Risk factors for diaphragmatic injury in subxiphoid video-assisted thoracoscopic surgery.

BACKGROUND: Subxiphoid video-assisted thoracoscopic surgery (VATS) is considered a safe and feasible operation for anterior mediastinal mass resection. However, diaphragmatic injury, presented as tearing or puncturing, may occur during subxiphoid VATS despite of low incidence. This study aims to explore risk factors for diaphragmatic injury in subxiphoid VATS, as well as strategies to reduce occurrence of the injury. METHODS: We retrospectively reviewed clinical records of 44 consecutive adult patients who underwent subxiphoid VATS. These patients were divided into two groups: diaphragmatic injury group and non-injury group. Perioperative outcomes and anatomic features derived from 3D CT reconstructions were compared between the two groups. RESULTS: Significant differences were observed in operation time (223.25 ± 92.57 vs. 136.28 ± 53.05, P = 0.006), xiphoid length (6.47 ± 0.85 vs. 4.79 ± 1.04, P = 0.001) and length of the xiphoid below the attachment point on the diaphragm (24.86 ± 12.02 vs. 14.61 ± 9.25, P = 0.029). Odds ratio for the length of the xiphoid below the attachment point on the diaphragm was 1.09 (1.001-1.186), P = 0.048 by binary logistic regression analysis. CONCLUSIONS: We identified the length of the xiphoid below the attachment point on the diaphragm as an independent risk factor for diaphragm injury during subxiphoid VATS. Prior to subxiphoid VATS, a 3D chest CT reconstruction is recommended to assess the patients' anatomic variations within the xiphoid process. For patients with longer xiphoid process, a higher incision at the middle and upper part of the xiphoid process, and partial xiphoid process resection or xiphoidectomy is preferred.

Silencing of m6A methyltransferase KIAA1429 suppresses the progression of non-small cell lung cancer by promoting the p53 signaling pathway and ferroptosis.

KIAA1429, an important component of the N6-methyladenine methyltransferase complex, is involved in the pathology of many types of cancer. In this study, the mechanisms through which KIAA1429 promotes non-small cell lung cancer (NSCLC) progression were explored using in vitro and in vivo experiments. Additionally, bioinformatics analysis of publicly available data was used to determine the relationship between KIAA1429 expression and NSCLC patient survival. The results showed that KIAA1429 was upregulated in NSCLC tissues and cells, and its high expression level was associated with low overall survival. Transcriptome analysis of KIAA1429-silenced NSCLC cells identified 346 differentially expressed genes, which were enriched in ferroptosis and the p53 signaling pathway. KIAA1429 silencing using small interfering (si) RNA promoted erastin-induced ferroptosis in NSCLC cells and activated the p53 signaling pathway. Moreover, si-KIAA1429 inhibited the proliferative, migratory, and invasive abilities of NSCLC cells in vitro and tumor growth in vivo. These in vitro effects were weakened by pifithrin-µ, a p53 inhibitor. Therefore, given its effects on ferroptosis and the p53 signaling pathway, targeting KIAA1429 could be an effective strategy for treating NSCLC.

Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

BACKGROUND: Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. AIM: To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. METHODS: The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. RESULTS: The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. CONCLUSION: PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

Neoadjuvant Camrelizumab for Non-Small Cell Lung Cancer: A Retrospective Multicenter, Real-World Study (CTONG2004).

