Metabolomics identifies phenotypic biomarkers of amino acid metabolism in milk allergy and sensitized tolerance.

BACKGROUND: A substantial proportion of sensitized individuals tolerate suspected foods without developing allergic symptoms; this phenomenon is known as sensitized tolerance. The immunogenic and metabolic features underlying the sensitized-tolerant phenotype remain largely unknown. OBJECTIVE: We aimed to uncover the metabolic signatures associated with clinical milk allergy (MA) and sensitized tolerance using metabolomics. METHODS: We characterized the serum metabolic and immunologic profiles of children with clinical IgE-mediated MA (n = 30) or milk-sensitized tolerance (n = 20) and healthy controls (n = 21). A comparative analysis was performed to identify dysregulated pathways associated with the clinical manifestations of food allergy. We also analyzed specific biomarkers indicative of different sensitization phenotypes in children with MA. The candidate metabolites were validated in an independent quantification cohort (n = 41). RESULTS: Metabolomic profiling confirmed the presence of a distinct metabolic signature that discriminated children with MA from those with milk-sensitized tolerance. Amino acid metabolites generated via arginine, proline, and glutathione metabolism were uniquely altered in children with sensitized tolerance. Arginine depletion and metabolism through the polyamine pathway to fuel glutamate synthesis were closely associated with suppression of clinical symptoms in the presence of allergen-specific IgE. In children with MA, the polysensitized state was characterized by disturbances in tryptophan metabolism. CONCLUSIONS: By combining untargeted metabolomics with targeted validation in an independent quantification cohort, we identified candidate metabolites as phenotypic and diagnostic biomarkers of food allergy. Our results provide insights into the pathologic mechanisms underlying childhood allergy and suggest potential therapeutic targets.

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis.

Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.

The diagnosis and treatment of pediatric clinical myocarditis in China: a multicenter retrospective study.

This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: • Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: • To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.

[Impact of different angles of pulmonary surfactant administration on bronchopulmonaryplasia and intracranial hemorrhage in preterm infants: a prospective randomized controlled study]. / ä¸åŒè§’åº¦æ³¨å ¥è‚ºè¡¨é¢æ´»æ€§ç‰©è´¨å¯¹æ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å’Œé¢ å† å‡ºè¡€çš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

Early versus the traditional start of oral intake following esophagectomy for esophageal cancer: a systematic review and meta-analysis.

BACKGROUND: Nil by mouth is considered the standard of care during the first days following esophagectomy. However, with the routine implementation of enhanced recovery after surgery, early oral intake is more likely to be the preferred mode of nutrition following esophagectomy. The present study aims to evaluate the safety and effectiveness of early oral intake following esophagectomy for esophageal cancer. METHODS: Comprehensive literature searches were conducted using PubMed, Web of Science, Embase, and Cochrane Library. Weighted mean differences (WMD) and odds ratios (OR) with 95% confidence intervals (CI) were calculated as the effect sizes for continuous and dichotomous variables, respectively. RESULTS: Fourteen studies with a total of 1947 patients were included. Length of hospital stay (WMD = - 3.94, CI: - 4.98 to - 2.90; P < 0.001), the time to first flatus (WMD = - 1.13, CI: - 1.25 to - 1.01; P < 0.001) and defecation (WMD = - 1.26, CI: - 1.82 to - 0.71; P < 0.001) favored the early oral intake group. There was no statistically significant difference in mortality (OR = 1.23, CI: 0.45 to 3.36; P = 0.69). Early oral intake also did not increase the risk of pneumonia and overall postoperative complications. CONCLUSIONS: Current evidence indicates early oral intake following esophagectomy seems to be safe and effective. It may be the preferred mode of nutrition following esophagectomy. However, more high-quality studies are still needed to further validate this conclusion.

Esophagectomy versus definitive chemoradiotherapy as initial treatment for clinical stage I esophageal cancer: a systematic review and meta-analysis.

