Minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for esophageal squamous cell carcinoma: case report.

Minimally invasive esophagectomy for cancer surgery remains associated with significant morbidity and surgical complications across the globe. Non-intubation video-assisted thoracic surgery (NIVATS) has been successfully employed in lung resection in recent years, but there are few reported cases with regard to the safety and feasibility of this approach in radical esophagectomy for patients with esophageal cancers. We present 4 consecutive cases with esophageal squamous cell carcinoma (ESCC) who received minimally invasive McKeown's esophagectomy under non-intubation general anesthesia from November 2022 to April 2023. All these patients were aged from 55 to 75 years old and were pathologically diagnosed with ESCC. All procedures of McKeown's esophagectomy in these patients were completed with non-invasive ventilation by laryngeal mask-assisted anesthesia. Operation duration ranged from 185 to 395 minutes and the estimated blood loss ranged from 25 to 60 ml in these 4 cases. No severe hypoxia was observed and transient hypercapnia was resolved intraoperatively. None of them was converted to endotracheal intubation with mechanical ventilation or to thoracotomy. The number of retrieved lymph nodes in mediastinum were 21-27 and all patients received R0 surgery with pathological stage as T1bN0M0 to T3N2M0. There was no serious complication (Clavien-Dindo grade III-IV) observed perioperatively and they were all discharged 11-14 days after the surgery with resumption of oral feeding. They are all alive without tumor recurrence at the date of data collection. The safety and efficacy of minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for patients with ESCC are warranted for explored in a larger cohort study.

Circular RNA circCHSY1 silencing inhibits the malignant progression of esophageal squamous cell carcinoma.

BACKGROUND: CircRNAs play a crucial role in the regulation of various cancers. This study aims to investigate the involvement of circCHSY1 in the development of esophageal squamous cell carcinoma (ESCC). METHODS: RNA levels were quantified using qRT-PCR, and protein levels were measured by western blot. The stability of circCHSY1 was analyzed using RNase R. The functional effect of circCHSY1 on cell behavior was evaluated by CCK-8, EdU, flow cytometry, transwell, tube formation, and xenograft tumor model assays. The associations among circCHSY1, miR-1229-3p, and Tectonic-1 (TCTN1) were certified by bioinformatics analysis, dual-luciferase reporter assay, and RNA pull-down assay. RESULTS: CircCHSY1 was up-regulated in both ESCC tissues and cell lines in comparison with the control groups. Knockdown of circCHSY1 inhibited the proliferation, migration, invasion, and tube formation and promoted apoptosis of ESCC cells. Mechanistically, circCHSY1 targeted miR-1229-3p, which was downregulated in ESCC tissues and cells. Inhibition of miR-1229-3p attenuated the effects mediated by circCHSY1 suppression. Besides, miR-1229-3p bound to TCTN1, and TCTN1 overexpression restored miR-1229-3p-induced effects in ESCC cells. Animal experiments revealed that circCHSY1 silencing suppressed tumor tumorigenesis in vivo. CONCLUSION: CircCHSY1 contributed to ESCC cell malignancy, and the underlying mechanism involved the circCHSY1/miR-1229-3p/TCTN1 axis, providing potential therapeutic targets for ESCC.

Associations of prior pulmonary tuberculosis with the incident COPD: a prospective cohort study.

BACKGROUND: Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population. OBJECTIVES: This study aimed to investigate the association of prior PTB with the risk of COPD. DESIGN: Prospective cohort study. METHODS: A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS). RESULTS: The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26-2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02-5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16-2.81, p = 0.008), male with aHR of 2.37 (1.47-3.83, p < 0.001), obesity with aHR of 3.35 (2.16-5.82, p < 0.001), previous smoking with aHR of 2.27 (1.39-3.72, p < 0.001), current drinking with aHR of 1.98 (1.47-3.83, p < 0.001), low physical activity with aHR of 2.62 (1.30-5.26, p = 0.007), and low PRS with aHR of 3.24 (1.61-6.53, p < 0.001), as well as high PRS with aHR of 2.43 (1.15-5.14, p = 0.019). CONCLUSION: A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

