A C-type lectin containing two carbohydrate recognition domains participates in the antibacterial response by regulating the JNK pathway and promoting phagocytosis.

C-type lectins (CTLs) are important immune-related molecules in crustaceans. However, the immunologic mechanism by which CTLs eliminate invading pathogens is still unclear. In this study, we studied the antimicrobial mechanism of a CTL containing two carbohydrate recognition domains (DClec). After Aeromonas hydrophila challenge, several antimicrobial peptides (ALF1, ALF4, ALF5 and lys-i2) were upregulated. The transcript levels of ALF1, ALF4 and ALF5 were downregulated after A. hydrophila challenge in groups with DClec interference or inhibition compared with the control group. Similar results were obtained after c-Jun N-terminal kinase (JNK) interference. This finding indicates that DClec might regulate the JNK signalling pathway and subsequently adjust antimicrobial peptide (AMP) expression. Additionally, we found that DClec was secreted into the hemolymph. Recombinant protein DClec (rDClec) agglutinated gram-positive or gram-negative bacteria. Both rDClec and the native DClec in hemolymph bound to different bacteria. In this process, Ca2+ promoted the rDClec bacterial binding ability. After DClec interference, the phagocytosis ability of hemocytes was lower than that of the control group. Therefore, DClec can facilitate bacterial elimination by promoting AMPs expression and hemocyte phagocytosis.

Synergistic photothermal-photodynamic-chemotherapy toward breast cancer based on a liposome-coated core-shell AuNS@NMOFs nanocomposite encapsulated with gambogic acid.

A multifunctional nanoplatform with core-shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal - organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer.

Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice.

Obstructive sleep apnea (OSA) patients exhibit different degrees of cognitive impairment, which is related to the activation of reactive oxygen species (ROS) production by chronic intermittent hypoxia (CIH) and the deposition of iron in the brain. As a central regulator of iron homeostasis, whether hepcidin is involved in OSA-induced cognitive impairment has not been clarified. In order to simulate OSA, we established the mouse model by reducing the percentage of inspired O2 (FiO2) from 21% to 5%, 20 times/h for 8 h/day. We found hepcidin was rising during CIH, along with increasing iron levels and neuron loss. Then, we constructed a mouse with astrocyte-specific knockdown hepcidin gene (shHamp). During CIH exposure, the shHamp mice showed a lower level of total iron and neuronal iron in the hippocampus, via stabilizing ferroportin 1 (FPN1) and decreasing L-ferritin (FTL) levels, when compared with wild-type (WT) mice. Furthermore, the shHamp mice showed a decrease of ROS by downregulating the elevated NADPH oxidase (NOX2) and 4-hydroxynonenal (4-HNE) levels mediated by CIH. In addition, the shHamp mice presented improved cognitive deficit by improving synaptic plasticity and BDNF expression in the hippocampus when subjected to CIH. Therefore, our data revealed that highly expressed hepcidin might promote the degradation of FPN1, resulting in neuronal iron deposition, oxidative stress damage, reduced synaptic plasticity, and impaired cognitive performance during CIH exposure.

[Effects of intermittent hypoxia stimulation with different frequencies on HT22 cell viability and expression of Hif-1α and p-NF-κB].

Intermittent hypoxia (IH) could induce cognitive impairment through oxidative stress and inflammation. However, the degree of cell damage is closely related to the IH stimulus frequency. IH stimulation with different frequencies also induces opposite results on neuronal cell lines. Therefore, this study was aimed to compare the effects of IH stimulation with three different frequencies on murine hippocampal neuronal HT22 cell activity, and to explore the molecular mechanism of the IH stimulus frequency-related neuron injury. HT22 cells were cultured and divided into control group and three IH stimulation groups with different frequencies. Oxygen concentration in the chamber was circulated between 21% and 1% (IH1 group, 6 cycles/h; IH2 group, 2 cycles/h; IH3 group, 0.6 cycle/h). Cell morphology was observed at 6, 12, 24 and 48 h of IH treatment. Cell viability was determined by the CCK-8 kit, lactate dehydrogenase (LDH) content in cell supernatant was determined by LDH kit, oxidative stress level was detected by the reactive oxygen species (ROS) probe, and protein expression levels of hypoxia inducible factor-1α (Hif-1α) and phosphorylated nuclear factor κB (p-NF-κB) were detected by Western blot. The results showed that, compared with control group, cell number and activity in the three IH groups were decreased, LDH content and ROS levels were increased with the prolongation of IH stimulation time, and the changes were most obvious in the IH1 group among those of the three IH groups. Hif-1α expression and the p-NF-κB/NF-κB ratio were also up-regulated with the prolongation of IH stimulation time, and the changes of IH1 group were the most significant. These results suggest that IH stimulation induces oxidative stress injury in HT22 cells, which is related to increased Hif-1α expression and NF-κB phosphorylation. Moreover, the higher frequency of IH stimulation induces more serious cell injury.