BACKGROUND: Esophagectomy and definitive chemoradiotherapy are commonly used in the treatment of stage I esophageal cancer (EC). The present study aims to compare the efficacy and safety of esophagectomy and definitive chemoradiotherapy as the initial treatment for clinical stage I EC. METHODS: This study was registered with the International Prospective Register of Systematic Reviews (CRD42020197203). Relevant studies were identified through PubMed, Web of Science, EMBASE, and Cochrane Library from database inception to June 30, 2020. Hazard ratio (HR) with 95% confidence intervals (CI) was employed to compare overall survival (OS) and progression-free survival (PFS). Odds ratio (OR) with 95% CI was employed to compare treatment-related death, complications, and tumor recurrence. RESULTS: A total of 13 non-randomized controlled studies involving 3,346 patients were included. Compared with definitive chemoradiotherapy, esophagectomy showed an improved OS (HR 0.69, 95% CI 0.55-0.86; P < 0.001), PFS (HR 0.47, 95% CI 0.33-0.67; P < 0.001), and a lower risk of tumor recurrence (OR 0.43, 95% CI 0.30-0.61; P < 0.001). There was no significant difference in the incidence of complications (OR 1.11, 95% CI 0.75-1.65; P = 0.60) and treatment-related death (OR 1.15, 95% CI 0.31-4.30; P = 0.84) between the two treatments. CONCLUSIONS: Current evidence shows esophagectomy has superior survival benefits as the initial treatment for clinical stage I EC. It is still the preferred choice for patients with clinical stage I EC. However, future high-quality randomized controlled trials are needed to validate this conclusion.

Subxiphoid versus intercostal video-assisted thoracic surgery for lung resection: a meta-analysis.

INTRODUCTION: To systematically evaluate the safety and advantages of subxiphoid approach video-assisted thoracic surgery (SA-VATS) compared with intercostal approach video-assisted thoracic surgery (IA-VATS) for lung resection, we conducted a meta-analysis of the current literature. MATERIAL AND METHODS: The literature search was conducted in PubMed, Web of Science, Cochrane Library, Embase, and China National Knowledge Infrastructure. RevMan 5.3 software was used to perform this meta-analysis. RESULTS: Eleven studies involving 934 patients were included. Compared with patients in the IA-VATS group, those in the SA-VATS group had lower pain scores on the day of the operation and at 24 h, 48 h and 72 h after the operation (p < .001) and suffered from less postoperative paraesthesia at the first, third and sixth months after the operation (p < .001). Moreover, there was no statistically significant difference between the two groups regarding postoperative complications, intraoperative blood loss, length of hospital stay, drainage amount, or chest tube duration. However, SA-VATS had a longer operative time (p < .001). CONCLUSIONS: SA-VATS is a safe surgical technique and has superior postoperative outcomes over IA-VATS for lung resection in terms of acute postoperative pain and chronic postoperative paraesthesia.

A Meta-analysis of Jejunostomy Versus Nasoenteral Tube for Enteral Nutrition Following Esophagectomy.

BACKGROUND: Postoperative nutritional therapy is of paramount importance for patients undergoing esophagectomy. The jejunostomy and nasoenteral tube are the popular routes for nutritional therapy. However, which one is the preferred route is unclear. This study aims to analyze the differences in safety and efficacy of the two routes for nutritional therapy. MATERIALS AND METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE (till September 17, 2020) were searched. The primary outcome was postoperative pneumonia. Secondary outcomes were the length of hospital stays (LOS), bowel obstruction, catheter dislocation, anastomotic leakage, overall postoperative complications, and postoperative albumin. Weighted mean differences (WMD) and odds ratios (OR) were calculated for statistical analysis. RESULTS: Ten studies involving a total of 1,531 patients in the jejunostomy group and 1,375 patients in the nasoenteral tube group were included. Compared with patients in the nasoenteral tube group, those in the jejunostomy group had a lower incidence of postoperative pneumonia (OR = 0.68, P < 0.001), shorter LOS (WMD = -0.85, P < 0.001), and lower risk of catheter dislocation (OR = 0.15, P = 0.001). There were no significant differences in the incidence of anastomotic leakage (OR = 0.84, P = 0.43), overall postoperative complications (OR = 0.87, P = 0.59), and postoperative albumin (WMD = -0.40, P = 0.24). However, patients in the jejunostomy group had a higher risk of bowel obstruction (OR = 8.42, P = 0.002). CONCLUSIONS: Jejunostomy for enteral nutrition showed superior outcomes in terms of postoperative pneumonia, LOS, and catheter dislocation. Jejunostomy may be the preferred enteral nutritional route following esophagectomy.

Is it necessary to routinely perform feeding jejunostomy at the time of esophagectomy? A systematic review and meta-analysis.

