Mitochondria are critically involved in reactive oxygen species (ROS)-dependent lung diseases, such as lung fibrosis, asbestos, chronic airway diseases and lung cancer. Mitochondrial DNA (mtDNA) encodes mitochondrial proteins and is more sensitive to oxidants than nuclear DNA. Damage to mtDNA causes mitochondrial dysfunction, including electron transport chain impairment and mitochondrial membrane potential loss. Furthermore, damaged mtDNA also acts as a damage-associated molecular pattern (DAMP) that drives inflammatory and immune responses. In this review, crosstalk among alveolar epithelial cells, alveolar macrophages and mitochondria is examined. ROS-related transcription factors and downstream cell signaling pathways are also discussed. We conclude that targeting oxidative stress with antioxidant agents, such as thiol molecules, polyphenols and superoxide dismutase (SOD), and promoting mitochondrial biogenesis should be considered as novel strategies for treating lung diseases that currently have no effective treatment options.

Background Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. We aimed to comprehensively investigate the roles of CDK1, CCNB1, and CCNB2 via multi-omics analysis and their relationships with immune infiltration in hepatocellular carcinoma (HCC). Material/Methods The transcriptional data and the epigenetic and genetic alterations of CDK1 , CCNB1 , and CCNB2 , as well as their impacts on prognosis in HCC patients, were identified using multiple databases. The correlations between expression of these genes and immune infiltration in HCC were then explored using the TIMER database. Results Overall, mRNA expression of CDK1 , CCNB1 , and CCNB2 was up-regulated in various tumor tissues including HCC. Higher expression of these genes was associated with poorer prognosis in HCC patients. Lower promoter methylation of these genes might cause higher expression levels in tumor tissues of HCC. Genetic alterations and several methylated-CpG sites in these genes were significantly associated with survival. Notably, expression levels of CDK1 , CCNB1 , and CCNB2 were positively correlated with infiltrating levels of CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells in HCC. In addition, significant correlations between the expression of these genes and various immune markers in HCC, such as PD-1, PDL-1, and CTLA-4, were also observed. Conclusions CDK1 , CCNB1 , and CCNB2 are potential prognostic biomarkers and associated with immune cell infiltration in HCC. The genes may be utilized to predict the reaction of immunotherapy. Combining inhibitors of these genes with immunotherapy may improve the survival time of HCC patients.

Background: Within the generalist-plus-specialist palliative care model, palliative care is mainly provided by nurses and physicians of hospital primary care teams. Palliative care consultation teams (PCCTs) support these clinicians in adequately caring for patients with advanced illnesses. Our team started in 2012. The aim of this study was to assess the self-perceived barriers, educational needs and awareness of available palliative care support options among our hospital primary care teams. In addition, palliative care referral patterns were evaluated.Methods: Single-center mixed methods study. Outcomes of two surveys of primary care team clinicians (2012 and 2016) on barriers to palliative care, educational needs and awareness of palliative care support options were compared (chi-square, Mann-Whitney U tests, qualitative analysis). Palliative care referral characteristics were evaluated [2012][2013][2014][2015][2016][2017], including referral timing (survival since referral) (descriptive statistics, Kaplan-Meier methodology). Predictions of survival at referral were analyzed (weighted Kappa).Results: In 2012 and 2016, the most frequently reported barrier was the late initiation of the palliative care approach. Clinicians reported a need for education on physical symptom management and basic palliative care principles. Awareness of support options increased from 2012 to 2016, including improved familiarity with the PCCT (56% vs. 85%, P<0.001) and positive appraisal of the team (8% vs. 40% gave an 'excellent' rating, P<0.001). The use of national symptom management guidelines also improved (23% vs. 53%, P<0.001). Of 1,404 referrals, 86% were for cancer patients. Referrals increased by 28% (mean) per year.Medical oncology clinicians referred most frequently (27%) and increasingly early in the disease trajectory (survival ≥3 months after referral) (P=0.016). Median survival after referral was 0.9 (range, 0-83.3) months.Referring physicians overestimated survival in 44% of patients (kappa 0.36, 95% CI: 0.30-0.42).Conclusions: Primary care team clinicians persistently reported needing support with basic palliative care skills. PCCTs should continuously focus on educating primary care teams and promoting the use of guidelines. Because physicians tend to overestimate survival and usually referred patients late for specialist palliative care, consultation teams should support primary care teams to identify, treat and refer patients with palliative care needs in a timely manner.

