Comparative study of the clinical efficacy of subcostal thoracoscopy and median sternotomy in treating thymoma: a propensity score-matching analysis.

OBJECTIVE: This study was performed to evaluate the clinical efficacy of subcostal thoracoscopy and median sternotomy as surgical approaches for thymoma resection and lymph node dissection. The feasibility, safety, and clinical outcomes of subcostal thoracoscopy were compared with those of median sternotomy. METHODS: The clinical data of 335 patients with thymoma were retrospectively analyzed. The patients were divided into the subcostal thoracoscopy group and the median sternotomy group. Propensity score matching was performed to obtain comparable subsets of 50 patients in each group. A comparative analysis was conducted on various parameters. RESULTS: All surgeries were successful, and no conversions to open thoracotomy were required in the subcostal thoracoscopy group. Significant differences in the operative time, intraoperative blood loss, chest tube drainage duration, postoperative hospital stay, patient satisfaction scores, pain assessment, and postoperative complications were observed between the two groups. However, there was no significant difference in the number of lymph nodes or lymph node stations dissected intraoperatively between the two groups. CONCLUSION: Subcostal thoracoscopy is not inferior to median sternotomy as a surgical approach for thymoma resection and lymph node dissection. Our research provides important new comparative data on minimally invasive thymoma resection.

Imprinted Dlk1-Gtl2 cluster miRNAs are potential epigenetic regulators of lamb fur quality.

BACKGROUND: Tan and Hu sheep are well-known local breeds in China, producing lamb fur with unique ornamental and practical values highly appreciated by consumers worldwide. Fur quality is optimal at one month of age and gradually declines with time. Despite active research on its genetic mechanism using transcriptomic and whole genome bisulfite sequencing analysis, the main effective gene locus has not been found, and its regulatory mechanism is still unclear, which limits the breeding and improvement of fur traits. RESULTS: Scapular skin samples from newborn (1-month old) and adult (24-month old) Tan sheep were utilized for small ribonucleic acid (RNA) sequencing Principal Component Analysis (PCA) showed that the newborn and adult groups were completely separated. Differential expression analysis of micro-RNAs (miRNAs) identified 32 up-regulated miRNAs and 48 down-regulated miRNAs in the newborn groups. All up-regulated miRNAs were located in the imprinted. Dlk1-Gtl2 locus on chromosome 18, whereas all down-regulated miRNAs were distributed across the sheep chromosomes, without a clear pattern of positional consistency. Further, by systematically analyzing the target genes and signaling pathways of all 32 up-regulated miRNAs, we found that the PI3K-AKT signaling pathway has the potential to be targeted and regulated by most of the miRNAs in the Dlk1-Gtl2 region. In addition, we also re-analyzed miRNA sequencing data from public databases on Hu lambs (full sibling Hu lambs with high- and low-quality fur characteristics). Again, it was found that most of the up-regulated miRNAs in lambs with high-quality fur were also located in the Dlk1-Gtl2 region, whereas this patter was not present for down-regulated miRNAs. CONCLUSION: Sequencing of miRNAs in conjunction with public databases was employed to identify miRNAs within the imprinted Dlk1-Gtl2 region on chromosome 18, suggesting their potential roles as epigenetic regulators of fur traits. Small RNAs located at the Dlk1-Gtl2 locus were identified as having the potential to systematically regulate the PI3K-AKT signaling pathway, thereby indicating the relevance of the Dlk1-Gtl2/PI3K-AKT axis in the context of fur traits. Selection of parental specific expressed imprinted genes in the process of conserving and exploiting lamb fur traits should be emphasized.

Neoadjuvant Camrelizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone for Chinese Patients With Resectable Stage IIIA or IIIB (T3N2) Non-Small Cell Lung Cancer: The TD-FOREKNOW Randomized Clinical Trial.

Importance: The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. Objective: To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. Design, Setting, and Participants: In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Interventions: Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. Main Outcomes and Measures: The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Results: Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. Conclusions and Relevance: This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04338620.

