Establishing and validation of the VBV score for assessing Lung ground-glass nodules based on high-resolution computed tomography.

BACKGROUND: The widespread utilization of chest High-resolution Computed Tomography (HRCT) has prompted detection of pulmonary ground-glass nodules (GGNs) in otherwise asymptomatic individuals. We aimed to establish a simple clinical risk score model for assessing GGNs based on HRCT. METHODS: We retrospectively analyzed 574 GGNs in 574 patients undergoing HOOK-WIRE puncture and pulmonary nodule surgery from January 2014 to November 2018. Clinical characteristics and imaging features of the GGNs were assessed. We analyzed the differences between malignant and benign nodules using binary logistic regression analysis and constructed a simple risk score model, the VBV Score, for predicting the malignancy status of GGNs. Then, we validated this model via other 1200 GGNs in 1041 patients collected from three independent clinical centers in 2022. RESULTS: For the exploratory phase of this study, out of the 574 GGNs, 481 were malignant and 93 were benign. Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. Then, we derived a VBV Score = vacuole sign + air bronchogram + intra-nodular vessel sign, to predict the malignancy of GGNs, with a sensitivity, specificity, and accuracy of 95.6%, 80.6%, and 93.2%, respectively. We also validated it on other 1200 GGNs, with a sensitivity, specificity, and accuracy of 96.0%, 82.6%, and 95.0%, respectively. CONCLUSIONS: Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. VBV Score showed good sensitivity, specificity, and accuracy for differentiating benign and malignant pulmonary GGNs.

Artificially Selected Grain Shape Gene Combinations in Guangdong Simiao Varieties of Rice (Oryza sativa L.).

BACKGROUND: Grain shape is a key trait in rice breeding. Although many QTLs and genes of grain shape have been identified, how different combinations of alleles of these genes affect grain shape is largely unknown. It is important to understand the effects of grain shape gene combinations for breeding by design. In the present study, we performed genetic dissection of the grain shapes in Guangdong Simiao varieties, a popular kind of rice in South China, to identify the effective alleles and their combination for breeding. RESULTS: We selected two hundred nineteen indica accessions with diverse grain shapes and fifty-two Guangdong Simiao varieties with long and slender grain shapes for genome-wide selection analysis. The results showed that four (GS3, GS5, GW5 and GL7) of the twenty grain shape genes fall into the regions selected for in Guangdong Simiao varieties. Allele analysis and frequency distribution of these four genes showed that GS3allele3 and GW5allele2 accounted for 96.2%, and GL7allele2 and GS5allele2 accounted for 76.9% and 74.5% of the Simiao varieties, respectively. Further analysis of the allelic combinations showed that 30 allelic combinations were identified in the whole panel, with 28 allelic combinations found in the international indica accessions and 6 allelic combinations found in Guangdong Simiao varieties. There were mainly three combinations (combinations 17, 18 and 19) in the Guangdong Simiao varieties, with combination 19 (GS3allele3 + GW5allele2 + GL7allele2 + GS5allele2) having the highest percentage (51.9%). All three combinations carried GS3allele3 + GW5allele2, while combinations 17 (GL7allele1) and 19 (GL7allele2) showed significant differences in both grain length and length/width ratio due to differences in GL7 alleles. Pedigree analysis of Guang8B, the maintainer of the first released Simiao male sterile line Guang8A, showed that the parent lines and Guang8B carried GS3allele3 + GW5allele2 + GS5allele2, while the GL7 allele differed, resulting in significant differences in grain size. CONCLUSION: The results suggest that specific alleles of GS3, GS5, GW5 and GL7 are the key grain shape genes used in the Guangdong Simiao varieties and selected for grain shape improvement. Combination 19 is the predominant allelic combination in the Guangdong Simiao varieties. Our current study is the first to dissect the genetics of grain shape in Guangdong Simiao varieties, and the results will facilitate molecular breeding of Guangdong Simiao varieties.

A spontaneous thermo-sensitive female sterility mutation in rice enables fully mechanized hybrid breeding.

