol-5 dimension (EQ-5D); biomarkers associated with diagnostic parameters of AMI and possible mechanisms on cardiovascular protection, such as creatine kinase, troponin T (TnT) level, troponin I (TnI) level, soluble suppression of tumorigenicity-2 (sST2), galectin-3 (Gal-3), fibroblast growth factor 21 (FGF21), and microRNA (miRNA) level. Discussion: This study aims to investigate whether SGLT2 inhibitors could improve LV function by measuring CMR, quality of life, and functional capacity in patients with AMI in real-world settings, providing evidence on the underlying mechanism of SGLT2 inhibitors on cardioprotection. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=173672, identifier ChiCTR2200065792.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Estudos Prospectivos , Qualidade de Vida , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.
Assuntos
Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Coração , Imageamento por Ressonância Magnética , Função Ventricular Esquerda , Volume Sistólico , Remodelação Ventricular , Valor Preditivo dos TestesRESUMO
PURPOSE: The purpose of this study was to predict the probability of postoperative pulmonary infection in elderly patients with hip fractures by developing and validating a precise model. METHODS: The clinical data of 1008 elderly hip fracture patients undergoing surgical treatment in Shanghai Tenth Peoples' Hospital were retrospectively selected. A univariate analysis and multivariate regression were used to analyze the independent risk factors for postoperative pulmonary infection in elderly patients with hip fractures. A risk prediction model was established, and a nomogram was drawn. The area under the ROC curve and HosmerâLemeshow test were used to evaluate the predictive effect of the model. RESULTS: The multivariate regression analysis indicated that age > 73, time from fracture to surgery (d) > 4 days, smoking, ASA ≥ III level, COPD, hypoproteinemia, red cell distribution width > 14.8%, mechanical ventilation time > 180 min, and stay in the ICU were independent risk factors for postoperative pulmonary infection in elderly patients. The AUCs of the model were 0.891 and 0.881, 0.843, respectively, in the two verification groups. For the HosmerâLemeshow test, the P values were 0.726 in the modeling group and 0.497 and 0.231 in the verification group (P > 0.05). CONCLUSION: Overall, this study uncovered different independent risk factors for postoperative pulmonary infection in patients with hip fractures. The nomogram can effectively predict the occurrence of postoperative pulmonary infection.
Assuntos
Fraturas do Quadril , Pneumonia , Humanos , Idoso , Nomogramas , Estudos Retrospectivos , China , Fraturas do Quadril/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Background: Total knee arthroplasty is currently a reliable treatment for end-stage knee osteoarthritis. However, chronic postsurgical pain (CPSP) is substantially thought to reduce patient satisfaction. NSAID-based oral analgesics were used to manage CPSP, but research on the duration of postoperative analgesic use (DAU) and prolonged analgesic use (PAU) are presently scarce. Methods: Preoperative, perioperative, and one-year or above postoperative follow-up data were collected from 162 patients who underwent total knee arthroplasty between 1 June 2018 and 1 March 2019, and the DAU and the discontinuation time of each patient after discharge were recorded. Observational statistical analysis, diagnostic test, and predictive nomogram construction were performed on the collected data. Results: The 3-month DAU has good diagnostic utility for poor outcome of postoperative months twelve (POM12). The constructed nomogram shows that gender, preoperative Numeric Rating Scale (NRS) movement pain scores, duration of surgery, postoperative days three (POD3) moderate to severe movement pain, and POD3 pain rescue medication were significant prognostic predictors of PAU after discharge. The area under the curve (AUC) of the 3-month, 6-month, and 12-month nomogram receiver operating characteristic (ROC) curves were calculated to be 0.741, 0.736, and 0.781. Conclusion: PAU was defined as more than three months of NSAID-based oral analgesic use after TKA. Prognostic predictors of PAU after TKA were identified, and visualized nomogram was plotted and evaluated. The evaluation indicated that the prediction model had the good predictive ability and was a valuable tool for predicting PAU after discharge.
