Novel PPFIA1-ALK, ALK-C2orf91(intergenic) double-fusion responded well to alectinib in an advanced lung adenocarcinoma patient: a case report.

Non-small cell lung cancers (NSCLCs) with anaplastic lymphoma kinase (ALK)-rearrangement have favorable responses to ALK inhibitors. However, ALK fusion mutations harbored approximately 90 distinct fusion partners. Patients with different ALK fusions might respond distinctly to different-generation ALK inhibitors. In this case report, we identified a novel non-reciprocal ALK fusion, ALK-C2orf91(intergenic) (A19: intergenic) and PPFIA1-ALK (P2:A20), by next-generation DNA sequencing in an advanced lung adenocarcinoma patient. After 2 months of alectinib, the targeted lung lesion regressed significantly, and evaluation of therapeutic efficiency indicated partial response. To date, the patient had achieved 12 months of progression-free survival from alectinib treatment. Our study extended the spectrum of ALK fusion partners in ALK-positive NSCLC, and we reported a new ALK fusion, PPFIA1-ALK and ALK-C2orf91(intergenic), and its sensitivity to alectinib firstly in lung cancer. We believe that this case report has an important clinical reference.

Clinical Characteristics, Course, and Long-Term Outcomes in Patients with Talaromyces marneffei Infection: A 10-Year Retrospective Cohort Study.

INTRODUCTION: Talaromyces marneffei (T. marneffei), a dimorphic fungus, causes local or disseminated infection in humans. We aimed to analyze the clinical characteristics, prognostic factors, and survival outcomes of patients with T. marneffei infection and compare the differences between human immunodeficiency virus (HIV)-positive and HIV-negative subgroups. METHODS: We retrospectively analyzed 241 patients with T. marneffei infection at the First Affiliated Hospital of Guangxi Medical University between January 2012 and January 2022. The overall population was stratified into HIV-positive (n = 98) and HIV-negative (n = 143) groups according to HIV status. Kaplan-Meier analysis and multivariate Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: With a median follow-up time of 58.9 months, 120 patients (49.8%) experienced disease progression and 85 patients (70.8%) died. The 5-year rates of OS and PFS were 61.4% (95% CI 55.0-68.6%) and 47.8% (95% CI 41.5-55.1%), respectively. As an independent factor, patients who were HIV positive had better PFS (HR 0.50, 95% CI 0.31-0.82; p < 0.01) than patients who were HIV negative. Compared with patients who were HIV positive, patients who were HIV negative were older and had more probabilities of underlying diseases, chest involvement, bone destruction, and higher count of neutrophils (all p < 0.05). Hemoglobin (PFS: HR 0.62; 95% CI 0.39-1.00; p < 0.05; OS: HR 0.45; 95% CI 0.22-0.89; p = 0.02) and lymphocyte count (PFS: HR 0.06; 95% CI 0.01-0.26; p < 0.01; OS: HR 0.08; 95% CI 0.01-0.40; p < 0.01) were independent prognostic factors for PFS and OS in patients who were HIV negative. CONCLUSIONS: Patients with T. marneffei infection have a poor prognosis. Patients who are HIV positive and HIV negative have relatively independent clinical characteristics. Multiple organ involvement and disease progression are more common in patients who are HIV negative.

A case of lung adenocarcinoma with MET∆ex14 mutation regressed after preoperative treatment with savolitinib, and successfully underwent radical resection.

Non-small cell lung carcinoma (NSCLC) is a complex disease, with many different potential gene mutations that drive its formation, occurrence, and development. It is estimated that about 3% of NSCLC patients are accompanied by MET exon 14 skipping (METex14) mutations, and the prognosis of such patients is generally poor, which forms a formidable challenge for us. Savolitinib (Orpathys) is the first highly selective MET inhibitor in China. Here, we presented an NSCLC patient with MET∆ex14 mutation, who was initially uncertain whether existed intrapulmonary metastasis and recently underwent percutaneous coronary intervention for acute myocardial infarction and received savolitinib 600 mg once a day. The tumor was significantly shrunk 6 months later, and no metastatic lesions were found. Eventually, it was determined that the patient was in the early stage of lung cancer. After experts' consultation and evaluation, the patient accepted radical tumor resection and recovered well. Therefore, savolitinib is an important treatment strategy for NSCLC patients with MET∆ex14 mutation, who was not suitable for surgery. Our experience may provide supporting evidence and guidance for implementing an effective therapeutic strategy for similar cases.