Male sterility enables hybrid crop breeding to increase yields and has been extensively studied. But thermo-sensitive female sterility, which is an ideal property that may enable full mechanization in hybrid rice breeding, has rarely been investigated due to the absence of such germplasm. Here we identify the spontaneous thermo-sensitive female sterility 1 (tfs1) mutation that confers complete sterility under regular/high temperature and partial fertility under low temperature as a point mutation in ARGONAUTE7 (AGO7). AGO7 associates with miR390 to form an RNA-Induced Silencing Complex (RISC), which triggers the biogenesis of small interfering RNAs (siRNAs) from TRANS-ACTING3 (TAS3) loci by recruiting SUPPRESSOR OF GENE SILENCING (SGS3) and RNA-DEPENDENT RNA POLYMERASE6 (RDR6) to TAS3 transcripts. These siRNAs are known as tasiR-ARFs as they act in trans to repress auxin response factor genes. The mutant TFS1 (mTFS1) protein is compromised in its ability to load the miR390/miR390* duplex and eject miR390* during RISC formation. Furthermore, tasiR-ARF levels are reduced in tfs1 due to the deficiency in RDR6 but not SGS3 recruitment by mTFS1 RISC under regular/high temperature, while low temperature partially restores mTFS1 function in RDR6 recruitment and tasiR-ARF biogenesis. A miR390 mutant also exhibits female sterility, suggesting that female fertility is controlled by the miR390-AGO7 module. Notably, the tfs1 allele introduced into various elite rice cultivars endows thermo-sensitive female sterility. Moreover, field trials confirm the utility of tfs1 as a restorer line in fully mechanized hybrid rice breeding.

MiRNA-146a rs2910164 Confers a Susceptibility to Digestive System Cancer: A Meta-Analysis Involving 59,098 Subjects.

BACKGROUND: MicroRNA (miR)-146a might participate in the occurrence of malignant tumor. The aim of the current investigation was to evaluate the relationship of microRNA-146a (miR-146a) rs2910164 C > G locus to the development of digestive system cancer (DSC). METHODS: We retrieved publications from PubMed, China Biology Medicine and EMBASE databases up to August 29, 2019. Finally, 56 independent case-control studies with 59,098 participants were included. The strength of the relationship between rs2910164 locus and a risk of DSC was assessed. The power value was also calculated in this study. RESULTS: We identified a correlation of rs2910164 locus in miR-146a with DSC development in dominant model (P = .035; power value = 0.994). MiR-146a rs2910164 locus was also identified to be correlated with a risk of DSC in Asians (GG/CG vs. CC: P = .033; power value = 0.989). Sensitivity analysis revealed that any individual study could not alter the final decision. In our study, no significant bias was found among these included studies (P > .1). The results of heterogeneity analysis suggested that small sample size (<1000 subjects), colorectal carcinoma, Asians, gastric carcinoma, esophageal squamous cell carcinoma, hepatocellular cancer, hospital-based study and high-quality score (≥7.0) subgroups contributed the heterogeneity to our findings. Galbraith radial plot determined that eleven outliers contributed to the main heterogeneity. CONCLUSION: In summary, this meta-analysis highlights that rs2910164 locus might be implicated in the risk of DSC. More studies are, therefore, needed to confirm our results.

Construction of a Nine-MicroRNA-Based Signature to Predict the Overall Survival of Esophageal Cancer Patients.

BACKGROUND: Esophageal cancer (EC) is a common malignant tumor. MicroRNAs (miRNAs) play a key role in the occurrence and metastasis and are closely related to the prognosis of EC. Therefore, it will provide a powerful tool to predict the overall survival (OS) of EC patients based on miRNAs expression in EC tissues and blood samples. METHODS: Five independent databases, TCGA, GSE106817, GSE113486, GSE122497, and GSE112264, were used to construct nine-miRna signature and nomograms for prognosis. The bioinformatics analysis was used to predict the enrichment pathways of targets. RESULTS: A total of 132 overexpressed miRNAs and 23 suppressed miRNAs showed significant differential expression in both EC serum and tissue samples compared with normal samples. We also showed that nine miRNAs were related to the prognosis of EC. Higher levels of miR-15a-5p, miR-92a-3p, miR-92a-1-5p, miR-590-5p, miR-324-5p, miR-25-3p, miR-181b-5p, miR-421, and miR-93-5p were correlated to the shorter survival time in patients with EC. In addition, we constructed a risk prediction model based on the levels of nine differentially expressed miRNAs (DEMs) and found that the OS time of EC patients with high-risk score was shorter than that of EC patients with low-risk score. Furthermore, our results showed that the risk prediction scores of EC samples were higher than those of normal samples. Finally, the area under the curve (AUC) was used to analyze the risk characteristics of EC and normal controls. By calculating the AUC and the calibration curve, the RNA signature showed a good performance. Bioinformatics analysis showed that nine DEMs were associated with several crucial signaling, including p53, FoxO, PI3K-Akt, HIF-1, and TORC1 signaling. Finally, 14 messenger RNAs (mRNAs) were identified as hub targets of nine miRNAs, including BTRC, SIAH1, RNF138, CDC27, NEDD4L, MKRN1, RLIM, FBXO11, RNF34, MYLIP, FBXW7, RNF4, UBE3C, and RNF111. TCGA dataset validation showed that these hub targets were significantly differently expressed in EC tissues compared with normal samples. CONCLUSION: We have constructed maps and nomograms of nine-miRna risk signals associated with EC prognosis. Bioinformatics analysis revealed that nine DEMs were associated with several crucial signaling, including p53, FoxO, PI3K-Akt, HIF-1, and TORC1 signaling, in EC. We think that this study will provide clinicians with an effective decision-making tool.

