The interaction between DNA methylation and tumor immune microenvironment: from the laboratory to clinical applications.

DNA methylation is a pivotal epigenetic modification that affects gene expression. Tumor immune microenvironment (TIME) comprises diverse immune cells and stromal components, creating a complex landscape that can either promote or inhibit tumor progression. In the TIME, DNA methylation has been shown to play a critical role in influencing immune cell function and tumor immune evasion. DNA methylation regulates immune cell differentiation, immune responses, and TIME composition Targeting DNA methylation in TIME offers various potential avenues for enhancing immune cytotoxicity and reducing immunosuppression. Recent studies have demonstrated that modification of DNA methylation patterns can promote immune cell infiltration and function. However, challenges persist in understanding the precise mechanisms underlying DNA methylation in the TIME, developing selective epigenetic therapies, and effectively integrating these therapies with other antitumor strategies. In conclusion, DNA methylation of both tumor cells and immune cells interacts with the TIME, and thus affects clinical efficacy. The regulation of DNA methylation within the TIME holds significant promise for the advancement of tumor immunotherapy. Addressing these challenges is crucial for harnessing the full potential of epigenetic interventions to enhance antitumor immune responses and improve patient outcomes.

CircRNA hsa_circ_0000043 acts as a miR-4492 sponge to promote lung cancer progression via BDNF and STAT3 expression regulation in anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide-transformed 16HBE cells.

Increasing evidence shows that circular RNA (circRNA) plays an important role in the progression of lung cancer. In this study, we found that has_circ_0000043 was highly expressed in 16HBE-T human bronchial epithelial cells that were malignantly transformed by benzo[a]pyrene-trans-7,8-diol-9,10-epoxide via circRNA microarray. We verified that hsa_circ_0000043 was also significantly overexpressed in lung cancer cell lines and tissues. Moreover, hsa_circ_0000043 overexpression was positively correlated with poor clinicopathological parameters, such as tumor-node metastasis stage, distant metastasis, lymph-node metastasis, and overall survival. In vitro assays revealed that hsa_circ_0000043 inhibition suppressed 16HBE-T cell proliferation, migration, and invasion. Furthermore, hsa_circ_0000043 inhibition suppressed tumor growth in a mouse xenograft model. We discovered that hsa_circ_0000043 binds with miR-4492, acting as a miR-4492 sponge. Decreased miR-4492 expression was also associated with poor clinicopathological parameters. Thus, hsa_circ_0000043 was shown to contribute to the proliferation, malignant transformation ability, migration, and invasion of 16HBE-T cells via miR-4492 sponging and BDNF and STAT3 involvement.

Development and validation of a pulmonary complications prediction model based on the Yang's index.

Background: Blunt chest trauma patients with pulmonary contusion are susceptible to pulmonary complications, and severe cases may develop respiratory failure. Some studies have suggested the extent of pulmonary contusion to be the main predictor of pulmonary complications. However, no simple and effective method to assess the severity of pulmonary contusion has been available yet. A reliable prognostic prediction model would facilitate the identification of high-risk patients, so that early intervention can be given to reduce pulmonary complications; however, no suitable model based on such an assumption has been available yet. Methods: In this study, a new method for assessing lung contusion by the product of the three dimensions of the lung window on the computed tomography (CT) image was proposed. We conducted a retrospective study on patients with both thoracic trauma and pulmonary contusion admitted to 8 trauma centers in China from January 2014 to June 2020. Using patients from 2 centers with a large number of patients as the training set and patients from the other 6 centers as the validation set, a prediction model for pulmonary complications was established with Yang's index and rib fractures, etc., being the predictors. The pulmonary complications included pulmonary infection and respiratory failure. Results: This study included 515 patients, among whom 188 developed pulmonary complications, including 92 with respiratory failure. Risk factors contributing to pulmonary complications were identified, and a scoring system and prediction model were constructed. Using the training set, models for adverse outcomes and severe adverse outcomes were developed, and area under the curve (AUC) of 0.852 and 0.788 were achieved in the validation set. In the model performance for predicting pulmonary complications, the positive predictive value of the model is 0.938, the sensitivity of the model is 0.563 and the specificity of the model is 0.958. Conclusions: The generated indicator, called Yang's index, was proven to be an easy-to-use method for the evaluation of pulmonary contusion severity. The prediction model based on Yang's index could facilitate early identification of patients at risk of pulmonary complications, yet the effectiveness of the model remains to be validated and its performance remains to be improved in further studies with larger sample sizes.