Associations of prior pulmonary tuberculosis with the incident COPDPrior pulmonary tuberculosis (PTB) indicates that an individual has a history of PTB. The impact of prior PTB on the risk of incident chronic obstructive pulmonary disease (COPD) has not been studied in a large prospective cohort study of European population. Here, we investigated the association between prior PTB and risk of COPD in 216,130 participants from the UK biobank (a large biomedical database). After a median follow up of more than 12 years, 2,788 incident COPD cases were recorded. Individuals with prior PTB at baseline had an 87% higher risk of developing incident COPD compared to those without history of PTB. Specifically, individuals with prior PTB presented with a higher risk of incident COPD among those who were older than 50 years, male, obese, had a previous history of smoking, are currently drinking, have low physical activity, and have a low and high genetic predicted lung function. This study suggested prior PTB as an important and independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

Alpinetin ameliorates bleomycin-induced pulmonary fibrosis by repressing fibroblast differentiation and proliferation.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with a poor prognosis. Alpinetin (ALP), derived from Alpinia katsumadai Hayata, has shown potential as a therapeutic measure of various diseases. However, the utilization of ALP in managing pulmonary fibrosis and its underlying mechanisms are still not fully understood. METHODS: A well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM) was used in this study. The antifibrotic effects of ALP on histopathologic manifestations and expression levels of fibrotic markers were examined. Subsequently, the impact of ALP on fibroblast differentiation, proliferation, apoptosis, and associated signaling pathways was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that ALP effectively mitigated BLM-induced pulmonary fibrosis in mice, as evidenced by histopathological manifestations and the expression levels of fibrotic markers. Furthermore, the in vitro experiments demonstrated that ALP treatment attenuated the ability of fibroblasts to differentiate into myofibroblasts. Mechanically, our findings provided evidence that ALP suppressed fibroblast-to-myofibroblast differentiation by repressing TGF-ß/ALK5/Smad signaling pathway. ALP was found to possess the capability of inhibiting fibroblast proliferation and promoting apoptosis of fibroblasts induced by TGF-ß. CONCLUSION: In general, ALP may exert therapeutic effects on pulmonary fibrosis by modulating the differentiation, proliferation, and apoptosis of fibroblasts. Although its safety has been demonstrated in mice, further studies are required to investigate the efficacy of ALP in treatment of patients with IPF.

Triptolide inhibits esophageal squamous cell carcinoma progression by regulating the circNOX4/miR-153-3p/SATB1 signaling pathway.

BACKGROUND: To explore the role and mechanism of triptolide in regulating esophageal squamous cell carcinoma (ESCC) progression by mediating the circular RNA (circRNA)-related pathway. METHODS: The expression levels of circNOX4, miR-153-3p and special AT-rich sequence binding protein-1 (SATB1) were measured by qRT-PCR. Cell proliferation was confirmed by cell counting kit-8 assay and colony formation assay. Flow cytometry was employed to measure cell apoptosis and cell cycle process. Moreover, cell migration and invasion were detected using transwell assay. The protein levels of epithelial-mesenchymal transformation markers and SATB1 were determined by western blot analysis. Furthermore, dual-luciferase reporter assay and RIP assay were performed to confirm the interaction between miR-153-3p and circNOX4 or SATB1. Xenograft tumor models were built to verify the effects of triptolide and circNOX4 on ESCC tumor growth. RESULTS: CircNOX4 was highly expressed in ESCC tissues and cells, and its expression could be reduced by triptolide. Triptolide could inhibit ESCC proliferation, cell cycle process, migration, invasion, EMT process, and promote apoptosis, while these effects were reversed by circNOX4 overexpression. MiR-153-3p could be sponged by circNOX4, and the promotion effect of circNOX4 on the progression of triptolide-treated ESCC cells was abolished by miR-153-3p overexpression. SATB1 was a target of miR-153-3p. Also, SATB1 knockdown reversed the enhancing effect of miR-153-3p inhibitor on the progression of triptolide-treated ESCC cells. Triptolide reduced ESCC tumor growth by regulating the circNOX4/miR-153-3p/SATB1 axis. CONCLUSION: Triptolide could hinder ESCC progression, which was mainly achieved by regulating the circNOX4/miR-153-3p/SATB1 axis.

