RESUMEN
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cancer. The present report details the treatment experience of a case of MTSCC, where the patient underwent a right-side laparoscopic nephrectomy in October 2020 at Zhuji People's Hospital (Zhuji, China). A total of 3 months post-operation, multiple metastases were discovered in the right renal area and retroperitoneum, with rapid disease progression observed in the subsequent 2 months. Treatment with tislelizumab combined with pazopanib was ineffective, and the patient subsequently died. Although MTSCC is generally considered a low-grade 'indolent' tumor, with most patients achieving long-term survival post-surgery, a minority of cases, especially those of a higher grade, may experience postoperative recurrence and metastasis. Due to the rarity of metastatic MTSCC, most studies are based on small sample sizes or case reports, and there is a lack of standardized systemic treatment and follow-up strategies for metastatic MTSCC. The present paper summarizes and analyzes the clinical features, treatment methods and prognosis of metastatic MTSCC cases reported in the literature, aiming to provide assistance for the treatment and follow-up management of metastatic MTSCC. Even in cases of distant metastasis, aggressive surgical treatment, metastasectomy combined with molecular targeted or immunotherapy, may still be recommended.
RESUMEN
Molecular chaperones are protective in neurodegenerative diseases by preventing protein misfolding and aggregation, such as extracellular amyloid plaques and intracellular tau neurofibrillary tangles in Alzheimer's disease (AD). In addition, AD is characterized by an increase in astrocyte reactivity. The chaperone HSPB1 has been proposed as a marker for reactive astrocytes; however, its astrocytic functions in neurodegeneration remain to be elucidated. Here, we identify that HSPB1 is secreted from astrocytes to exert non-cell-autonomous protective functions. We show that in human AD brain, HSPB1 levels increase in astrocytes that cluster around amyloid plaques, as well as in the adjacent extracellular space. Moreover, in conditions that mimic an inflammatory reactive response, astrocytes increase HSPB1 secretion. Concomitantly, astrocytes and neurons can uptake astrocyte-secreted HSPB1, which is accompanied by an attenuation of the inflammatory response in reactive astrocytes and reduced pathological tau inclusions. Our findings highlight a protective mechanism in disease conditions that encompasses the secretion of a chaperone typically regarded as intracellular.
Asunto(s)
Enfermedad de Alzheimer , Astrocitos , Humanos , Astrocitos/metabolismo , Proteínas tau/metabolismo , Placa Amiloide/patología , Neuroprotección , Chaperonas Moleculares/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Proteínas de Choque Térmico/metabolismoRESUMEN
BACKGROUND: Reasonable postoperative humeroradial and humeroulnar joint spaces maybe an important indicator in biomechanical stability of smart internal fixation surgery for coronoid process basal fractures (CPBF). The aim of this study is to compare elbow articular stresses and elbow-forearm stability under smart internal fixations for the CPBF between normal elbow joint spaces and radius-shortening, and to determine the occult factor of radius-ulna load sharing. METHODS: CT images of 70 volunteers with intact elbow joints were retrospectively collected for accurate three-dimensional reconstruction to measure the longitudinal and transverse joint spaces. Two groups of ten finite element (FE) models were established prospectively between normal joint space and radius-shortening with 2.0â¯mm, including intact elbow joint and forearm, elbow-forearm with CPBF trauma, anterior or posterior double screws-cancellous bone fixation, mini-plate-cancellous bone fixation. Three sets of physiological loads (compression, valgus, varus) were used for FE intelligent calculation, FE model verification, and biomechanical and motion analysis. RESULTS: The stress distribution between coronoid process and radial head, compression displacements and valgus angles of elbow-forearm in the three smart fixation models of the normal joint spaces were close to those of corresponding intact elbow model, but were significantly different from those of preoperative CPBF models and fixed radius-shortening models. The maximum stresses of three smart fixation instrument models of normal joint spaces were significantly smaller than those of the corresponding fixed radius-shortening models. CONCLUSIONS: On the basis of the existing trauma of the elbow-forearm system in clinical practice, which is a dominant factor affecting radius-ulna load sharing, the elbow joint longitudinal space has been found to be the occult factor affecting radius-ulna load sharing. The stability and load sharing of radius and ulna after three kinds of smart fixations of the CPBF is not only related to the anatomical and biomechanical stability principles of smart internal fixations, but also closely related to postoperative elbow joint longitudinal space.