Nomogram for predicting the risk of postoperative myasthenic crisis in patients with thymectomy.

OBJECTIVE: This study aimed to develop and validate internally a clinical predictive model, for predicting myasthenic crisis within 30 days after thymectomy in patients with myasthenia gravis. METHODS: Eligible patients were enrolled between January 2015 and May 2019. The primary outcome measure was postoperative myasthenic crisis (POMC). A predictive model was constructed using logistic regression and presented in a nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to examine the performance. The study population was divided into high- and low-risk groups according to Youden index. Calibration curves with 1000 replications bootstrap resampling were plotted to visualize the calibration of the nomogram. Decision curve analyses (DCA) with 1000 replications bootstrap resampling were performed to evaluate the clinical usefulness of the model. RESULTS: A total of 445 patients were enrolled. Five variables were screened including thymus imaging, onset age, MGFA classification, preoperative treatment regimen, and surgical approach. The model exhibited moderate discriminative ability with AUC value 0.771. The threshold probability was 0.113, which was used to differentiate between high- and low-risk groups. The sensitivity and specificity were 72.1% and 77.1%, respectively. The high-risk group had an 8.70-fold higher risk of POMC. The calibration plot showed that when the probability was between 0 and 0.5, the deviation calibration curve of the model was consistent with the ideal curve. INTERPRETATION: This nomogram could assist in identifying patients at higher risk of POMC and determining the optimal surgical time for these patients.

Clinical Comparative Analyses of Thymectomy Between Subxiphoid and Subcostal Arch Thoracoscopic Resection and Median Sternotomy for the Treatment of Thymoma With Myasthenia Gravis in Chinese Patients.

INTRODUCTION: This study aims to retrospectively compare the efficacy and safety of subxiphoid and subcostal arch thoracoscopic resection (SR) and the median sternotomy (MS) for thymoma with myasthenia gravis (MG) via propensity-matched analysis. METHODS: We retrospectively analyzed 502 patients with thymoma and MG in Tangdu Hospital of the Fourth Military Medical University from December 2012 to December 2017. The patients were allocated to SR group (n = 424) and MS group (n = 78). Perioperative outcomes were compared between SR group and MS group by using propensity-matched analysis. RESULTS: All SR and MS operations were accomplished successfully. Most postoperative outcomes between the two groups showed no significant difference such as remission of MG and postoperative complication (P > 0.05). There were statistically significant differences between MS group and SR group in operation time [(116.3 ± 33.7) min versus (52.2 ± 31.3) min], intraoperative blood loss [(145.2 ± 26.7) mL versus (51.2 ± 10.3) mL], chest drainage duration (3.4 d versus 0 d), days of hospital-stay (5.2 d versus 2.7 d), patient satisfaction score (5.9 ± 2.3 versus 8.7 ± 1.2), the incidence of complications and pain scores, with all P values < 0.05. CONCLUSIONS: This study suggests that subxiphoid and subcostal arch thoracoscopic resection is a less invasive procedure with good safety and feasibility as compared with median sternotomy for thymoma with myasthenia gravis.

Curved Porous PdCu Metallene as a High-Efficiency Bifunctional Electrocatalyst for Oxygen Reduction and Formic Acid Oxidation.