Antitumor effects of flavokawain-B flavonoid in gemcitabine-resistant lung cancer cells are mediated via mitochondrial-mediated apoptosis, ROS production, cell migration and cell invasion inhibition and blocking of PI3K/AKT Signaling pathway.

The Editors of JBUON issue an Expression of Concern to 'Antitumor effects of flavokawain-B flavonoid in gemcitabine resistant lung cancer cells are mediated via mitochondrial mediated apoptosis, ROS production, cell migration and cell invasion inhibition and blocking of PI3K/AKT Signaling pathway', by Rong Hua, Yaofei Pei, Haiyong Gu, Yifeng Sun, Yi He, JBUON 2020;25(1):262-267; PMID: 32277640. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

MALAT1 rs619586 A/G polymorphisms are associated with decreased risk of lung cancer.

ABSTRACT: Lung cancer is the leading cause of cancer-associated mortality worldwide. Genetic factors are reported to play important roles in lung carcinogenesis. To evaluate genetic susceptibility, we conducted a hospital-based case-control study on the effects of functional single nucleotide polymorphisms (SNPs) in long non-coding RNAs (lncRNAs) and microRNAs on lung cancer development. A total of 917 lung cancer cases and 925 control subjects were recruited. The MALAT1 rs619586 A/G genotype frequencies between patient and control groups were significantly different (P < .001), specifically, 83.85% vs 75.88% (AA), 15.60% vs 21.79% (AG), and 0.55% vs 2.32% (GG). When the homozygous genotype MALAT1 rs619586 AA was used as the reference group, AG (AG vs AA: adjusted odds ratio [OR] 0.65, 95% confidential interval [CI] 0.51-0.83, P = .001) and GG genotypes were associated with significantly decreased risk of lung cancer (GG vs AA: adjusted OR 0.22, 95% CI 0.08-0.59, P = .003). In the dominant model, MALAT1 rs619586 AG/GG variants were also associated with a significantly decreased risk of lung cancer (adjusted OR 0.61, 95% CI 0.48-0.78, P < .001). In the recessive model, when MALAT1 rs619586 AA/AG genotypes were used as the reference group, the GG homozygous genotype was also associated with significantly decreased risk for lung cancer (adjusted OR 0.24, 95% CI 0.09-0.64, P = .004). Hsa-miR-34b/c rs4938723 T > C, pri-miR-124-1 rs531564 C > G and hsa-miR-423 rs6505162 C > A SNPs were not associated with lung cancer risk. Our collective data indicated that MALAT1 rs619586 A/G SNPs significantly reduced the risk of lung cancer. Large-scale studies on different ethnic populations and tissue-specific biological characterization are required to validate the current findings.

Association between microRNA-146a, -499a and -196a-2 SNPs and non-small cell lung cancer: a case-control study involving 2249 subjects.