BACKGROUND: Camrelizumab has shown encouraging efficacy in advanced non-small cell lung cancer (NSCLC), either as monotherapy or combined with chemotherapy. However, evidence of neoadjuvant camrelizumab for NSCLC remains lacking. METHODS: Patients with NSCLC treated with neoadjuvant camrelizumab-based therapy followed by surgery between December 2020 and September 2021 were retrospectively reviewed. Demographic and clinical data, details of neoadjuvant therapy and surgical information were retrieved. RESULTS: In this multicenter retrospective real-world study, 96 patients were included. Ninety-five patients (99.0%) received neoadjuvant camrelizumab combined with platinum-based chemotherapy, with a median of 2 cycles (range 1-6). The median interval from the last dose to surgery was 33 days (range 13-102 days). Seventy patients (72.9%) underwent minimally invasive surgery. Lobectomy was the most frequent surgical procedure (94 [97.9%]). The median estimated intraoperative blood loss was 100 mL (range 5-1200 mL), and the median operative time was 3.0 h (range 1.5-6.5 h). The R0 resection rate was 93.8%. Twenty-one patients (21.9%) experienced postoperative complications, with the most common being cough and pain (both 6 [6.3%]). The overall response rate was 77.1% (95% CI 67.4-85.0%), and the disease control rate was 93.8% (95% CI 86.9-97.7%). Twenty-six patients (27.1%, 95% CI 18.5-37.1%) had pathological complete response. Neoadjuvant treatment-related adverse events of grade ≥ 3 were reported in seven patients (7.3%), with the most frequent being abnormal liver enzymes (two [2.1%]). No treatment-related deaths were reported. CONCLUSION: The real-world data indicated that camrelizumab-based therapy had promising efficacy for NSCLC in the neoadjuvant setting, with manageable toxicities. Prospective studies investigating neoadjuvant camrelizumab are warranted.

Effectiveness and safety of camrelizumab in inoperable or advanced non-small cell lung cancer patients: a multicenter real-world retrospective observational study (CTONG2004-ADV).

Background: Camrelizumab plus chemotherapy have been approved as standards for the treatment of advanced non-small cell lung cancer (NSCLC) patients based on two phase III trials. However, clinical trial results may not be representative of the general population, as clinical trials often have specific inclusion and exclusion criteria. Our research aims to investigate the real-world effectiveness and safety of camrelizumab in inoperable or advanced NSCLC patients. Methods: This multicenter retrospective observational study included inoperable or advanced pathologically confirmed NSCLC patients who received at least one dose of camrelizumab at 22 hospitals. Clinical and follow-up data of camrelizumab were collected retrospectively from the medical records. The primary outcome was the objective response rate (ORR) and secondary outcomes were disease control rate (DCR), 6-month progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Multivariate logistic and Cox regression analyses were applied to identify potential predictive factors of ORR and PFS, respectively. Results: Between July 2019 and March 2021, 336 patients were included. Adenocarcinoma was seen in 58.4% and stage IV disease in 69.3%. Twenty-nine (8.6%) had liver metastasis at baseline. Most patients received camrelizumab in the first-line setting (74.1%) and in combination with chemotherapy (60.7%). The ORR was 40.2% [95% confidence interval (CI): 34.9-45.6%] and DCR was 85.1% (95% CI: 81.3-88.9%), while the 6-month PFS and OS rates were 73.0% (95% CI: 67.1-78.0%) and 93.1% (95% CI: 89.8-95.4%), respectively. In multivariate analyses, liver metastasis [odds ratio (OR), 0.324; 95% CI: 0.115-0.915; P=0.033] and increasing lines of camrelizumab treatment (vs. first line, second line: OR, 0.347; 95% CI: 0.162-0.741; P=0.006; ≥ third line: OR, 0.126; 95% CI: 0.043-0.367; P<0.001) were negatively associated, while a longer duration of camrelizumab treatment was positively associated with ORR and PFS. TRAEs were recorded in 164 (48.8%) patients, without new safety signal. Conclusions: We conducted a comprehensive overview of the effectiveness and safety profile of camrelizumab in a broader NSCLC population in real world NSCLC patients, and subgroup analysis indicated the presence of liver metastasis was associated with worse outcomes.

Prognostic value of circulating tumor DNA using target next-generation sequencing in extensive-stage small-cell lung cancer.