Feeding jejunostomy (FJ) is a routine procedure at the time of esophagectomy in some centers. With the widespread popularization of enhanced recovery after surgery, the necessity of FJ has been increasingly questioned. This study aims to analyze the differences in safety and effectiveness between with (FJ group) or without (no-FJ group) performing FJ at the time of esophagectomy. PubMed, Embase, Web of Science, and Cochrane Library were comprehensively searched for relevant studies, including randomized controlled trials and cohort studies. The primary outcome was the length of hospital stay (LOS). Secondary outcomes were overall postoperative complications, postoperative pneumonia, intestinal obstruction, and weight loss at 3 and 6 months after esophagectomy. Weighted mean differences (WMD) and odds ratios (OR) were calculated for statistical analysis. About 12 studies comprising 2,173 patients were included. The FJ group had a longer LOS (WMD = 2.05, P = 0.01) and a higher incidence of intestinal obstruction (OR = 11.67, P < 0.001) than the no-FJ group. The incidence of overall postoperative complications (OR = 1.24, P = 0.31) and postoperative pneumonia (OR = 1.43, P = 0.13) were not significantly different, nor the weight loss at 3 months (WMD = 0.58, P = 0.24) and 6 months (P > 0.05) after esophagectomy. Current evidence suggests that routinely performing FJ at the time of esophagectomy appears not to generate better postoperative outcomes. FJ may need to be performed selectively rather than routinely. More studies are required to further verify.

Compound heterozygous mutations in ABCG5 or ABCG8 causing Chinese familial Sitosterolemia.

BACKGROUND: Sitosterolemia (STSL), also known as phytosterolemia, is a rare autosomal recessive hereditary disease caused by mutations in the ABCG5 or ABCG8 genes. The disease is a result of disorders in lipoprotein metabolism, and is characterized by tendinous and tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, and thrombocytopenia and hemolytic anemia in several patients. The manifestations of STSL are diverse and can easily be misdiagnosed. In recent years, cases of this disease in children have been reported in succession. There is therefore a need for clinicians to improve identification of STSL and perform early intervention. METHODS: We evaluated four children with STSL caused by genetic mutations in ABCG5 or ABCG8, as well as their family members, by analyzing their clinical characteristics and performing Trio-whole exome sequencing. The biological consequences of the mutations were analyzed using various bioinformatics software. We also analyzed the consequences of a mutation commonly observed in STSL patients on the structure of the protein involved. RESULTS: We identified five previously unreported pathogenic mutations of different phenotypes of STSL: ABCG5 NM_022436:c.1337G>A; ABCG8 NM_022437:c.965-1G>A, c.323-1G>C, c.1418C>G and c.1534G>A. We also report the structural changes brought about by a mutation common in STSL patients, as well as the possible consequences of these changes. CONCLUSIONS: Our findings further broaden the genotypic and phenotypic profiles of the onset of STSL in the pediatric population and provide information for the diagnosis and treatment of this disease.

Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family.

Generalized epilepsy with febrile seizures plus (GEFS+) is a complex familial epilepsy syndrome. It is mainly caused by mutations in SCN1A gene, encoding type 1 voltage-gated sodium channel α-subunit (NaV1.1), and GABRA1 gene, encoding the α1 subunit of the γ-aminobutyric acid type A (GABAA) receptor, while seldom related with SCN9A gene, encoding the voltage-gated sodium channel NaV1.7. In this study, we investigated a Chinese family with an autosomal dominant form of GEFS+. DNA sequencing of the whole coding region revealed a novel heterozygous nucleotide substitution (c.5873A>G) causing a missense mutation (p.Y1958C). This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT, and MutationTaster). Our finding reports a novel likely pathogenic SCN9A Y1958C heterozygous mutation in a Chinese family with GEFS+ and provides additional supports that SCN9A variants may be associated with human epilepsies.

Effect of Osimertinib on the expression of serum mmp-7 and mmp-9 in patients with non-small cell lung cancer.

The purpose was to investigate the efficacy and safety of Osimertinib in the treatment of advanced non-small cell lung cancer and to analyze its effects on the expression of serum matrix metalloproteinase-7 (MMP-7) and matrix metallo-proteinase-9 (MMP-9). Eighty patients were equally divided into observation and control group. The observation group was given Osimertinib combined with conventional chemotherapy and the other was treated with conventional chemotherapy alone. The short-term efficacy, the levels of serum MMP-7, MMP-9 and adverse reactions were compared. The effectiveness and clinical benefit rate of the observation group were 62.50% and 92.50% respectively, significantly higher than the control group. There was no significant difference in MMP-7 and MMP-9 before treatment however there was a significant difference after treatment, and the serum MMP-7 & MMP-9 levels showed a trend of increasing with decreasing efficacy. After treatment, comparing with control group, serum MMP-7 and MMP-9 levels were significantly lower, the Karnofsky score was significantly higher, and the improvement effect of the quality of life was statistically significant. Besides, the incidence of leukopenia, thrombocytopenia, anemia and gastrointestinal symptoms were significantly lower. In the treatment of patients with advanced non-small cell lung cancer, Osimertinib significantly reduced the expression of serum MMP-7, MMP-9, improved the clinical benefit and quality of life of patients. The clinical efficacy was significant with a high safety.