Designing high-efficiency and newly developed Pd-based bifunctional catalytic materials still faces tremendous challenges for oxygen reduction reaction (ORR) and formic acid oxidation reaction (FAO). Metallene materials with unique structural features are considered strong candidates for enhancing the catalytic performance. In this work, we synthesized copper-doped two-dimensional curved porous Pd metallene nanomaterials via a simplistic one-pot solvothermal method. The updated catalysts served as sturdy bifunctional electrocatalysts for cathodal ORR and anodic FAO. In particular, the developed PdCu metallene exhibits excellent half-wave potential (0.943 V vs RHE) and mass activity (MA) (1.227 A mgPt-1) in alkaline solutions, which are 1.09 and 6.26 times higher than those of commercial Pt/C, respectively, indicating that the nanomaterials have abundant active sites, displaying surpassing catalytic performance for oxygen reduction. Furthermore, in an acidic formic acid electrolyte, PdCu metallene exhibits prominent MA with a value of 0.905 A mgPd-1, which is 2.76 times that of commercial Pd/C. The remarkable bifunctional catalytic performance of metallene materials can be attributed to the special structure and electronic effects. This work shows that metallene materials with curved and porous properties provide a scientific idea for the development and design of efficient and steady electrocatalysts.

Potential prognostic markers of retained placenta in dairy cows identified by plasma metabolomics coupled with clinical laboratory indicators.

The complex etiopathology of retained placenta (RP) and hazards associated with it has made it crucial for researchers and clinical veterinarians to study pathogenesis, early-warning diagnosis, and treatment. This study aimed to screen the potential prognostic markers of RP in dairy cows using plasma metabolomics coupled with clinical laboratory indicators. Blood samples were collected from 260 dairy cows at 21, 14, 7, and 0 days before parturition and 7, 14, and 21 days after parturition. Consequently, 10 healthy cows and 10 cows with RP with similar parity, body condition score, and age were included in the study. The changes in clinical laboratory indicators of the enrolled cows from 21 before parturition to 21 days after parturition were assessed. After initial overview of the multivariate statistical data using PCA analysis, the data were subjected to orthogonal partial least-squares discriminant analysis. Compared with cows with RP at 7 days before parturition, the levels of endothelin and 6-keto-prostaglandin F1α were increased in healthy cows, while the level of estradiol and progesterone decreased. Adenine dinucleotide phosphate, hypoxanthine, guanine dinucleotide phosphate, inosine monophosphate, and L-arginine were revealed as potential prognostic markers of cows with RP at 7 days before parturition involved in the regulation of taste transduction, purine and glutathione metabolism, and autophagy. The best period for the early-warning diagnosis of RP in dairy cows is 7 days before parturition, and purine metabolism and autophagy may play a vital role in the occurrence and development of RP in dairy cows.

Thymectomy and Risk of Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study.

This study aims to investigate the association between thymectomy and the risk of generalization in patients with ocular myasthenia gravis (MG). Data on patients with ocular MG from seven neurological centers in China were retrospectively reviewed. Ocular MG naïve to immunotherapy was categorized according to whether thymectomy was performed (thymectomized group vs. nonsurgical group). Patients in the thymectomized group all underwent surgery within 2 years since ocular symptom onset. The main outcome measure was the generalization. The follow-up period was defined from the date of ocular symptom onset to the date of generalization confirmation, immunotherapy initiation, or last follow-up (defined as 60 months). Of 519 eligible patients (mean [SD] age, 48.7 [15.2] years, 46.6% women), 31 (23.7%) of 131 generalized in the thymectomized group and 122 (31.4%) of 388 did in the nonsurgical group during a median follow-up of 19 months (IQR 8.0-50.0). Thymectomy was independently associated with reduced generalization risk (adjusted HR 0.41, 95% CI 0.25-0.66, P < 0.001). Multivariable stratified analysis also verified this association across the subgroups. Kaplan-Meier curves showed that the 5-year cumulative rate was significantly lower in the thymectomized group than in the nonsurgical group. To conclude, thymectomy may be considered effective in modifying the progression from ocular to generalized MG irrespective of thymoma.

Plasma Metabolomics Reveals Pathogenesis of Retained Placenta in Dairy Cows.