Prognosis and surgical outcomes of the total thymectomy versus thymomectomy in non-myasthenic patients with early-stage thymoma: A systematic review and meta-analysis.

Whether thymectomy (TM) or thymomectomy (TMM) is better for non-myasthenic patients with early-stage thymoma. We conducted a meta-analysis to compare the clinical outcomes and prognoses of non-myasthenic patients with early-stage thymoma treated using thymectomy versus thymomectomy. PubMed, Embase, Cochrane Library and CNKI databases were systematically searched for relevant studies on the surgical treatment (TM and TMM) of non-myasthenic patients with early-stage thymoma published before March 2022. The Newcastle-Ottawa scale was used to evaluate the quality of the studies, and the data were analyzed using RevMan version 5.30. Fixed or random effect models were used for the meta-analysis depending on heterogeneity. Subgroup analyses were performed to compare short-term perioperative and long-term tumor outcomes. A total of 15 eligible studies, including 3023 patients, were identified in the electronic databases. Our analysis indicated that TMM patients might benefit from a shorter duration of surgery (p = 0.006), lower blood loss volume (p < 0.001), less postoperative drainage (p = 0.03), and a shorter hospital stay (p = 0.009). There were no significant differences in the overall survival rate (p = 0.47) or disease-free survival rate (p = 0.66) between the two surgery treatment groups. Likewise, TM and TMM were similar in the administration of adjuvant therapy (p = 0.29), resection completeness (p = 0.38), and postoperative thymoma recurrence (p = 0.99). Our study revealed that TMM might be a more appropriate option in treating non-myasthenic patients with early-stage thymoma.

Sleeve Lobectomy After Neoadjuvant Chemoimmunotherapy Versus Chemotherapy for Squamous Cell Lung Cancer: A Multicenter, Retrospective Study.

Introduction: To analyze the feasibility and efficacy of sleeve lobectomy after neoadjuvant immunotherapy in multicenter patients with squamous cell lung cancer. Methods: We retrospectively identified patients who received neoadjuvant immunotherapy (n = 14) or chemotherapy alone (n = 33) at five thoracic surgery centers between 2018 and 2020. The primary end point was 30-day major complications. The secondary end point was major pathologic response. Multivariate analysis was performed with a log-binomial regression model adjusting potential risk factors. Results: All patients received induction therapy and underwent sleeve lobectomy without 90-day postoperative deaths. The distribution of age, sex, nutrition status, pulmonary and cardiac function, tumor stage, surgical approach, and location of the pulmonary lobe was well balanced between the two cohorts. In the immunotherapy cohort, two patients (14.3%) experienced a pulmonary major complication, whereas nine pulmonary major complications and one cardiac major complication (30.3%) occurred in the chemotherapy cohort (p = 0.302). Conclusions: Neoadjuvant immunotherapy in addition to chemotherapy did not increase 30-day risk of postoperative complications, and immunotherapy is a favorable factor affecting pathologic downstage and response. Therefore, sleeve lobectomy after induction chemoimmunotherapy appears safe and feasible.

Chimeric RNA RRM2-C2orf48 plays an oncogenic role in the development of NNK-induced lung cancer.

Chimeric RNAs have been used as biomarkers and therapeutic targets for multiple types of cancers. However, less attention has been paid to their mechanism of action in neoplasia. Here, we reported that high-expressed chimeric RNA RRM2-C2orf48 was found in malignantly transformed BEAS-2B cells induced by 4-(methyl nitrosamine)-1-(3-pyridinyl)-1-butanone (NNK) in 74 lung cancer patients and several lung cancer cell lines. The expression level of RRM2-C2orf48 was significantly correlated with lymph node metastasis, distant metastasis, tumor-lymph node-metastasis (TNM) stage, and smoking. Overexpressing RRM2-C2orf48 promoted cell growth and accelerated the process of NNK-induced lung cancer. RRM2-C2orf48 knockdown inhibited the growth of RRM2-C2orf48-overexpressing BEAS-2B cells. Finally, we identified miR-219a-2-3p as a potential target of RRM2-C2orf48 in lung cancer. In summary, chimeric RNA RRM2-C2orf48 accelerated the process of NNK-induced lung cancer, and miR-219a-2-3p may be involved in this process.