Effects of Blood Hemoadsorption Therapy with HA-380 in Total Arch Replacement for Acute Type A Aortic Dissection: A Retrospective Observational Study.

INTRODUCTION: This study aimed to evaluate whether the addition of a hemoadsorption (HA) cartridge, HA-380, in the cardiopulmonary bypass (CPB) circuit in acute type A aortic dissection (ATAAD) surgery reduced inflammatory cytokine levels and decreased postoperative complications. METHODS: A retrospective observational cohort study was conducted between March 1, 2021, and February 28, 2022. Patients with ATAAD undergoing emergent total arch replacement surgery were divided into the control (CON) and HA groups on the basis of the addition of the HA-380 cartridge in the CPB circuit. RESULTS: Overall, 121 patients met the eligibility criteria; 2 patients in each group who died within the first postoperative week were excluded. Further, 57 and 60 patients in the CON and HA groups, respectively, were included in the pooled analysis. The major perioperative data, baseline values of interleukin-6 (IL-6) and C-reactive protein, and therapeutic interventions were similar in the two groups (all, p > 0.05). The serum IL-6 levels increased more rapidly in the CON group than those in the HA group postoperatively (205.73 ± 174.72 vs. 146.13 ± 64.15 pg/mL, p = 0.020). The HA group had a lower incidence of postoperative acute kidney injury (AKI) and severe acute respiratory distress syndrome than the CON group (25.4 vs. 44.6%, p = 0.032 and 18.3 vs. 35.1%, p = 0.040, respectively). Logistic regression analyses showed that HA may be a protective factor against postoperative AKI. The incidence of bleeding, delirium, and stroke as well as the lengths of intensive care unit and hospital stay in both groups were similar (all, p > 0.05). CONCLUSIONS: The use of HA-380 in the CPB circuit may attenuate inflammatory response and reduce major complications following ATAAD surgery. HA may be associated with lower rate of postoperative AKI.

Protectin Conjugates in Tissue Regeneration 1 Inhibits Macrophage Pyroptosis by Restricting NLRP3 Inflammasome Assembly to Mitigate Sepsis via the cAMP-PKA Pathway.

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1ß release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases.

Triplication is the main evolutionary driving force of NLP transcription factor family in Chinese cabbage and related species.

The NODULE-INCEPTION-like protein (NLP) is a plant-specific transcription factor (TF) family that plays an important role in both signal transduction and nitrate assimilation. However, the NLP gene family in Chinese cabbage (Brassica rapa) has yet to be studied. Here we identified 17, 16, and 32 NLP genes in Chinese cabbage, Brassica oleracea, and Brassica napus, respectively. We found that duplication of those NLP genes almost always originated from genome-wide duplication events. Further analysis (using Arabidopsis as a reference) revealed that the NLP family in Chinese cabbage and B. oleracea was characterized by direct expansion caused by whole-genome duplication. By contrast, indirect expansion characterized B. napus, which arose from hybridization and fusion of the two species. In addition, phylogenetic and homology analyses showed that the Brassica NLP gene family has been highly conserved in evolution. Finally, we also identified optimal codons for four studied species. Altogether, through comparative genome analysis methods, we presented compelling evidence that triplication is the main driving force for the NLP TF family's evolution in Chinese cabbage and related Brassica plants, a process evidently highly conserved. This work will help in better understanding the impact of genome-wide duplication on gene families of plants.

Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease and rapidly escalating epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogenesis of COVID-19 remains to be elucidated. We aimed to clarify correlation of systemic inflammation with disease severity and outcomes in COVID-19 patients. METHODS: In this retrospective study, baseline characteristics, laboratory findings, and treatments were compared among 317 laboratory-confirmed COVID-19 patients with moderate, severe, or critically ill form of the disease. Moreover, the longitudinal changes of serum cytokines, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hsCRP), and hsCRP to lymphocyte count ratio (hsCRP/L) as well as their associations with disease severity and outcomes were investigated in 68 COVID-19 patients. RESULTS: Within 24 h of admission, the critically ill patients showed higher concentrations of inflammatory markers including serum soluble interleukin (IL)-2 receptor, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), ferritin, procalcitonin, LDH, hsCRP, and hsCRP/L than patients with severe or moderate disease. The severe cases displayed the similar response patterns when compared with moderate cases. The longitudinal assays showed the levels of pro-inflammatory cytokines, LDH, hsCRP, and hsCRP/L gradually declined within 10 days post admission in moderate, severe cases or those who survived. However, there was no significant reduction in cytokines, LDH, hsCRP, and hsCRP/L levels in critically ill or deceased patients throughout the course of illness. Compared with female patients, male cases showed higher serum concentrations of soluble IL-2R, IL-6, ferritin, procalcitonin, LDH, and hsCRP. Multivariate logistic regression analysis revealed that IL-6 > 50 pg/mL and LDH > 400 U/L on admission were independently associated with disease severity in patients with COVID-19. CONCLUSION: Exuberant inflammatory responses within 24 h of admission in patients with COVID-19 may correlate with disease severity. SARS-CoV-2 infection appears to elicit a sex-based differential immune response. IL-6 and LDH were independent predictive parameters for assessing the severity of COVID-19. An early decline of these inflammation markers may be associated with better outcomes.

Claudin-1 regulates pulmonary artery smooth muscle cell proliferation through the activation of ERK1/2.

Tumor necrosis factor alpha (TNF-α), a crucial inflammatory cytokine, is involved in the pathogenesis of pulmonary arterial hypertension (PAH). TNF-α can induce claudin-1 (CLDN1) expression and CLDN1 has been reported to be associated with the regulation of cellular functions including cell proliferation, migration. Thus, we aimed to explore whether CLDN1 participated in the etiology of PAH. Our study showed that CLDN1 expression was markedly increased in the lungs of rats with monocrotaline(MCT)-induced PAH, especially in the pulmonary arterial smooth muscle sections. We also found that CLDN1 expression in primary human PASMCs was up-regulated by TNF-α, and the Nuclear factor-κB (NF-κB) inhibitor BAY 11-7082 suppressed CLDN1 up-regulation by TNF-a. CLDN1 overexpression by adenoviral transduction promoted PASMCs proliferation, while knockdown of CLDN1 by siRNA inhibited TNF-α-induced cell proliferation. Mechanistic studies revealed that CLDN1 regulated human PASMC proliferation through the activation of ERK1/2. Together, our findings indicate that up-regulation of CLDN1 promotes PASMC proliferation contributing to pulmonary arterial remodeling in PAH.

CXCR4 inhibitor attenuates allergen-induced lung inflammation by down-regulating MMP-9 and ERK1/2.

Chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor chemokine receptor 4 (CXCR4) have been recognized to play a crucial role in the pathogenesis of bronchial asthma, but the underlying molecular mechanisms are yet to be fully addressed. In the present report we demonstrated that CXCL12/CXCR4 signaling mediates allergic airway inflammation through induction of matrix metalloproteinase 9 (MMP-9) in a murine asthmatic model. We noted that administration of AMD3100, a specific CXCR4 antagonist, significantly attenuated OVA-induced asthmatic responses along with reduced epithelial MMP-9 expression. Our studies in a bronchial epithelial cell line, 16HBE cells, further revealed that CXCL12/CXCR4 signaling synergizes with IL-13 to enhance epithelial MMP-9 expression. Our mechanistic studies demonstrated that CXCL12/CXCR4 enhances epithelial MMP-9 expression by inducing ERK1/2 expression and activation. Together, these studies would bring novel insight into the understanding for the role of CXCL12/CXCR4 signaling in asthmatic responses during the course of bronchial asthma development.

