Objective To explore the value of CT and MRI on invasive range and preoperative staging of the laryngeal carcinoma in the aged patients.Methods CT and MRI information of 26 cases with laryngeal catcinoma was analyzed retrospectively. The tumor invasive extent and staging with CT and MRI were compared with operation-pathologic results.ResultsThe sensitivity, positive predictive value and the accuracy of tumor staging of CT and MRI in assessing invasion of latyngeal catcinoma were higher 〔94.5% (121/128) vs 94.0% (79/84) and 85.3% (121/142) vs 86.9% (79/91) and 80.0% (12/15) vs 85.7% (6/7), respectively〕.But 5.4% (7/128) and 5.9% (5/84) invasion were missed with CT and MRI.Conclusions CT and MRI are useful in assessing invasive range and preoperative staging of latyngeal catcinoma, and it is helpful to clinical treatment of this disease.
Abstract Liver tumor is difficult to cure for its high degree of malignancy and rapid progression characteristics. Ferroptosis as a new model of inducing cell death is expected to break the treatment bottleneck of liver tumors. Here, a strategy to induce ferroptosis in HepG2 cells with acid‐degradable tumor targeted nanosheets Cu‐Hemin‐PEG‐Lactose acid (Cu‐Hemin‐PEG‐LA) is proposed. After highly ingested by HepG2 cells, Cu‐Hemin‐PEG‐LA nanosheets are degraded by weak acid and release Cu(II) and hemin, which consuming intracellular glutathione (GSH) content and increasing the expression of heme oxygenase 1 (HMOX1) protein, respectively. Furthermore, the expression of glutathione peroxidase 4 protein (GPX4) is down‐regulated by consumption intracellular GSH content via converting GSH into glutathione oxidized (GSSG), which is named the classical mode. The intracellular Fe 2+ content is overloaded by the significant up‐regulation of HMOX1 expression, which is denoted as nonclassical mode. The synergistic effect of classical and nonclassical mode increased the intracellular lipid reactive oxide species, induced the occurrence of ferroptosis and up‐regulated the expression of BH3 interacting domain death agonist (BID), apoptosis‐inducing factor (AIF), and endonuclease G proteins (EndoG). The synergistic strategy demonstrate the excellent ferroptosis induction ability and antitumor efficacy in vivo, which provides great potential for the clinical transformation of ferroptosis.
clinical observations suggest that alternans in action potential (AP) characteristics presages breakdown of normal ordered cardiac electrical activity culminating in ventricular arrhythmogenesis. We compared such temporal nonuniformities in monophasic action potential (MAP) waveforms in left (LV) and right ventricular (RV) epicardia and endocardia of Langendorff-perfused murine wild-type (WT), and Scn5a(+/-) hearts modelling Brugada syndrome (BrS) for the first time.a dynamic pacing protocol imposed successively incremented steady pacing rates between 5.5 and 33 Hz. A signal analysis algorithm detected sequences of >10 beats showing alternans. Results were compared before and following the introduction of flecainide (10 microm) and quinidine (5 microm) known to exert pro- and anti-arrhythmic effects in BrS.sustained and transient amplitude and duration alternans were both frequently followed by ventricular ectopic beats and ventricular tachycardia or fibrillation. Diastolic intervals (DIs) that coincided with onsets of transient (tr) or sustained (ss) alternans in MAP duration (DI*) and amplitude (DI') were determined. Kruskal-Wallis tests followed by Bonferroni-corrected Mann-Whitney U-tests were applied to these DI results sorted by recording site, pharmacological conditions or experimental populations. WT hearts showed no significant heterogeneities in any DI. Untreated Scn5a (+/-) hearts showed earlier onsets of transient but not sustained duration alternans in LV endocardium compared with RV endocardium or LV epicardium. Flecainide administration caused earlier onsets of both transient and sustained duration alternans selectively in the RV epicardium in the Scn5a (+/-) hearts.these findings in a genetic model thus implicate RV epicardial changes in the arrhythmogenicity produced by flecainide challenge in previously asymptomatic clinical BrS.
Bone destruction is a hallmark of multiple myeloma (MM). It has been reported that proteasome inhibitors (PIs) can reduce bone resorption and increase bone formation in MM patients, but the underlying mechanisms remain unclear.Mesenchymal stem cells (MSCs) were treated with various doses of PIs, and the effects of bortezomib or carfilzomib on endoplasmic reticulum (ER) stress signaling pathways were analyzed by western blotting and real-time PCR. Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were used to determine the osteogenic differentiation in vitro. Specific inhibitors targeting different ER stress signaling and a Tet-on inducible overexpressing system were used to validate the roles of key ER stress components in regulating osteogenic differentiation of MSCs. Chromatin immunoprecipitation (ChIP) assay was used to evaluate transcription factor-promoter interaction. MicroCT was applied to measure the microarchitecture of bone in model mice in vivo.We found that both PERK-ATF4 and IRE1α-XBP1s ER stress branches are activated during PI-induced osteogenic differentiation. Inhibition of ATF4 or XBP1s signaling can significantly impair PI-induced osteogenic differentiation. Furthermore, we demonstrated that XBP1s can transcriptionally upregulate ATF4 expression and overexpressing XBP1s can induce the expression of ATF4 and other osteogenic differentiation-related genes and therefore drive osteoblast differentiation. MicroCT analysis further demonstrated that inhibition of XBP1s can strikingly abolish bortezomib-induced bone formation in mouse.These results demonstrated that XBP1s is a master regulator of PI-induced osteoblast differentiation. Activation of IRE1α-XBP1s ER stress signaling can promote osteogenesis, thus providing a novel strategy for the treatment of myeloma bone disease.
Objective To analyze the cause and treatment of relapsing clubfoot with Ponseti method. Methods Four hundred and seventy eight cases (male 386 and female 92) with 714 feet (bilateral in 236 cases, single foot in 242) were managed with Ponseti method in this hospital from Jan. of 2000 to Apr. of 2008. According to the Dimeglio classification:Type Ⅰ 29 feet, Type Ⅱ 275 feet, Type Ⅲ 308 feet and Type Ⅳ 102 feet. All were treated with serial cast, percutaneous Achilles tenotomy and brace with an abduction orthosis. All cases got regular follow-up. Relapsing were recorded, the relation between the type, using of brace and the recurrence were analyzed. The relapsing patients were treated with recasting for 4 or 5 times, and then percutaneous Achilles tenotomy and/or anterior tibial tendon transfer according to the different types. Results All cases were given follow-up visit. Eighty-nine feet of 714 feet recurred (12. 46%), 26 in type Ⅱ, 30 in type Ⅲ, and 33 in type Ⅳ. Relapses occurred in 6. 01% (38 feet) of the 632 feet which were compliant with brace while 62. 20% (52 feet) of 82 un-compliant patients. The main age of recurrence was 2 to 2. 5 years old and the main deformities were equino and varus. These recrudescent ones were corrected with advance casting for 4 or5 times. Eighteen feet underwent percutaneous Achilles tenotomy, 61 feet underwent anterior tibial tendon transfer and 10 got both surgery. All the patients got excellent results at last (average 38 months of follow-up). Conclusions The two factors for the recurrence of clubfoot treated with the Ponseti method are the compliance with the brace and the severity of the deformity. The recurrence is usually expected 2 to 4 months after the brace was given up and the main deformities were equino and varus. All the recrudescent would be corrected with recasting for 4 or 5 times, then undergoing percutaneous Achilles tenotomy and/or anterior tibial tendon transfer in the light of the different types.
Key words:
Equinus deformity; Recurrence
Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking. Case Description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment. Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.