Targeting blood-brain barrier for sepsis-associated encephalopathy: Regulation of immune cells and ncRNAs.

Sepsis causes significant morbidity and mortality worldwide, most surviving patients show acute or chronic mental disorders, which are known as sepsis-associated encephalopathy (SAE). SAE involves many pathological processes, including the blood-brain barrier (BBB) damage. The BBB is located at the interface between the central nervous system and the surrounding environment, which protects the central nervous system (CNS) from the invasion of exogenous molecules, harmful substances or microorganisms in the blood. Recently, a growing number of studies have indicated that the BBB destruction was involved in SAE and played an important role in SAE-induced brain injury. In the present review, we firstly reveal the pathological processes of SAE such as the neurotransmitter disorders, oxidative stress, immune dysfunction and BBB destruction. Moreover, we introduce the structure of BBB, and describe the immune cells including microglia and astrocytes that participate in the BBB destruction after SAE. Furthermore, in view of the current research on non-coding RNAs (ncRNAs), we explain the regulatory mechanism of ncRNAs including long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) on BBB in the processes of SAE. Finally, we propose some challenges and perspectives of regulating BBB functions in SAE. Hence, on the basis of these effects, both immune cells and ncRNAs may be developed as therapeutic targets to protect BBB for SAE patients.

Roles and signaling pathways of CITED1 in tumors: overview and novel insights.

CBP/p300 interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 (CITED1) is a transcriptional activator belonging to the non-DNA-binding transcription co-regulator family. It regulates diverse pathways, including the transforming growth factor/bone morphogenetic protein/SMAD, estrogen, Wnt-ß-catenin, and androgen-AR signaling pathways, by binding to CBP/p300 co-activators through its conserved transactivation domain CR2. CITED1 plays an important role in embryonic development and a certain regulatory role in the occurrence and development of various tumors. In this article, the biological characteristics, expression regulation, participating signaling pathways, and potential roles of CITED1 in the clinical diagnosis and treatment of tumors are reviewed.

Interventional treatment of keratoacanthoderma: a case report.

This current case report describes a 56-year-old male patient with a skin mass on his lip that had been growing for 1 year. The pathological findings demonstrated that the epidermis was characterized by hyperkeratosis, hyperplasia and hypertrophy and was formed in the shape of a crater. The skin on both ends had developed into a ball-like growth that resembled a volcanic cone. There was invasive growth of heterotype squamous epithelium and a small number of inflammatory cells infiltrating the dermis. Immunohistochemistry demonstrated an increase in P16 (the focus, +) and the hot spot Ki-67 index. The diagnosis was of tumour-like hyperplasia, malignancy and moderate-to-severe dysplasia confirming that it was keratoacanthoma. The patient underwent surgical resection and was discharged from hospital, but the tumour returned. Paclitaxel and cisplatin were administered intraoperatively and bilateral lingual artery perfusion chemoembolization was undertaken six times. This procedure led to an excellent postoperative recovery and discharge from hospital. Tumour therapy was regarded as successful. The patient's medical history included acute lymphoblastic leukaemia L1 and long-term immunosuppressant use. After a 6-month period of follow-up, he died from systemic organ failure as a consequence of having too many ailments.

Efficacy and safety of transarterial chemoembolization with CalliSpheres® Microspheres in head and neck cancer.

Objective: Transarterial 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. Methods: A 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. Results: There 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. Conclusion: CSM-TACE illustrates favorable treatment response and survival benefits as well as a tolerable safety profile in HNC patients.

Case Report: Vemurafenib Treatment in Brain Metastases of BRAFS365L -Mutant Lung Papillary Cancer by Genetic Sequencing of Cerebrospinal Fluid Circulating Tumor DNA Detection.

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.

Effective Treatment with Cabozantinib in an Advanced Non-Small-Cell Lung Cancer Patient Harboring a CD74-ROS1 Fusion: A Case Report.

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.

Study on the expression of p53 and MMP-2 in patients with lung cancer after interventional therapy.

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.