Effects of Mitochondrial ATP-Sensitive Potassium Channel in Rats with Acute Myocardial Infarction and Its Association with the AKT/mTOR Pathway.

BACKGROUND: Myocardial infarction is associated with the autophagy and apoptosis of cardiomyocytes, and the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway plays a crucial role in this mechanism. METHODS: Acute myocardial infarction rat models were assessed 0.5, 2, 4, and 6 hours after the induction of the myocardial infarction using hematoxylin and eosin staining, triphenyl tetrazolium chloride staining, myocardial enzyme measurements, and levels of autophagic activity. Additionally, diazoxide, 5-hydroxydecanoate, and LY294002 were intraperitoneally administered to rat models at peak myocardial injury to assess their effects on cardiac injury. The expression levels of autophagy-related and apoptosis-related proteins, as well as p-AKT and p-mTOR, were measured. Electron microscopy was used to assess the ultrastructure and the number of autophagosomes in the cardiac tissue. RESULTS: We demonstrated that the degree of myocardial injury and the level of autophagy were significantly elevated in the experimental cohort compared with the control cohort. In addition, the myocardial infarct size was significantly smaller in diazoxide-treated acute myocardial infarction rats compared with untreated rats. Diazoxide also decreased the levels of myocardial injury markers, autophagy, and apoptosis, while it also induced the levels of AKT and mTOR phosphorylation, decreased the number of autophagosomes, and improved the myocardial ultrastructure of the acute myocardial infarction rats. 5-Hydroxydecanoate treatment resulted in an opposite effect to those observed upon diazoxide treatment. LY294002 was also able to reverse diazoxide treatment effects. CONCLUSION: Peak levels of myocardial tissue injury and autophagy were observed 2 hours post-acute myocardial infarction induction in rats. Diazoxide treatment inhibited myocardial autophagy and apoptosis while protecting cardiac tissue from ischemic injury, which is likely to have proceeded through activation of the AKT/mTOR pathway.

Comparison of Efficacy and Safety between Thrombolysis Plus Anticoagulation vs. Anticoagulation Alone for the Treatment of Acute Submassive Pulmonary Embolism: A Systematic Review and Meta-analysis.

OBJECTIVE: The objective of this study is to compare the efficacy and safety of thrombolysis plus anticoagulant therapy vs. anticoagulant therapy alone in acute submassive pulmonary embolism (PE). MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Library databases were searched for randomized clinical trials comparing thrombolytic therapy and anticoagulation vs. anticoagulation alone in acute submassive PE patients from 1 Jan 1980 to 20 Jan 2021, with no drug or dose restrictions. Data on upgraded treatment of clinical deterioration, all-cause mortality, PE recurrence and bleeding events were extracted and analyzed using Revman 5.3 software. RESULTS: A total of 10 randomized controlled trials involving 1871 patients were included in the study after screening. In terms of efficacy, thrombolysis combined with anticoagulant therapy reduced the need for upgrading treatment (3.6 vs. 10.9%, risk ratio (RR) 0.36, 95% confidence interval (CI) 0.24- 0.54, p<0.00001) and PE recurrence (0.8 vs. 2.9%, RR 0.33, 95% CI 0.16-0.69, p=0.003) in patients with acute submassive PE. Compared with anticoagulant therapy alone, the concomitant use of thrombolysis was associated with lower all-cause mortality (1.3 vs. 3.0%, RR 0.47, 95% CI 0.26-0.87, p=0.02), but it increased minor bleeding rate (31.4 vs. 8.4%, RR 3.71, 95% CI 2.82-4.88, p<0.0001) and major bleeding rate (8.8 vs. 2.6%, RR 3.35, 95%CI 2.03-5.54, p<0.0001). CONCLUSION: The use of thrombolysis plus anticoagulant therapy in acute submassive PE was negatively associated with patients requiring escalation of treatment, PE recurrence, and all-cause mortality, but it was positively associated with bleeding.

miR-17-5p/HOXA7 Is a Potential Driver for Brain Metastasis of Lung Adenocarcinoma Related to Ferroptosis Revealed by Bioinformatic Analysis.