circRNA_141539 can serve as an oncogenic factor in esophageal squamous cell carcinoma by sponging miR-4469 and activating CDK3 gene.

The abnormal expression and regulation of circular RNA (circRNA) is involved in the occurrence and development of a variety of tumors. The current study aimed to determine the role of circRNA_141539 in esophageal squamous cell carcinoma (ESCC). CircRNA_141539 expression in ESCC was detected via circRNA chip analysis and verified via reverse transcription-quantitative PCR. Associations between circRNA_141539, patient clinicopathological characteristics and prognosis were also statistically analyzed. Additionally, the effects of circRNA_141539 on ESCC cell proliferation and invasion were assessed. A dual-luciferase assay was performed to analyze the interaction between circRNAs, microRNAs (miRs) and mRNAs. The results revealed that circRNA_141539 was significantly up-regulated in patients with ESCC. Furthermore, high circRNA_141539 expressions were significantly associated with TNM stage, differentiation and poor prognosis, revealing high diagnostic value (P<0.05). Furthermore, circRNA_141539 overexpression promoted cell proliferation and invasion, while circRNA_141539 silencing inhibited cell proliferation and invasion (P<0.05). The dual-luciferase reporter assay identified that circRNA_141539 directly binds to miR-4469 and also revealed that cyclin-dependent kinase-3 (CDK3) was negatively regulated by miR-4469. The results indicated that circRNA_141539 served as an oncogenic factor in ESCC by sponging miR-4469 and activating CDK3 expression. circRNA_141539 may present as a novel diagnostic and prognostic biomarker and a therapeutic target for patients with ESCC.

[Erratum] circRNA_001275 upregulates Wnt7a expression by competitively sponging miR­370­3p to promote cisplatin resistance in esophageal cancer.

Following the publication of the above article, the authors have realized that certain intended corrections were not carried over to the published version of the article. First, the description of the results of Figs. 5 and 6 did not match the figures; Edu and Transwell invasion assays were intended to have been excluded from the manuscript during the proofreading stage, although these data were presented in the description of the results for Figs. 5 and 6. Consequently, the text for the "circRNA_001275 promotes cell proliferation" subsection of the Results section towards the end of p. 153 should have read as follows: "MTT assay was used to detect the effects of circRNA_001275 on cell proliferation. The results showed that cell viability was significantly increased in the circRNA_001275 OE group, and significantly decreased in the si circRNA_001275 group (both P<0.05, Fig. 5A and B), compared with the corresponding control groups." Furthermore, the text in the subsequent subsection ("circRNA_001275 inhibits cell apoptosis") should have read as follows: "Hoechst 33258 staining was used to detect the effects of circRNA_001275 on apoptosis. The apoptosis rate was significantly decreased in the circRNA_001275 OE group, and significantly increased in the si circRNA_001275 group (both P<0.05; Fig. 6), compared with the corresponding control group. Secondly, Fig. 5B was omitted from Fig. 5 in the published article; and thirdly, a higher­resolution version of Fig. 6 was submitted during the revision stages, although the version of this figure that was deemed to have been too low in quality was the one that appeared in the final proofs. The corrected / updated versions of Figs. 5 and 6 are shown opposite. The Editor of International Journal of Oncology regrets that certain of these errors were introduced into the article during the production stages, and apologizes both to the authors and to the readership. [the original article was published in International Journal of Oncology 57: 151­160, 2020; DOI: 10.3892/ijo.2020.5050].

[Effects of Xiaotan Huayu Liqiao Formula on cognitive impairment in mice exposed to chronic intermittent hypoxia].