[Intermittent abdominal pain and abdominal distension with fatigue and massive ascites in a 13-year-old boy].

A 13-year-old boy was admitted due to intermittent abdominal pain for one year with massive ascites. The purified protein derivative (PPD) test after admission yielded positive results (3+), and ascites examination revealed a yellow color. There were 634×109 nucleated cells/L in the ascites, among which 82.2% were mononuclear cells and 17.8% were multinuclear cells. The Rivalta test yielded a positive result and revealed that the ascites was exudate, suggesting the possibility of tuberculosis infection. The symptoms were not relieved after isoniazid-rifampicin anti-tuberculosis therapy and symptomatic/supportive treatment. Plain CT scan of the abdomen and contrast-enhanced CT showed that the lesion was located at the left wall of the transverse colon, with uneven thickening of the peritoneum and heterogeneous enhancement. Colonoscopic biopsy found signet ring cells in the mucosa and immunohistochemical examination revealed Syn (-), CgA (-), CD56 (-), CK(pan) (+), CDX-2 (+), CK20 (+), Muc-1 (+) and Ki-67 (+, about 80%). PET-CT scan showed an abnormal increase in fluorodeoxyglucose metabolism, which was shown as a mass near the splenic flexure of the transverse colon, with a maximum standard uptake value of 9.9, indicating a highly active lesion; this was consistent with the metabolic changes of malignant tumors. Surgical operation was performed and intraoperative exploration revealed massive ascites, a hard mass located at the hepatic flexure of the colon, involvement of the serous coat and surrounding tissues, stenosis of the bowel, lymph node enlargement around the superior mesenteric vessels and the gastrocolic ligament, and multiple metastatic nodules in the greater omentum, the abdominal wall and the pelvic cavity. The results of postoperative pathology were consistent with those of colonoscopic biopsy, i.e., poorly differentiated mucinous adenocarcinoma of the transverse colon and partly signet-ring cell carcinoma. Therefore, the boy was diagnosed with colon signet-ring cell carcinoma with peritoneal metastasis and tuberculosis infection. When a child is suffering from intractable abdominal pain, unexplained intestinal obstruction and massive intractable ascites, the possibility of malignancy should be considered. Abdominal plain CT scan as well as contrast-enhanced CT scan should be performed as early as possible, and enteroscopy should be performed when necessary.

[Clinical efficacy of pulmonary surfactant combined with budesonide for preventing bronchopulmonary dysplasia in very low birth weight infants].

OBJECTIVE: To explore the clinical efficacy of intratracheal instillation of pulmonary surfactant (PS) combined with budesonide for preventing bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants. METHODS: Thirty VLBW infants with gestational age <32 weeks who developed neonatal respiratory distress syndrome (NRDS) (grade III-IV) suffering from intrauterine infection were randomly assigned into a PS + budesonide group and a PS alone group. The changes were compared between the two groups in arterial blood gas indexes, oxygenation index (OI), duration of mechanical ventilation, duration of oxygen supplementation, incidence of BPD, mortality rate at 36 weeks corrected gestational age and incidences of other complications except BPD. RESULTS: Compared with the PS alone group, the PS+budesonide group had a lower incidence of BPD, shorter duration of mechanical ventilation and oxygen supplementation (P<0.05). On the 2nd to 6th day after treatment, the PS+budesonide group had higher pH value of arterial blood gas and OI and lower carbon dioxide partial pressure compared with the PS alone group (P<0.05). There were no significant differences in the mortality rate at 36 weeks corrected gestational age and the incidences of other complications except BPD between the two groups (P>0.05). CONCLUSIONS: Intratracheal instillation of PS combined with budesonide can effectively reduce the incidence of BPD in VLBW premature infants with severe NRDS.

Association between glutathione S-transferases P1 Ile105Val polymorphism and susceptibility to esophageal cancer: evidence from 20 case-control studies.