Objectives: Present study aims to identify the essential mRNAs responsible for the development of brain neurovascular-related metastases (BNM) among lung adenocarcinoma (LUAD) patients. Further, we attempted to predict brain metastases more accurately and prevent their development in LUAD patients. Methods: Transcriptome data analysis was used to identify differentially expressed mRNAs (DEMs) associated with brain metastasis, and thereby the ferroptosis index (FPI) is calculated using a computational model. Meanwhile, the DEmRNAs linked with FPI, and brain metastasis were derived by the intersection of these two groups of DEMs. We also constructed a ceRNA network containing these DEmRNAs, identifying the HCP5 /hsa-miR-17-5p/HOXA7 axis for analysis. Further, a clinical cohort was employed to validate the regulatory roles of molecules involved in the ceRNA regulatory axis. Results: Here we report the development of a ceRNA network based on BNM-associated DEMs and FPI-associated DEmRNAs which includes three core miRNAs (hsa-miR-338-3p, hsa-miR-429, and hsa-miR-17-5p), three mRNAs (HOXA7, TBX5, and TCF21), and five lncRNAs (HCP5, LINC00460, TP53TG1). Using gene set enrichment analysis (GSEA) and survival analysis, the potential axis of HCP5 /hsa-miR-17-5p/HOXA7 was further investigated. It is found that HOXA7 and ferroptosis index are positively correlated while inhibiting tumor brain metastasis. It may be that HCP5 binds competitively with miR-17-5p and upregulates HOXA7 to increase iron death limiting brain cancer metastases. Conclusions: The expression of both HOXA7 and HCP5 is positively correlated with FPI, indicating a possible link between ferroptosis and BNM. According to the results of our study, the ferroptosis-related ceRNA HCP5 /hsa-miR-17-5p/HOXA7 axis may contribute to the development of BNM in LUAD patients.

Impact of KMN network genes on progression and prognosis of non-small cell lung cancer.

The Knl1-Mis12-Ndc80 (KMN) network genes (including KNL, MIS12 and NDC80 complexes) encode a highly conserved network of protein complexes that act in cell mitosis. In recent years, multiple studies revealed that KMN network genes also play a vital role in tumor appearance and growth. However, the role of the KMN gene network in non-small cell lung cancer (NSCLC) remains unknown. In this study, we analyzed the effects of KMN genes expression and clinical phenotype in patients with lung adenocarcinoma (LUAD). The expression of KMN network genes and related clinical information was extracted from The Cancer Genome Atlas. The samples were classified into cluster I and II by consistent clustering. We analyzed the gene distribution by principal component analysis, and the potential risk characteristics were analyzed using the least absolute shrinkage and selection operator Cox regression algorithm. Univariate and multivariate Cox regression analyses were used to analyze the clinical information. The Database for Annotation, Visualization, and Integrated Discovery, Gene MANIA and gene set enrichment analysis were used to analyze function and correlation among genes of the KMN network. The expression levels of nine out of ten KMN genes were significantly up-regulated in LUAD and were associated with poor overall survival (OS). Higher expression of NDC80 and KNL1 was related to low OS in both univariate and multivariate analyses. According to two independent prognostic KMN network genes (KNL1 and NDC80), a risk signature was established to predict the prognosis of patients with LUAD. Additionally, the genes NDC80 and KNL1 were considerably enriched in pathways associated with signaling pathways, biological processes, and the cell cycle. The results indicate that KMN network genes are intimately related to lung adenocarcinoma. KMN network genes are involved in the malignant process of LUAD. Assessment of NDC80 and KNL1 might be helpful for prognostic stratification and treatment strategy development.