BACKGROUND: Chemotherapy remains the mainstay of treatment for small-cell lung cancer (SCLC). Liquid biopsies provide a convenient and non-invasive detection method for monitoring disease progression in patients with SCLC. METHODS: We performed next-generation sequencing of 159 plasma samples from 69 patients with extensive-stage (ES)-SCLC. Circulating tumor (ct)DNA levels were quantified in haploid genome equivalents per mL (hGE/mL). MuTect2 was used to detect single nucleotide variants and short insertions/deletions. The "enrichKEGG" function in the "clusterProfiler" R package was used to enrich the mutated genes that only appeared during disease progression. RESULTS: In our cohort, 66 of 69 (95.7%) plasma samples at the time of diagnosis had detectable somatic mutations; TP53 (89%) and RB1(56%) were the most frequent mutations, as well as copy number variations in some common SCLC-related genes such as RB1. Combination ctDNA and tissue testing improved the overall detection rate of actionable mutations from 19.4% to 26.9% compared with that of tissue detection alone. In addition, ctDNA levels changed dynamically during the course of treatment and were significantly associated with decreased progression-free survival. Notably, actionable mutations were detected at the time of diagnosis and during disease progression. CONCLUSIONS: Our study revealed a dynamic somatic mutation profile through continuous ctDNA detection and confirmed that ctDNA levels can reflect tumor burden and predict PFS in patients with extensive stage-SCLC. Furthermore, we demonstrated that plasma ctDNA assays can provide real-time information on somatic mutations for potential targeted therapies for SCLC.

B3GNT3 as a prognostic biomarker and correlation with immune cell infiltration in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common malignant cancer in humans and because of low long-term survival rates, exploration of the molecular mechanisms underlying its progression, as well as novel prognostic predictors, is urgently needed. B3GNT3, a type II transmembrane protein located in the Golgi apparatus, is essential for forming extended core 1 oligosaccharides and is reportedly involved in malignant transformation. Methods: The Cancer Genome Atlas (TCGA) and GSE68465 were used to analyze the expression of B3GNT3 in LUAD and normal tissues and overall survival. Real time quantitative polymerase chain reaction (qPCR) and western blot were conducted to measure the mRNA and protein levels of B3GNT3, respectively. Functional enrichment of differentially expressed genes was explored using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We performed univariate and multivariate Cox regression analyses and a meta-analysis to reveal an independent factor for LUAD. We evaluated the correlation between immune infiltration levels and cumulative survival in the TIMER database. The correlation between B3GNT3 and immune cell infiltration was assessed via Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT). The association of DNA methylation of B3GNT3 and prognosis was determined. A nomogram that incorporated expression and clinical features was additionally built for prognostic prediction. Cell proliferation, cloning, and invasion were conducted to validate the roles of B3GNT3 in LUAD. Results: B3GNT3 was more highly expressed in LUAD tissues than in normal lung tissues, consistent with the mRNA and protein levels in LUAD cells. B3GNT3 was an independent factor for LUAD. Moreover, the levels of B3GNT3 were related to immune cell infiltration in LUAD microenvironments. DNA methylation of B3GNT3 correlated with the mRNA of B3GNT and overall survival of LUAD patients. The expression of B3GNT3 was highly valuable for the prediction of diagnosis. Knockdown of B3GNT3 inhibited LUAD cell viability and cloning ability, and hindered invasion. Conclusions: B3GNT3 was highly associated with immune cell infiltration, acting as an important biomarker for the prognosis and diagnosis of LUAD.

Elucidating the anatomy of the quadrivial pattern of the right upper lobe bronchus using 3D-CT images.