Conversion Surgery Following Immunochemotherapy in Initially Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma-A Real-World Multicenter Study (RICE-Retro).

Purpose: The present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario. Materials and Methods: In this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared. Results: One hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery. Conclusion: Our results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

[Association of miR-146a rs2910164 G/C polymorphism with its abnormal expression and risk of gastric cancer].

OBJECTIVE: To assess the influence of rs2910164 G/C single nucleotide polymorphism (SNP) of the miR-146a gene on its expression and susceptibility to gastric cancer. METHODS: Fifty three gastric cancer patients and six gastric cancer cell lines were selected for determining the miR-146a expression by Taqman quantitative PCR. A model was constructed to assess the influence of miR-146a overexpression on the growth of AGS gastric cancer cells. A case-control study involving 417 gastric cancer patients and 420 cancer-free individuals was then conducted, and the allelic and genotypic frequencies of the rs2910164 G/C SNP were compared. The genotypes of all subjects were determined by using a Taqman allelic discrimination assay. A Taqman assay was also used to quantify mature and pri-miR-146a transcripts among 65 gastric cancer patients with known genotypes. RESULTS: The expression of miR-146a was down-regulated among the 53 gastric cancer patients and six gastric cancer cell lines. Over-expression of miR-146a has suppressed the growth of gastric cancer by inhibiting the G1/S-phase transition of AGS cells. The case-control study showed that subjects with GC/CC genotypes had significantly lower risk for gastric cancer compared with those with GG genotype. In addition, miR-146a G/C SNP has significantly increased the level of mature miR-146a in those with GC/CC genotype compared with GG genotype. CONCLUSION: Down-regulation of miR-146a may play an important role in the pathogenesis of gastric cancer. The rs2910164 polymorphism of the miR-146a gene may reduce the risk of gastric cancer by influencing the processing of mature miR-146a.

Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan-cancer cohort.

Tumour-derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell-free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we integrated landscape of CH mutations in 11,725 pan-cancer patients of Chinese and explored effects of CH on liquid biopsies in real-world. We first identified 5933 CHs based on panel sequencing of matched DNA of white blood cell and cfDNA on 301 genes for 5100 patients, in which CH number of patients had positive correlation with their diagnosis age. We observed that canonical genes related to CH, including DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2 and SF3B1, were dominant in the Chinese cohort and 13.29% of CH mutations only appeared in the Chinese cohort compared with the Western cohort. Analysis of CH gene distribution bias indicated that CH tended to appear in genes with functions of tyrosine kinase regulation, PI3K-Akt signalling and TP53 activity, suggesting unfavourable effects of CH mutations in cancer patients. We further confirmed effect of driver genes carried by CH on somatic mutations in liquid biopsy of cancer patients. Forty-eight actionable somatic mutations in 17 driver genes were considered CH genes in 92 patients (1.80%) of the Chinese cohort, implying potential impacts of CH on clinical decision-making. Taken together, this study exhibits strong evidence that gene mutations from CH interfere accuracy of liquid biopsies using cfDNA in cancer diagnosis and treatment in real-world.

A genome-wide screen for differentially methylated long noncoding RNAs identified that lncAC007255.8 is regulated by promoter DNA methylation in Beas-2B cells malignantly transformed by NNK.

Tobacco exposure is well known to induce genetic and epigenetic changes that contribute to the pathogenesis of lung cancer. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a significant tobacco-specific carcinogen, but the oncogenic mechanisms of NNK have not been thoroughly elucidated. In this study we found that DNA methyltransferase 1 (DNMT1) was overexpressed in malignantly transformed human bronchial epithelial Beas-2B cells induced by NNK (2B-NNK cells), by treatment with NNK (400 µg/mL) for 7 days. An Arraystar Human noncoding RNA Promoter Microarray was used to detect the DNA methylation status of the promoter region of long noncoding RNAs (lncRNAs). The result showed that 1010 differentially methylated fragments were present in the lncRNA promoter region. QRT-PCR revealed that the expression of lncRNA AC007255.8 was remarkably downregulated in 2B-NNK cells and lung cancer tissues. Furthermore, Methylation-specific PCR showed that the methylation of the lncRNA AC007255.8 promoter was increased in 2B-NNK cells and lung cancer tissues. The reduced expression of lncRNA AC007255.8 was significantly associated with hypermethylation of lncRNA AC007255.8 promoter region. LncRNA AC007255.8 overexpression could result in decreased cell proliferation and increased cell apoptosis in 2B-NNK cells. In conclusion, NNK induced lncRNA AC007255.8 promoter hypermethylation via upregulation of DNMT1 in Beas-2B cells, leading to downregulation of lncRNA AC007255.8, and ultimately the enhancement of cell proliferation and the inhibition of apoptosis. This research affords novel insights into the epigenetic mechanisms of lung cancer, and will stimulate further research into the involvement of aberrant DNA methylation of non-coding regions of the genome in the pathogenesis of lung cancer.

