LncRNA PCAT1 Interacts with DKC1 to Regulate Proliferation, Invasion and Apoptosis in NSCLC Cells via the VEGF/AKT/Bcl2/Caspase9 Pathway.

Long noncoding RNAs (lncRNAs) are increasingly recognized as indispensable components of the regulatory network in the progression of various cancers, including nonsmall cell lung cancer (NSCLC). The lncRNA prostate cancer associated transcript 1 (PCAT1) has been involved in tumorigenesis of multiple malignant solid tumors, but it is largely unknown that what is the role of lncRNA-PCAT1 and how it functions in the progression of lung cancer. Herein, we observed that lncRNA PCAT1 expression was upregulated in both human NSCLC tissues and cell lines, which was determined by qualitative polymerase chain reaction analysis. Then, gain-and loss-of-function manipulations were performed in A549 cells by transfection with a specific short interfering RNA against PCAT1 or a pcDNA-PCAT1 expression vector. The results showed that PCAT1 not only promoted NSCLC cell proliferation and invasion but also inhibited cell apoptosis. Bioinformatics and expression correlation analyses revealed that there was a potential interaction between PCAT1 and the dyskerin pseudouridine synthase 1 (DKC1) protein, an RNA-binding protein. Then, RNA pull-down assays with biotinylated probes and transcripts both confirmed that PCAT1 directly bounds with DKC1 that could also promote NSCLC cell proliferation and invasion and inhibit cell apoptosis. Moreover, the effects of PCAT1 and DKC1 on NSCLC functions are synergistic. Furthermore, PCAT1 and DKC1 activated the vascular endothelial growth factor (VEGF)/protein kinase B (AKT)/Bcl-2/caspase9 pathway in NSCLC cells, and inhibition of epidermal growth factor receptor, AKT, or Bcl-2 could eliminate the effect of PCAT1/DKC1 co-overexpression on NSCLC cell behaviors. In conclusion, lncRNA PCAT1 interacts with DKC1 to regulate proliferation, invasion, and apoptosis in NSCLC cells via the VEGF/AKT/Bcl-2/caspase9 pathway.

Expert consensus on resection of chest wall tumors and chest wall reconstruction.

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V) It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T3-4N0-1M0. As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years.

Diagnostic value of serum human epididymis protein 4 in esophageal squamous cell carcinoma.

BACKGROUND: Numerous studies have demonstrated that human epididymis protein 4 (HE4) is overexpressed in various malignant tissues including ovarian, endometrial, lung, breast, pancreatic, and gastric cancers. However, no study has examined the diagnostic impact of HE4 in patient with esophageal squamous cell carcinoma (ESCC) until now. AIM: To analyze the value of four serum tumor markers for the diagnosis of ESCC, and examine the associations of serum levels of HE4 with ESCC patients' clinicopathological characteristics. METHODS: The case group consisted of 80 ESCC patients, which were compared to a control group of 56 patients with benign esophageal disease. Serum levels of HE4, carcinoma embryonic antigen (CEA), alpha fetal protein, and carbohydrate antigen 19-9 (CA19-9) were detected by ELISA. The associations of serum HE4 levels with ESCC patients' clinicopathological characteristics such as gender, tumor location, and pathological stage were also examined after operation. RESULTS: The result of ELISA showed that serum HE4 level was significantly higher in the patients with ESCC than in the controls, and the staining intensity was inversely correlated with the pathological T and N stages. Serum HE4 levels had a sensitivity of 66.2% and specificity of 78.6% when the cutoff value was set at 3.9 ng/mL. Moreover, the combined HE4 and CA19-9 increased the sensitivity to 83.33%, and interestingly, the combination of HE4 with CEA led to the most powerful sensitivity of 87.5%. Furthermore, A positive correlation was observed between HE4 serum levels and pathological T and N stages (P = 0.0002 and 0.0017, respectively), but there was no correlation between HE4 serum levels and ESCC patient gender (P = 0.4395) or tumor location (P = 0.6777). CONCLUSION: The results of this study suggest that detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of ESCC.

Metabolic profiles of serum samples from ground glass opacity represent potential diagnostic biomarkers for lung cancer.