Decreased concentration of IL-35 in plasma of patients with asthma and COPD.

BACKGROUND: IL-35 has been found to be involved in many inflammatory diseases in humans but its role in asthma and chronic obstructive pulmonary disease (COPD) is not clear. The plasma level of IL-35 in patients with asthma and COPD needs to be measured. OBJECTIVE: The aim of this study was to examine the plasma concentrations of IL-35 in newly diagnosed asthmatic and COPD patients and control subjects and investigate correlations of lung function, age, sex, smoking history with the levels of IL-35 in plasma in these diseases. METHODS: Blood samples were collected from patients with newly diagnosed asthma (44, 12 males, aged 33.75?8.94), newly diagnosed COPD (36, 36 males, aged 68.03 ± 8.94), and healthy control groups (23, 9 males, aged 30.06 ± 7.50). We determined the IL-35 levels in plasma by enzyme-linked immunosorbent assay. RESULT: The median and the range of values for IL-35 were 118.55 pg/ml (range 74.43~1767.22 pg/ml) in patients with asthma, 136.09 pg/ml (range 62.54~697.49 pg/ml) in patients with COPD and 275.86 pg/ml (range 26.11~1766.20 pg/ml) in control subjects. The levels of IL-35 in plasma showed a positive correlation with FEV1% and FVC% in asthmatic patients whose plasma IL-35 values were over 150 pg/ml. A positive correlation was also found between plasma IL-35 and FVC% in COPD patients whose plasma IL-35 values were over 150 pg/ml. CONCLUSIONS: These findings suggest that IL-35 may very probably be involved in the Th2 and Th17 mediated inflammation process of asthma and COPD. Its role in the mechanisms of COPD and asthma in human beings, as well as its therapeutic value in these diseases, need further investigation.

Inhibitory effect of dexamethasone on expression of cysteine-rich 61 protein in airway epithelial cells of allergic mouse models.

In order to study whether cysteine-rich 61 protein (cyr61) is involved in the pathogenesis of asthma and its relation to airway inflammation, the effect of dexamethasone (Dxm) on the expression of cyr61 in the lung tissues of asthmatic mice was investigated. Forty BALB/c mice were divided into asthma group (n=15), control group (n=10) and Dxm group (n=15). The asthma group was sensitized and challenged by ovalbumin (OVA). The mice in Dxm group were intraperitoneally administered with Dxm after OVA challenge. The expression of cyr61 in the lung tissues was detected by using immunohistochemistry, and that of eotaxin protein in the bronchoalveolar lavage fluid (BALF) by using enzyme-linked immunosorbent assay (ELISA). The number of inflammatory cells in BALF was also analyzed. The results showed that the cyr61 expression was highest in asthma group (P<0.05), followed by Dxm group (P<0.05) and control group. The cyr61 had a positive correlation with the total nucleated cells (r=0.867, P<0.05), especially eosinophils (r=0.856, P<0.05), and eotaxin level (r=0.983, P<0.05) in the BALF. Our findings suggested that cyr61 is expressed in airway epithelial cells and has a positive correlation with eotaxin and number of airway infiltrating eosinophils.

Relationship between CCR2-V64I polymorphism and cancer risk: a meta-analysis.