Objective: To investigate the improvement effects of Xiaotan Huayu Liqiao Formula on cognitive impairment in mice exposed to chronic intermittent hypoxia (CIH), and to explore the related mechanisms. Methods: Forty-eight male C57 BL/6 mice were randomly divided into four groups as Normoxia, CIH, Formula+CIH and Formula group. Mice were exposed to normoxia in the normoxia and formula group, or intermittent hypoxia in CIH or Formula+CIH group (in the chambers, mice were filled with 100% N2 to produce FiO2 of 9% for 1. 5 min. The FiO2 gradually returned to 21% over the remainder of each cycle. The exposure cycle was repeated every 3 min, 8 h/day for 35 days). Mice were treated with Xiaotan Huayu Liqiao Formula at the dose of 26. 8 g/kg by intragastric administration before CIH exposure. Meanwhile, mice in CIH and normoxia group were given the same volume of normal saline. When the experiment lasts for 26-35 d, Morris water maze was used to detect cognitive dysfunction in mice. At the end of 35 days, Y-maze was performed in each group. After anesthesia, hippocampus was isolated for morphological observation and Western blot ananlysis. Nissl staining and electron microscopy were adopted to assess the neuronal damage in hippocampus, and Western blot was used to detect the levels of PSD-95 and synapsin expression. Results: Compared with normoxia group,the performance of CIH mice was significantly reduced in Morris water maze and Y-maze(P＜0. 01,P＜0. 01). Both the number of Nissl staining positive cells and the thickness of the postsynaptic density in hippocampus were significantly reduced. And, the levels of PSD-95 expression in hippocampus was also decreased in the CIH group(P＜0. 01), however, no significant change of synapsin expression was observed. Compared to CIH group, administration of Xiaotan Huayu Liqiao Formula markedly improved performance of mice in Morris water maze and Y-maze (P＜0. 01), increased Nissl staining positive cells and the thickness of the postsynaptic density and PSD-95 expression in hippocampus (P＜0. 01). Conclusion: Xiaotan Huayu Liqiao Formula could alleviate the structural and functional impairment of the postsynaptic dense area, and improved CIH-induced cognitive dysfunction.

Large-scale transcriptome analysis identified RNA methylation regulators as novel prognostic signatures for lung adenocarcinoma.

BACKGROUND: The abnormal expression of genes is an essential factor affecting the prognosis of cancer. RNA modification is a way of regulating post-transcriptional levels, including m6A, m5C, m1A RNA methylation. Studies have found that RNA methylation regulates tumorigenesis development and stem cell regeneration. However, there are few studies on lung adenocarcinoma. This study aims to explore the clinical value of RNA methylation for lung adenocarcinoma. METHODS: We summarized thirty-one RNA methylation regulators. The training set was obtained from The Cancer Genome Atlas (TCGA) database, and the test set was obtained from the Gene Expression Omnibus (GEO) database. The Wilcoxon test was used to analyze the expression of RNA methylation regulators. We constructed tumor subgroup models and risk models based on the expression of those regulators. Principal component analysis (PCA) and the receiver operating characteristic (ROC) confirmed the accuracy of the models. Real-time polymerase chain reaction (PCR) validates the results in vitro. RESULTS: Most RNA methylation regulators had distinct expressions in tumor tissues and adjacent tissues (P<0.05). All the models showed high predictive performance (AUC: 0.65-0.82), and the five-year survival of patients in each group was statistically different (P<0.05). The patients in the high-risk group were more likely to have a higher stage, more lymph node metastases, and distant metastases, showing a poor clinical outcome. Patients with high expression of NOP2 or HNRNP were more likely to have a poorly differentiated in vitro experiment. CONCLUSIONS: With our study, we found that the expressions of most RNA methylation regulators were significantly different in cancer and para-cancerous tissues. Different molecular phenotypes constructed by RNA methylation regulators can be independent risk factors for the prognosis of lung adenocarcinoma. Our study demonstrates the critical role of RNA methylation in lung adenocarcinoma, and it is expected to supply a reference for the prognostic stratification and treatment strategy development of lung adenocarcinoma.

Analysis of expression differences of immune genes in non-small cell lung cancer based on TCGA and ImmPort data sets and the application of a prognostic model.