RESUMO
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a multifactorial disease, and agnogenic ONFH, otherwise known as idiopathic ONFH, is rare in clinic. Idiopathic ONFH that exhibits severe necrosis and progresses extremely rapidly is called rapidly destructive hip disease (RDHD). RDHD greatly affects patients but is rarely reported in clinical practice and literature. CASE PRESENTATION: In this study, a 64-year-old male patient with complete collapse and necrosis of the right femoral head complicated with severe bone destruction at 10 months after left total hip arthroplasty (THA) was reported. The period from the intact structure of the right femoral head to the first discovery of its complete collapse, according to imaging results, was 7 months. The duration from the occurrence of symptoms in the right hip joint to the first discovery of complete collapse and necrosis of the femoral head was only 5 months. At present, the cause has not been determined based on medical history, symptoms, signs, imaging evaluation results, laboratory examination results, and pathological examination results, though it has been identified as severe idiopathic aseptic necrosis of the femoral head with rapid progression, or RDHD. Finally, right THA was performed, and a good outcome was observed in the patient at present. CONCLUSIONS: As a rare hip joint disease, RDHD greatly influences the normal life of patients. RDHD of the contralateral side after unilateral THA is even scarcer. Left THA may be one of the important factors accelerating the necrosis of the right femoral head. Hopefully, with this case report, more attention will be paid to the contralateral hip joint in patients undergoing unilateral THA by clinicians and rehabilitation physicians, and a clinical reference will be provided for the research on RDHD.
Assuntos
Artroplastia de Quadril , Necrose da Cabeça do Fêmur , Osteoartrite do Quadril , Artroplastia de Quadril/métodos , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Full-dose prednisone (FP) regimen in the treatment of high-risk immunoglobulin A nephropathy (IgAN) patients, is still controversial. The pulsed intravenous methylprednisolone combined with alternative low-dose prednisone (MCALP) might have a more favorable safety profile, which has not been fully investigated. Eighty-seven biopsy-proven IgAN adult patients and proteinuria between 1 and 3.5 g/24 h after ACEI/ARB for at least 90 days were randomly assigned to 6-month therapy: (1) MCALP group: 0.5 g of methylprednisolone intravenously for three consecutive days at the beginning of the course and 3rd month respectively, oral prednisone at a dose of 15 mg every other day for 6 months. (2) FP group: 0.8-1.0 mg/kg/days of prednisone (maximum 70 mg/day) for 2 months, then tapered by 5 mg every 10 days for the next 4 months. All patients were followed up for another 12 months. The primary outcome was complete remission (CR) of proteinuria at 12 months. The percentage of CR at 12th and 18th month were similar in the MCALP and FP groups (51% vs 58%, P = 0.490, at 12th month; 60% vs 56%, P = 0.714, at 18th month). The cumulative dosages of glucocorticoid were less in the MCALP group than FP group (4.31 ± 0.26 g vs 7.34 ± 1.21 g, P < 0.001). The analysis of the correlation between kidney biopsy Oxford MEST-C scores with clinical outcomes indicated the percentages of total remission was similar between two groups with or without M1, E1, S1, T1/T2, and C1/C2. More patients in the FP group presented infections (8% in MCALP vs 21% in FP), weight gain (4% in MCALP vs 19% in FP) and Cushing syndrome (3% in MCALP vs 18% in FP). These data indicated that MCALP maybe one of the choices for IgAN patients with a high risk for progression into ESKD.Trial registration: The study approved by the Chinese Clinical Trial Registry (registration date 13/01/2018, approval number ChiCTR1800014442, https://www.chictr.org.cn/ ).
Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Prednisona/administração & dosagem , Proteinúria/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adulto , Progressão da Doença , Redução da Medicação , Quimioterapia Combinada , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/imunologia , Glucocorticoides/efeitos adversos , Humanos , Falência Renal Crônica/imunologia , Falência Renal Crônica/prevenção & controle , Masculino , Metilprednisolona/efeitos adversos , Prednisona/efeitos adversos , Estudos Prospectivos , Proteinúria/diagnóstico , Proteinúria/imunologia , Pulsoterapia , Indução de Remissão , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
CD147, also known as EMMPRIN or basigin, is a transmembrane glycoprotein receptor that activates matrix metalloproteinases and promotes inflammation. CD147 function is regulated by posttranslational modifications of which glycosylation has attracted the most attention. In this study, we demonstrated that glycosylated CD147 was the dominant form in heart tissue, and its levels were markedly elevated in response to transverse aortic constriction (TAC). Adeno-associated virus 9-mediated, cardiac-specific overexpression of wild-type CD147 in mice significantly promoted pressure overload-induced pathological cardiac remodeling accompanied by augmented oxidative stress and ferroptosis. By contrast, mutations of CD147 glycosylation sites notably weakened these detrimental effects of CD147. Mechanistically, CD147 exacerbated TAC-induced pathological cardiac remodeling via direct binding with the adaptor molecule TRAF2 and subsequent activation of TAK1 signalling, which was dependent on glycosylation of CD147. Collectively, our findings provide the first evidence that CD147 promoted pathological cardiac remodeling and dysfunction in a glycosylation-dependent manner through binding the adaptor protein TRAF2 and activating the downstream TRAF2-TAK1 signalling pathway. Thus, glycosylation of CD147 may be a potent interventional target for heart failure treatment.