Background: A preoperative understanding of the thoracic anatomy of the patients with the quadrivial pattern of branching of the right upper lobe is key to successful surgery. We analyzed the quadrivial pattern of division of the right upper lobe bronchus of patients using three-dimensional (3D) computed tomography (CT) angiography and bronchography. Methods: A total of 212 consecutive adult patients who had undergone thoracic CT scans before surgery at the Zhujiang Hospital of the Southern Medical University from August 2020 to August 2021 was used for retrospective study. The 3D-CT images were taken using Mimics software. Radiology technicians processed all the 3D images, and thoracic surgeons confirmed the validity of all the reconstructions. Results: Six (2.83%) were identified as having a quadrivial pattern of division of the right upper lobe bronchus with 1 female, and 5 males. Based on the number of pulmonary artery branches, 5 (83.3%) and 1 (16.7%) were classified as "trunk superior (Tr.sup) + ascending artery (A.asc) and Tr.sup + trunk inferior (Tr.inf) + ascending artery (A.asc) (1/6, 16.7%). Based on the number of ascending artery branches, the patients were also divided into type A (3/6, 50%) and type B (3/6, 50%). The patients were also divided into 1 of the following three types based on the origins of the A2: (I) A2 originates from A6 (1/6, 16.7%); (II) A2 originates from the pulmonary trunk (4/6, 66.7%); and (III) A2a originates from A3, and A2b originates from the pulmonary artery stem (1/6, 16.7%). According to the number of A1b branches, patients were divided into two types: (I) 1 branch (4/6, 66.7 %); and (II) 2 branches (2/6, 33.3 %). In the present study, anterior + central type was observed which classified into two types: (I) type Iab, the anterior vein ran from V1a to V1b (4/6, 66.7%); and (II) type Ib, the anterior vein ran from V1b only (2/6, 33.3%). Conclusions: 3D-CT was successfully used for analyzing the quadrivial bronchovascular patterns of the right upper lobe bronchus. Our study provides certain references to perform anatomical pulmonary segmentectomy, which should improve the success rate of operations.

Analysis of whole-exome data of cfDNA and the tumor tissue of non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) has the highest cancer mortality rate in the world, but currently there is no effective method of dynamic monitoring. Gene mutation is an important factor in tumorigenesis and can be detected using high-throughput sequencing technology. This study aimed to analyze the driving genes in the tumor of NSCLC patients by whole exon sequencing, and to compare and analyze the subclones of the tumor at different time points. METHODS: We collected 87 cases of NSCLC tumor tissues, para-cancer tissues, and peripheral blood samples for detecting cell-free DNAs (cfDNAs) from January 2016 to December 2018, and whole-exome sequencing was performed. The gene mutation map of NSCLC was drawn in detail by second-generation sequencing data analysis and new driver genes were found. In addition, we performed a subclonal analysis of tumors from different stages of the same patient to further describe the tumor heterogeneity. RESULTS: We found that the clonal analysis obtained by cfDNA detection was similar to the clonal analysis of the tissue samples, so real-time monitoring of tumor changes can be carried out through monitoring cfDNA. CONCLUSIONS: This study provides evidence for studying the gene mutation information of NSCLC and shows the importance of cfDNA in the analysis of tumor subcloning information.

KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/STAT3 axis.

BACKGROUND: Small cell lung cancer (SCLC) is a devastating and aggressive neuroendocrine carcinoma characterized by high cellular proliferation and early metastatic spread. Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) can regulate tumor generation and development, including in SCLC. The current study aimed to assess the effect of the lncRNA, KCNQ1OT1, on the proliferation, apoptosis, and chemoresistance of SCLC and the potential underlying molecular mechanism. METHODS: Matched chemo-resistant and sensitive cells were applied to RNA isolation and followed by expression profiling by microarray analysis and subsequent quantitative polymerase chain reaction (qPCR) validation. Cell viability and apoptosis were determined by Cell Counting Kit-8 and flow cytometry to examine the chemoresistance and apoptosis of KCNQ1OT1 knockdown with lentivirus-mediated RNA interference. Furthermore, cell proliferation was studied by colony formation, and invasion and migration were tested by Transwell cell invasion and wound-healing assays, respectively. A tumor xenograft model was established to determine the role of KCNQ1OT1 in tumor growth and chemoresistance in response to KCNQ1OT1 knockdown in vivo. Western blot analysis, qPCR, and immunohistochemistry were used to detect the levels of messenger RNA (mRNA) Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway-related markers. RESULTS: Higher expression of KCNQ1OT1 was detected in SCLC chemo-resistant verso chemo-sensitive cells. Knockdown of KCNQ1OT1 inhibited SCLC cell viability and cloning ability, hindered cell migration and invasion, induced apoptosis in vitro, and suppressed tumor growth and chemoresistance in vivo, by activating the JAK2/STAT3 signaling pathway. CONCLUSIONS: This is the first study to indicate that lncRNA KCNQ1OT1 promotes cell proliferation and invasion, and prevents apoptosis of SCLC by activating the JAK2/STAT3 pathway.