BACKGROUND: There has been little investigation carried out into the activity of immune-related genes in the prognosis of non-small cell lung cancer (NSCLC). Our study set out to analyze the correlation between the differential expression of immune genes and NSCLC prognosis by screening the differential expression of immune genes. Based on the immune genes identified, we aimed to construct a prognostic risk model and explore some novel molecules which have predictive potential for therapeutic effect and prognosis in lung cancer. METHODS: Immune gene transcriptome data and clinical data of NSCLC samples were extracted from TCGA database, and transcription factors in the ImmPort dataset were obtained. The data were divided into two groups: normal tissues and tumor tissues. The expression levels of immune genes were compared using the edgeR algorithm, and then differential expression analysis was performed. The survival analysis was carried out by combining differential immune genes with clinical survival time, so that the immune genes influencing the prognosis of NSCLC could be determined. A risk score was calculated based on the expression levels of the immune genes related to the prognosis of NSCLC and their corresponding coefficients to construct a prognostic risk model. This model was used to calculate patient risk scores and perform clinical correlation analysis. The selected molecules were further verified by clinical samples. RESULTS: By comparing NSCLC tissues with normal tissues, a total of 6,778 differentially expressed genes were found (P<0.05), of which 490 were differential immune-related genes. Survival analysis determined 28 differential immune genes to be associated with prognosis (P<0.05). We calculated the patient risk value based on the immune gene prognosis model. The survival curve was drawn according to the patient risk score and showed that the survival prognosis was significantly different for the high-risk and the low-risk groups (P<0.05). The area under the receiver operating characteristic (ROC) curve (AUC) was 0.723, which represented a relatively high true-positive rate. All of the results proved the reliability of our immune gene risk prognostic model. After drawing the risk curve, S100A16, IGKV4, S100P, ANGPTL4, SEMA4B, and LGR4 were found to be the high-risk immune genes in NSCLC. Clinical correlation analysis of survival-related differential immune genes revealed that in patients with lymph node metastasis, ANGPTL4 was positively correlated with T stage, S100a16 and SEMA4B were upregulated, and VIPR1 was downregulated. Further analysis revealed that VIPR1 was decreased in metastatic lung cancer compared to non-metastatic lung cancer. Furthermore, the real-time PCR detection of the clinical samples showed that S100A16 expression in lung cancer was increased, while VIPR1 expression in lung cancer was downregulated, which was consistent with the results of our bioinformatics analysis. CONCLUSIONS: Based on big data from the TCGA and ImmPort databases, our study analyzed the relationship between differential expression of immune-related genes and clinical data, and constructed a prognostic model based on the immune genes identified. Two novel molecules, S100A16 and VIPR1, were verified to possibly have significant biological function in NSCLC. Our research may provide us with new insight into the immune genes by which the malignant biological behavior of NSCLC is mediated.

circRNA_001275 upregulates Wnt7a expression by competitively sponging miR­370­3p to promote cisplatin resistance in esophageal cancer.

Circular RNAs (circRNAs) are aberrantly expressed in various tumors and are associated with tumorigenesis. The present study aimed to determine the role of circRNA_001275 in cisplatin­resistant esophageal cancer. Three pairs of cisplatin­resistant tissues and corresponding adjacent tissues were collected and subjected to circRNA chip analysis. Additionally, the effect of circRNA_001275 on cisplatin­resistant cells was investigated. The relationship between circRNA_001275, microRNAs (miRs) and target genes were analyzed using luciferase assays, and validated via reverse transcription­quantitative PCR (RT­qPCR) and western blotting. The results showed that circRNA_001275 was significantly upregulated in cisplatin­resistant esophageal cancer tissues and cells (P<0.05). Overexpression of circRNA_001275 promoted the proliferation and invasion, and decreased the apoptosis of cisplatin­resistant cells. On the other hand, circRNA_001275 silencing inhibited cell proliferation and invasion, and promoted cell apoptosis (P<0.05). Dual­luciferase reporter assays revealed that circRNA_001275 directly binds to miR­370­3p, and that Wnt family member 7A (Wnt7a) is targeted by miR­370­3p. RT­qPCR and western blotting further demonstrated that circRNA_001275 serves as an miR­370­3p sponge to upregulate Wnt7a expression. In conclusion, the present study revealed that circRNA_001275 was upregulated in cisplatin­resistant esophageal cancer and promoted cisplatin resistance by sponging miR­370­3p to upregulate Wnt7a expression. Therefore, circRNA_001275 may serve as a potential diagnostic biomarker and therapeutic target for patients with cisplatin­resistant esophageal cancer.

LncRNA XIST facilitates cell growth, migration and invasion via modulating H3 histone methylation of DKK1 in neuroblastoma.

Long non-coding RNAs (lncRNAs) have been confirmed to be aberrantly expressed and involved in the progression of neuroblastoma. This study aimed to explore the expression profile of lncRNA X-inactive specific transcript (XIST) and its functional involvement in neuroblastoma. In this study, the relative level of XIST in neuroblastoma tissues and cell lines was detected by qPCR, and DKK1 protein expression was determined using western blot. The effect of XIST on cell growth, invasion and migration in vitro and in tumorigenesis of neuroblastoma was assessed. The level of H3K27me3 in DKK1 promoter was analyzed with ChIP-qPCR. Interaction between XIST and EZH2 was verified by RNA immunoprecipitation (RIP) and RNA pull-down assay. XIST was significantly upregulated in neuroblastoma tissues (n = 30) and cells lines, and it was statistically associated with the age and International Neuroblastoma Staging System (INSS) staging in neuroblastoma patients. Downregulation of XIST suppressed the growth, migration and invasion of neuroblastoma cells. EZH2 inhibited DKK1 expression through inducing H3 histone methylation in its promoter. XIST increased the level of H3K27me3 in DKK1 promoter via interacting with EZH2. Downregulation of XIST increased DKK1 expression to suppress neuroblastoma cell growth, invasion, and migration, which markedly restrained the tumor progression. In conclusion, XIST downregulated DKK1 by inducing H3 histone methylation via EZH2, thereby facilitating the growth, migration and invasion of neuroblastoma cells and retarding tumor progression.

Smoking status and subsequent gastric cancer risk in men compared with women: a meta-analysis of prospective observational studies.

BACKGROUND: Smoking is one of the well-established risk factors for gastric cancer incidence, yet whether men are more or equally susceptible to gastric cancer due to smoking compared with women is a matter of controversy. The aim of this study was to investigate and compare the effect of sex on gastric cancer risk associated with smoking. METHODS: We conducted a systemic literature search in MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify studies published from inception to December 2018. We included prospective observational studies which reported effect estimates with 95% confidence intervals (CIs) for associations of current or former smokers with the incidence of gastric cancer by sex. We calculated the ratio of relative risk (RRR) with corresponding 95% CI based on sex-specific effect estimates for current or former smokers versus non-smokers on the risk of gastric cancer. RESULTS: We included 10 prospective studies with 3,381,345 participants in our analysis. Overall, the summary RRR (male to female) for gastric cancer risk in current smokers was significantly increased compared with non-smokers (RRR: 1.30; 95% CI: 1.05-1.63; P = 0.019). Furthermore, there was no significant sex difference for the association between former smokers and gastric cancer risk (RRR: 1.20; 95% CI: 0.92-1.55; P = 0.178). However, the result of sensitivity analysis indicated the pooled result was not stable, which was altered by excluding a nested case-control study (RRR: 1.31; 95% CI: 1.10-1.57; P = 0.002). CONCLUSION: This systematic review showed a potential sex difference association between current smokers and the risk of gastric cancer. The sex differential in smokers can give important clues for the etiology of gastric cancers and should be examined in further studies.

The role of EGFR mutation as a prognostic factor in survival after diagnosis of brain metastasis in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor (EGFR) and overall survival (OS) in NSCLC patients with brain metastases. METHODS: Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017. RESULTS: 4373 NSCLC patients with brain metastases in 18 studies were involved. Mutated EGFR associated with significantly improved OS compared with wild type. Subgroup analyses suggested that this relationship persisted in studies conducted in Eastern, with retrospective design, with sample size ≥500, mean age of patients ≥65.0 years, percentage male < 50.0%, percentage of patients receiving tyrosine kinase inhibitor ≥30.0%. Finally, although significant publication bias was observed using the Egger test, the results were not changed after adjustment using the trim and fill method. CONCLUSIONS: This meta-analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases. It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases.

Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation.

Molecular hydrogen is reported to be used medically to ameliorate various systemic pathological conditions. This study aimed to investigate the effect of hydrogen (H2 ) gas on hypertension induced by intermittent hypoxia in rats. The adult rats were exposed to chronic intermittent hypoxia (CIH) 8 hours/day for 5 weeks and/or H 2 gas 2 hours/day. We found that the systolic and diastolic blood pressure (BP) increased significantly in rats exposed to intermittent hypoxia, both of which were markedly attenuated after H treatment. Furthermore, intermittent hypoxia exposure elevated renal sympathetic nerve activity, consistent with plasma norepinephrine. Additionally, H 2 gas significantly improved CIH-induced abnormal vascular relaxation. Nevertheless, inhalation of H 2 gas alone did not cause such changes. Moreover, H 2 gas-treated rats exposed to CIH showed a significant reduction in 8-hydroxy-2 deoxyguanosine content and increases in superoxide dismutase activity, indicating improved oxidative stress. Taken together, these results indicate that H 2 gas has significant effects on the reduction of BP without any side effects. Mechanistically, inhibition of sympathetic activity and reduction of systemic vascular resistance may participate in this process via the antioxidant activity of H 2 .

[Bosentan ameliorates hypertension in rats exposed to chronic intermittent hypoxia through inhibiting renal sympathetic nerve activity].

The purpose of this study is to investigate the effect of the oral endothelin antagonist Bosentan on blood pressure and renal sympathetic nerve activity (RSNA) in rats exposed to chronic intermittent hypoxia (CIH), and to explore the sympathoexcitation mechanism of endothelin-1 (ET-1) in CIH-induced hypertension. Twenty-four male SD rats were randomly divided into normoxia, CIH and Bosentan groups. Rats in the normoxia group were exposed to normoxic environment, and rats in CIH or Bosentan group were exposed to intermittent hypoxia for 3 weeks. Bosentan was given at 50 mg/kg by intragastric administration before intermittent hypoxia exposure in Bosentan group. Systolic blood pressure (SBP) was measured by BP-2000, and the change of RSNA to sodium nitroprusside (SNP) or phenylephrine (PE) was recorded by PowerLab signal acquisition system. Serums of all rats were collected and the contents of ET-1 and norepinephrine (NE) were measured by ELISA. Results showed that blood pressure was gradually increased following CIH exposure compared with the normoxia group during the 3 weeks (P < 0.01, P < 0.01, P < 0.001). The basal RSNA was increased and baroreflex sensitivity was decreased in rats exposed to CIH. Furthermore, the blood pressure was positively correlated with the level of ET-1 in serum in rats exposed to CIH (r = 0.833, P = 0.01). Bosentan administration significantly decreased SBP and basal RSNA, increased the baroreflex sensitivity, and decreased serum NE level in rats exposed to CIH. These results suggest that ET-1 is related with blood pressure elevation in rats exposed to CIH, and Bosentan reverses CIH-induced hypertension by decreasing RSNA.

[Improvement of hydrogen on liver oxidative stress injury in chronic intermittent hypoxia rats].

OBJECTIVE: To explore the effects of hydrogen on liver injury in chronic intermittent hypoxia rats and the related oxidative stress mechanism. METHODS: Twenty-four male adult SD rats were randomly divided into 3 groups(n=8):the normoxia group (Norm), the chronic intermittent hypoxia group (CIH), the chronic intermittent hypoxia and hydrogen group (H2 + CIH). Rats in Norm group were exposed in air, those in the other 2 groups suffered from chronic intermittent hypoxia conditions for 5 weeks. Before the CIH treatment, rats in H2+CIH group inhaled hydrogen gas at 67% concentration for 1 hour. The serum biochemical indicators of oxidative stress, pro-inflammatory cytokine, liver enzyme and blood lipid were inspected after five weeks treatment, the pathological changes of liver tissue were also observed in the transmission electron microscope. RESULTS: Compared with Norm group, the microstructure of liver cells was severely injured, and the serum levels of glutamic-pyruvic transaminase(ALT),glutamic-oxalacetic transaminase (AST) were significantly higher in CIH group (P<0.05); the serum level of 8-hydroxy-2 deoxyguanosine(8-OHdG) and interleukin-6(IL-6) was significantly higher, the serum level of superoxide dismutase (SOD) was significantly lower. Compared with CIH group, the pathology of liver microstructure were significantly improved and the serum levels of ALT, AST were significantly lower in H2+CIH group (P<0.05); the serum levels of 8-OHdG and IL-6 were significantly lower, the serum level of SOD was significantly higher. Compared with Norm group, the serum level of IL-1 was higher, the serum level of TC, TG, and low density lipoprotein(LDL) were lower, but there was no statistical difference with those in CIH group. There was no statistical difference in the serum level of high density lipoprotein (HDL)among the three groups. CONCLUSIONS: Pre-treatment with hydrogen could improve the liver injury caused by chronic intermittent hypoxia, and reducing oxidative stress level for protecting the liver cells damage.

