Integrative Analysis of lncRNAs, miRNAs, and mRNA-Associated ceRNA Network in an Atopic Dermatitis Recurrence Model.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.

Calycosin Suppresses Epithelial Derived Initiative Key Factors and Maintains Epithelial Barrier in Allergic Inflammation via TLR4 Mediated NF-κB Pathway.

BACKGROUND/AIMS: Calycosin is a bioactive component of Astragali Radix, a Chinese herb for treating allergy. We have previously demonstrated that calycosin effectively inhibited allergic inflammation efficiently. The aim of this study was to explore the mechanism of calycosin on epithelial cells in allergic inflammation. METHODS: An initial stage of atopic dermatitis (AD) model in which mice were just sensitized with FITC, was established in vivo and immortalized human keratinocytes (HaCaT cells) were utilized in vitro. Initiative key cytokines, TSLP and IL-33, were measured by ELISA, qPCR, immunofluorescence and Western blot. The junctions in epithelial cells were observed by electron microscopy and tight junctions (TJs) (Occludin and ZO-1) were assessed by Western blot and immunofluorescence. TLR4, MyD88, TAK1, TIRAP and NF-κB were measured by qPCR or Western blot. RESULTS: The results showed that TSLP and IL-33 were inhibited significantly by calycosin in the initial stage of AD model. Simultaneously, calycosin attenuated the separated gap among the epithelial cells and increased the expression of TJs. TSLP/IL-33 and TJs were similarly affected in LPS-stimulated HaCaT cells in vitro. Meanwhile, calycosin not only inhibited the expressions of TLR4, MyD88, TAK1 and TIRAP, but also reduced NF-κB activation in vitro and in vivo. An NF-κB inhibitor enhanced the expressions of TJs and reduced that of TSLP/IL-33 in LPS-stimulated HaCaT cells. CONCLUSION: These results indicated that calycosin reduced the secretion of TSLP/IL-33 and attenuated the disruption of epithelial TJs by inhibiting TLR4 mediated NF-κB signaling pathway. These findings help to understand the beneficial effects of calycosin on AD, and to develop effective preventive or therapeutic strategies to combat this disease and other epithelial barrier deletion-mediated allergic diseases.

Long noncoding RNA SPRY4-IT1 is upregulated in esophageal squamous cell carcinoma and associated with poor prognosis.

LncRNA SPRY4-IT1 has been shown to promote the progression of melanoma. However, the role of lncRNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to investigate the clinical significance and biological functions of SPRY4-IT1 in ESCC. The expression levels of lncRNA SPRY4-IT in 92 ESCC patients and 8 ESCC cell lines were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in ESCC cell lines. Both in vitro and in vivo assays were performed to further explore its role in tumor progression. SPRY4-IT1 levels were significantly higher in ESCC tissues and cells than in corresponding adjacent noncancerous tissues and nontumorigenic esophageal epithelial cells, and the ESCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. The multivariate analysis revealed that SPRY4-IT1 expression level is an independent prognostic factor in ESCC patients. In vitro assays demonstrated that knockdown of SPRY4-IT1 reduced cell proliferation, invasiveness, and migration. In vivo assays demonstrated that knockdown of SPRY4-IT1 decreases cell growth. SPRY4-IT1 is a novel molecule involved in ESCC progression, which may provide a potential prognostic biomarker and a potential target for therapeutic intervention.

Upregulation of the long non-coding RNA PlncRNA-1 promotes esophageal squamous carcinoma cell proliferation and correlates with advanced clinical stage.

