The Nobel Prize in Physiology or Medicine for the year 2021 was awarded to Ardem Patapoutian and David Julius for their discoveries of temperature-sensitive receptors (TRP channels) and tactile receptors (Piezo channels), both of which were previously unknown. TRP channels are at the heart of the human ability to detect temperature, and they also play crucial regulatory functions in the occurrence and progression of cancer. Despite this, there have been no research conducted on the prognostic significance of TRP channels in individuals with esophageal squamous cell carcinoma (ESCC). In GEO and TCGA cohorts, unsupervised clustering was first conducted based on 18 TRP channel-associated differentially expressed genes (DEGs) extracted from MSigDB database and KEGG database. Two TRP subtypes were identified and patients in subtype B had the best prognosis among the two subtypes. Significant differences in staging and grading existed among the different subtypes. In GEO cohort, univariate Cox analysis were performed to screen prognosis related genes. A TRP channel-related prognostic signature, which included 7 signature-related genes, was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were divided into a high-risk group and low-risk group by the median risk score. In GEO and TCGA cohorts, Receiver operating characteristic (ROC) curves, principal component analysis (PCA), and univariate and multivariate Cox regression were performed to confirm the validity of signature. Following a more in-depth study of the TME based on the risk signature, it was discovered that the high-risk group had higher immune cell infiltration and lower tumor purity, indicating a bad prognosis. Patients with high risk scores also had increased immune checkpoint expression, indicating that these patients may be more likely to benefit from immunotherapy than other patients. We also found that paclitaxel, cisplatin, and 5-fluorouracil displayed a better response in treating the low-risk score ESCC patients. This study also adopted GTEx and qRT-PCR to perform experimental verification processes. In summary, we identified a TRP channel-associated prognostic signature. This signature can predict prognosis and immune microenvironment in ESCC.

Background Autophagy has been found to be involved in the multidrug resistance (MDR) of cancers, but whether it is associated with resistance of small cell lung cancer (SCLC) has not been studied. Here, we hypothesized that a potential autophagy-regulating miRNA, miR-199a-5p, regulated cisplatin-resistant SCLC. Methods We validated the MDR of H446/EP using CCK-8 and LDH. We tested the binding of miR-199a-5p to p62 using the Dual-Luciferase assay and validated the association of miR-199a-5p and p62 in SCLC samples. We overexpressed (OE) and knocked down (KD) miR-199a-5p in H446 and H446/EP and determined the expression of miR-199a-5p, autophagy-related proteins, and the formation of autophagolysosomes using QPCR, western blotting, and MDC staining respectively. These results were validated in an orthotopic H446 mouse model of SCLC. Results H446/EP was resistant to cisplatin, etoposide, paclitexal, epirubicin, irinotecan, and vinorelbine. Exposure of cisplatin at 5 μg/ml for 24 h increased LC3II/LC3I, ATG5, p62, and the formation of autophagolysosomes in H446 cells, but not in H446/EP cells. The expression of miR-199a-5p was up-regulated in H446/EP compared to H446. MiR-199a-5p directly targeted the p62 gene. The expression of miR-199a-5p and p62 were correlated in SCLC samples. In H446 and H69PR, the OE of miR-199a-5p increased LC3II/LC3I, p62, and the formation of autophagolysosomes, but not ATG5, while the KD of miR-199a-5p decreased p62, but did not affect LC3II/LC3I, ATG5, and the formation of autophagolysosomes. In H446/EP, the OE of miR-199a-5p decreased p62 only. These results were generally consistent to results in the animal tumor samples. Conclusions The regulation of autophagy by the miR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance.

Background Esophageal cancer is one of the most common cancers across the globe; the 5‐year survival of esophageal cancer patients is still low. MicroRNA (miRNA) dysregulation has been implicated in cancer development, and the miRNAs play a pivotal role in esophageal cancer pathogenesis. It is urgently needed to find out how miRNA dysregulation was involved in esophageal cancer (EC) development. Methods Through experiments in vivo and in vitro, we explored potential signaling pathways, miR‐493/Wnt5A/c‐JUN loop, in EC. Their mechanistic roles in EC cell proliferation, migration, and invasion were investigated through multiple validation steps in EC9706 and TE13 cell lines and EC specimens. Results Overexpression of miR‐493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. Moreover, miR‐493 downregulation is an unfavorable factor in EC and negatively correlated with Wnt5A. The existence of miR‐493 is also an important attribute of metabolism. Based on mechanism analyses, we show that miR‐493 inhibits the activity of c‐JUN and p‐PI3K/p‐AKT with enhanced p21 and directly regulates Wnt5A expression and function, whereas c‐JUN binds the promoter region of miR‐493 and suppressed the expression of miR‐493, forming a negative feedback loop. Conclusions The miR‐493/Wnt5A/c‐JUN loop is a molecular feedback loop that refers to the development of esophageal cancer cells and a potential target for the treatment of esophageal cancer.