Influence of body mass index on postoperative complications after thymectomy in myasthenia gravis patients.

OBJECTIVES: It is not clear whether being overweight or obese influences postoperative complications in myasthenia gravis (MG) patients. We retrospectively investigated an association between body mass index (BMI) and postoperative complications in MG. MATERIALS AND METHODS: Fifty-nine MG patients who had undergone transsternal thymectomy were classified as low or high BMI based on the criteria for Asian-Pacific populations. An association between BMI and complications was analyzed. RESULTS: MG patients with high BMI had significantly higher rates of major adverse complications (P = 0.033), postoperative respiratory failure (P = 0.045), and longer postoperative hospitalization (P = 0.005). The optimal cutoff value of BMI for postoperative respiratory failure was 23.3 kg/m2, with a sensitivity of 75.0% and a specificity of 64.7% (P = 0.046). CONCLUSIONS: MG patients with a BMI indicating overweight or obesity have a higher risk of postoperative complications after thymectomy. Thus, close monitoring must be performed when surgery is necessary.

Expression and Role of Oct3/4 in Injury-Repair Process of Rat Alveolar Epithelium after 5-Fu Treatment.

OBJECTIVE: We aimed to investigate how the embryonic stem cell-related gene Oct3/4 changes during the injury-repair process of distal pulmonary epithelium induced by 5-fluorouracil (5-Fu). METHODS: We have developed the lung injury model induced by 5-Fu and observed the dynamic changes of Oct3/4 by indirect immunofluorescence, Western blot, and quantitative real-time PCR. Immunofluorescence double staining was used to compare the positions of Oct3/4(+) cells and other reported alveolar epithelial stem cells. RESULTS: Oct3/4(+) cells were not found in normal rat lung epithelial cells. However, after treatment with 5-Fu, Oct3/4(+) cells appeared at 12 h, reached the peak at 24 h, then decreased at 48 h, and eventually disappeared at 72 h. Oct3/4 was localized in the nucleus. We found that the sites of Clara cell secretory protein and surfactant protein-C dual positive cells were apparently different from Oct3/4(+) cells. CONCLUSIONS: Our results revealed that, in rat alveolar epithelium, expression of Oct3/4 could be induced after treatment with 5-Fu, then decreased gradually, and was silenced following the alveolar epithelial differentiation. We hold that Oct3/4(+) cells are lung stem cells, which can provide new evidence for identification and isolation of lung epithelial stem cells.

Paraneoplastic Cushing's syndrome associated with bronchopulmonary carcinoid tumor in youth: A case report and review of the literature.

Paraneoplastic Cushing's syndrome (CushingPS) caused by bronchopulmonary carcinoid tumors presents a diagnostic challenge for clinicians. The present study reports the case of an 18-year-old male patient presenting with rapid weight gain, polyuria, polydipsia and progressive muscle weakness. Chemical and imaging findings suggested ectopic secretion of adrenocorticotropin. Whole-body 18fluorine-fluorodeoxyglucose (18FDG-PET/CT) positron-emission tomography revealed an increased uptake of 18FDG-PET/CT in the right middle lung mass and lobar lymph node. Postoperative pathology confirmed the presence of a typical carcinoid, as well as a lobar lymph node metastasis. The patient underwent a right middle lobectomy with mediastinal lymph node resection, which resulted in symptom clearance, followed by rapid weight loss. No CushingPS or tumor recurrence was observed at the 3-month postoperative follow-up.

Dormancy activation mechanism of tracheal stem cells.

Accurate markers and molecular mechanisms of stem cell dormancy and activation are poorly understood. In this study, the anti-cancer drug, 5-fluorouracil, was used to selectively kill proliferating cells of human bronchial epithelial (HBE) cell line. This method can enrich and purify stem cell population. The dormant versus active status of stem cells was determined by phosphorylation of RNAp II Ser2. The surviving stem cells were cultured to form stem cell spheres expressing stem cell markers and transplanted into nude mice to form a teratoma. The results demonstrated the properties of stem cells and potential for multi-directional differentiation. Bisulfite sequencing polymerase chain reaction showed that demethylation of the Sox2 promoter by 5-FU resulted in Sox2 expression in the dormant stem cells. This study shows that the dormancy and activation of HBE stem cells is closely related to epigenetic modification.