BRAF mutations, primarily sensitizing mutations, such as BRAFV600E, have been proven to response to the BRAF inhibitor, Dabrafenib combined with trametinib therapy, but there have been no data demonstrating that it has activity against NSCLC-related brain metastases (BM). How patients harboring BRAFS365L mutation (a rare mutation following BRAFV600E-inhibitor treatment) in NSCLC is unknown. Vemurafenib, another BRAF inhibitor, can reverse the resistance that develops with the BRAFS365L mutation following dabrafenib combined with trametentinib treatment in melanoma, but none has been reported in NSCLC. Lung papillary cancer, as a rare typing, occupies about 4% of NSCLC. Hence, we reported the first case of a patient with BM of lung papillary carcinoma harboring a BRAFV600E mutation who benefited from dabrafenib combined with trametinib, and following the development of the BRAFS365L mutation, vemurafenib remained an effective therapeutic option. Moreover, we found that the next-generation sequencing (NGS) of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) may potentially provide more accurate information about intracranial lesions than ctDNA in the blood serum, which will be a better detection method.

The aim of the study was to investigate the expression of tumor suppressor gene p53 and MMP-9 in non-small cell lung cancer (NSCLC) before and after chemotherapy, and investigate its association with the effect of chemotherapy and prognosis. Fifty-eight elderly NSCLC patients comprised the observation group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of p53 and MMP-9 in lung cancer tissues before and after chemotherapy. Immunohistochemistry and western blot analysis were used to detect the expression of p53 and MMP-9 proteins in NSCLC tissue before and after chemotherapy. Terminal deoxynucleotidyl transferase nick end-labeling (TUNEL) was used to detect apoptotic cells. The association between the effect of chemotherapy and the expression of p53 and MMP-9 in lung cancer tissues was analysed. RT-qPCR results showed that the expression of p53 and MMP-2 mRNA in the tumor tissue after chemotherapy was significantly lower than that in the tumor tissue before chemotherapy. Western blot analysis revealed that the expression of p53 and MMP-2 protein in the tumor tissue after chemotherapy was significantly decreased. The positive expression of p53 and MMP-2 in lung cancer tissues before chemotherapy was 76.25 and 71.25%, respectively, and were reduced to 27.50 and 23.75%, respectively, after chemotherapy. After chemotherapy, the positive rates of p53 and MMP-2 were significantly lower than those before chemotherapy. TUNEL results showed that the apoptosis index increased significantly after chemotherapy. Efficiency of chemotherapy in patients with a negative expression of p53 and MMP-2 in lung cancer before chemotherapy was significantly higher than that in patients with a positive p53 and MMP-2 expression. A significant difference was found in the expression levels of p53 and MMP-2 in lung cancer before and after chemotherapy. The findings of the present study indicate that the expression levels of p53 and MMP-2 can be used as a predictor of chemotherapy sensitivity.

ObjectiveTransarterial chemoembolization with CalliSpheres® Microspheres (CSM-TACE) presents favorable efficacy and tolerable safety in several cancers, while its application in head and neck cancer (HNC) is unclear. Thus, the current pilot study aims to evaluate the efficacy and safety of CSM-TACE in treating HNC.MethodsA total of 15 HNC patients receiving CSM-TACE at the Second Affiliated Hospital of Dalian Medical University from March 2017 to December 2021 were enrolled in this study. Moreover, treatment information, treatment response, progression-free survival (PFS), overall survival (OS), changes in liver and renal function indices, and adverse events were recorded.ResultsThere were nine patients receiving CSM-TACE as first-line treatment and six patients receiving CSM-TACE as second- or above-line treatment; meanwhile, there were seven, seven, and one patient undergoing one time, two times, and three times of CSM-TACE, respectively. Furthermore, the objective response rate (ORR) and the disease control rate (DCR) were 60.0% and 100%, respectively, at the first month; meanwhile, the ORR and the DCR were 53.3% and 73.3%, respectively, at the second month. Moreover, the 1-year PFS rate was 34.1%, and the 1-year OS rate was 38.9%. Additionally, no change in liver function indices (namely, total protein, albumin, total bilirubin, alanine aminotransferase, and aspartate aminotransferase) or in renal function indices (namely, creatinine and blood urea nitrogen) was found before and 1 month after treatment (all P > 0.05). Meanwhile, no severe adverse events were found during and after CSM-TACE.ConclusionCSM-TACE illustrates favorable treatment response and survival benefits as well as a tolerable safety profile in HNC patients.

With the rapid development of converters in a variety of industrial fields, the fault diagnosis of power switching devices has become an important factor in ensuring the safe and reliable operation of related systems. In recent years, machine learning has performed well in many fault diagnosis tasks. The success of these advanced methods depends on sufficient marked samples for each fault type. However, in most industrial applications, it is expensive and difficult to collect fault samples, and the fault diagnosis model trained under the limited samples cannot meet the requirements of fault diagnosis accuracy. In order to solve this problem, this study proposes a few-shot learning method based on fault sample generation to realize the open-circuit fault diagnosis of IGBT in a three-phase PWM converter. This method is the deformation of the auto-encoder called the disturbance auto-encoder generation model. By designing the model structure and training algorithm constraints, the encoder learns the nonlinear transferable disturbance from the normal operating sample pairs. Then, the disturbance is applied to the decoder to synthesize new fault samples to realize the training of the fault diagnosis model with limited samples. The biggest advantage of this method is that it can achieve 95.90% fault diagnosis accuracy by only collecting the samples in the normal operating conditions of the target system. Finally, the feasibility and advantages of the proposed method are verified by comparative experiments.

Cabozantinib has been shown to have potent anti-ROS1 activity in many solid malignancies, particularly against those with solvent-front resistance mutations following crizotinib therapy. With regard to the most common CD74-ROS1 fusion, the efficacy of cabozantinib has only been demonstrated in vitro. Therefore, we evaluate the efficacy of cabozantinib in a patient with advanced non-small-cell lung cancer (NSCLC) harboring a CD74-ROS1 fusion in the present study. A 40-year-old female patient presented with 1-month history of cough, white sputum and chest pain. Chest CT scan revealed a consolidation in the middle lobe of the right lung together with multiple cavity lesions spreading in both lungs. Histopathological analysis of biopsy samples from the lesion in the middle lobe of the right lung suggested lung adenocarcinoma. After two lines of chemotherapy and EGFR-TKI therapy, a CD74-ROS1 rearrangement was detected and the patient was administered with cabozantinib for 1.5 years. Since cabozantinib resistance developed, crizotinib therapy was applied and demonstrated clinical effectiveness until now. Together, we report the first case of cabozantinib effectiveness in treating a CD74-ROS1-positive advanced NSCLC patient. Crizotinib remained as an effective therapeutic option following the acquisition of cabozantinib resistance.