MicroRNA (miR) acts as a negative regulator of gene expression. Many literatures have suggested that miRs may be involved in the process of cell proliferation, inflammation, oxidative stress, energy metabolism and epithelial-mesenchymal transition. Thus, miRs may be implicated in the occurrence of non-small cell lung cancer (NSCLC). In the current investigation, we included 2249 subjects (1193 NSCLC patients and 1056 controls) and designed a study to identify the relationship of miR-146a rs2910164 C/G, -499a rs3746444 A/G and -196a-2 rs11614913 T/C with the risk of NSCLC. The risk factors (e.g., body mass index (BMI), sex, smoking, drinking and age) was used to adjust the odds ratios (ORs) and 95% confidence intervals (CIs). After conducting a power value assessment, we did not confirm that the miR-single nucleotide polymorphisms (SNPs) genotypic distributions were different in NSCLC cases and controls. However, the association of miR-196a-2 rs11614913 with a decreased risk of NSCLC was identified in the female subgroup (adjusted P=0.005, power = 0.809 for TC vs. TT, and adjusted P=0.004, power = 0.849 for CC/TC vs. TT). In addition, gene-gene interaction analysis showed that rs11614913 TC/3746444 AA and rs11614913 CC/rs3746444 AA could also reduce the susceptibility to NSCLC (rs11614913 TC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.001, power = 0.912 and rs11614913 CC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.003, power = 0.836). In conclusion, in overall comparisons, we did not confirm that the rs2910164, rs3746444, and rs11614913 SNPs genotypic distributions were different in NSCLC cases and controls. However, this case-control study demonstrates that miR-196a-2 rs11614913 may be a protective factor for the development of NSCLC among female patients.

Loss of FBP1 promotes proliferation, migration, and invasion by regulating fatty acid metabolism in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China. Recent studies have shown fatty acid metabolism is involved in the progression of various cancers through regulating the function of various types of cells. However, the relationship between fatty acid metabolism and tumorigenesis of ESCC remains unclear. Here, in this study, the expression of FBP1 was dramatically decreased in ESCC tissues compared with the adjacent non-ESCC tissues. The cell proliferation, migration, invasion and fatty acid metabolism were evaluated in ESCC cells using transfection of shFBP1 vectors. We found loss of FBP1 promoted ESCC cell proliferation, migration and invasion, which correlated with the activated fatty acid metabolism in vitro. Moreover, the content of phospholipids, triglycerides, neutral lipids and the protein expression levels of fatty acid metabolism related FASN, ACC1 and SREBP1C proteins were significantly increased following down-regulation of FBP1. Furthermore, FBP1 was found to be directly targeted by miR-18b-5p in ESCC cells. In addition, miR-18b-5p inhibitor treatment obviously reversed the increased fatty acid metabolism induced by loss of FBP1 in ESCC cells. These findings explored a detailed molecular mechanism of tumorigenesis and progression of ESCC and might provide a potential novel method to treat ESCC in clinic.

Long non-coding RNA CASC8 polymorphisms are associated with the risk of esophageal cancer in a Chinese population.

BACKGROUND: Esophageal cancer (EC) is an important disease that threatens public health and safety. Although there are numerous treatment options for esophageal cancer including surgery, radiation therapy, and chemotherapy, these treatments have limited effects. Its morbidity and mortality vary widely among countries and regions. Esophageal cancer is classified into squamous cell carcinoma (ESCC) and esopheageal adenocarcinoma (EADC). Here, we examined the genetic susceptibility to ESCC in relation to functional single nucleotide polymorphisms (SNPs) in the long non-coding RNA (lncRNA) CASC8. METHODS: To detect the susceptibility to ESCC in relation to functional polymorphisms in CASC8, a hypothesis-driven study was performed to identify CASC8 SNPs in 949 patients with ESCC and 1369 control subjects. RESULTS: The CASC8 rs1562430 GG genotype was significantly associated with increased ESCC risk in men, patients younger than 63 years, non-smokers, and nondrinkers. CONCLUSIONS: CASC8 rs1562430 A > G may cause susceptibility to ESCC and CASC8 SNPs may play a vital role in ESCC risk, thereby serving as a potential biomarker for diagnosing ESCC. A larger sample size and multifactor information are needed to confirm these results.

Antitumor effects of flavokawain-B flavonoid in gemcitabine-resistant lung cancer cells are mediated via mitochondrial-mediated apoptosis, ROS production, cell migration and cell invasion inhibition and blocking of PI3K/AKT Signaling pathway.