BACKGROUND: Recent studies revealed that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. PlncRNA-1 is one of lncRNAs that is associated with cell apoptosis and proliferation of prostate cancer. AIM: This study aimed to assess the potential role of PlncRNA-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PlncRNA-1 in 73 pairs of ESCC and their matched normal tissues. The correlation of PlncRNA-1 with clinicopathological features and clinical stages was also analyzed. Cancer cell proliferation and apoptosis were assessed following knock-down of PlncRNA-1 by MTT, colony formation assay, and flow cytometry. RESULTS: The expression of PlncRNA-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (69.8 %, p < 0.05), and the high level of PlncRNA-1 expression was significantly correlated with advanced clinical stage (p < 0.01) and lymph node metastasis (p < 0.05). Furthermore, knockdown of PlncRNA-1 reduced cell proliferation and increased the apoptosis in vitro. CONCLUSIONS: PlncRNA-1 plays an important role in ESCC cell proliferation. Overexpression of PlncRNA-1 is correlated with advanced tumor stage and lymph node metastasis, and may serve as a potential prognostic marker and therapeutic target for ESCC.

Incidence, mortality, and predictive factors associated with acute respiratory distress syndrome in multiple trauma patients living in high-altitude areas: a retrospective study in Shigatse.

Background: Acute respiratory distress syndrome (ARDS) is a severe complication that can lead to fatalities in multiple trauma patients. Nevertheless, the incidence rate and early prediction of ARDS among multiple trauma patients residing in high-altitude areas remain unknown. Methods: This study included a total of 168 multiple trauma patients who received treatment at Shigatse People's Hospital Intensive Care Unit (ICU) between January 1, 2019 and December 31, 2021. The clinical characteristics of the patients and the incidence rate of ARDS were assessed. Univariable and multivariable logistic regression models were employed to identify potential risk factors for ARDS, and the predictive effects of these risk factors were analyzed. Results: In the high-altitude area, the incidence of ARDS among multiple trauma patients was 37.5% (63/168), with a hospital mortality rate of 16.1% (27/168). Injury Severity Score (ISS) and thoracic injuries were identified as significant predictors for ARDS using the logistic regression model, with an area under the curve (AUC) of 0.75 and 0.75, respectively. Furthermore, a novel predictive risk score combining ISS and thoracic injuries demonstrated improved predictive ability, achieving an AUC of 0.82. Conclusions: This study presents the incidence of ARDS in multiple trauma patients residing in the Tibetan region, and identifies two critical predictive factors along with a risk score for early prediction of ARDS. These findings have the potential to enhance clinicians' ability to accurately assess the risk of ARDS and proactively prevent its onset.

Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis.

Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern of the lncRNA HOTAIR and assess its biological role in the development and progression of esophageal squamous cell carcinoma (ESCC), HOTAIR expression in ESCC tissues and adjacent noncancerous tissues were collected from 78 patients and measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). HOTAIR correlation with clinicopathological features and prognosis was also analyzed. Suppression of HOTAIR using siRNA treatment was performed in order to explore its role in tumor progression. Notably elevated HOTAIR expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (96%, P < 0.01), showing a high correlation with cancer metastasis (P < 0.01), elevated TNM (2009) stage classification (P < 0.01), and lowered overall survival rates (P = 0.003). Multivariate analysis revealed that HOTAIR expression (P = 0.003) is also an independent prognostic factor for comparison of TNM stage (P = 0.024) and lymph node metastasis (P = 0.010). Furthermore, in vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. Thus, HOTAIR is a novel molecule involved in both ESCC progression and prognosis. Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers.

Overexpression of KPNA2 correlates with poor prognosis in patients with gastric adenocarcinoma.

This study aims to investigate the expression and significance of KPNA2 in human gastric adenocarcinoma progression and prognosis. Using immunohistochemistry and real-time reverse transcriptase polymerase chain reaction assay, we identified abnormally elevated expression of KPNA2 in gastric adenocarcinoma tissues compared to paired normal stomach mucosa tissues in 30 patients (p < 0.05). In order to investigate the correlations between KPNA2 and the clinicopathological features of gastric adenocarcinoma, the expression of KPNA2 in 142 patients with gastric adenocarcinoma was detected by immunohistochemistry, and the results showed that overexpression of KPNA2 was associated with the size of tumor (p < 0.001), histological grade (p < 0.001), lymph node involvement (p = 0.001), and tumor node metastasis stage (p < 0.001). Kaplan-Meier survival analysis showed that patients with high KPNA2 expression showed a significantly shorter overall survival time compared with patients with low KPNA2 expression. Multivariate analysis suggested that KPNA2 expression might be an independent prognostic indicator (p < 0.001) for the survival of patients with gastric adenocarcinoma. In conclusion, overexpression of KPNA2 is closely related to progression of gastric adenocarcinoma and might be regarded as an independent predictor of poor prognosis for gastric adenocarcinoma.