Identification of SRXN1 and KRT6A as Key Genes in Smoking-Related Non-Small-Cell Lung Cancer Through Bioinformatics and Functional Analyses.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide. Although cigarette smoking is an established risk factor for lung cancer, few reliable smoking-related biomarkers for non-small-cell lung cancer (NSCLC) are available. An improved understanding of these biomarkers would further the development of new biomarker-targeted therapies and lead to improvements in overall patient survival. METHODS: We performed bioinformatic analysis to screened potential target genes, then quantitative PCR, western, siRNA, CCK-8, flow cytometry, tumorigenicity assays in nude mice were performed to validated the function. RESULTS: In this study, we identified 83 smoking-related genes (SRGs) based on an integration analysis of two Gene Expression Omnibus (GEO) datasets, and 27 hub SRGs with potential carcinogenic effects by analyzing a dataset of smokers with NSCLC in The Cancer Genome Atlas (TCGA) database. A survival analysis revealed three genes with potential prognostic value, namely SRXN1, KRT6A and JAKMIP3. A univariate Cox analysis revealed significant associations of elevated SRXN1 and KRT6A expression with prognosis. A receiver operating characteristic (ROC) curve analysis indicated the high diagnostic value of SRXN1 and KRT6A for smoking and cancer. Quantitative PCR and western blotting validated the increased expression of SRXN1 and KRT6A mRNA and protein, respectively, in lung cancer cell lines and NSCLC tissues. In patients with NSCLC, SRXN1 and KRT6A expression was associated with the tumor-node-metastasis (TNM) stage, presence of metastasis, history of smoking and daily smoking consumption. Furthermore, inhibition of SRXN1 or KRT6A suppressed viability and enhanced apoptosis in the A549 human lung carcinoma cell line. Tumorigenicity assays in nude mice confirmed that the siRNA-mediated downregulation of SRXN1 and KRT6A expression inhibited tumor growth in vivo. CONCLUSIONS: In summary, SRXN1 and KRT6A act as oncogenes in NSCLC and might be potential biomarkers of smoking exposure and the early diagnosis and prognosis of NSCLC in smokers, which is vital for lung cancer therapy.

[Value of preoperative localization techniques for solitary pulmonary nodules in singleport thoracoscopic surgery].

ObjectiveTo evaluate the value and clinical effect of different preoperative localization techniques for solitary pulmonary nodules (SPN) before single-port thoracoscopic surgery.MethodFrom January 2018 to June 2019, 54 patients diagnosed with solitary pulmonary nodules received single-port thoracoscopic surgery in Thoracic Department of General Hospital of Southern Theater Command of PLA. Based on the location methods of the nodules, the patients were divided into group A (34 cases) with preoperative CT-guided Hook-wire (a common positioning needle usually using in mammary gland) positioning and group B (20 cases) with preoperative CT-guided methylene blue location.ResultsThe success rate of localization in group A was 94.18% (32/34), significantly higher than that in group B [85% (17/20), P < 0.05). No intraoperative conversion to thoracotomy occurred in group A, while the conversion rate was 10% (2/20) in group B (P < 0.05). The average positioning cost was significantly higher in group A than in group B (1715±109 vs 1021±86 RMB yuan, P < 0.05), but the total hospitalization cost was similar between the two groups (50 114±3788 vs 47871±5902 RMB yuan, P>0.05). The length of hospital stay was significantly shorter in group A than in group B (6.71±1.23 vs 8.19±2.61 days, P < 0.05).ConclusionCompared with the traditional methylene blue localization method, Hook-wire localization positioning can significantly increase the success rate of localization, and can be used as the standard preoperative localization method in patients undergoing single-port thoracoscopic pulmonary nodule resection, especially in those with deep nodule location from the visceral pleura.