PURPOSE: Drug resistance in lung cancer is a growing and challenging problem affecting the overall treatment and quality of the patient's life. The main purpose of the current study was to investigate the anticancer effects of flavokawain-B in gemcitabine-resistant non-small lung cancer cells (NSCLC) along with evaluating its mode of action by studying its effects on programmed cell death, ROS production, cell migration and invasion and PI3K/AKT signalling pathway. METHODS: Cell proliferation rate was studied using MTS cell viability assay while apoptosis induction by flavokawain-B was studied by fluorescence microscopy using DAPI staining as well as flow cytometry using Annexin V-FITC/propidium iodide (PI). Effects on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were studied by flow cytometry using Rh-123 and DCH-DA dyes respectively. Effects on cell migration and cell invasion were examined by in vitro wound healing assay and transwell assay respectively. Changes in PI3K/AKT protein expressions were evaluated by western blot. RESULTS: Flavokawain-B selectively inhibited the viability of the human NSCLC cell line A549, indicating lower toxicity compared with normal lung cancer (NLC) CCL-151 cells and both showed dose-dependent inhibition. DAPI and annexin V-FITC/PI staining showed that flavokawain-B led to a dose-dependent onset of apoptosis in lung cancer cells characterized by shrunken cells, fragmented nuclei and chromatin condensation. Western blot showed that flavokawain-B resulted in downregulation of Bcl-2 and upregulation of Bax in a dose dependent manner. Flavokawain-B treatment led to increase of intracellular ROS concentration and decrease of mitochondrial membrane potential (MMP) both showing dose-dependence. It also led to suppression of cell migration and invasion along with blocking PI3K/AKT signalling pathway. CONCLUSIONS: Flavokawain-B targets gemcitabine-resistant NSCLC cells selectively without inducing any significant toxicity in normal cells and these effects are mediated via apoptosis induction, ROS production, loss of MMP, suppression of cell migration and invasion and blocking PI3K/AKT signalling pathway.

Multidisciplinary team approach on a case of bronchopleural fistula after video-assisted thoracoscopic segmentectomy: a case report.

Bronchopleural fistula (BPF) is one of the most severe complications after lung surgery including pneumonectomy, lobectomy, and segmentectomy. BPF is dangerous and complicated. We reported a case of 41-year-old man who underwent a segmentectomy of the right lung through video-assisted thoracoscopy. The patient was diagnosed with BPFs by CT and the symptom of fever, cough with malodorous yellow phlegm. The patient underwent CT-guided thoracic catheter drainage treatment, as advised by a multidisciplinary team including experts from the thoracic surgery department, respiratory medicine department, and interventional department. Later, the patient underwent assisted postural drainage in combination with anti-infection treatment and nutritional support treatment. The patient recovered well. The patient's symptoms were completely relieved. The bronchial stump fistula healed, and the chest abscess disappeared.

The value of enhanced CT scanning for predicting lymph node metastasis along the right recurrent laryngeal nerve in esophageal squamous cell carcinoma.

BACKGROUND: The right recurrent laryngeal nerve (RRLN) is the region most prone to lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Nodal involvement may be underestimated by traditional imaging prediction criteria, such as a short axis diameter of 10 mm. The purpose of this study was to determine a more accurate imaging criterion to guide clinical treatment strategy selection. METHODS: The clinical data of 307 patients with thoracic ESCC who underwent surgery at Shanghai Chest Hospital between January 2018 and December 2018 were retrospectively analyzed. Utilizing 1-mm layer thickness enhanced computed tomography (CT), the RRLN lymph node short diameter (LNSD) size was measured. Univariate and multivariate analyses were performed to determine the risk factors for lymph node metastasis along the RRLN. RESULTS: In our study, RRLN lymph node metastasis occurred in 60 (19.5%) patients and general lymph node metastasis occurred in 150 (48.9%) patients. Of the resected lymph nodes along the RRLN, 14.5% (121/832) were positive. Multivariate analysis identified LNSD [odds ratio (OR), 1.236] as an independent risk factor for RRLN lymph node metastasis. In CT evaluation, a short diameter of 6.5 mm in the RRLN lymph nodes is a critical predictor of metastasis at this site (sensitivity =50%, specificity =83.4%) and a larger short diameter was associated with a higher risk of metastasis (P<0.001). CONCLUSIONS: A 6.5 mm cutoff in LNSD can be applied to clinically predict lymph node metastasis in the RRLN region for patients with ESCC.

Adjuvant therapy for pathological T3N0M0 esophageal squamous cell carcinoma.

