diabetic cardiomyopathy (dcM) is a leading contributor to the increased morbidity and mortality rates associated with diabetes. Persistent inflammation has previously been reported to be involved in the pathogenesis of DCM. However, the exact underlying molecular mechanisms remain to be fully elucidated. In the present study, the role of spleen tyrosine kinase (Syk) and c-Jun N-terminal kinase (JNK) in NLR family pyrin domain-containing 3 (NLRP3 inflammasome) activation in DCM were investigated in vivo and in vitro. Streptozotocin (65 mg/kg) was injected intraperitoneally into Sprague-Dawley rats to induce a rat model of diabetes. Neonatal rat cardiomyocytes and H9c2 cells were cultured to detect the expression of JNK, NLRP3 and its associated downstream molecules, following treatment with Syk/JNK inhibitor or Syk/JNK-small interfering (si)RNA in high glucose (HG) conditions. It was revealed that the protein and mRNA expression levels of phospho (p)-Syk, p-JNK, NLRP3 and its associated downstream molecules, including interleukin (IL)-1β, were upregulated in vivo and in vitro. The JNK inhibitor significantly decreased the expression of NLRP3 and its downstream molecules in neonatal rat cardiomyocytes and H9c2 cells treated with HG. Furthermore, Syk-siRNA and the Syk inhibitor markedly inhibited the HG-induced activation of JNK, followed by the downregulation of NLRP3 and its downstream molecules at the mRNA and protein levels in cells. Therefore, it was demonstrated that the HG-induced activation of NLRP3 was mediated by the activation of Syk/JNK, which subsequently increased the protein expression levels of mature IL-1β, suggesting that the Syk/JNK/NLRP3 signaling pathway serves a critical role in the pathogenesis of DCM.
Diabetic nephropathy (DN) is a serious complication of diabetes and can cause an increased mortality risk. It was previously reported that NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in the pathogenesis of diabetes. However, the underlying mechanism is not clearly understood. In the present study, the effects of spleen tyrosine kinase (Syk) and c-Jun N-terminal kinase (JNK) on the NLRP3 inflammasome were examined in vivo and in vitro. Sprague-Dawley rats were injected intraperitoneally with streptozotocin (65 mg/kg) to induce diabetes. HK2 cells and rat glomerular mesangial cells (RGMCs) were examined to detect the expression of JNK and NLRP3 inflammasome-associated proteins following treatment with a Syk inhibitor or Syk-small interfering (si)RNA in a high glucose condition. In the present study, it was revealed that the protein and mRNA expression levels of NLRP3 inflammasome-associated molecules and the downstream mature interleukin (IL)-1β were upregulated in vivo and in vitro. The Syk inhibitor and Syk-siRNA suppressed high glucose-induced JNK activation, and subsequently downregulated the activation of the NLRP3 inflammasome and mature IL-1β in HK2 cells and RGMCs. Furthermore, high glucose-induced apoptosis of HK2 cells was reduced by the Syk inhibitor BAY61-3606. Therefore, the present results determined that high glucose-induced activation of the NLRP3 inflammasome is mediated by Syk/JNK activation, which subsequently increased the protein expression level of IL-1β and mature IL-1β. The present study identified that the Syk/JNK/NLRP3 signaling pathway may serve a vital role in the pathogenesis of DN.
Background Patellar chondroblastoma is a relatively rare tumor that occurs in the patella. Chondroblastoma invasion is even rarer, accounting for about 2%, and has a lack of early specific signs. It is a rare benign tumor of cartilage origin, which often occurs in the epiphyseal of long bone in patients aged 12–20 years and has a good prognosis. At present, literature on this condition is limited and lack of relatively complete diagnosis and treatment procedures. This paper reports a case of patellar chondroblastoma that healed well after surgical treatment and systematically summarizes its clinical manifestations, imaging characteristics, differential diagnosis, and treatment methods. For Chondroblastoma of the patella, a disease with a low incidence, a complete and comprehensive diagnosis and treatment process can improve the diagnosis and treatment ability of the disease and improve the patient's satisfaction with the diagnosis and treatment, and finally achieve satisfactory results.Case Description: On February 21, 2022, a 26-year-old male patient was admitted to the hospital due to “discomfort after right knee activity for more than 6 months”. The patient had no obvious inducement to feel swelling of the right lower limb, and no chills, high fever, or paresthesia 6 months prior, and the self-reported pain during the activity was especially significant during flexion. Routinely laboratory testing after admission ruled out contraindications to surgery, and imaging clearly showed lesions in the right patella. According to the patient's signs and related examinations, the diagnosis and treatment team preliminarily diagnosed benign patellar lesions and planned elective surgical treatment. After 6 months of close follow-up and rehabilitation guidance, the function of the affected limb gradually returned to the normal level and no unexpected adverse events occurred during the entire diagnosis and treatment.Conclusions We recommend the following: (I) strive for early treatment to reduce the probability of deterioration and possible pathological fracture; (II) the most commonly used curettage should ensure thorough removal of the lesions; (III) combined internal fixation may have a positive effect on improving the postoperative dependence of patients and encouraging them to perform early functional exercise.
Background: Thoracolumbar metastases is a difficult disease to deal with in spinal surgery. The aim of this study is to investigate the clinical efficacy of bone-filled mesh vertebroplasty combined with posterior spinal internal fixation in the treatment of thoracolumbar metastases. Methods:The clinical data of 68 patients with thoracolumbar vertebral metastases from January 2018 to April 2020 were retrospectively analyzed. A total of 37 cases underwent bone filling mesh pocket vertebroplasty combined with posterior spinal internal fixation as the observation group, and 31 cases underwent routine vertebroplasty combined with posterior spinal internal fixation as the control group. The visual analogue scale (VAS) scores, Oswestry disability index (ODI) scores, Karnofsky performance status (KPS) scores, and the heights of the anterior margin and middle of the diseased vertebra were compared between the 2 groups before and 1 week, 3 months, 6 months, and 1 year after surgery.Results: All cases successfully completed the operation, and there was no pulmonary embolism, paraplegia, or perioperative death in follow-up reported. Intraoperative bone cement leakage occurred in 4 cases with a total of 6 vertebrae in the observation group (leakage rate: 14.29%), and in 8 cases with a total of 11 vertebrae in control group (leakage rate: 31.43%). The differences in VAS scores, ODI scores, KPS scores, and the heights of the anterior margin and middle of the diseased vertebra between preoperative and postoperative periods at 1 week, 3 months, 6 months, and 1 year in both groups were statistically significant (P<0.05), while the differences between the 2 groups were not statistically significant (P<0.05). Conclusions:The application of bone-filled mesh vertebroplasty combined with posterior internal pedicle screws fixation for the treatment of thoracolumbar metastases can not only reduce the injury of the operation, but also achieve the purpose of relieving pain, controlling local tumor growth to a certain extent, restoring neural function, and rebuilding the stability of the spine, which has important clinical value.
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