Assuntos
Basigina/efeitos adversos , Cardiomegalia/fisiopatologia , Animais , Glicosilação , Humanos , Masculino , CamundongosRESUMO
BACKGROUND: Acromial anatomy has been found to be correlated with degenerative full-thickness rotator cuff tears in current studies. However, research on the relationship between acromial anatomy and articular-sided partial thickness of rotator cuff tears (PTRCTs) is still lacking. The purpose of this study was to evaluate whether these imaging graphic parameters exhibit any association between acromial anatomy and degenerative articular-sided PTRCTs. METHODS: Between January 2016 and December 2018, a total of 91 patients without a history of trauma underwent arthroscopy as an articular-sided PTRCT group. In the control group, with age- and sex-matched patients, we selected 91 consecutive outpatient patients who underwent shoulder magnetic resonance imaging (MRI) because of shoulder pain and an MRI diagnosis of only synovial hyperplasia and effusion. MRI was used to measure the acromial type, acromiohumeral distance (AHD), lateral acromial angle (LAA), acromion index (AI), and critical shoulder angle (CSA) by 2 independent observers. RESULTS: The acromion type, AHD and LAA showed no difference between degenerative articular-sided PTRCTs and controls (P = 0.532, 0.277, and 0.108, respectively). AI and CSA were significantly higher in degenerative articular-sided PTRCTs (P = 0.002 and 0.003, respectively). A good correlation was found between AI and CSA to measurement(Pearson correlation coefficient = 0.631). CONCLUSIONS: Our study revealed that higher AI and CSA were found in degenerative articular-sided PTRCTs. Acromial anatomy with a large acromial extension was associated with the occurrence of degenerative articular-sided PTRCTs.
Assuntos
Lesões do Manguito Rotador , Articulação do Ombro , Acrômio/diagnóstico por imagem , Artroscopia , Humanos , Imageamento por Ressonância Magnética , Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Articulação do Ombro/diagnóstico por imagemRESUMO
BACKGROUND: Severe peripheral nerve injury leads to skeletal muscle atrophy and impaired limb function that is not sufficiently improved by existing treatments. Fibroblast growth factor 6 (FGF6) is involved in tissue regeneration and is dysregulated in denervated rat muscles. However, the way that FGF6 affects skeletal muscle repair after peripheral nerve injury has not been fully elucidated. METHODS: In this study, we investigated the role of FGF6 in the regeneration of denervated muscles using myoblast cells and an in vivo model of peripheral nerve injury. RESULTS: FGF6 promoted the viability and migration of C2C12 and primary myoblasts in a dose-dependent manner through FGFR1-mediated upregulation of cyclin D1. Low concentrations of FGF6 promoted myoblast differentiation through FGFR4-mediated activation of ERK1/2, which upregulated expression of MyHC, MyoD, and myogenin. FGFR-1, FGFR4, MyoD, and myogenin were not upregulated when FGF6 expression was inhibited in myoblasts by shRNA-mediated knockdown. Injection of FGF6 into denervated rat muscles enhanced the MyHC-IIb muscle fiber phenotype and prevented muscular atrophy. CONCLUSION: These findings indicate that FGF6 reduces skeletal muscle atrophy by relying on the ERK1/2 mechanism and enhances the conversion of slow muscle to fast muscle fibers, thereby promoting functional recovery of regenerated skeletal muscle after innervation.