Available epidemiological studies had estimated the correlation between glutathione S-transferases P1 (GSTP1) Ile105Val polymorphism and esophageal cancer (EC) risk. However, the conclusions were controversial and inconclusive. An updated meta-analysis was conducted to explore whether GSTP1 polymorphism could be contributed to the EC risk. Ultimately, a total of 2,992 cases and 4,758 controls from 20 previous studies were included. Crude odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were used to assess the strength of the associations. Pooled results suggested that GSTP1 Ile105Val polymorphism significantly increased the risk of developing EC in Caucasians under three genetic models (G vs. A, OR 1.146, 95 % CI 1.031-1.275, P = 0.012, I(2) = 30.40 %; GA vs. AA, OR 1.208, 95 % CI 1.036-1.408, P = 0.016, I(2) = 50.30 %; GG+GA vs. AA, OR 1.219, 95 % CI 1.053-1.410, P = 0.008, I(2) = 44.50 %). However, no significant correlation was found in Asians, African and mixed ethnicities analyses. Moreover, similar results were detected for any genetic model in esophageal squamous cell carcinoma and esophageal adenocarcinoma when stratifying for pathologic types. This meta-analysis provides new evidences that GSTP1 Ile105Val gene polymorphism contributes to EC susceptibility in Caucasians.

[Experimental studies on the role of GATA4 in the endocardial cushions development].

OBJECTIVE: To investigate the role of GATA4 gene in the endocardial cushions development. METHODS: Target gene eukaryote expression vectors were constructed by pcDNA3.1(-) vector plasmid, and were identified by DNA sequence analysis. Recombinant plasmids were transfected into Hela cells with lipofectamine 2000, meanwhile Hela cells transfected with empty vector or those without transfection served as transfection control group and blank control group, respectively. Real-time PCR and Western blot were performed to detect the relative expression of mRNA and protein of transcription factors GATA4, Sox9, Scleraxis and ECM proteins Aggrecan, Tenascin in each group. RESULTS: The relative mRNA expression of GATA4 in experimental group was significantly higher than in transfection control group and blank control group. GATA4 mRNA expression in Hela(GATA4), Hela(H436Y), Hela(Null) and Hela group was 310.83 ± 2.39, 146.35 ± 1.74, 0.94 ± 0.32, 1.00 ± 0.28, respectively (F = 72.508, P < 0.05). Western blot results were consistent with the results obtained by qRT-PCR. The relative mRNA and protein expressions of Sox9, Scleraxis, Aggrecan and Tenascin in both experimental groups were significantly higher than that in transfection control group and blank control group (P < 0.05), and above gene expressions were significantly downregulated in GATA4(H436Y) group, while they were similar between transfection control group and blank control group (all P > 0.05). CONCLUSIONS: GATA4 H436Y mutation reduces it's transcriptional activation, which might serve as a theoretical framework to demonstrate the roles of GATA4 gene in endocardial cushion development.

MYLK and MYL9 expression in non-small cell lung cancer identified by bioinformatics analysis of public expression data.

Gene expression microarrays are widely used to investigate molecular targets in cancers, including lung cancer. In this study, we analyzed online non-small cell lung cancer (NSCLC) microarray databases, to screen the key genes and pathways related to NSCLC by bioinformatics analyses. And then, the expression levels of two selected genes in the down-regulated co-pathways, myosin light chain kinase (MYLK) and myosin regulatory light chain 9 (MYL9), were determined in tumor, paired paraneoplastic, and normal lung tissues. First, gene set enrichment analysis and meta-analysis were conducted to identify key genes and pathways that contribute to NSCLC carcinogenesis. Second, using the total RNA and protein extracted from lung cancer tissues (n = 240), adjacent non-cancer tissues (n = 240), and normal lung tissues (n = 300), we examined the MYLK and MYL9 expression levels by quantitative real-time PCR and Western blot. Finally, we explored the correlations between mRNA and protein expressions of these two genes and the clinicopathological parameters of NSCLC. Fifteen up-regulated and nine down-regulated co-pathways were observed. A number of differentially expressed genes (CALM1, THBS1, CSF3, BMP2, IL6ST, MYLK, ROCK2, IL3RA, MYL9, PPP2CA, CSF2RB, CNAQ, GRIA2, IL10RA, IL10RB, IL11RA, LIFR, PLCB4, and RAC3) were identified (P < 0.01) in the down-regulated co-pathways. The expression levels of MYLK and MYL9, which act downstream of the vascular smooth muscle contraction signal pathway and focal adhesion pathway, were significantly lower in cancer tissue than those in the paraneoplastic and normal tissues (P < 0.05). Moreover, the expression levels of these two genes in stages III and IV NSCLC were significantly increased, when compared to stages I and II, and expressions levels in NSCLC with lymphatic metastasis were higher than that without lymphatic metastasis (P < 0.05). Additionally, significant lower expression levels of the two genes were found in smokers than in nonsmokers (P < 0.05). In contrast, gender, differentiated degrees, and pathohistological type appeared to have no impact on these gene expressions (P > 0.05). These findings suggested that low MYLK and MYL9 expressions might be associated with the development of NSCLC. These genes may be also relevant to NSCLC metastasis. Future investigations with large sample sizes needed to verify these findings.