Osimertinib is an effective epidermal growth factor receptor-tyrosine kinase inhibitor choice for lung cancer with epidermal growth factor receptor exon 18-25 kinase domain duplication: report of two cases.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are an effective treatment for common EGFR mutations in non-small-cell lung cancer (NSCLC). Rarer EGFR mutations such as kinase domain duplications (KDDs) have been identified, but the optimal therapy following treatment resistance remains unknown. We report two patients who were diagnosed with NSCLC including KDD. For case 1, afatinib (40 mg once daily) was at first effective but then became ineffective. Consequently, osimertinib therapy (80 mg once daily) was administered. As of 26 May 2021, the osimertinib therapy achieved a stable disease state according to the chest computed tomography scan. As for case 2, the patient received second-line chemotherapy and anlotinib (12 mg once daily) for 6 months and died in May 2020. Here, we describe osimertinib as an effective therapy for EGFR-KDD positive lung adenocarcinoma and thereby provide a new alternative for further treatment following resistance to first- and second-generation EGFR-TKIs.

Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma.

Aberrant DNA modifications affect the tumorigenesis and progression of lung cancer. However, the global methylation status of tumor cells and the heterogeneous methylation status of cells within the same tumor need further study. We used publicly available single-cell RNAseq data to investigate the impact and diversity of global methylation status on lung adenocarcinoma. Clustering cells into subgroups and cell differentiation pseudotime analysis, based on expression profile, demonstrated that the global methylation status was crucial to lung adenocarcinoma function and progression. Hypermethylated tumor cells had increased activity related to the hypoxia response. Hyper- and hypomethylated cells indicated upregulation in pathways involving focal adhesion and cell junctions. Pseudotime analysis showed that cell clusters with unique methylation activities were located at the ends of the putative trajectories, suggesting that DNA methylation and demethylation activities were essential to tumor cell progression. Expression of SPP1 was associated with the global methylation status of tumor cells and with patient prognosis. Our study identified the importance and diversity of global DNA methylation status by analysis at the single-cell level. Our findings provide new information about the global DNA methylation status of tumor cells and suggest new approaches for precision medical treatments for lung adenocarcinoma.

Identification of the Unique Clinical and Genetic Features of Chinese Lung Cancer Patients With EGFR Germline Mutations in a Large-Scale Retrospective Study.

BACKGROUND: Epidemiological surveys have suggested that lung cancer has inherited susceptibility and shows familial aggregation. However, the distribution and prevalence of epidermal growth factor receptor (EGFR) germline variants and their roles in lung cancer genetic predisposition in Chinese population remain to be elucidated. METHODS: In this study, EGFR germline and somatic variants were retrospectively reviewed from the next-generation sequencing results of 31,906 patients with lung cancer. Clinical information was also collected for patients with confirmed EGFR germline mutations. RESULTS: A total of 22 germline EGFR variants were identified in 64 patients with lung cancer, accounting for 0.2% of the total cases studied. Five patients were diagnosed as multiple primary carcinomas. Family history was documented in 31.3% (20/64) of patients, 55% of which were diagnosed as lung cancer. G863D was the most frequent EGFR germline mutation, followed by P848L, D1014N, and K757R. Somatic EGFR-sensitive mutations were identified in 51.6% of patients with germline EGFR mutations. The proportion of L858R mutation, exon 19 deletion, and rare sensitive mutation was 50%, 17.6%, and 32.4%, respectively. D1014N and T790M mutations were common in young patients. The family members of patients with P848L, R776H, V769M, and V774M mutations were more commonly diagnosed with cancers. A total of 19 patients were confirmed to have received EGFR tyrosine kinase inhibitors (TKIs), but the response to EGFR-TKIs differed among patients with different EGFR mutations. CONCLUSION: Chinese patients with lung cancer harbored unique and dispersive EGFR germline mutations and showed unique clinical and genetic characteristics, with varied response patterns to EGFR-TKI treatment.

Coexistence of a secondary STRN-ALK, EML4-ALK double-fusion variant in a lung adenocarcinoma patient with EGFR mutation: a case report.