BACKGROUND: Lung cancer is a leading cause of cancer deaths worldwide. Low-dose computed tomography (LDCT) screening trials indicated that LDCT is effective for the early detection of lung cancer, but the findings were accompanied by high false positive rates. Therefore, the detection of lung cancer needs complementary blood biomarker tests to reduce false positive rates. METHODS: In order to evaluate the potential of metabolite biomarkers for diagnosing lung cancer and increasing the effectiveness of clinical interventions, serum samples from subjects participating in a low-dose CT-scan screening were analyzed by using untargeted liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). Samples were acquired from 34 lung patients with ground glass opacity diagnosed lung cancer and 39 healthy controls. RESULTS: In total, we identified 9 metabolites in electron spray ionization (ESI)(+) mode and 7 metabolites in ESI(-) mode. L-(+)-gulose, phosphatidylethanolamine (PE)(22:2(13Z,16Z)/15:0), cysteinyl-glutamine, S-japonin, threoninyl-glutamine, chlorate, 3-oxoadipic acid, dukunolide A, and malonic semialdehyde levels were observed to be elevated in serum samples of lung cancer cases when compared to those of healthy controls. By contrast, 1-(2-furanylmethyl)-1H-pyrrole, 2,4-dihydroxybenzoic acid, monoethyl carbonate, guanidinosuccinic acid, pseudouridine, DIMBOA-Glc, and 4-feruloyl-1,5-quinolactone levels were lower in serum samples of lung cancer cases compared with those of healthy controls. CONCLUSIONS: This study demonstrates evidence of early metabolic alterations that can possibly distinguish malignant ground glass opacity from benign ground glass opacity. Further studies in larger pools of samples are warranted.

Combined blockade of renin-angiotensin-aldosterone system reduced all-cause but not cardiovascular mortality in dialysis patients: A mediation analysis and systematic review.

BACKGROUND AND AIMS: Full blockade of renin-angiotensin-aldosterone system (RAAS) is believed to decrease morbidity and mortality of patients with chronic kidney disease. In non-dialysis patients, combined RAAS blockade with two different RAAS blockers causes more adverse events without improving survival, but its role in maintenance dialysis patients is still unclear. We conducted a systematic review and mediation analysis to investigate the efficacy and safety of combined RAAS blockade in dialysis patients. METHODS: Comprehensive search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library database to June 2017 to identify relevant studies. Studies comparing combined with single RAAS blockade and reporting all-cause death, cardiovascular death, hypotension or hyperkalemia in dialysis patients were included. Effect sizes were calculated with randomized effects model and summarized as odd ratios (OR). RESULTS: A total of 9 studies with 13,050 dialysis patients were included. Compared with single blockade, combined blockade significantly reduced all-cause mortality (OR 0.71, 95% confidence interval 0.54-0.93, p = 0.01), while cardiovascular mortality remained unchanged (0.85, 0.45-1.59, p = 0.61). Combined blockade tended to increase odd of hypotension but not odd of hyperkalemia (1.54, 1.00-2.38, p = 0.05; 0.89, 0.76-1.05, p = 0.17). Further mediation analysis indicated that hypotension might exert a suppression effect on the survival benefit of angiotensin-converting enzyme inhibitor plus angiotensin receptor blocker treatment on cardiovascular mortality. CONCLUSIONS: Combined RAAS blockade might be a promising treatment in dialysis patients to further reduce mortality if blood pressure was well controlled.

PIK3CA gene mutations in Northwest Chinese esophageal squamous cell carcinoma.

AIM: To evaluate PIK3CA gene mutational status in Northwest Chinese esophageal squamous cell carcinoma (ESCC) patients, and examine the associations of PIK3CA gene mutations with clinicopathological characteristics and clinical outcome. METHODS: A total of 210 patients with ESCC who underwent curative resection were enrolled in this study. Pyrosequencing was applied to investigate mutations in exons 9 and 20 of PIK3CA gene in 210 Northwest Chinese ESCCs. The associations of PIK3CA gene mutations with clinicopathological characteristics and clinical outcome were examined. RESULTS: PIK3CA gene mutations in exon 9 were detected in 48 cases (22.9%) of a non-biased database of 210 curatively resected Northwest Chinese ESCCs. PIK3CA gene mutations were not associated with sex, tobacco use, alcohol use, tumor location, stage, or local recurrence. When compared with wild-type PIK3CA gene cases, patients with PIK3CA gene mutations in exons 9 experienced significantly better disease-free survival and overall survival rates. CONCLUSION: The results of this study suggest that PIK3CA gene mutations could act as a prognostic biomarker in Northwest Chinese ESCC patients.