Association between ERCC2 Lys751Gln polymorphism and lung cancer risk: a meta-analysis involving 23,370 subjects.

Recent studies report a correlation between excision repair cross-complementing group 2 (ERCC2) Lys751Gln polymorphism and an increased risk of lung cancer, but results are controversial and inconclusive. Thus, we conducted a comprehensive meta-analysis in order to assess the correlation between them. Our study uses an odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the strength of the association; we also performed Begg's funnel plot and the Egger's test to assess the publication bias of previous articles. Finally, our meta-analysis is comprised of 28 full studies, including 23,370 subjects (10,242 cases and 13,128 controls). Our overall research shows that ERCC2 Lys751Gln polymorphism carries an increased risk of developing lung cancer (C vs. A: OR = 1.160, 95% CI = 1.081-1.245, p = .000; CC vs. AA: OR = 1.252, 95% CI = 1.130-1.388, p = .000; CA vs. AA: OR = 1.152, 95% CI = 1.060-1.252, p = .001; CC+CA vs. AA: OR = 1.186, 95% CI = 1.089-1.292, p = .000; CC vs. CA+AA: OR = 1.196, 95% CI = 1.087-1.316, p = .000). In ethnic subgroup analyses, we find a significant risk among Caucasians (C vs. A: OR = 1.106, 95% CI = 1.048-1.166, p = .000; CC vs. AA: OR = 1.233, 95% CI = 1.103-1.378, p = .000; CC+CA vs. AA: OR = 1.113, 95% CI = 1.033-1.199, p = .005; CC vs. CA+AA: OR = 1.185, 95% CI = 1.069-1.313, p = .001) and among Asians under two genetic models (CA vs. AA: OR = 1.265, 95% CI = 1.034-1.549, p = .023; CC+CA vs. AA: OR = 1.252, 95% CI = 1.015-1.544, p = .036). These results were confirmed by similar findings, demonstrated by stratified analyses in study design and histological typing. This meta-analysis indicates that ERCC2 Lys751Gln polymorphism may lead to an increased susceptibility to lung cancer risk among Caucasians and Asians.

Natural selection and functional diversification of the epidermal growth factor receptor EGFR family in vertebrates.

BACKGROUND: Genes that have been subject to adaptive evolution can produce varying degrees of pathology or differing symptomatology. ErbB family receptor activation will initiate a number of downstream signaling pathways, such as mitogen-activated protein kinase (MAPK), activator of transcription (STAT), the modulation of calcium channels, and so on, all of which lead to aggressive tumor behavior. However, the evolutionary mechanisms operating in the retention of ErbB family genes and the changes in selection pressures are not clear. RESULTS: Sixty-two full-length cDNA sequences from 27 vertebrate species were extracted from the UniProt protein database, NCBI's GenBank and the Ensembl database. The result of phylogenetic analysis showed that the four ErbB family members in vertebrates might be formed by gene duplication. In order to determine the mode of evolution in vertebrates, selection analysis and functional divergence analysis were combined to explain the relationship of the site-specific evolution and functional divergence in the vertebrate ErbB family. Our results indicate that the acceleration of asymmetric evolutionary rates and purifying selection together were the main force for the production of ErbBs, and positive selections were detected in the ErbB family. CONCLUSION: An evolutional phylogeny of 27 vertebrates was presented in our study; the tree showed that the genes have evolved through duplications followed by purifying selection, except for seven sites, which evolved by positive selection. There was one common site with positive selection and functional divergence. In the process of functional differentiation evolving through gene duplication, relaxed selection may play an important part.