The ideal methods for the management of rib fractures.

The clinical treatment choices for multiple rib fractures and flail chest are controversial. For example, among conservative treatment and surgical treatment, different studies have different conclusions and recommendations. Furthermore, early clinical research was mainly focused on the treatment of flail chest due to its severity. Nowadays, the treatment for multiple rib fractures patients without a flail chest is drawing an increased clinical interest. However, we are facing many challenges for the treatment of rib fractures, such as insufficient understanding of the available treatment options, lack of clinical research, lack of the internationally recognized clinical indication for the surgical stabilization of rib fractures (SSRF), and the constant controversies and debates in terms of treatment options, surgery timing, and surgical techniques. All these challenges make it difficult to select the most appropriated clinical decisions for the proper treatment of a rib fracture, resulting in a seriously hindered development of novel rib fractures treatment choices. The concepts and ideas for traditional rib fractures treatment are relatively old, and even have some misunderstandings or errors. With the emergence of more and more research, the understandings of the rib fractures treatment has gradually improved; for example, the benefits provided to patients under the open reductions and internal fixation of fractures treatment. In this article, we outlined the new concepts in rib fractures treatment, which mainly included four parts, damage control, pain management, fixation selection, and quality of life. We hope these concepts help practitioners better manage rib fracture patients.

Silencing of lncRNA AFAP1-AS1 suppressed lung cancer development by regulatory mechanism in cis and trans.

Although the long noncoding RNA AFAP1-AS1 has been shown to be involved in various types of cancer, its involvement in lung cancer remains poorly understood. In the current study, we found that AFAP1-AS1 was substantially over expressed in lung cancer tissues and cell lines. In addition, AFAP1-AS1 expression level was proven to be associated with the malignant features of lung cancer. Knockdown of AFAP1-AS1 significantly suppressed cell proliferation by increasing cell apoptosis and G0/G1 phase retardation of cell cycle in lung cancer cells. Furthermore, AFAP1-AS1 knockdown could suppress tumor growth of lung cancer in BALB/c nude mice. We also identified that AFAP1-AS1 silencing could influence the expression of AFAP1 and KRT1 on mRNA and protein level by cis and trans regulatory mechanism. Moreover, the oncogenic activities of AFAP1-AS1 on cell proliferation are partially mediated by KRT1. In summary, these findings demonstrate that AFAP1-AS1 plays an essential role in promoting lung cancer development in vitro and vivo. It indicated that AFAP1-AS1 is a promising prognostic predictor for patients with lung cancer.

Biomarkers for early diagnosis, prognosis, prediction, and recurrence monitoring of non-small cell lung cancer.

Despite advances in the management of non-small cell lung cancer, it remains to be the leading cause of cancer-related deaths worldwide primarily because of diagnosis at a late stage with an overall 5-year survival rate of 17%. A reduction in mortality was achieved by low-dose computed tomography screening of high-risk patients. However, the benefit was later challenged by the high false positive rate, resulting in unnecessary follow-ups, thus entailing a burden on both the health care system and the individual. The diagnostic dilemma imposed by imaging modalities has created a need for the development of biomarkers capable of differentiating benign nodules from malignant ones. In the past decade, with the advancements in high-throughput profiling technologies, a huge amount of work has been done to derive biomarkers to supplement clinical diagnosis. However, only a few of them have efficient sensitivity and specificity to be utilized in clinical settings. Therefore, there is an urgent need for the development of sensitive and specific means to detect and diagnose lung cancers at an early stage, when curative interventions are still possible. Due to the invasiveness of tissue biopsies and inability to capture tumor heterogeneity, nowadays enormous efforts have been invested in the development of technologies and biomarkers that enable sensitive and cost-effective testing using substrates that can be obtained in a noninvasive manner. This review, primarily focusing on liquid biopsy, summarizes all documented potential biomarkers for diagnosis, monitoring recurrence treatment response.

Functional role of lncRNA DB327252 in lung cancer.