Vitamin D3 repressed astrocyte activation following lipopolysaccharide stimulation in vitro and in neonatal rats.

Vitamin D3 has been reported to be an immunity modulator and high levels of vitamin D3 are correlated with a decreased risk for developing diseases in the central nervous system. Astrocytes are important immune cells and contribute toward inflammation during neurological diseases. The vitamin D receptor has been reported to be expressed in astrocytes; however, the effect of vitamin D3 on astrocyte activation has not been studied. Here, we found that lipopolysaccharide stimulation in astrocytes could enhance the expression of vitamin D receptor and Cyp27B1, which encodes the enzyme for converting vitamin D3 into its active form. Vitamin D3 suppressed the expression of proinflammatory cytokines tumour necrosis factor-α, interleukin-1ß, vascular endothelial growth factor, and also TLR4 in activated astrocytes. Astrocyte activation was further found to be suppressed after the administration of vitamin D3 in neonatal rats injected with lipopolysaccharide in vivo. We demonstrated the antiactivation effect of vitamin D3 in astrocytes after lipopolysaccharide stimulation. Considering the function of reactive astrocytes in augmenting inflammatory response in neurodegeneration and brain injury, the finding that vitamin D3 administration may inhibit astrocyte activation may be potentially useful for the treatment of central nervous system disorders.

Relationships of uPA and VEGF expression in esophageal cancer and microvascular density with tumorous invasion and metastasis.

OBJECTIVE: To investigate uPA and VEGF expression in esophageal cancer and relations with tumorous invasion and metastasis. METHODS: Immunohistochemistry was used to detect uPA and VEGF expression in the normal epithelial tissue of esophageal mucosa and cancer tissue and detect CD34 labeled micrangium and analyze the relationships with clinical pathological features and tumor angiogenesis. RESULTS: Positive rates for uPA and VEGF protein expression were significantly greater in esophageal cancer than normal epithelial tissue (P < 0.05), the two being linked (P <0.05). In addition, uPA and VEGF protein expression of the high microvessel density (MVD) group was significantly lower than in the low MVD group (P < 0.05), with relation to clinical pathological staging, differentiation and lymph node metastasis (P < 0.05). CONCLUSION: In esophageal cancer tissue, uPA and VEGF proteins are overexpressed and promote tumor angiogenesis, indicative of a poor prognosis.

[Impact on electrochemical degradation of phenol with different coated electrodes and inhibitors].

Four lead dioxide electrodes on Ti substrates were prepared by thermal-deposition and electro-deposition. Scanning electron microscopy (SEM) was used to study the characterization of surface of electrodes. High performance liquid chromatograph was applied to detect the concentration of the aromatic hydroxylation 2,5-DHBA to determine the amount of .OH with 2-HBA as the capture matter. This study investigated effect of different coated electrodes and inhibitors on degradation of phenol by hydroxyl radicals generated by electrolysis in terms of the measurement of hydroxyl radicals and degradation of phenol. The experimental results show that the highest concentration of hydroxyl radicals generated by thermal-deposition, electro-deposition mingled with nothing, electro-deposition mingled with Bi or La were 0.781 micromol/L, 1.048 micromol/L, 1.838 micromol/L, 2.044 micromol/L, respectively. When phenol was electrolyzed by electrodes prepared by the four electrodes, the removal efficiencies of phenol at 1.5 h were 87.30%, 93.55%, 97.95% and 98.70%, and TOC removal efficiencies at 5 h were 86.76%, 94.26%, 98.53% and 99.60%, respectively. The highest concentration of hydroxyl radicals when CO3(2), PO4(3) or CH3COO-existed was no detected, 0.170 micromol/L, 0.270 micromol/L, and the removal efficiencies of phenol were 99.06%, 99.98% and 99.79%, respectively. The degradation of phenol with electrodes prepared by electro-deposition is better than the electrodes prepared by thermal-deposition, and the electrode mingled with La is better than the electrode mingled nothing and with Bi. The electrode mingled with La is the best. The degradation of phenol is inhibited when CO3(2-), PO4(3-) or CH3COO- exists, and the inhibiting effect of CO3(2-) is the strongest. The catalytic characteristics of electrodes and degradation of phenol by them are different when the electrodes are prepared by different methods or with different additives; the higher the concentration of hydroxyl is, the better the degradation of phenol is. Inhibitors capture hydroxyl radicals, and isn't in favor of degradation of phenol.