Stereotactic Body Radiotherapy Versus Surgery for Early-Stage Non-Small-Cell Lung Cancer.

BACKGROUND: Surgery is the gold standard therapy for patients with early-stage non-small-cell lung cancer (NSCLC). However, stereotactic body radiotherapy (SBRT) may provide as an alternative for patients who are medically inoperable or refuse surgical resection. The optimal treatment (SBRT or surgery) for patients with early-stage NSCLC is not clear. METHODS: A systematic search was performed from PubMed, MEDLINE, Embase, and the Cochrane Library. Study heterogeneity and publication bias were estimated. RESULTS: Fourteen cohort studies involving 1438 participants (719 who received SBRT and 719 who received surgery) were included in the meta-analysis. The main bias sources between the two groups, such as age, gender, tumor diameter, forced expiratory volume in 1 s, and Charlson comorbidity index were matched. The surgery was associated with a better overall survival (OS) and long-term distant control (DC) for early-stage NSCLC. The pooled OR and 95% confidence interval (CI) for 1-y, 3-y, 5-y OS, and 5-y DC were 1.56 (1.12-2.15), 1.86 (1.50-2.31), 2.43 (1.80-3.28), and 2.74 (1.12-6.67), respectively. No difference was found between the treatments in the 1-y and 3-y disease-free survival; 1-y, 3-y and 5-y locoregional control; or 1-y and 3-y DC. CONCLUSIONS: Our results found a superior OS and long-term DC for early-stage NSCLC after surgery compared with SBRT after propensity score matching.

[Establishment of A Patient-derived Xenotransplantation Animal Model for Small Cell Lung Cancer and Drug Resistance Model].

BACKGROUND: Small cell lung cancer (SCLC) is characterized by poor differentiation, high malignancy and rapid growth fast, short double time, early and extensive metastatic malignancy. In clinical, chemotherapy is the main treatment method, while resistance to multiple chemotherapy drugs in six to nine months has been a major clinical challenge in SCLC treatment. Therefore, It has important clinical value to building SCLC aninimal model which is similar to patients with SCLC. Animal model of xenotransplantation (PDX) from the patients with small cell lung cancer can well retain the characteristics of primary tumor and is an ideal preclinical animal model. The study is aimed to establish SCLC PDX animal model and induce the chemoresistance model to help to study the mechanism of chemoresistance and individual treatment. METHODS: Fresh surgical excision or puncture specimens from SCLC patients were transplanted into B-NSGTM mice subcutaneous tissues with severe immunodeficiency in one hour after operation the B-NSGTM mice subcutaneous in 1 hour, and inject chemotherapy drugs intraperitoneally after its tumor growed to 400 mm³ with EP which is cisplatin 8 mg/kg eight days and etoposide 5 mg/kg every two days until 8 cycles. Measure the tumor volum and mice weights regularly, then re-engrafted the largest tumor and continue chemotherapy. RESULTS: Nine cases were conducted for B-NSG mice modeling. Three of nine cases could be engrafted to new B-NSG mice at least two generation. The SCLC PDX animal models have been established successfully. After adopting chemotherapy drugs, the chemoresistance PDX models have been established. High homogeneity was found between xenograft tumor and patient's tumor in histopathology, immunohistochemical phenotype (Syn, CD56, Ki67). CONCLUSIONS: The SCLC PDX animal model and the chemoresistance PDX animal model have been successfully constructed, the success rate is 33%, which provides a platform for the clinical research, seeking for biological markers and choosing individual treatment methods of SCLC.