ALK-positive disease is characterized by the presence of ALK gene rearrangements that encode driver fusion oncoproteins. EML4-ALK fusion is regarded as the most common type in advanced nonsmall cell lung cancers. STRN-ALK is a novel ALK fusion partner in NSCLC and is considered sensitive to targeted therapy. However, there was no study regarding effective therapy for EML4-ALK and STRN-ALK double fusion variants in EGFR-resistant mutant lung cancer. TP53, RB1, and EGFR exon 21 L858R were found in tumor tissues and plasma from patients with capture-based NGS. After 3 months of gefitinib treatment, an NGS of plasma circulating tumor DNA showed that all variants disappeared significantly, and the tumor mass regressed on CT. However, after 10 months, the patient developed drug resistance and the disease progressed with the appearance of new metastatic lesions in the liver and bones. A repeated NGS test revealed EGFR exon20 T790M and the appearance of a novel double-fusion EML4-ALK and STRN-ALK. A combined therapeutic regimen of crizotinib plus osimertinib showed a promising prognosis confirmed with lung CT scans showing stable lesions without any new metastasis. Moreover, a subsequent genotype by NGS also showed the disappearance of STRN-ALK and EGFR exon20 T790M. The therapeutic efficacy of crizotinib plus osimertinib on EML4-ALK and STRN-ALK double-fusion variant in patients with EGFR-resistant mutant lung cancer may provide a supportive reference for the patients with such genetic alteration.

Clinical significance of circPVT1 in patients with non-small cell lung cancer who received cisplatin combined with gemcitabine chemotherapy.

OBJECTIVE: CircPVT1 was identified as a tumor-promoted circRNA that is upregulated in several cancers. We researched clinical significance of circPVT1 in patients with non-small cell lung cancer (NSCLC) who received cisplatin combined with gemcitabine chemotherapy. METHODS: Reverse transcriptase polymerase chain reaction assays were performed to detect circPVT1 expression in 96 patients with NSCLC. In addition, Kaplan-Meier methods were performed to analyze survival of patients with NSCLC. RESULTS: There is no significant difference between circPVT1 and age, sex, histologic type, lymphatic invasion, or vascular invasion in patients with NSCLC and there is significant difference between circPVT1 and differentiation or p-TNM stage in patients with NSCLC. In addition, after cisplatin combined with gemcitabine chemotherapy, circPVT1 expression was decreased, and circPVT1 expression in the chemotherapy-resistant group was higher than in the chemotherapy-sensitive group. Survival of patients with NSCLC was associated with high circPVT1 expression. CONCLUSIONS: Our study revealed the clinical significance of circPVT1 in NSCLC after cisplatin combined with gemcitabine chemotherapy. After treatment, circPVT1 expression was decreased and circPVT1 expression in chemotherapy-resistant patients was higher than in chemotherapy-sensitive patients. Decreased circPVT1 expression in chemotherapy-sensitive patients is more notable than in chemotherapy-resistant patients. Therefore, it is possible to determine the effect of therapy after receiving chemotherapy by detecting the expression of circRNA in serum.

Circular RNA hsa_circ_0096157 contributes to cisplatin resistance by proliferation, cell cycle progression, and suppressing apoptosis of non-small-cell lung carcinoma cells.

Circular RNAs (circRNAs) play a major role in cancer development and chemotherapy resistance. This study aimed to characterize circRNA profiles associated with Cisplatin (diamminedichloroplatinum, DDP) resistance of non-small-cell lung carcinoma (NSCLC) cells. The half-maximal inhibitory concentration (IC50) of A549 and A549/DDP cells was determined using CCK-8 assay. Further, circRNA profiles and differentially expressed genes in A549 and A549/DDP cells were characterized by deep sequencing and cell proliferation was measured using MTS assay. Cell cycle progression was analyzed using flow cytometry. Apoptosis experiment was performed by TUNEL assay and flow cytometry. Cell migration and invasion were assessed using the Transwell system. Finally, signalling protein levels related to cell cycle progression and migration were measured by western blot. CCK-8 assay showed that A549/DDP cells obtained strong DDP resistance. Further deep sequencing results showed that 689 circRNAs and 87 circRNAs were significantly upregulated and downregulated in A549/DDP cells compared to A549 cells, respectively. Moreover, the circRNA hsa_circ_0096157 with the highest expression level in A549/DPP cells was further analyzed for its potential mechanism of DDP resistance in A549/DDP. With or without DDP treatment, hsa_circ_0096157 knockdown inhibited proliferation, migration, invasion and cell cycle progression but promoted apoptosis of A549/DDP cells. In addition, the western blot results also showed that hsa_circ_0096157 knockdown in A549/DDP cells increased P21 and E-cadherin but decreased CDK4, Cyclin D1, Bcl-2, N-cadherin, and Vimentin protein expression levels, indicating that cell cycle progression might be inhibited by increased P21 protein level to inhibit the expression of CDK4-cyclin D1 complex and decreased Bcl-2 protein level; and migration and invasion were suppressed by the increased E-cadherin and decreased N-cadherin and Vimentin expression levels. In contrast, hsa_circ_0096157 overexpression in A549 cells caused the opposite cellular and molecular alterations. DDP resistance in NSCLC cells was associated with significant circRNA profile alterations. Moreover, increased hsa_circ_0096157 expression contributed to DDP resistance in NSCLC cells by promoting cell proliferation, migration, invasion and cell cycle progression and inhibiting apoptosis.