[Effects of fluoride drop or fluoride ion infiltration in toddler period on demineralization of first permanent molar of children].

OBJECTIVE: To observe the effect of fluoride drop or fluoride ion infiltration on demineralization of the first permanent molar of children. METHODS: 45 children applied by fluoride drop over 3 years in Chengdu and 40 controls were selected. 45 children applied by fluoride ion infiltration more than 3 years in Xiamen and 40 controls were selected in this study. Demineralization of the different sites of the first permanent molar was evaluated by KaVo DIAGNOdent. The effect of FD and FII in toddler period on demineralization of the first permanent molar was evaluated. RESULTS: Early demineralization of the first permanent molar in children without fluoride drop were more severe than that of children with fluoride drop in toddle period (P < 0.01). There was no significantly difference between demineralization of first permanent molar in children with fluoride ion infiltration and control group (P > 0.05). CONCLUSION: Fluoride drop in toddle period can help the remineralization of newly erupted first permanent molar of children. There is no effect of fluoride ion infiltration on demineralization of newly erupted first permanent molar of children.

[2-year clinic effect of fluoride drop on dental caries prevention of primary teeth].

OBJECTIVE: To study the preventive effects of fluoride drop on dental caries for children. METHODS: The comparative method was carried out in 1 200 children aged from 3 to 4. The subjects were divided into three groups: fluoride drop group, fluoride toothpaste group and control group. The research period was 2 years. RESULTS: The results demonstrated that new dfs was 1.35 +/- 0.57 in the fluoride drop group after one year, 1.85 +/- 0.57 after two years. The new dfs was 1.53 +/- 1.09 in the fluoride toothpaste group after one year and 2.75 +/- 1.33 after two years. There was no significant difference of the dfs reduction between fluoride drop and toothpaste group. CONCLUSION: Fluoride drop is effective in the prevention of dental caries in Chinese kindergarten and primary school children.

[Analysis of oral microflora early colonized in infants].

OBJECTIVE: To observe the dynamic changes of oral microflora early colonized in infants. METHODS: The oral swab samples for the study were taken in 1 day, 1, 3, 6, 9, 12 months after birth from 12 healthy neonates. By choosing suitable diluted concentration, the samples were incubated aerobically, facultative anaerobically and anaerobically. The strains were identified by observing colony characteristics, Gram staining and biochemical tests. RESULTS: S. salivarius was the most frequent microflora, followed by S. mitis, S. sanguis, S. gordonii and S. mutans occurred in oral cavity after tooth eruption. Veillonella spp. can be detected in oral cavity of 1-month-old babies, A. odontolyticus was isolated from 8.3% infants of more than 3 months old. L. acidophilus maintained the lower prevalence in oral cavity of babies. Leptotrichia buccalis and Capnocytophaga spp. occurred in oral cavity of some dentate infants. CONCLUSION: S. solivarius and S. mitis are predominant species in oral cavity of the infants, Veillonella spp. is the first and the most anaerobic species appeared in oral cavity of healthy babies. A. odontolyticus is the first actinomyces detected in oral cavity. With the increasing months, kind and amount of microflora increase dramatically.

Quantitative assessment of enamel hypomineralization by KaVo DIAGNOdent at different sites on first permanent molars of children in China.

PURPOSE: The purpose of this study was to identify the most caries-susceptible site of pits and fissures on first permanent molars by quantitative evaluation of the mineralization in both caries-active and caries-free children, and to provide helpful information for cost-effective, targeted prevention. METHODS: Eighty-four caries-free and 85 caries-active children were selected from 800 6- to 7-year-old children with fully erupted first permanent molars. Hypomineralization of the central fossa (CF) and lingual pit (LP) of the maxillary or buccal pit (BP) of mandibular first permanent molars were evaluated by KaVo DIAGNOdent. Statistical analysis included grouped t test and single-factor variance analysis and paired comparison. RESULTS: CF of mandibular first permanent molars had significantly greater hypomineralization than other sites. The hypomineralization of the maxillary CF is more severe than that of LP. The extent of the hypomineralization of each site at the first permanent molar in caries-active children was significantly higher than that in caries-free children. CONCLUSIONS: Central fossae of first mandibular molars are the most hypomineralized sites in both caries-free and caries-active groups. The results suggest that preventive interventions should be targeted at the CF of mandibular molars with special concern given to the caries-active population.