Objective: LINC00662 is oncogenic in some human cancers, but no much was revealed concerning to its specific action in tumor angiogenesis. Given that, our study investigated the role of LINC00662 from esophageal squamous cell carcinoma (ESCC) cells-derived extracellular vehicles (EVs) in angiogenesis through microRNA (miR)-195-5p/vascular endothelial growth factor A (VEGFA) axis.Methods: Clinical tissue samples were collected from patients with ESCC, in which LINC00662, miR-195-5p and VEGFA expression was analyzed. ESCC cells were transfected, from which EVs were isolated. Human umbilical vein endothelial cells (HUVECs) were co-cultured with the pretreated EVs. After that, viability, colony formation ability, invasion, migration and tube formation ability of HUVECs were observed. Tumor xenograft in nude mice was performed to detect the effect of LINC00662, miR-195-5p or EV specific inhibitor GW4869 on tumor development.Results: LINC00662 and VEGFA were upregulated while miR-195-5p was downregulated in the cancer tissue of patients with ESCC. EVs derived from ESCC cells promoted viability, colony formation ability, invasion and tube formation ability of HUVECs. Downregulation of LINC00662 or upregulation of miR-195-5p reversed the promotion of EVs derived from ESCC cells on the viability, colony formation ability, invasion and tube formation ability of HUVECs in vitro and in vivo. VEGFA overexpression reversed EVs carrying restored miR-195-5p induced effects on HUVECs in vitro.Conclusion: In summary, elevated LINC00662 transferred by ESCC cells-derived EVs induces angiogenesis through downregulating miR-195-5p and upregulating VEGFA.

PurposeTo explore the risk factors of acute respiratory distress syndrome (ARDS) secondary to thoracic trauma and the therapeutic effect of protective lung ventilation in patients with acute respiratory distress syndrome complicated with thoracic trauma.MethodsWe collected 206 patients with thoracic trauma admitted to our hospital from September 2017 to March 2021, counted the incidence of ARDS and analyzed the risk factors of ARDS. To observe the clinical efficacy of the application of lung-protective ventilation therapy in patients with thoracic trauma combined with ARDS.ResultsAmong 206 patients with thoracic trauma, there were 82 cases of combined ARDS, and its incidence was 39.81%. The 82 patients with ARDS were randomly divided into the control group and the observation group with 42 cases each, and different ventilation methods were used for treatment. The results showed that the mechanical ventilation time (MVT) was shorter in the observation group than in the control group, and the incidence of ventilator-associated lung injury (VALI) and case fatality rate (CFR) were lower than those in the control group (P < 0.05). Arterial partial pressure of oxygen (Pa02), arterial blood carbon dioxide partial pressure (PaCO2), and Oxygenation index (arterial partial pressure of oxygen/Fraction of inspiration O2, PaO2/FiO2) were significantly improved better in both groups after treatment; compared with the control group, patients in the observation group had higher Pa02 levels and lower PaCO2 levels at 8 h and 24 h after ventilation (P < 0.05). Multivariate analysis revealed that blunt trauma, massive blood transfusion, procalcitonin (PCT) level, tumor necrosis factor-α (TNF-α) level, and acute physiology and chronic health score (APACHE II) were all risk factors for Thoracic trauma with ARDS.ConclusionRisk factors for the development of ARDS after thoracic trauma are blunt injuries, massive blood transfusion, high PCT and TNF-α levels, and high APACHE II scores, which can be given active interventions in the early stage of clinical practice to improve patient prognosis. The use of protective lung ventilation therapy can improve the clinical outcome of patients with thoracic trauma combined with ARDS, which is important for improving the ventilation effect and respiratory function of patients.