Background: Additional studies comparing several reconstruction methods after proximal gastrectomy have been published; of note, it is necessary to update systematic reviews and meta-analysis from the current evidence-based literature. Aim: To expand the current knowledge on feasibility and safety, and also to analyze postoperative outcomes of several reconstructive techniques after proximal gastrectomy. Methods: PubMed, Google Scholar, and Medline databases were searched for original studies, and relevant literature published between the years 1966 and 2019 concerning various reconstructive techniques on proximal gastrectomy were selected. The postoperative outcomes and complications of the reconstructive techniques were assessed. Meta-analyses were performed using Rev-Man 5.0. A total of 29 studies investigating postoperative outcomes of double tract reconstruction, jejunal pouch interposition, jejunal interposition, esophagogastrostomy, and double flap reconstruction were finally selected in the quantitative analysis. Result: Pooled incidences of reflux esophagitis for double tract reconstruction, jejunal pouch interposition, jejunal interposition esophagogastrostomy, and double flap reconstruction were 8.6%, 13.8%, 13.8%, 19.3%, and 8.9% respectively. Meta-analysis showed a decreased length of hospital in the JI group as compared to the JPI group (heterogeneity: Chi 2 = 1.34, df = 1 (P = 0.25); I 2 = 26%, test for overall effect: Z = 2.22 (P = 0.03). There was also a significant difference between JI and EG in length of hospital stay with heterogeneity: Chi 2 = 1.40, df = 3 (P = 0.71); I 2 = 0%, test for overall effect: Z = 5.04 (P < 0.00001). Operative time was less in the EG group as compared to the JI group (heterogeneity: Chi 2 = 31.09, df = 5 (P < 0.00001); I 2 = 84%, test for overall effect: Z = 32.35 (P < 0.00001).

Asthma is characterized by airway inflammation and mucus hypersecretion. Curcumin possessed a potent anti-inflammatory property involved in the PPARγ-dependent NF-κB signaling pathway. Then, the aim of the current study was to explore the value of curcumin in asthmatic airway inflammation and mucus secretion and its underlying mechanism. In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce chronic asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were obtained. MCP-1, MUC5AC, and PPARγ expression and the phosphorylation of NF-κB p65 and NF-κB p65 DNA-binding activity were measured in both the lungs and BEAS-2B cells. shRNA-PPARγ was used to knock down PPARγ expression. We found that OVA-induced airway inflammation and mucus hypersecretion in mice, OVA and IL-4-induced upregulation of MCP-1 and MUC5AC, suppression of PPARγ, and activation and translocation of NF-κB p65 were notably improved by curcumin both in vivo and in vitro. Our data also showed that these effects of curcumin were significantly abrogated by shRNA-PPARγ. Taken together, our results indicate that curcumin attenuated OVA-induced airway inflammation and mucus hypersecretion in mice and suppressed OVA- and IL-4-induced upregulation of MCP-1 and MUC5AC both in vivo and in vitro, most likely through a PPARγ-dependent NF-κB signaling pathway.

Available study revealed non-small cell lung cancer (NSCLC) patients faced a risk of disease flare after cessation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There was no data concerning the prognostic value of disease flare. This study aimed to investigate the prevalence of disease flare in a Chinese cohort, and analyzed its prediction to survival. A cohort of 227 NSCLC patients with acquired resistance to EGFR TKI was retrospectively analyzed. Prevalence and clinical features of disease flare after TKI cessation were reviewed. Survival data were analyzed between patients with flare and those without flare. EGFR gene mutations in tumors were detected. Twenty of 227 (8.8 %) patients were determined with disease flare after TKI cessation. The median interval from TKI cessation to disease flare was 7 days (range 3-18). Forty percent of patients complained of deteriorated dyspnea attributable to malignant effusion. Thirty percent of patients had progressive lesions in the brain. After TKI cessation 35 % of flare patients died before challenge of subsequent treatment. No response was observed in 30 % of flare patients undergoing subsequent chemotherapy. When compared with the non-flare group, patients with disease flare demonstrated comparable progression-free survival (10.1 vs. 9.9 months; P = 0.973), shorter post-TKI survival (4.1 vs. 6.1 months; P < 0.001), and a significantly poor overall survival (16.6 vs. 21.6 months; P = 0.002). Disease flare after cessation of EGFR TKI occurred in Chinese NSCLC population and predicted a poor survival.

Pulmonary artery intimal sarcoma is a highly aggressive disease, and is most often misdiagnosed as pulmonary thromboembolism (PTE) due to the similar clinical symptoms and its rarity, which leads to the use of inappropriate treatments such as prolonged anticoagulant therapy. We reported a case of pulmonary artery intimal sarcoma in a patient who was misdiagnosed as having PTE. Pathology after surgery confirmed malignant disease. We concluded that when a patient presents with mild clinical manifestations yet with strong imaging manifestations, pulmonary artery malignancy should be suspected.

The aim of this study was to identify disease-causing gene mutations in a Chinese family affected with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a 4-generation pedigree of 27 members in the Southern Chinese Han population, including 11 individuals diagnosed with ADNFLE. DNA samples were collected from 15 family members, chinese han people, including seven affected and eight unaffected individuals. None of these patients had night blindness or visual disorders. Four affected individuals were screened for mutations using whole-exome sequencing, and 13 potentially interesting mutations shared by all the four affected individuals were validated using the Sanger sequencing method. Only one novel missense mutation c.464G>A (p.G155D) in the CABP4 gene, encoding the neuronal Ca2+-binding protein 4 (CaBP4), was present in all seven affected individuals in this family as revealed by PCR with blood DNA samples using CABP4 primers. The mutation was also found in one young unaffected family member, but was absent from 300 unrelated control subjects. The p.G155D mutation, located near the Ca2+ binding motif EF-hand 1 and the L-type Ca2+ channel (Cav1.4) binding motif within the N-terminal lobe of CaBP4, is predicted to affect protein function according to the bioinformatics tools PolyPhen-2 and SIFT. These findings suggest that mutations in the CABP4 gene may be linked to ADNFLE.