[Effects of minimally invasive versus open esophagectomy on circulating tumor cells in patients with esophageal cancer].

OBJECTIVE: To investigate the effects of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on the level of circulating tumor cells (CTCs) in patients with esophageal cancer (EC). METHODS: A total of 73 patients with EC undergoing MIE (n=38) or OE (n=35) in our department between October, 2015 and October, 2017 were enrolled, with 10 patients with benign esophagus disease and 10 healthy volunteers as controls. The levels of CTCs in the peripheral blood of the participants were detected using CanPatrolTM technique and analyzed for their association with the operation methods and perioperative complications. RESULTS: CTCs were detected in 60.3% (44/73) of the EC patients but in none of the control subjects. CTC level after the surgery was significantly higher than that during the surgery, and CTC level during the surgery was significantly higher than that before surgery (P<0.001). The preoperative and intra-operative CTC levels were not significantly different between MIE and OE groups (P>0.05), but the postoperative CTC level was significantly lower in MIE group than in OE group, and postoperative increment of CTC level (from the preoperative level) was significantly lower in MIE group than in OE group (P<0.001). The total incidence of postoperative complications was significantly lower in MIE group than in OE group (28.9% vs 54.3%, P=0.023), and in both groups, CTC levels in patients with complications were significantly higher than those in patients without complications (P=0.001 and P=0.005 in MIE and OE groups, respectively). CONCLUSION: MIE may help to reduce the number of peripheral blood CTCs early after the operation, and dynamic monitoring CTCs level assists in evaluation of the prognosis of EC patients. CTC level may serve as an indicator for monitoring the prognosis of EC.

ω-3 Polyunsaturated Fatty Acid Postconditioning Protects the Isolated Perfused Rat Heart from Ischemia-Reperfusion Injury.

AIMS: This study aimed to evaluate the cardioprotective effects of ω-3 polyunsaturated fatty acids (PUFAs) postconditioning against ischemia-reperfusion (I/R) injury. METHODS: Sixty Sprague-Dawley rats were randomly divided into 4 groups (n = 15 for each) and used to generate the Langendorff isolated perfused rat heart model. The sham group received a continuous perfusion of 150 min. The remaining three I/R-treated groups sequentially received a 30-min perfusion, a 30-min cardioplegia, and a 90-min reperfusion. The I/R-ischemic preconditioning (IP) group additionally received three cycles of 20-s reperfusion and 20-s coronary reocclusion preceded the 90 min of reperfusion. The I/R-ω group were perfused with ω-3 PUFAs for 15 min before the 90 min of reperfusion. The myocardial infarct size, the degree of mitochondrial damage, the antioxidant capacity of the myocardium, and the cardiac functions during reperfusion were compared among groups. RESULTS: Compared with the I/R group, the I/R-ω group had significantly reduced myocardial infarct size, reduced levels of lactate dehydrogenase and malondialdehyde, elevated superoxide dismutase level, and elevated rising (+dp/dtmax) and descending (-dp/dtmax) rate of left ventricular pressure. The I/R-ω group had a significantly lower rate of mitochondrial damage in myocardial tissue compared with the I/R and I/R-IP groups. CONCLUSION: ω-3 PUFA postconditioning possesses good cardioprotective effects and may be developed into a therapeutic strategy for myocardial I/R injury.

H3K27me3 induces multidrug resistance in small cell lung cancer by affecting HOXA1 DNA methylation via regulation of the lncRNA HOTAIR.