Assuntos
Fator 6 de Crescimento de Fibroblastos/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Músculo Esquelético/metabolismo , Traumatismos dos Nervos Periféricos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Regeneração/genética , Animais , Diferenciação Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Fator 6 de Crescimento de Fibroblastos/antagonistas & inibidores , Fator 6 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Denervação Muscular/métodos , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Proteína MyoD/genética , Proteína MyoD/metabolismo , Mioblastos/metabolismo , Mioblastos/patologia , Miogenina/genética , Miogenina/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Nervo Isquiático/lesõesAssuntos
Articulação do Cotovelo , Cistos Glanglionares , Cotovelo , Seguimentos , Humanos , Nervo UlnarRESUMO
BACKGROUND: Intraneural ganglion (IG) cysts have been considered curiosities and their pathogenesis remains controversial. OBJECTIVE: To clarify ulnar nerve at the elbow (UNE) pathogenesis and long-term surgical outcomes by presenting 9 rare cases of IG of the UNE. METHODS: Surgical treatment of IG was performed. Clinical symptoms, physical examinations, and electromyogram were evaluated pre- and postoperatively. At least 4 yr of follow-up was performed. RESULTS: The Tinel's sign became negative and local elbow pain disappeared in all 9 patients after surgery, and the average visual analog scale/score dropped from 4.9 (3-8) to 0 (0-0) after 6.2 d (2-10) on average. Two patients retained positive Froment test, "claw hand" and paresthesias with the 2-point discrimination much different from the contralateral little finger. Postoperative the UK Medical Research Council muscle strength score (MRC) grades of the flexor carpi ulnaris and the flexor digitorum profundus muscle of the fourth and fifth digits recovered to M4-M5 from M0-M2 in all 9 patients. The postoperative MRC grades of the third to fourth lumbrical muscles, the interossei, and the hypothenar recovered to M3-M5 from M0-M2 in 7 patients. Cystic articular branch (CAB) was found in all 9 patients intraoperatively. No symptomatic recurrence of IG was seen. The mean motor nerve conduction velocity of ulnar nerve across the elbow recovered from 5.3 to 41.2 m/s. CONCLUSION: A unifying articular theory is responsible for the pathogenesis of IG of UNE and disconnection of the CAB would prevent recurrence. The long-term outcome is good after surgical treatment of IG of UNE.
Assuntos
Articulação do Cotovelo/cirurgia , Cistos Glanglionares/cirurgia , Nervo Ulnar/cirurgia , Adulto , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/fisiologia , Eletromiografia/métodos , Feminino , Seguimentos , Cistos Glanglionares/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Fatores de Tempo , Resultado do Tratamento , Nervo Ulnar/diagnóstico por imagem , Nervo Ulnar/fisiologiaRESUMO
BACKGROUND: Gluteal muscle contracture (GMC) is a notable problem in some developing countries and includes features such as a snapping sound of the hip, abnormal gait, and unusual posture when patients squat with the knees together. Arthroscopic release can not only resolve symptoms, as previously reported, but can also greatly improve accompanying patellofemoral instability. This study was conducted to evaluate the effect of arthroscopic release of GMC on patellofemoral instability and its underlying mechanism. METHODS: A total of nearly 500 patients who underwent arthroscopic release of GMC over 2.5 years were filtered, and 54 patients were enrolled in the study. The selected research subjects all had combined patellofemoral instability preoperatively. The Lysholm scores and CT scans of the knee were evaluated pre- and postoperatively. RESULTS: The mean follow-up time was 12.2 months. All of the surveyed patients had satisfactory clinical outcomes for hip snapping sounds and abnormal gait. In addition, a significant difference (p < 0.05) was observed between pre- and postoperative Lysholm scores, along with significant knee pain relief. Furthermore, the changes in CT scan parameters were significant as well. The average patellar tilt angle (PTA), patellofemoral index (PFI), and lateral patellar displacement (LPD) were obviously decreased (p < 0.05) after the release. Conversely, the mean lateral patellofemoral angle (LPFA) showed a clear difference (p < 0.05) between preoperative and postoperative CT examinations. CONCLUSIONS: Arthroscopic release of GMC can reduce the tilt and lateral shift of the patella and enhance its stability due to the release of the iliotibial band.