BACKGROUND AND OBJECTIVES: The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism. METHODS: Electronic searches of PubMed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association. RESULTS: Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR=1.84, 95% CI=1.35-2.51, AA vs GA/GG, P=0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR=2.06, 95% CI=1.02-4.15, AA vs GA/GG, P=0.11), cervical cancer (OR=3.34, 95% CI=1.48-7.50, AA vs GG, P=0.56), and oral cancer (OR=2.04, 95% CI=1.46-2.84, GA vs GG, P=0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR=2.31, 95% CI=1.45-3.68, AA vs GA/GG, P=0.16) and Asians (OR=1.88, 95% CI=1.12-3.16, AA vs GA/GG, P=0.92). CONCLUSION: This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.

The hMLH1 promoter polymorphisms and cancer susceptibility in Asian populations: a meta-analysis.

BACKGROUND: A variety of studies have evaluated the associations between polymorphisms in the promoter regions of the hMLH1 and cancer risk. However, the results remain inconclusive. To better understand the roles of the hMLH1 polymorphisms and cancer risk, we conducted a comprehensive meta-analysis to investigate the association between the hMLH1 -93G/A and 1151T/A (Val384Asp) polymorphisms and cancer risk in Asian population. METHODS: We performed a meta-analysis by conducting searches of the published studies in Pub Med, CNKI, CBM, ISI web of knowledge and Google scholar search databases. Finally, 12 studies were included into our meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between hMLH1 polymorphisms and cancer risk. Statistical analysis was performed with Review Manager 5.0. RESULTS: Twelve studies addressing two hMLH1 polymorphisms were analyzed among a total of 4128 cancer cases and 4678 controls. For hMLH1 -93G/A, there was no evidence that the hMLH1 -93G/A polymorphism was significantly associated with an increased cancer risk (P>0.05) in Asian populations (heterozygote comparison: OR=0.89 [95% CI (0.75, 1.060)] P=0.20; dominant model comparison: OR=0.98 [95% CI (0.83, 1.15)] P=0.79). In subgroup analysis based on cancer types and the sources of control, no associations were found in colorectal cancer, gastric cancer and "other cancers" under the any gene model except for lung cancer (recessive model comparison: OR=1.69 [95% CI (1.30, 2.19)] P<0.0001). For hMLH1 1151T/A, the polymorphism significantly associated with an increased cancer risk in Asians: OR=1.88 [95% CI (1.49, 2.25)], P<0.0001, and OR=1.87 [95% CI (1.49, 2.25)], P<0.0001. CONCLUSIONS: Our investigations demonstrated that the hMLH1 -93G/A polymorphism is not a candidate for susceptibility to overall cancers, and that the hMLH1 1151T/A polymorphism is significantly associated with higher cancer risk in Asian populations. Further studies with large sample size for hMLH1 should be conducted.

Effect of dexamethasone on expression of AGR2 protein in asthmatic mice.

This study examined the expression of the anterior gradient-2 (AGR2) protein and Muc5ac protein in the lung tissues of asthmatic mice and the effect of dexamethasone, with an attempt to explore the role of AGR2 in the over-secretion of mucus in the airway. Eighteen BALB/c mice were divided into asthma group, control group and dexamethasone group. In dexamethasone group, dexamethasone was intraperitoneally administered. Expression of AGR2 protein and Muc5ac protein in the murine lung tissues was immunohistochemically detected. IL-13 level was determined in the bronchoalveolar lavage fluid (BALF) by ELISA. The results exhibited that the expression of AGR2 protein in asthma group (0.522±0.041) was significantly higher than that in normal controls (0.361±0.047) (P<0.01) and bore a positive linear relationship to the expression of Muc5ac protein (r=0.873, P<0.05) and IL-13 level (r=0.828, P<0.05). Expression of AGR2 protein in the dexamethasone group (0.456±0.049) was significantly lower than that in the asthma group. It was concluded that: (1) the expression of AGR2 protein was significantly higher in asthmatic mice as compared with their normal counterparts; (2) the expression was obviously related to the expression of Muc5ac protein and IL-13; (3) dexamethasone could down-regulate the expression of AGR2 protein. Our findings suggested that AGR2 might be involved in the over-secretion of mucus in the airway in asthma.

Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: a meta-analysis.

PURPOSE: Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1-1607 1G/2G, MMP2-735 C/T, MMP2-1306 C/T, MMP3-1171 5A/6A and MMP9-1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case-control studies. To clarify these associations, we conducted a meta-analysis. METHODS: We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the strength of the association. RESULTS: There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1-1607,increased lung cancer risk was found under dominant model (MMP1-1607 1G/2G: OR=1.14, 95%CI=1.03-1.26, P=0.01), but not in the Caucasian population. For MMP2-1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR=0.63, 95%CI=0.46-0.88, P=0.0006; recessive, OR=0.61, 95%CI=0.38-0.99, P=0.04). For MMP9-1562 C/T, TT genotype decreased this risk under the recessive model (OR=0.38, 95%CI=0.19-0.75, P=0.005), but not in the Asian population. For MMP2-735 C/T and MMP3-1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models. CONCLUSIONS: MMP1-1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found that MMP2-1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9-1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2-735 C/T and MMP3-1171 5A/6A. Further studies with larger sample sizes should be carried out.

Interleukin-12B rs3212227 polymorphism and cancer risk: a meta-analysis.

IL-12 plays a very important role in the development and progress of cancer. IL-12B rs3212227 polymorphism has been reported and many studies have focused on the role of this polymorphism in various cancers. However, the association between IL-12B rs3212227 polymorphism and cancer risk remains controversial. Therefore, we performed a systematic meta-analysis to estimate the overall cancer risk associated with this gene polymorphism and to quantify any potential between-study heterogeneity. PubMed and Embase databases were searched for case-control studies published up to April 1, 2012 that investigated IL-12B rs3212227 polymorphism and cancer risk. Odds ratios (OR) with 95 % confidence intervals (95 % CI) were used to access the strength of this association. Heterogeneity among articles and publication bias were also verified. Ten studies with 2,954 cancer patients and 3,276 healthy controls were included. This meta-analysis showed that there was a significant association between IL-12B rs3212227 polymorphism and overall cancer risk (CC/AC vs AA: OR = 1.32, 95 % CI = 1.06-1.63). When stratified by cancer type, we found a significant increased risk in cervical and nasopharyngeal cancer (OR = 1.34, 95 % CI = 1.04-1.73; OR = 2.03, 95 % CI = 1.57-2.63, respectively). In the stratified analysis, we also observed a similar association in population-based studies (OR = 1.34, 95 % CI = 1.00-1.80), Asian populations (OR = 1.33, 95 % CI = 1.06-1.67) and European populations (OR = 1.54, 95 % CI = 1.04-2.28). According to the results of our meta-analysis, IL-12B rs3212227 polymorphism probably is associated with a high risk of cancer.

Diagnostic value of interleukin 21 and carcinoembryonic antigen levels in malignant pleural effusions.

The aim of this study was to evaluate the diagnostic value of interleukin 21 (IL-21) and carcinoembryonic antigen (CEA) in tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs). Pleural effusion samples from 103 patients were classified on the basis of diagnosis as TPE (n=51) and MPE (n=52). The concentration of IL-21 was determined by ELISA. Lactate dehydrogenase (LDH), adenosine dehydrogenase (ADA) and CEA levels were also determined in all patients. A significant difference was observed in the levels of ADA and CEA (P<0.01), but not in the levels of LDH (P>0.05) between TPE and MPE. The concentration of IL-21 in MPE was significantly higher compared to TPE (P<0.01). With a threshold value of 4.32 pg/ml, IL-21 had a sensitivity of 76.9% (40/52) and a specificity of 80.4% (41/51). Combined detection of IL-21 and CEA had a sensitivity of 69.2% (36/52) and a specificity of 92.2% (47/51). These two markers can contribute to the differential diagnosis of MPEs.