Hypoxia-inducible factor-1α attenuates myocardial inflammatory injury in rats induced by coronary microembolization.

To investigated the role of HIF-1α in myocardial inflammatory injury in rats induced by CME and its possible mechanism. Forty SD rats were separated randomly and equally into four groups, i.e. CME+HIF-1α stabilizer dimethyloxalyl glycine (CME+DMOG) group, CME+HIF-1α inhibitor YC-1 (CME+YC-1) group, CME group, and Sham group. HBFP staining, myocardial enzyme assessment, and cardiac ultrasound were used to measure microinfarct, serum c-troponin I (cTnI) level, and Cardiac function. ELISA and western blot were applied for detecting NLRP3 inflammasome pathway and TLR4/MyD88/NF-κB signaling level.Pro-inflammatory factors of IL-18, IL-1ß and TNF-α increased their expression levels after CME, which indicated inflammatory responses in the myocardium. Additionally, in the inflammatory process, NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling were involved. DMOG reverses these effects of CME, whereas YC-1 aggravates these effects. HIF-1α may attenuate myocardial inflammatory injury induced by CME and improve cardiac function, which can perhaps be explained by the fact that TLR4/MyD88/NF-κB signaling pathway activation is inhibited.

Potential therapeutic targets of the nuclear division cycle 80 (NDC80) complexes genes in lung adenocarcinoma.

Background: Lung cancer is the most common cancer worldwide, both in terms of the incidence and mortality. NDC80 complex comprising of NDC80, NUF2, SPC24, and SPC25 is a heterotetrameric protein complex located in the outer layer of the kinetochore and plays a critical role in mitosis. This study focuses on the effects of NDC80 complex genes on clinical features and prognosis in lung adenocarcinoma (LUAD). Materials and methods: Expression of NDC80 complex in LUAD and related clinical information was extracted from the TCGA website. NDC80 complex gene functional analysis and correlation analysis was conducted by using DAVID, BiNGO, Gene MANIA, STRING and GSEA. Survival probability was predicted by nomogram. Statistical analysis was used to predict NDC80 complex gene expression on clinical features and prognosis in patients with LUAD. Results: Expression of NDC80, NUF2, SPC24 and SPC25 was significantly elevated in LUAD tumors compared with normal tissues (P < 0.05). These genes showed diagnostic values for LUAD (P < 0.001 for each; area under the curve (AUC), 0.958, 0.968, 0.951, and 0.932 respectively); combinatorial analysis of these genes was more advantageous than single analysis alone (P < 0.001; AUC > 0.900 for each). Expression of both NDC80 and SPC25 correlated with the prognosis of LUAD (P < 0.001; AUC > 0.600 for each). Higher expression of NDC80, NUF2, SPC24 and SPC25 was associated with low overall survival (OS) in univariate analysis. Higher expression of NDC80 and SPC25 was associated with low OS in multivariate analysis. High expression of NDC80 combined with high expression of SPC25 was predictive of poor OS in LUAD in joint analysis. Conclusion: NDC80 complex gene might be an early indicator of diagnosis and prognosis of LUAD. The combined detection of NDC80, NUF2, SPC24 and SPC25 may become a new research direction in LUAD diagnosis and a new target for tumor targeted gene therapy.

The miRNA-149-5p/MyD88 axis is responsible for ursolic acid-mediated attenuation of the stemness and chemoresistance of non-small cell lung cancer cells.