The complex etiology and pathogenesis of retained placenta (RP) bring huge challenges for researchers and clinical veterinarians in investigating the pathogenesis and treatment schedule. This study aims to investigate the pathogenesis of RP in dairy cows by plasma metabolomics. As subjects, 10 dairy cows with RP and 10 healthy dairy cows were enrolled according to strict enrollment criteria. Imbalanced antioxidant capacity, reduced Th1/Th2 cytokine ratio, and deregulation of total bilirubin (T-bil), alkaline phosphatase (ALP), and reproductive hormones were shown in dairy cows with RP by detecting biochemical indicators, oxidation and antioxidant markers, and cytokines in serum. Plasma metabolites were detected and analyzed by a liquid chromatography-mass spectrometry (LC-MS) system coupled with multivariate statistical analysis software. A total of 23 potential biomarkers were uncovered in the plasma of dairy cows with RP. The metabolic pathways involved in these potential biomarkers are interconnected, and the conversion, utilization, and excretion of nitrogen were disturbed in dairy cows with RP. Moreover, these potential biomarkers are involved in the regulation of antioxidant capacity, inflammation, and autocrine or paracrine hormone. All of these findings suggest that an imbalance of these potential biomarkers might be responsible for the imbalanced antioxidant capacity, reduced Th1/Th2 cytokine ratio, and deregulation of reproductive hormones in dairy cows with RP. The regulation of metabolic pathways involved in these potential biomarkers represents a promising therapeutic strategy for RP.

Correction: Genomic mapping identifies two genetic variants in the MC1R gene for coat colour variation in Chinese Tan sheep.

[This corrects the article DOI: 10.1371/journal.pone.0235426.].

Genomic mapping identifies two genetic variants in the MC1R gene for coat colour variation in Chinese Tan sheep.

Coat colour is one of the most important economic traits of sheep and is mainly used for breed identification and characterization. This trait is determined by the biochemical function, availability and distribution of phaeomelanin and eumelanin pigments. In our study, we conducted a genome-wide association study to identify candidate genes and genetic variants associated with coat colour in 75 Chinese Tan sheep using the ovine 600K SNP BeadChip. Accordingly, we identified two significant SNPs (rs409651063 at 14.232 Mb and rs408511664 at 14.228 Mb) associated with coat colour in the MC1R gene on chromosome 14 with -log10(P) = 2.47E-14 and 1.00E-13, respectively. The consequence of rs409651063 was a missense variant (g.14231948 G>A) that caused an amino acid change (Asp105Asn); however, the second SNP (rs408511664) was a synonymous substitution and is an upstream variant (g.14228343G>A). Moreover, our PCR analysis revealed that the genotype of white sheep was exclusively homozygous (GG), whereas the genotypes of black-head sheep were mainly heterozygous (GA). Interestingly, allele-specific expression analysis (using the missense variant for the skin cDNA samples from black-head sheep) revealed that only the G allele was expressed in the skin covered with white hair, while both the G and A alleles were expressed in the skin covered with black hair. This finding indicated that the missense mutation that we identified is probably responsible for white coat colour in Tan sheep. Furthermore, qPCR analysis of MC1R mRNA level in the skin samples was significantly higher in black-head than white sheep and very significantly higher in GA than GG individuals. Taken together, these results help to elucidate the genetic mechanism underlying coat colour variation in Chinese indigenous sheep.

Preliminary evaluation and discussion of the safety of left innominate vein resection.

BACKGROUND: To evaluate the safety of resection of anterior mediastinal lesions involving the left innominate vein (LIV) and analyze the risk factors affecting LIV resection safety. METHODS: Patients who underwent anterior mediastinal lesion and LIV resection from January 2010 to December 2018 in the Department of Thoracic Surgery of Tangdu Hospital, Air Force Medical University, were followed up, and preoperative, intraoperative and postoperative factors were analyzed. RESULTS: Forty-eight patients who underwent anterior mediastinal lesion and LIV resection from January 2010 to December 2018, except for 2 who died of lung infection-induced respiratory failure, were followed up, with an average follow-up time of 32 months (range, 6-72 months). Postoperative: in 31 cases (67.39%), patients did not manifest LIV resection-associated complications; in 15 cases (32.61%), patients manifested mild LIV resection-associated complications; no patient manifested severe LIV resection-associated complications. The average operation time, average blood loss and average hospitalization time were 155.17 min, 324.13 mL and 11.83 days, respectively. Univariate analysis showed that the degree of LIV invasion and surgical approach were risk factors for predicting LIV resection safety. CONCLUSIONS: For anterior mediastinal lesions involving the LIV, LIV resection is a simple, safe and effective surgical procedure.