BACKGROUND: The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) serves as a powerful predictor of tumor progression and overall survival in patients. Our previous studies showed that HOTAIR modulated HOXA1 DNA methylation by reducing DNMT1 and DNMT3b expression in drug-resistant small cell lung cancer (SCLC). Moreover, H3 lysine 27 trimethylation (H3K27me3) is catalyzed by enhancer of zeste homolog 2 (EZH2) and plays a critical role in SCLC chemoresistance. However, it is not completely clear whether H3K27me3 affects HOXA1 DNA methylation or whether this effect is mediated by HOTAIR. METHODS: The levels of EZH2 and H3K27me3 were identified in SCLC tissues by immunohistochemical (IHC) staining and in SCLC multidrug-resistant cells by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were used to detect and analyze the biological function of H3K27me3. Then, we assessed the role of HOTAIR in the regulation of EZH2 and H3K27me3 by using lentivirus and small interfering RNA. Further, bisulfite sequencing PCR was conducted to detect the methylation levels of HOXA1 DNA. Finally, Western blotting was performed to examine the regulatory role of H3K27me3 in controlling HOTAIR expression in SCLC. RESULTS: In this study, we found that EZH2 and H3K27me3 levels were markedly higher in SCLC tissues and multidrug-resistant SCLC cells. The results indicated that H3K27me3 was related to multidrug resistance. HOTAIR overexpression and knockdown showed that EZH2 and H3K27me3 were regulated by HOTAIR. Moreover, H3K27me3 affected HOXA1 DNA methylation levels. Strikingly, we found that H3K27me3 acted as a negative feedback regulator of HOTAIR. CONCLUSIONS: Our study showed that H3K27me3 affects HOXA1 DNA methylation via HOTAIR regulation, indicating that H3K27me3 may be a potential therapy target for SCLC chemoresistance.

[Establishment of a rabbit model of cardiopulmonary bypass in acute cerebral embolism phase].

OBJECTIVE: To establish a stable and feasible rabbit model of cardiopulmonary bypass (CPB) in acute cerebral embolism phase for studying the effects of CPB on brain tissues and the timing of surgical intervention of acute cerebral embolism. METHODS: Fifty-four rabbits were randomized into group A (n=18) to receive CPB without middle cerebral artery occlusion (MCAO) and group B to undergo CPB at 24 h (group B1, n=18) or 1 week (group B2, n=18) after MCAO. Through a supraorbital margin approach, electrocoagulation was carried out to occlude the main stem of the left MCA under direct vision to establish MCAO. Magnetic resonance imaging (MRI) was performed at both 24 h and 1 week after MCAO, and the severity of cerebral embolization was evaluated. CPB was established by cannulation of the ascending aorta and the right atrium through a median sternotomy incision. MRI was performed at 2 h after CPB to observe the brain tissues. RESULTS: MCAO was successfully established in groups B1 and B2, and all the rabbits survived after MCAO. In both groups A and B, MRI examination detected no cerebral hemorrhage or new embolism 2 h after CPB. CONCLUSIONS: We have established a stable and feasible CPB model in rabbits with acute cerebral embolism to allow study of the mechanisms of CPB-related organ damage and its interventions.

[Investigation of the technique of esophageal stent re-implantation].

OBJECTIVE: To analyze the causes of failure of esophageal stent implantation and explore technical improvement of re-implantation of esophageal stent (RIES). METHODS: According to the conditions of the failed stent implantation, 32 patients who required RIES underwent placement of more appropriate esophageal stents with an improved implantation technique. The patients were followed up for 6 months after the operation to evaluate the effects of RIES. RESULTS: The success rate of the operation was 96.9% in these cases, and the esophageal conditions including stricture and fistula were effectively relieved. During the 6-month follow-up, stent migration occurred in 4 cases (12.5%), and esophageal fistula in the upper edge of the re-implanted stent occurred in 2 cases. No stent loss, bleeding, or stricture was found in these cases. CONCLUSION: The improved technique is effective for stent re-implantation after failed esophageal stent implantation with reduced complications associated with esophageal stenting.