Although the inhibitory roles of ursolic acid (UA) have been established in various tumors, its effects on the stemness of non-small cell lung cancer (NSCLC) cells are still unclear. Here, we constructed NSCLC cells with paclitaxel resistance (A549-PR) and showed that A549-PR exhibited a remarkably stronger stemness than the parental A549 cells, which is evident by the increase of spheroid formation capacity, stemness marker expression, and ALDH1 activity. Additionally, UA significantly reduced the stemness and paclitaxel resistance of A549-PR cells. Mechanistic investigations revealed that UA inhibited the miR-149-5p/MyD88 signaling, which is responsible for UA-mediated effects on the stemness of A549-PR cells. Notably, miR-149-5p/MyD88 axis promoted the stemness of A549 cells, while inhibition of this axis attenuated the stemness of A549-PR cells. Therefore, these results suggest that UA could attenuate the stemness and chemoresistance of NSCLC cells through targeting miR-149-5p/MyD88 axis.

Role of high-mobility group B1 in myocardial injury induced by coronary microembolization in rats.

OBJECTIVE: This study aimed to explore the effects of high-mobility group B1 (HMGB1) on coronary microembolization (CME)-induced myocardial inflammation, myocardial apoptosis, and cardiac function injury in rats. METHODS: Forty Sprague-Dawley rats were divided into sham operation group (sham group), microembolization group (CME group), CME + HMGB1 siRNA (HMGB1 siRNA) group, and CME + scrambled siRNA (control siRNA) group (10 rats in each group). The CME model group was constructed by injecting microembolism spheres into the apex of the left ventricle after clamping the ascending aorta. The sham group was constructed by injecting the same amount of saline. The HMGB1 siRNA group was injected with HMGB1 siRNA transfection complex via the tail vein 72 hours before CME modeling. The control siRNA group was injected with the same amount of scrambled siRNA mixture through the tail vein 72 hours before CME modeling. The cardiac function, serum cardiac troponin I level, and apoptotic index were examined 12 hours after the surgery. The levels of HMGB1, nuclear factor-κB (NF-κB) p65, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, cleaved caspase-3, tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß) were detected. RESULTS: Myocardial dysfunction, enhanced serum cardiac troponin I level, and apoptotic index were induced following CME. Moreover, CME increased the expression of HMGB1, NF-κB p65, GRP78, CHOP, cleaved caspase-12, cleaved caspase-3, TNF-α, and IL-1ß. HMGB1 siRNA reversed these effects, whereas scrambled siRNA had no effect. CONCLUSIONS: Inhibition of HMGB1 expression reduced CME-induced myocardial injury and improved cardiac function. Hence, it may serve as a new target for preventing and treating the CME-induced myocardial injury.

Influence of rs1746048 SNPs on clinical manifestations and incidence of acute myocardial infarction in Guangxi Han population.

A relationship of the CXCL12 gene rs1746048 SNPs with AMI has been reported in American, European, Caucasian, and Pakistani populations. However, little is known about this association in the Guangxi Han population. In this study, we detect associations between rs1746048 SNPs and susceptibility, risk factors, clinical characteristics, and gene-environment interactions for AMI. 300 AMI patients and 300 healthy controls of Chinese Han were enrolled. Genotyping of rs1746048 SNPs was performed using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and then confirmed by direct sequencing. Significant differences in both genotypic and allelic frequencies of rs1746048 SNPs between AMI and the control group were not detected (P > 0.05 for each). The frequency of CC genotypes of rs1746048 SNPs was the highest in the 2 h < DT ≤ 6 h subgroup (P < 0.05). The frequencies of the CT genotype and the T allele were significantly higher in the severe complications subgroup of AMI (P < 0.05). There were interactions between the subjects with rs1746048 SNPs and smoking or alcohol consumption (P < 0.017 for each). Rs1746048 SNPs were not correlated with the risk of AMI in present study. For the first time, we discovered that the CC genotype of the rs1746048 SNPs was significantly correlated with DT of AMI; the frequencies of the CT genotype and the minor T allele were positively correlated with the severe complications of AMI. Also, the interaction between the rs1746048 SNPs and smoking or alcohol appears to increase the risk of AMI exposure.