Do early prednisolone and other immunosuppressant therapies prevent generalization in ocular myasthenia gravis in Western populations: a systematic review and meta-analysis.

BACKGROUND: The majority of ocular myasthenia gravis (OMG) patients will progress to generalized myasthenia gravis (GMG), usually within 2 years of disease onset. The aim of this meta-analysis was to evaluate the effect of early prednisolone and other immunosuppressants therapy on the generalization rate in OMG patients. METHODS: We searched the CENTRAL, EMBASE, and MEDLINE databases via the Ovid SP database for all relevant publications on 16 July 2018. RESULTS: Eight studies comprising a total of 547 participants were included in our meta-analysis. Compared with pyridostigmine treatment, prednisolone and other immunosuppressants therapy produced an odds ratio (OR) for the development of GMG of 0.19 [95% confidence interval (CI), 0.11-0.30; I 2 = 37%], indicating that early prednisolone and other immunosuppressants therapy reduced the generalization rate in OMG by 81%. CONCLUSIONS: Early prednisolone and other immunosuppressants therapy can significantly reduce the risk of generalization in OMG patients, and should be considered in newly diagnosed OMG patients. Due to the inclusion of retrospective studies, this noted effect might have been related to corticosteroids, especially when immunosuppressants used at low dosages and in mild disease. Additionally, the data derived from Western populations, thus a prospective randomized controlled trial (RCT) is warranted to confirm this effect of early prednisolone and other immunosuppressants therapy on OMG generalization both in Western and Asian populations.

Effects of DKK1 overexpression on bone metastasis of SBC-3 cells.

Among all malignancies, lung cancer is the leading cause of cancer-related deaths in China. Bone metastasis is one of the most common complications and one of the most important factors affecting the prognosis of lung cancer patients, which resulting in very poor therapeutic effects. Previously, we have demonstrated that the expression levels of Dickkopf1 (DKK1), a protein involved in cell regulation and proliferation, was dramatically higher in cells that have a tendency to metastasize and invade the bone tissue (SBC-5 cells) compared with cells that do not (SBC-3 cells). Downregulation of DKK1 in SBC-5 cells inhibited cell malignancy in vitro, and the formation of bone metastasis in vivo. However, whether upregulating DKK1 would be sufficient to induce aggressive tumor behavior (proliferation, migration, invasion and metastasis) in SBC-3 cells remained to be investigated. The present study aimed to examine the role of DKK1 in SBC-3 cells, as well as to investigate the SBC-3 ability to metastasize and invade the bone tissue. The results demonstrated that upregulation of DKK1 in SBC-3 cells enhanced cell proliferation, colony formation, cell migration and invasion in vitro, as well as bone metastasis in vivo. These results indicate that DKK1 may be an important regulator in the development of small cell lung cancer (SCLC), and targeting DKK1 may be an effective method for preventing and/or treating skeletal metastases in SCLC cases.

Clinical application of harmonic scalpel in subxiphoid and subcostal arch approach for resection of anterior mediastinal lesion / 中国胸心血管外科临床杂志