[Relationship between early spontaneous cardioversion of atrial fibrillation and thyroid hormone metabolism after mitral replacement in patients with rheumatic heart disease].

OBJECTIVE: To analyze the relationship between early spontaneous cardioversion of atrial fibrillation (AF) and thyroid hormone metabolism after mitral replacement in patients with rheumatic heart disease, and explore the treatment strategy of early spontaneous cardioversion after mitral valve replacement. METHODS: According to the occurrence of cardioversion, 138 patients with mitral valve replacement were divided into conversion group and non-conversion group, and based on the duration of sinus rhythm, the patients in conversion group were divided into < 3 days group and > 3 days group. Triiodothyronine (T3) was detected by radioimmunoassay in all the patients. RESULTS: T3 metabolism decreased significantly after the operation in all the patients. Early spontaneous cardioversion of AF occurred 2 h after the operation in 52 cases (37.7%), and 28 (20.3%) of the cases had a duration of sinus rhythm longer than 3 days. T3 was significantly decreased in conversion group and non-conversion group by 44.5% and 58.7% at 2 h, by 40.0% and 52.4% at 24 h and by 28.6% and 37.7% at 72 h after the operation, respectively. The levels of T3 in conversion group was significantly higher than the levels in non-conversion group, and showed no significant variation with the duration of sinus rhythm. CONCLUSION: Enhancement of T3 levels after mitral valve replacement may increase the probability of early spontaneous cardioversion of AF, but can not affect the duration of sinus rhythm. This finding supports the supplementation of T3 perioperatively in patients undergoing cardiac surgeries.

[Hemocompatibility evaluation in vitro of small-caliber expanded polytetrafluoroethylene vessel with silk fibroin coating sulfonated by low temperature plasma].

OBJECTIVE: To evaluate the hemocompatibility of a small-caliber expanded polytetrafluoroethylene vessel with silk fibroin coating sulfonated by low temperature plasma treatment. METHODS: The composite blood vessel was prepared by first coating the small-caliber expanded polytetrafluoroethylene vessel with silk fibroin followed by sulfonation by low temperature plasma treatment. After hemolysis test in vitro, dynamic coagulation time test, blood platelet adhesion test, and recalcification time test were performed to evaluate the hemocompatibility of the composite blood vessel. RESULTS: Scanning electronic microscopy revealed obvious platelets adhesion on the conventional artificial (control) vessel, which seldom occurred on the composite vessel. The curve of absorbance-clotting time of the composite vessel declined more slowly than that of the control vessel. The recalcification time of the composite blood vessel averaged 603 s, significantly longer than that of the control vessel (480 s, P = 0.000). CONCLUSION: The composite blood vessel has good antithrombotic activity and hemocompatibility as a promising vascular prosthesis.

[Expression of special AT-rich sequence-binding protein mRNA and its clinicopathological significance in non-small cell lung cancer].

OBJECTIVE: To detect the expression of AT-rich sequence-binding protein (SATB1) mRNA in non-small cell lung cancer (NSCLC) and explore the role of SATB1 in the development of NSCLC. METHODS: The total RNA was extracted from NSCLC tissues and normal lung tissues and reverse transcribed into cDNA. Real-time fluorescence quantitative RT-PCR was performed for detecting the expression of SATB1 mRNA these tissues. RESULTS: The expression of SATB1 mRNA was 13-fold higher in NSCLC tissues than in normal lung tissues (P<0.001), and in metastatic and nonmetastatic NSCLC, the expression was 23.63 and 5.57 folds that in normal lung tissues, respectively. CONCLUSION: SATB1 mRNA expression might be associated with the development and lymph node metastasis of NSCLC and may potentially used as an indicator for predicting the prognosis of NSCLC.