BACKGROUND: Tumors invading the depth of adventitia (T3) are the most common pathological type of esophageal squamous cell carcinoma (ESCC). For patients without lymph nodes metastasis, the role of adjuvant therapy is uncertain. This study was intended to retrospectively analyze the survival effects of postoperative adjuvant therapy in such patients. METHODS: A total of 200 patients with pathological T3N0M0 (pT3N0M0) ESCC from January 2012 to September 2014 were enrolled, including a surgery-alone group (Group S) of 111 patients and a surgery followed with adjuvant chemo/radiation/chemoradiation therapy group (Group S + aCRT) of 89 patients. RESULTS: There was no significant difference in preoperative basic characteristics and postoperative complications between the two groups. Among all patients, 5-year overall survival (OS) rate was 56.6% and the 5-year disease-free survival (DFS) rate was 51.1%, respectively. The 5-year OS rate was 47.2% in Group S, and 68.4% in Group S + aCRT (P=0.004). The 5-year DFS rate was 44.4% in Group S and 59.3% in Group S + aCRT (P=0.036). The 5-year OS and DFS were improved by adjuvant chemoradiotherapy in the subgroups of males, tumor located at the middle of thoracic esophagus, moderate differentiation, number of resected lymph nodes <15. Multivariate analysis showed that adjuvant chemoradiotherapy and female were associated with improved survival. CONCLUSIONS: In our study, the adjuvant therapy was associated with improved survival for patients with pT3N0M0 ESCC.

Minor alleles of genetic variants in second heart field increase the risk of hypoplastic right heart syndrome.

Hypoplastic right heart syndrome(HRHS) is characterized by hypoplastic right ventricle (RV); Numerous transcriptional cascades in the second heart field (SHF) regulate RVdevelopment. The relationship of SHF gene variants with human HRHS remains unknown. The whole lengths of 17 SHF genes were sequenced in 16 HRHS, and the selected single-nucleotide variants (SNVs) were then genotyped in HRHS, other congenital heart disease (CHD) and healthy control. Luciferase assay was performed to verify the effect of FOXC2: rs34221221A>GandTBX20: rs59854940C>Gat the transcription level. There were 151 (12.86%) novel SNVs after sequence analysis, of which three were in exons (one was synonymous SNV and two were nonsynonymous SNVs), two in promoter, and most SNVs (89.95%) were in intronic regions. Genotype analyses revealed that the minor alleles of FOXC2: rs34221221 A>G and TBX20: rs59854940 C>G could increase HRHS risk (P<0.05), but not in other CHD or healthy control. Luciferase assay showed that the minor G allele in rs34221221 significantly increased FOXC2 transcription while in rs59854940 it decreased TBX20 transcription significantly. Novel variants of SHF gene associated with HRHS were identified. Minor alleles in two variants from FOXC2 and TBX20 could increase the risk of HRHS.

Osteopontin plays important roles in pulmonary arterial hypertension induced by systemic-to-pulmonary shunt.

Recent studies indicated that osteopontin (OPN) was involved in the genesis and progression of pulmonary arterial hypertension (PAH); however, its role in congenital heart disease-associated PAH (CHD/PAH) remains unknown. Our results showed that OPN was increased in lungs and plasma of patients with Eisenmenger syndrome; moreover, OPN and αVß3-integrin expression levels were augmented in rat lungs exposed to systemic-to-pulmonary shunt. Cell culture assay demonstrated that distal pulmonary arterial smooth muscle cells (PASMCs) from rat lungs suffering from volume and pressure overload exhibited enhanced proliferation compared with those from healthy rats. Mechanical stretch (20% at 1 Hz) increased OPN expression and activated ERK1/2 and protein kinase B (Akt) signal pathway in distal PASMCs from healthy rats. Interestingly, OPN enhanced the proliferation and migration of PASMCs while blocking αVß3-integrin with neutralizing antibody LM609 or Arg-Gly-Asp peptidomimetic antagonist cyclo(Ala-Arg-Gly-Asp-3-aminomethylbenzoyl) (XJ735), rectified the proliferative and migratory effects of OPN, which were partially mediated via ERK1/2 and Akt signaling pathways. Furthermore, surgical correction of systemic-to-pulmonary shunt, particularly XJ735 supplementation after surgical correction of systemic-to-pulmonary shunt, significantly alleviated the pulmonary hypertensive status in terms of pulmonary hemodynamic indices, pulmonary vasculopathy, and right ventricular hypertrophy. In summary, OPN alteration in lungs exposed to systemic-to-pulmonary shunt exerts a deteriorative role in pulmonary vascular remodeling through modulating the proliferation and migration of PASMCs, at least in part, via ανß3-ERK1/2 and ανß3-Akt signaling pathways. Antagonizing OPN receptor ανß3-integrin accelerated the regression of pulmonary vasculopathy after surgical correction of systemic-to-pulmonary shunt, indicating a potential therapeutic strategy for patients with CHD/PAH.-Meng, L., Liu, X., Teng, X., Gu, H., Yuan, W., Meng, J., Li, J., Zheng, Z., Wei, Y., Hu, S. Osteopontin plays important roles in pulmonary arterial hypertension induced by systemic-to-pulmonary shunt.