AIFM1, negatively regulated by miR-145-5p, aggravates hypoxia-induced cardiomyocyte injury.

BACKGROUND: Hypoxia-induced apoptosis is linked to the pathogenesis of myocardial infarction. The role of apoptosis-inducing factor mitochondria associated 1 (AIFM1) in cardiomyocyte injury remains unclear. This study was aimed at probing into the role and the underlying regulatory mechanism of AIFM1 in myocardial injury. METHODS: H9c2 cardiomyocytes and C57BL/6 mice were used for myocardial hypoxic/ischemic injury and myocardial infarction animal models. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the expression levels of AIFM1 mRNA and miR-145-5p. Western blot was used for examining the expression levels of AIFM1, caspase-3, cleaved caspase-3, p-53, and γ-H2AX. Cell viability was examined by cell counting kit-8 (CCK-8) assay and BrdU assay. Interaction between AIFM1 and miR-145-5p was determined by bioinformatics analysis, qRT-PCR, Western blot, and dual-luciferase reporter assay. RESULTS: AIFM1 expression was markedly highly elevated, while miR-145-5p expression was significantly down-regulated in the myocardial infarction animal model and H9c2 cells under hypoxia. Augmentation of AIFM1 led to a dramatic decrease of cell viability, accompanied by an increase of the secretion of the inflammatory cytokines IL-1ß, TNF-α, IL-6, and the expression of cleaved caspase-3. Furthermore, AIFM1 was identified as a target of miR-145-5p. In addition, miR-145-5p/AIFM1 axis regulated the expression of p53. CONCLUSION: AIFM1 may exacerbate myocardial ischemic injury by promoting inflammation and the injury of cardiomyocytes, and its up-regulation may be partly due to the down-regulation of miR-145-5p.

Whole-genome sequencing to characterize the genetic structure and transmission risk of Mycobacterium tuberculosis in Yichang city of China.

Objective: The burden of both general and drug-resistant tuberculosis in rural areas is higher than that in urban areas in China. To characterize the genetic structure and transmission risk of Mycobacterium tuberculosis in rural China, we used whole genome sequencing to analyze clinical strains collected from patients in two counties of Yichang for three consecutive years. Methods: From 2018 to 2020, sputum samples were collected for cultures from patients with suspected tuberculosis in Yidu and Zigui county, and DNA was extracted from the positive strains for genome sequencing. The online SAM-TB platform was used to identify the genotypes and drug resistance-related mutations of each strain, establish a phylogenetic tree, and calculated the genetic distances between pairwise strains. Twelve single nucleotide polymorphisms (SNPs) were used as thresholds to identify transmission clusters. The risk of related factors was estimated by univariable and multivariable logistic regression. Results: A total of 161 out of the collected 231 positive strains were enrolled for analysis, excluding non-tuberculous mycobacterium and duplicate strains from the same patient. These strains belonged to Lineage 2 (92, 57.1%) and Lineage 4 (69, 42.9%), respectively. A total of 49 (30.4%) strains were detected with known drug resistance-related mutations, including 6 (3.7%) multidrug-resistant-TB (MDR-TB) strains and 11 (6.8%) RIF-resistant INH-susceptible TB (Rr-TB) strains. Six of the MDR/Rr-TB (35.3%) were also resistant to fluoroquinolones, which made them pre-extensively drug-resistant TB (pre-XDR-TB). There were another seven strains with mono-resistance to fluoroquinolones and one strain with resistance to both INH and fluoroquinolones, making the overall rate of fluoroquinolones resistance 8.7% (14/161). A total of 50 strains (31.1%) were identified as transmission clusters. Patients under 45 years old (adjusted odds ratio 3.46 [95% confidential intervals 1.28-9.35]), treatment-naive patients (6.14 [1.39-27.07]) and patients infected by lineage 4 strains (2.22 [1.00-4.91]) had a higher risk of transmission. Conclusion: The drug resistance of tuberculosis in rural China, especially to the second-line drug fluoroquinolones, is relatively serious. The standardized treatment for patients and the clinical use of fluoroquinolones warrant attention. At the same time, the recent transmission risk of tuberculosis is high, and rapid diagnosis and treatment management at the primary care needs to be strengthened.

A randomised trial on the therapeutic effectiveness of bronchoalveolar lavage under fiberoptic bronchoscopy in patients with severe lung infection living in the Tibetan plateau area.

BACKGROUND: People living in plateau areas are prone to upper respiratory tract infections and secondary lung infections. The current study aimed to explore the effects of bronchoalveolar lavage under fiberoptic bronchoscope for the treatment of patients with severe pulmonary infection living in plateau areas. METHODS: 148 patients with severe lung infection admitted to the intensive care unit of Shigatse People's Hospital (Shigatse, Tibet Autonomous Region, China) between July 2019 and January 2021 were enrolled. Patients were randomly assigned to the observational group or the control group. For all patients, basic clinical data including sex, age, body mass index (BMI), blood pressure, diabetes history, stroke history, presence or absence of chronic obstructive pulmonary disease, lung infection (gram-positive bacterial infection, gram-negative bacterial infection, fungal infection, acute lung abscess), surgical history, and postoperative inhalation injury. were collected. The control group received conventional treatment, and the observational group received bronchoalveolar lavage under fiberoptic bronchoscopy. Pearson's correlation was used to analyze the correlations between bronchoalveolar lavage under fiberoptic bronchoscopy and inflammatory factors levels. Logistic regression was used to investigate the correlation between bronchoalveolar lavage under fiberoptic bronchoscopy and the effectiveness of the treatment. RESULTS: Before treatment, no significant difference existed in the basic data of the observational group and the control group. After treatment, the parameters of respiratory mechanics and inflammatory factors in the 2 groups were significantly improved compared with those before treatment (P<0.05). At the same time, in the observational group, the clinical parameters were significantly higher than those of the control group, and the levels of inflammatory factors were significantly lower than those of the control group (all P<0.05). After full adjustment for age, sex, BMI, gram-negative infection, diabetes, and acute lung abscess, compared with the control group, the therapeutic effectiveness in the observational group was increased by 23% (OR =1.23, 95% CI: 1.09-1.51, P=0.007). CONCLUSIONS: For patients with severe lung infection who are resident in high altitude areas, compared with conventional treatments, bronchoalveolar lavage under fiberoptic bronchoscopy can significantly improve chest, lung, and total dynamic compliance, as well as reduce the levels of the inflammatory factors procalcitonin (PCT) and transforming growth factor-ß, thus increasing the effectiveness of the treatment.

Dummy molecularly imprinted microspheres prepared by Pickering emulsion polymerization for matrix solid-phase dispersion extraction of three azole fungicides from fish samples.

Dummy molecularly imprinted microspheres (DMIMs) were synthesized by Pickering emulsion polymerization and used as the matrix solid-phase dispersion extraction (MSPD) sorbent for sample pre-treatment of azole fungicides in fish samples. Alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol (DCE) was used as the fragment dummy template for the imprinting of climbazole (CBZ), clotrimazole (CMZ) and miconazole (MNZ). The morphology of the microspheres were characterized by scanning electron microscopy (SEM) and nitrogen adsorption measurements, narrow diameter distribution (20-50 µm) with regular spherical shape and high surface area (SBET = 408.91 ± 6.72 m2 g-1) were achieved. Good class-selectivity of the DMIMs was found for CBZ, CMZ and MNZ by static adsorption experiments. The imprinted microspheres as MSPD sorbent was then evaluated for the extraction and purification of CBZ, CMZ and MNZ in fish samples. The extracted azole fungicides were detected by HPLC-DAD analysis at 225 nm. MSPD conditions including elution, mass ratio of sample/sorbent and washing were carefully evaluated. The optimized MSPD method have good recoveries (89.2-101.5%) and reproducibility (RSDs 1.6-4.8%, n = 5) for fish samples spiked at 0.5, 2.5 and 12.5 µg g-1. The limits of detection (LODs) were 0.045, 0.036 and 0.033 µg g-1 for CBZ, CMZ and MNZ, respectively. The results show that this method has a good application prospect for the pretreatment of azole fungicides in fish samples.

Aging-Resistant Behavior and Room Temperature Electron Spin Resonance of Nd3+ in Singly and Doubly Doped BaTiO3 Ceramics Associated with Preservation History.

The (Ba0.96Nd0.04)Ti0.99O3 (BN4T) and (Ba0.96Nd0.04)(Ti0.94Ce0.05)O3 (BN4TC5) ceramics were prepared via the mixed oxide route exhibited tetragonal and pseudo-cubic structures, respectively. After they were preserved over a long period of time, a broader electron spin resonance (ESR) signal at g = 2.338 and a narrow ESR signal at g = 2.151 were detected at room temperature (RT) for BN4T and BN4TC5, respectively. They most likely originated from the Nd3+ Kramers ions in BN4T and Nd3+-Ce4+ defect complexes in BN4TC5 ceramics, respectively. The origins of these two ESR signals and the aging-resistant dielectric behavior are further discussed.

Multifunctional Ti-xCu coatings for cardiovascular interfaces: Control of microstructure and surface chemistry.

Ti-xCu coatings with varied Cu contents were deposited by hybrid HiPIMS/DC magnetron co-sputtering to achieve optimum microstructures and surface chemistries for applications as multi-functional, blood-contacting interfaces. We have demonstrated that control over the chemistry and microstructure of the coatings provides interfaces that simultaneously exhibit antibacterial properties, show endothelial cell (EC) compatibility, and prevent smooth muscle cell (SMC) proliferation. Using XRD and HRTEM analyses, we identified distinct microstructures for coatings with various Cu/(Cu + Ti) atomic concentrations. The corrosion resistance was controlled by the microstructure of the Ti-xCu coatings and decreased with increases in the Cu atomic concentration. XPS and ICP-MS results provided evidence that copper ions are released from the coatings upon immersion in PBS solution. We have demonstrated that the Cu-containing phases are weak points that are attacked and corroded easily, resulting in the release of Cu ions from the coatings. The coatings with Cu/(Ti + Cu) ratios ranging from 3 to 65 at.% inhibited the viability of SMCs significantly. The optimized coating with Ti and Cu/CuTix crystals and Cu/(Ti + Cu) ratio of 16 at.% showed significant improvements in EC compatibility as well as reduced viability of SMCs, holding great promise for the surface modification of cardiovascular devices such as stents and coronary implants. The coatings with amorphous phases and Cu/(Ti + Cu) ratios of 55 and 65 at.% showed excellent antibacterial properties against Staphylococcus aureus bacteria. The coating with 55.0 at.% Cu is an encouraging material for the surface engineering of blood-contacting implant surfaces that have antibacterial properties but are not cytotoxic to SMCs.

Yu-Ping-Feng-San ameliorates recurrent allergic inflammation of atopic dermatitis by repairing tight junction defects of the epithelial barrier.

BACKGROUND: Atopic dermatitis (AD) is a common allergic inflammatory skin disease, concomitant with a high relapse rate. Yu-Ping-Feng-San (YPFS), a well-known Chinese herbal decoction, reduces the AD relapse rate and recurring severity incidence. However, the underlying mechanism of YPFS on resisting AD recurrence is still unknown and further study is needed. PURPOSE: To evaluate the effects of YPFS on recurrent allergic inflammation of AD in a murine model and to investigate the underlying mechanisms in vivo and ex vivo. METHODS: A fluorescein isothiocyanate (FITC)-induced AD relapsing mouse model was established to study the effects of YPFS and three active components, claycosin, formononetin, and cimifugin, on recurrent allergic inflammation in vivo. Histological analyses of ear tissue inflammation were evaluated by hematoxylin and eosin staining. Production of interleukin (IL)-4, IL-5, IL-13, and interferon-gamma in mice ear tissues, IgE in serum, and thymic stromal lymphopoietin (TSLP) in cell cultures were measured by ELISAs. Tight junction (TJ) expression was detected by immunohistochemistry and western blots. Epithelial barrier integrity was observed with electron microscopy, transepithelial electric resistance (TER), and paracellular flux measurements. HaCaT cells were utilized for ex vivo cellular analyses. RESULTS: In the recurrent phase of AD, YPFS exhibited both short- and long-term anti-allergic inflammatory efficacy with reduced ear tissue inflammation and decreased IL-4, IL-5, IL-13, and IgE production. The three active components, claycosin, formononetin, and cimifugin, showed similar effects as YPFS. Stimulus-induced decreased TER and increased FITC-dextran flux in air-liquid interface cultures of HaCaT cells were significantly repaired by YPFS and the three active components. Notably, the upregulated TJ (CLDN-1 and occludin) expression of epithelium was observed only with YPFS and the three components-treated mice as opposed to the result using conventional anti-allergy medicines. Restored TJ expression by YPFS three components was also detectable in the remission phase of AD. Moreover, decreased TJ expression influenced the effects of YPFS on epithelial cells-derived TSLP production. CONCLUSIONS: YPFS ameliorated recurrent allergic inflammation of AD by repairing TJ defects of epithelial barriers. Intervening epithelial barrier functions could be a preventive and therapeutic approach for recurrent allergic inflammation of AD.

Expression level of beta-catenin is associated with prognosis of esophageal carcinoma.

AIM: To examine the association of beta-catenin with the clinicopathologic features and prognosis of esophageal squamous cell carcinoma (ESCC). METHODS: Beta-catenin mRNA expression level in 40 ESCC patients (28 males and 12 females, age range 38-82 years, median 60 years) was analyzed by real-time PCR. Beta-catenin mRNA expression levels in tumor cells were categorized as weaker (level 1) or equal to or stronger (level 2) than those in endothelial cells. We examined the correlation between the beta-catenin expression and the clinicopathological factors and prognosis of ESCC patients. RESULTS: Level 2 beta-catenin expression was found in 29 patients. ESCC with level 2 expression had a higher rate of lymphnode metastasis (0.0776 +/- 0.0369 vs 0.3413 +/- 0.1803, P < 0.001) and deeper tumor invasion (0.0751 +/- 0.0356 vs 0.3667 +/- 0.1928, P < 0.001), and a poorer survival rate (P = 0.0024) than ESCC with level 1 expression. CONCLUSION: Beta-catenin expression in ESCC is of great importance.

Association of ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 with the prognosis of esophageal squamous cell carcinoma.

In our previous study, Human Signal Transduction in Cancer Gene Array was used in 12 fresh tumor samples to detect the gene expression profiles in the esophageal squamous cell carcinoma (ESCC) tissues matched adjacent non-cancerous samples. Among genes up-regulated at least twofold, ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 were found. So subsequently, the aim of this study was to investigate the prognosis and clinicopathologic roles of ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC tissue. The mRNA and protein expression levels of ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 genes in 70 ESCC and adjacent non-cancerous paraffin-embedded samples were determined by Real-Time Quantitative PCR (RT-PCR) and immunohistochemical staining. The mRNA expression level of ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC was significantly higher than that in the adjacent non-cancerous tissues (0.0821 ± 0.0416 vs. 0.0185 ± 0.0201, P = 0.0000; 1.9934 ± 1.9888 vs. 0.8863 ± 0.665, P = 0.0184; 0.0298 ± 0.0215 vs. 0.0189 ± 0.0187, P = 0.0017; 2.098 ± 0.091 vs. 1.016 ± 0.078, P = 0.0000; 2.181 ± 2.158 vs. 0.931 ± 0.894, P = 0.0152; respectively), and the protein expression level of determined genes was also significantly higher than that in the adjacent non-cancerous tissues (0.2835 ± 0.0844 vs. 0.2352 ± 0.0670, P = 0.0003; 0.3830 ± 0.0947 vs. 0.2721 ± 0.1474, P = 0.0000; 0.2637 ± 0.0348 vs. 0.2042 ± 0.0180, P = 0.0000; 0.2058 ± 0.0316 vs. 0.1218 ± 0.0518, P = 0.0000; 0.2736 ± 0.0834 vs. 0.2251 ± 0.0571, P = 0.0001; respectively). Then, the overexpression of mRNA and protein levels of ß-catenin, Wnt1 and Bmi-1 was aggressively associated with lymph node metastasis, advanced pathological stage, and prognosis of the patients with ESCC (P < 0.05). The up-expression of Hoxa9 mRNA and protein was also aggressively associated with lymph node metastasis and advanced pathological stage (P < 0.05); however, the overexpression of Hoxa9 protein was not associated with the prognosis (P > 0.05). Meanwhile, the hypo-expression of Smad4 mRNA was aggressively associated with advanced pathological stage and prognosis of the patients with ESCC (P < 0.05); however, the hypo-expression of Smad4 protein was neutral to the prognosis and lymph node metastasis (P > 0.05). ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 protein expression analysis showed that the positive outcomes of the combined detection of Wnt1 and ß-catenin expression or Wnt1, ß-catenin and Bmi-1 expression were significantly worse than those of a single target protein expression (P < 0.05). Meantime, the prognosis of the combined positive expression of Wnt1, ß-catenin, and Bmi-1 was poorer than that in the combined positive expression of Wnt1 and ß-catenin (P < 0.05). The prognosis of ESCC patients with the overexpression of Wnt1/ß-catenin and Bmi-1 was relatively poor, and the level of Wnt1/ß-catenin and Bmi-1 was conversely correlated with advanced pathological stage and lymph node metastasis. The expression level of Smad4 and Hoxa9 mRNA was also associated with the prognosis of the patients with ESCC, pathological stage, and lymph node metastasis; however, they might not be the independent prognostic factor.

CLINICAL ANALYSIS OF ENDOSCOPIC INTERVENTIONAL THERAPY COMBINED WITH TRADITIONAL QINGYILIDAN SOUP IN THE TREATMNET OF ACUTE BILIARY PANCREA-TITIS / 现代医院

Objective To study the curative effect of endoscopic interventional therapy combined with tradi-tional Qingyilidan decoction in the treatment of patients with acute biliary pancreatitis.Methods 100 patients with acute biliary pancreatitis in our hospital from September 2013 to August 2014 were selected and randomly divided into observation group and control group with 50 cases in each.The control group was given implementation of oral Chi-nese medicine and enema treatment, and the patients in the observation group were treated with endoscopic interven-tional.The curative effects of the two groups were then compared.Results The recovery time of symptoms and signs in the observation group was significantly shorter than that of the control group (p<0.05).The excellent and good rate of curative effect evaluation in the observation group was significantly higher than that of the control group ( p<0.5).The restoration time of various biochemical indexes in the observation group was significantly shorter than that of the control group (p<0.05).Conclusion The curative effect of endoscopic interventional therapy combined with traditional Chinese medicine preparation in the treatment of acute biliary pancreatitis was significantly better than the single use of traditional Chinese medicine preparation.It is characterized by high security and therefore is worthy of clinical application.

Association of Wnt1/beta-catenin with clinical pathological characteristics and prognosis of esophageal squamous cell carcinoma.