Assuntos
Artroscopia/métodos , Contratura/cirurgia , Instabilidade Articular/cirurgia , Músculo Esquelético/cirurgia , Articulação Patelofemoral/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Nádegas/diagnóstico por imagem , Nádegas/cirurgia , Contratura/diagnóstico por imagem , Feminino , Humanos , Instabilidade Articular/diagnóstico por imagem , Masculino , Músculo Esquelético/diagnóstico por imagem , Articulação Patelofemoral/diagnóstico por imagem , Adulto JovemRESUMO
MicroRNA-26a-5p (miR-26a-5p) has been reported to be involved in the tumorigenesis of several tumors, but its function in breast cancer is still unknown. In this study, miR-26a-5p was found significantly downregulated in both of the breast cancer tissues and cell lines, and low expression of miR-26a-5p predicted a poor prognosis for breast cancer patients. Overexpression of miR-26a-5p could significantly inhibit breast cancer cell growth. Further studies revealed that overexpression of miR-26a-5p downregulated the protein levels of Cyclin D1, CDK4, and CDK6, but upregulated the expression levels of p21, p27, and p53. In mechanism, miR-26a-5p targeted the 3'UTR of ring finger protein 6 (RNF6) mRNA and inhibited RNF6 expression in breast cancer cells. Moreover, overexpression of miR-26a-5p inhibited RNF6/ERα/Bcl-xL axis in breast cancer cells. In contrast, inhibiting miR-26a-5p upregulated RNF6/ERα/Bcl-xL axis. Further studies indicated that miR-26a-5p mediated RNF6/ERα/Bcl-xL axis through regulating the stability of ERα protein. Collectively, downregulation of miR-26a-5p plays essential roles in breast cancer by mediating RNF6/ERα/Bcl-xL axis, which might provide important implications for the therapeutics of breast cancer.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , MicroRNAs/genética , Análise de SobrevidaRESUMO
This study planned to explore the effects of M2c macrophages on epithelial-to-mesenchymal transition (EMT) of human renal proximal tubular epithelial cells (HK-2). Human monocytic leukaemia cells were induced by TPA and IL-10 to differentiate M2c macrophages. Subsequently HK-2 cells were co-cultured with the M2c macrophages in Transwell chamber. After 48 h of co-culturing the HK-2 cells were detected in the mRNA and protein expression of E-cadherin, α-SMA and vimentin with RT-PCR, immunofluorescence and Western blot respectively. Besides, the migration ability of the HK-2 cells was estimated with Transwell migration assay. ANOVA was used to compare the difference between groups and Student's t-test to conduct multiple comparisons of two groups. P < 0.05 was considered statistically significant. The results showed that the mRNA and protein expression of α-SMA and vimentin of the HK-2 cells were increased but the E-cadherin decreased significantly after 48 h co-culturing with the M2c macrophages (P < 0.05 or P < 0.01). And the migration ability of HK-2 cells were also increased significantly (P < 0.05). It may be concluded that polarized M2c macrophages may have a promoting effect on the EMT of HK-2 cells.
Assuntos
Comunicação Celular/imunologia , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Túbulos Renais/citologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Biomarcadores , Células Epiteliais/patologia , Fibrose , Humanos , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologiaRESUMO
BACKGROUND Experimental studies have reported nonsteroidal anti-inflammatory drugs (NSAIDs) could impair tendon healing. The purpose of this study was to investigate whether NSAIDs could affect recovery of knee joint function in patients after anterior cruciate ligament (ACL) reconstruction. MATERIAL AND METHODS We enrolled 40 patients treated with celecoxib and 40 patients treated with tramadol, who underwent ACL reconstruction from January 2011 to December 2017. Visual analogue scale (VAS) and functional outcomes were collected and evaluated. The follow-up period was 12 months. RESULTS In both groups, all patients obtained pain release after surgery, compared with that before surgery. But no significant differences were observed between the 2 groups in VAS scores. We also did not find any differences between the 2 groups at 1 year of follow-up, in terms of anterior drawer test, Lachman test, side-to-side laxity assessed by KT-2000, IKDC score, Lysholm score, and Tegner scale. However, the celecoxib group showed a reduced incidence of nausea compared to the tramadol group (P=0.048). CONCLUSIONS The use of NSAIDs after ACL reconstruction is relatively safe and could decrease adverse side effects which were caused by opioid drugs.
Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Anti-Inflamatórios não Esteroides/farmacologia , Cicatrização/efeitos dos fármacos , Adulto , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior , Artroscopia/métodos , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Tendões/cirurgiaRESUMO
Tendinopathy is a common musculoskeletal disorder with characteristic hypervascularity. The mechanism of angiogenesis in tendinopathy remains unclear. The present study aimed to investigate the roles of miR-148a-3p in angiogenesis development of tendinopathy. In this study, we demonstrated that miR-148a-3p expression was increased in tendinopathy tissues and positively correlated with CD34 levels which is a specific marker for angiogenesis. We identified Krüppel-like factor 6 (KLF6) as a direct target gene of miR-148a-3p in tenocytes. Furthermore, reduced levels of KLF6 in tendinopathy tissues was showed using qRT-PCR and immunohistochemical analysis, compared with controls. A negative correlation between the levels of KLF6 mRNA and miR-148a-3p was observed. Then, we verified that miR-148a-3p could regulate Tsp-4 expression by targeting KLF6 in tenocyte and was positively correlated with Tsp-4 levels in tendinopathy tissues. In a coculture system of tenocytes with endothelial cells (ECs), we observed that transfection of Lv-miR-148a-3p markedly upregulated EC angiogenesis. In summary, our data establish a novel molecular mechanism by which miR-148a-3p upregulates Tsp-4 expression in tenocytes to promote EC angiogenesis by targeting KLF6, which could be helpful for the treatment of tendinopathy in the future.