@#Objective    To evaluate the clinical outcomes of harmonic scalpel in subxiphoid and subcostal arch approach for resection of anterior mediastinal lesion. Methods    We retrospectively analyzed the clinical data of 217 patients with anterior mediastinal lesion at the Department of Thoracic Surgery of Tangdu Hospital of the Fourth Military Medical University from June 2015 to June 2017, among whom 162 underwent thoracoscopic surgery via subxiphoid and subcostal arch approach with harmonic scalpel (a harmonic scalpel group, 95 males and 67 females at an average age of 46.2±18.7 years ranging from 22 to 72 years) and 55 with Ligasure (a Ligasure group, 29 males and 26 females at an average age of 47.7±12.9 years ranging from 31 to 68 years). Operation time, intraoperative blood loss, intraoperative conversion rate, postoperative hospital stay, patients satisfaction score, patients pain score and postoperative complications were compared between both groups. Results    All operations were accomplished successfully, and there was no death or conversion to thoracotomy. There was a statistical difference in operation time (58.6±34.8 min vs. 72.8±32.6 min, P=0.01), and intraoperative blood loss (36.2±18.7 ml vs. 41.9±12.9 ml, P=0.04). There was no statistical difference between the two groups in length of hospital stay (4.2±2.6 d vs. 4.5±1.9 d, P=0.36), pain score at postoperative day 1, 3 and 30 (8.3±0.9 vs. 8.5±0.6, P=0.13; 6.4±1.5 vs. 6.9±1.1, P=0.19; 1.3±0.7 vs. 1.4±0.9, P=0.40), patients’ satisfaction score (8.6±1.2 vs. 8.4±1.7, P=0.34), or incidence of postoperative complications (5.6% vs. 9.1%, P=0.35). Conclusion    Har-monic scalpel plays an important role in resection of anterior mediastinal lesion via subxiphoid and subcostal arch approach. All tissues are separated and blood vessels are dissected only by the harmonic scalpel, so it is very important for   us to handle the harmonic scalpel skillfully.

Knockdown of MALAT1 expression inhibits HUVEC proliferation by upregulation of miR-320a and downregulation of FOXM1 expression.

Regulation of cancer angiogenesis could be a useful strategy in cancer therapy. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA), and can induce cancer cell proliferation, while lncRNAs, generally are able to act as microRNA (miRNA) sponges. The latter is a type of competitive endogenous RNA (ceRNA) that regulates expression of the targeting miRNAs and protein-coding genes. This study investigated the proliferative role of MALAT1 in human umbilical vein endothelial cells (HUVECs) and the underlying molecular events. The data showed that knockdown of MALAT1 expression using MALAT1 siRNA inhibited HUVEC proliferation and also significantly decreased levels of FOXM1 mRNA and protein in vitro, while knockdown of FOXM1 expression reduced HUVEC proliferation. Annotation of HUVEC microarray data revealed that seven miRNAs, including miR-320a, were upregulated after knockdown of MALAT1 expression in HUVECs. MALAT1 was shown to reciprocally interact with miR-320a, i.e., expression of one negatively regulated levels of the other, whereas knockdown of MALAT1 expression promoted miR-320a levels. Furthermore, miR-320a could directly target and inhibit FOXM1 expression in HUVECs. Knockdown of MALAT1 expression enhanced miR-320a expression but reduced FOXM1 expression resulting in downregulation of HUVEC proliferation. However, such an effect was inhibited by miR-320a depletion. In conclusion, this study demonstrates that miR-320a plays an important role in mediating the effects of MALAT1 on HUVEC proliferation by suppression of FOXM1 expression. Thus, targeting of this gene pathway could be a novel strategy in cancer therapy.

37LRP induces invasion in hypoxic lung adenocarcinoma cancer cells A549 through the JNK/ERK/c-Jun signaling cascade.

We previously reported that 37-kDa laminin receptor precursor involved in metastasis of lung adenocarcinoma cancer cells. In this study, we further revealed that hypoxia induced 37-kDa laminin receptor precursor expression and activation of extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase in lung adenocarcinoma cancer cells. In addition, we further demonstrated that the c-Jun N-terminal kinase inhibitor SP600125 and extracellular signal-regulated protein kinase inhibitor U0126 blocked the c-Jun activity and abolished hypoxia-induced 37-kDa laminin receptor precursor expression and promoter activity in a concentration-dependent manner. However, the p38 mitogen-activated protein kinase inhibitor did not affect 37-kDa laminin receptor precursor expression and c-Jun activity in response to hypoxia. Furthermore, downregulated c-Jun expression by short interfering RNA could also inhibit hypoxia-induced 37-kDa laminin receptor precursor expression and transcriptional activity. The inhibition of 37-kDa laminin receptor precursor expression by SP600125 and U0126 could be rescued by c-Jun overexpression. Studies using luciferase promoter constructs revealed a significant increase in the activity of promoter binding in the cells exposed to hypoxia, which was lost in the cells with mutation of the activator protein 1 binding site. Electrophoresis mobility shift assay and chromatin immunoprecipitation demonstrated a functional activator protein 1 binding site within 37-kDa laminin receptor precursor gene regulatory sequence located at -271 relative to the transcriptional initiation point. Hypoxia-induced invasion of A549 cells was inhibited by the pharmacologic inhibitors of c-Jun N-terminal kinase (SP600125) and extracellular signal-regulated protein kinase (U0126) as well as 37-kDa laminin receptor precursor-specific siRNA or antibody. Our results suggest that hypoxia-elicited c-Jun/activator protein 1 regulates 37-kDa laminin receptor precursor expression, which modulates migration and invasion of lung adenocarcinoma cells.

Colobronchial fistula: the pathogenesis, clinical presentations, diagnosis and treatment.

BACKGROUND: Colobronchial fistula (CBF) is rare and easy to be delayed in clinic. There is no systemic study about this disease. The pathogenesis, clinical presentations, diagnosis and treatment of CBF were analyzed in this study. METHODS: The clinical data from 37 cases of CBF, which included one case in our institute and the other 36 cases in literature from January 1960 to August 2016, were reviewed and analyzed. The etiology, clinical presentations, diagnostic and therapeutic methods, and outcomes were summarized. RESULTS: The causes of CBF included Crohn's disease, postoperative intraperitoneal adhesion, diaphragmatic hernia, pulmonary infection or abscess, colonic malignancy, colonic interposition, radiation, hyperthermic intraperitoneal chemotherapy (HIPEC), diaphragmatic mesh repair, pulmonary tuberculosis and pyonephrosis. Based on the anatomical location and the causes of fistula, CBF were divided into four types: type I, CBF secondary to the adhesion among colon, diaphragm and lung; type II, CBF secondary to diaphragmatic hernia; type III, CBF secondary to sub diaphragmatic abscess or emphysema; type VI, CBF secondary to colon interposition. The characteristic clinical presentations of CBF was productive cough with foul smelling sputum (78.38%), most of the patients were finally confirmed the diagnosis by barium enema or water-soluble contrast enema study (67.57%) and computer tomography (CT) scan/with multiplanar reconstruction (16.22%); 35 cases (94.59%) accepted the surgical treatment. Among 31 patients with recorded follow-up data, 26 patients recovered unevenly, but 5 patients died in 1 month after treatment. CONCLUSIONS: CBF is a rare but can not be ignored disease. Anything which may induce the direct or indirect connection between colon and lung tissue may result in CBF. Productive cough with foul smelling sputum is the characteristic symptom. Radiological investigations such as barium enema and/or CT scan with multiplanar reconstruction are valuable for the confirmation of CBF. Surgery based on the etiology is the foundation of treatment.

Update on the diagnosis and treatment of tracheal and bronchial injury.

Tracheal and bronchial injury, including iatrogenic injury and traumatic injury, the former usually occurred in the operation, intubation or bronchoscopy. The latter was occurred in a variety of blunt trauma, often combined with a variety of complex injuries. The therapeutic approach can be differentiated, surgical or conservative, no criteria has been universally accepted. Successful treatment of tracheobronchial injuries requires early diagnostic evaluation. This article aims to review the indications and therapeutic options for tracheal and bronchial injuries.