BACKGROUND: Lung cancer becomes a concerning health issue and is considered one of the most deadly cancers in the worldwide. Most recently, long non-coding RNAs (lncRNAs) are newfound non-coding RNAs that are thought as one of the major players in a range of biological processes of human diseases. Although lncRNAs are involved in numerous cancer types, the precise understandings of lncRNAs' functional roles and mechanisms in lung cancer are limited. In this study, we looked for lung cancer related lncRNAs. METHODS: The quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) technique was utilized to investigate the lncRNA DB327252 expression in 91 paired clinical lung cancer tissues and related cell lines. Moreover, its biological functions were also evaluated in the development of lung cancer. RESULTS: The results indicated that the expression of DB327252 was up-regulated in lung cancer tissues compared to the cancer-adjacent normal tissues (P<0.05); and the up-regulated expression is likely to relate to those with bigger tumor size, adenocarcinoma and advanced TNM stage (P<0.05). In addition, the knockdown of DB327252 inhibited the growth and proliferation of tumor cell in vitro and in vivo. According to the observation from our study, we found that the knockdown of the DB327252 expression, led to G0/G1 phase cell-cycle arrested, colony formation suppressed in vitro, and tumor growth inhibited in a nude mouse xenograft model. Our experimental results also suggest that lncRNA DB327252 may be a lncRNA related to lung cancer and acts an important role in A549 and 16HBE-T cancer cells, which provides evidence that DB327252 has an oncogene-like function in lung cancer. CONCLUSIONS: The lncRNA DB327252 is up-regulated in lung cancer, and its expression implies that it was probable related to biologic functions of lung cancer.

Subcostal thoracoscopic extended thymectomy for patients with myasthenia gravis.

BACKGROUND: Extended thymectomy is indicated for patients with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for subcostal thoracoscopic extended thymectomy (STET) on patients with MG. METHODS: Clinical data of 15 eligible patients who underwent STET in our department from February 2015 to November 2015 by the same surgical team were retrospectively analyzed. The operation time, blood loss, duration of postoperative hospital stay, thoracic drainage periods were concerned. RESULTS: All the surgeries were finished successfully without conversion to sternotomy. Mean operation time was 157.53±40.31 min (range, 73-275 min). Mean blood loss was 56.33±7.07 mL (range, 10-200 mL). Mean pleural drainage volume in the first 24 hours was 72.67±17.68 mL (range, 0-250 mL). Mean postoperative thoracic drainage periods were 1.20±0.71 days (range, 0-3 days). Mean duration of postoperative hospital stay was 6.13±0.71 days (range, 3-22 days). CONCLUSIONS: This procedure showed satisfactory results for patients with MG. Moreover, the STET approach is more easily for surgeons to fully reveal the bilateral phrenic nerve and the upper thymic poles. We believe that STET is a satisfactory procedure for performing extended thymectomy in well selected patients.

A phosphoproteomic study reveals shp-1 cleavage reprograms LPS signaling via a PI-3K/NF-κB and mTORC1 related mechanism.

The reprogrammed lipopolysaccharide (LPS) pathway has been reported to render patients more susceptible to the development of post-traumatic multiple organ dysfunction syndrome (MODS). To facilitate thorough understanding of this mechanism, a phosphoproteomic study was utilized to screen the potential signaling molecules. Interestingly, a truncated form of Src homology 2-domain-containing tyrosine phosphatase 1 (shp-1) emerged in human THP-1 macrophages sequentially treated with H2O2 and LPS and not with either of the treatments alone. Subsequent immunoblot analysis confirmed the cleavage of shp-1 and reduction of shp-1 activity in rat alveolar macrophages, mast cells, and neutrophils. Mechanistically, calpain is essential but not sufficient for shp-1 cleavage. In addition, shp-1 cleavage renders the activation of phosphatidylinositol 3-kinase (PI-3K)/nuclear factor-κB (NF-κB) and mechanistic target of rapamycin complex 1 (mTORC1) in macrophages, resulting in enhanced cytokine induced neutrophil chemoattractant (CINC) secretion, which is critical for neutrophil recruitment in MODS. On the other hand, shp-1 cleavage results in the activation of PI-3K/Akt, enhancing the survival of neutrophils. Collectively, these results highlight the cleavage of shp-1 as a critical event in reprogramming LPS pathway to promote both neutrophil recruitment and survival and provide a novel mechanistic framework for the investigation of the post-traumatic MODS.

A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer.

Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 µmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G0/G1 in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer.