KAT8 enhances the resistance of lung cancer cells to cisplatin by acetylation of PKM2.

Cisplatin (CDDP)-based chemotherapy resistance is a major challenge for lung cancer treatment. PKM2 is the rate-limiting enzyme of glycolysis, which is associated with CDDP resistance. KAT8 is an acetyltransferase that regulates lung cancer progression. Thus, we aimed to explore whether KAT8 regulates PKM2 acetylation to participate in CDDP resistance. CDDP resistance was analyzed by CCK-8, flow cytometry and western blotting. To explore the regulation of KAT8 on PKM2, coimmunoprecipitation (Co-IP), immunofluorescence and immunoprecipitation followed by western blotting were performed. Glycolysis was determined using glucose consumption, lactate production, ATP level detection kits and extracellular acidification rate assay. We observed that KAT8 levels were downregulated in CDDP-treated A549 and PC9 cells. Interference with KAT8 inhibited cell viability, promoted apoptosis and upregulated PARP1 and cleaved-PARP1 levels of A549 cells treated with CDDP, suggesting the sensitivity to CDDP was enhanced, while KAT8 overexpression attenuated the CDDP sensitivity. Moreover, KAT8 interacted with PKM2 to promote the PKM2 K433 acetylation. PKM2 K433 mutated plasmids inhibited the si-KAT8-regulated cell viability, apoptosis and glycolysis compared with PKM2-WT. Besides, KAT8 reversed the inhibition of tumor growth caused by CDDP. In conclusion, KAT8-mediated PKM2 K433 acetylation was associated with the resistance of lung cancer cells to CDDP. The findings may provide a new idea for the treatment of CDDP-resistant lung cancer.

Single-cell and bulk RNA sequencing data jointly reveals VDAC2's impacts on prognosis and immune landscape of NSCLC.

Non-small cell lung cancer (NSCLC) is characterized by stronger metastatic ability and worse prognosis. In NSCLC, hypoxia is a major cause of invasion and metastasis through promoting angiogenesis. In present study, NSCLC cell clusters were extracted from single cell-sequencing dataset GSE131907, which were combined with hypoxia-related genes to group clusters. qRT-PCR and western blot were used to validate the expression of target gene. Nine NSCLC clusters were extracted, which were divided into two hypoxia-related subgroups, C1 and C2. Totally 101 differentially expressed prognostic genes were identified between subgroups. Of which, VDAC2 showed excellent prognostic value for NSCLC and was selected for further analysis. VDAC2 was upregulated in tumor samples in TCGA and was correlated with advanced stages. In vitro experiments validated this trend. Five crucial immune cells showed differential infiltration proportions between high and low VDAC2 expression groups. VDAC2 knockdown significantly inhibited the proliferation and invasion ability of NSCLC cells. Integrating single cell and bulk sequencing data as well as wet lab experiments, hypoxia-related VDAC2 exhibited important prognostic value and showed the promise of becoming immune-therapy target in NSCLC.

Cerebral microbleeds in patients with ischemic cerebrovascular disease taking aspirin or clopidogrel.

Cerebral microbleeds (CMBs) may be markers of intracerebral bleeding risk in patients receiving antithrombotic drugs. This study aimed to analyze CMBs and white matter hyperintensities (WMHs) in patients taking aspirin or clopidogrel.This retrospective study included patients with ischemic cardiovascular disease administered 75 mg/day aspirin (n = 150) or clopidogrel (n = 150, matched for age and gender) for >1 year (Affiliated Hospital of Inner Mongolia Medical University, China, from July, 2010 to July, 2015). Patients underwent T2-weighted imaging, T1-weighted imaging, diffusion-weighted imaging (DWI) and enhanced T2*-weighted angiography (ESWAN) imaging (3.0-Tesla scanner). Baseline vascular risk factors for CMBs and macroscopic bleeding (MB) were evaluated using univariate and multivariate analyses.The aspirin and clopidogrel groups did not differ significantly in baseline characteristics or prevalences of CMBs or MB. The odds of MB were higher in patients with CMBs than in patients without CMBs in both the aspirin (odds ratio, 95% confidence interval: 4.09, 1.93-8.68; P < .001) and clopidogrel (6.42, 2.83-14.57; P < .001) groups. The odds of WMHs were also higher in patients with CMBs in both the aspirin (3.28, 1.60-6.71; P = .001) and clopidogrel (4.09, 1.91-8.75; P < .001) groups. Patients receiving treatment for >5 years showed elevated risk of CMBs in the aspirin (0.17; 0.09-0.36; P < .001) and clopidogrel (0.15, 0.07-0.33; P < .001) groups as well as higher odds of MB in the aspirin (0.34, 0.16-0.71; P = .004) and clopidogrel (0.37, 0.17-0.80; P = .010) groups.The WMHs and MB were associated with CMBs in patients taking aspirin or clopidogrel for >1 year, and long-term use increased the risks of CMB and bleeding.

Application of uniportal video-assisted thoracoscopic surgery without chest tube in enhanced recovery after thoracic surgery / 中国胸心血管外科临床杂志

@#Objective    To investigate the clinical feasibility and safety of uniportal video-assisted thoracoscopic surgery (VATS) without chest tube in enhanced recovery thoracic surgery. Method    The clinical data of patients with pulmonary bulla, pulmonary nodules and mediastinal tumors who underwent uniportal VATS in Department of Thoracic Surgery in the Affiliated Hospital of Inner Mongolia Medical University between January 2015 to May 2018 were retrospectively analyzed. A total of 78 patients did not receive closed thoracic drainage tube (a tube-free group), including 30 males and 48 females aged 32.5±8.3 years, 92 patients closed thoracic drainage tube after operation (a control group), including 38 males and 54 females aged 31.4±13.6 years. The surgery-related indicators, postoperative complications and visual analogue score (VAS) were compared between the two groups. Results    The time of early ambulation and hospital stay after operation in the tube-free group (1.0±0.3 d, 3.3±0.7 d) were significantly shorter than those in the control group (1.8±0.6 d, 5.2±0.8 d) (P=0.000, P=0.000). The VAS pain scores on the first, second and third day after operation in the tube-free group (4.5±1.8, 3.6±2.4, 2.5±1.4) were also significantly lower than those in the control group (6.8±2.2, 5.7±2.9, 3.9±1.2) (P=0.000, P=0.000, P=0.000). Operation time and intraoperative blood loss in the tube-free group (55.3±12.2 min, 21.5±5.1 mL) and the control group (57.1±6.5 min, 22.2±3.5 mL) were not statistically different (P=0.220, P=0.146). There was no pulmonary infection in both groups, and the wound healing rate was 100.0%. There was no significant difference in pneumothorax, pleural effusion, arrhythmia and re-insertion of chest drain between the tube-free group (5 patients, 8 patients, 1 patient, 3 patients) and the control group (1 patient, 4 patients, 2 patients, 1 patient, P=0.145, P=0.134, P=0.885, P=0.499). Conclusion    In strictly screened patients undergoing uniportal thoracoscopic surgery, no thoracic closed drainage tube can relieve postoperative pain, promote early ambulation activities and enhanced recovery of patients.

Application of spontaneous breathing anesthesia combined with tubeless uniportal thoracoscopy in pulmonary bullae resection: A randomized controlled trial / 中国胸心血管外科临床杂志

@#Objective    To explore the safety and feasibility of spontaneous breathing anesthesia combined with tubeless uniportal thoracoscopy in pulmonary bullae surgery. Methods    Totally 112 patients with pulmonary bullae in the Affiliated Hospital of Inner Mongolia Medical University from March 2015 to May 2017 were enrolled. According to the random number chosen by computer, the patients were randomly divided into two groups: a tubeless group (spontaneous breathing anesthesia combined with tubeless uniportal thoracoscopy) and a control group (uniportal thoracoscopy by general anesthesia with tracheal intubation) . There were 49 males and 7 females with an average age of 25.5±6.5 years in the tubeless group, and 50 males and 6 females with an average age of 23.5±4.5 years in the control group. The difference of the lowest intraoperative arterial oxygen saturation (SaO2), SaO2 at postoperative one hour, operation time, postoperative awakening time, hospital stay, hospitalization cost and postoperative pain score were analyzed. Results    There was no significant difference between the two groups in the operation time, the lowest SaO2, SaO2 at one hour after the operation and the partial pressure of carbon dioxide (PaCO2). The awakening time and duration of postoperative hospital stay in the tubeless group was shorter than those in the control group (P=0.000). The cost of hospitalization in the tubeless group was less than that in the control group (P=0.000). The discomfort caused by urinary tract and visual analogue score (VAS) in the tubeless group were better than those in the control group. Conclusion    It is safe and feasible to use spontaneous breathing anesthesia combined with tubeless uniportal thoracoscopy in pulmonary  bullae resection.