Prognosis of limited resection versus lobectomy in elderly patients with invasive lung adenocarcinoma with tumor size less than or equal to 2 cm.

BACKGROUND: This study aimed to evaluate the prognostic difference between limited resection and lobectomy among elderly patients with small size lung adenocarcinoma. METHODS: A total of 666 patients >65 years old with stage I lung adenocarcinoma and tumor size ≤2 cm were included. The patient survival was evaluated by disease-free survival (DFS) and overall survival (OS). Results: No DFS or OS advantage was found between the lobectomy and wedge resection groups when tumor sizes were ≤1 cm (DFS, P=0.112; OS, P=0.294). The wedge resection group had a significantly worse OS (P=0.041) than that in the lobectomy group when tumor sizes were >1 cm and ≤2 cm. CONCLUSIONS: We conclude that wedge resection may be a reasonable surgical choice for elderly patients with tumor sizes ≤1 cm.

Natural variation in the promoter of rice calcineurin B-like protein10 (OsCBL10) affects flooding tolerance during seed germination among rice subspecies.

Rice (Oryza sativa L.) has two ecotypes, upland and lowland rice, that have been observed to show different tolerance levels under flooding stress. In this study, two rice cultivars, upland (Up221, flooding-intolerant) and lowland (Low88, flooding-tolerant), were initially used to study their molecular mechanisms in response to flooding germination. We observed that variations in the OsCBL10 promoter sequences in these two cultivars might contribute to this divergence in flooding tolerance. Further analysis using another eight rice cultivars revealed that the OsCBL10 promoter could be classified as either a flooding-tolerant type (T-type) or a flooding-intolerant type (I-type). The OsCBL10 T-type promoter only existed in japonica lowland cultivars, whereas the OsCBL10 I-type promoter existed in japonica upland, indica upland and indica lowland cultivars. Flooding-tolerant rice cultivars containing the OsCBL10 T-type promoter have shown lower Ca2+ flow and higher α-amylase activities in comparison to those in flooding-intolerant cultivars. Furthermore, the OsCBL10 overexpression lines were sensitive to both flooding and hypoxic treatments during rice germination with enhanced Ca2+ flow in comparison to wild-type. Subsequent findings also indicate that OsCBL10 may affect OsCIPK15 protein abundance and its downstream pathways. In summary, our results suggest that the adaptation to flooding stress during rice germination is associated with two different OsCBL10 promoters, which in turn affect OsCBL10 expression in different cultivars and negatively affect OsCIPK15 protein accumulation and its downstream cascade.

Should minimally invasive lung adenocarcinoma be transferred from stage IA1 to stage 0 in future updates of the TNM staging system?

BACKGROUND: The 8th International Association Study of Lung Cancer (IASLC) TNM classification staging project for lung cancer has classified patients with adenocarcinoma in situ (AIS) into stage 0, while patients with a minimally invasive adenocarcinoma (MIA) were classified into stage IA1. However, MIA patients, similar to AIS patients, have an approximately a 100% 5-year survival. This study aimed to investigate if MIA could be transferred from stage IA to stage 0 in the next TNM staging system. METHODS: We retrospectively reviewed 1,524 consecutive patients with a pathologically confirmed AIS, MIA and an invasive adenocarcinoma (IADC) in stage IA1. Disease-free survival (DFS) and overall survival (OS) were analyzed to evaluate survival difference between these three groups. RESULTS: There were 412 AIS, 675 MIA and 437 IADC patients in stage IA1. No statistically significant differences for DFS and OS (P=0.109) were seen between the AIS and MIA groups. Patients of the IADC group had significantly worse DFS (P=0.003) but the OS rate (P=0.941) was insignificant when compared with the MIA patients. Similar survival results were seen when comparisons were made between the IADC and AIS/MIA groups. The IADC group had a worse DFS (P=0.001) rate but no OS (P=0.380) difference with the AIS/MIA groups. CONCLUSIONS: Patients with AIS and MIA had similar post-surgical survival rates. We propose that MIA may potentially be transferred from IA1 to stage 0 in the future.