The aim of this study was to investigate the correlation between Wnt1/beta-catenin expression and the clinicopathologic features and prognosis of patients with esophageal squamous cell carcinoma (ESCC). The mRNA and protein expression levels of Wnt1/beta-catenin genes in 70 ESCC and 15 adjacent noncancerous paraffin-embedded samples were determined by real-time quantitative polymerase chain reaction and immunohistochemical staining. The mRNA expression level of Wnt1/beta-catenin in ESCC was significantly higher than that in the adjacent noncancerous tissues (1.9934 +/- 1.9888 vs. 0.8863 +/- 0.665, p = 0.0184; 0.2854 +/- 0.1298 vs. 0.0128 +/- 0.0158, p = 0.0000, respectively), and the overexpression of Wnt1/beta-catenin mRNA was aggressively associated with lymph node metastasis and advanced pathological stage (p < 0.0001). The protein expression level of Wnt1/beta-catenin was also significantly higher than that in the adjacent noncancerous tissues (0.3830 +/- 0.0947 vs. 0.2721 +/- 0.1474, p = 0.0002; 0.2835 +/- 0.0844 vs. 0.2352 +/- 0.0670, p = 0.0210, respectively); however, the overexpression was not associated with clinicopathologic characteristics. Meanwhile, the protein expression level of Wnt1 had no relevance with that of beta-catenin. The overexpression of Wnt1/beta-catenin might be an important molecular marker to predict the clinicopathologic stage and prognosis of ESCC, and the level of Wnt1/beta-catenin mRNA was conversely correlated with lymph node metastasis and advanced pathological stage. The overexpression of Wnt1/beta-catenin mRNA should also predict poor prognosis of ESCC; however, it might not be an independent prognostic factor.

Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma.

AIM: To investigate the role of perioperative chemoradiotherapy (CRT) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Using preoperative computed tomography (CT)-based staging criteria, 238 patients with ESCC (stage II-III) were enrolled in this prospective study between January 1997 and June 2004. With informed consent, patients were randomized into 3 groups: preoperative CRT (80 cases), postoperative CRT (78 cases) and surgery alone (S) (80 cases). The 1-, 3-, 5- and 10-year survival were followed up. Progression-free survival (PFS) was chosen as the primary endpoint by treatment arm measured from study entry until documented progression of disease or death from any cause. The secondary endpoint was overall survival (OS) determined as the time (in months) between the date of therapy and the date of death. Other objectives were surgical and adjuvant therapy complications. RESULTS: With median follow-up of 45 mo for all the enrolled patients, significant differences in the 1-, 3-, 5-, 10-year OS (91.3%, 63.5%, 43.5%, 24.5% vs 91%, 62.8%, 42.3%, 24.4% vs 87.5%, 51.3%, 33.8%, 12.5%, P = 0.0176) and PFS (89.3%, 61.3%, 37.5%, 18.1% vs 89.1%, 61.1%, 37.2%, 17.8% vs 84.5%, 49.3%, 25.9%, 6.2%, P = 0.0151) were detected among the 3 arms. There were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). For the patients who had radical resection, significant differences in median PFS (48 mo vs 61 mo vs 39.5 mo, P = 0.0331) and median OS (56.5 mo vs 72 mo vs 41.5 mo, P = 0.0153) were detected among the 3 arms, but there were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). The local recurrence rates in the preoperative CRT, postoperative CRT group and S group were 11.3%, 14.1% and 35%, respectively (P < 0.05). No significant differences were detected among the 3 groups when comparing complications but tended to be in favor of the postoperative CRT and S groups (P > 0.05). Toxicities of CRT in the preoperative or postoperative CRT arms were mostly moderate, and could be quickly alleviated by adequate therapy. CONCLUSION: Rational application of preoperative or postoperative CRT can provide a benefit in PFS and OS in patients with locally advanced ESCC.

Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma.

AIM: To investigate the role of neoadjuvant chemoradiotherapy in prognosis and surgery for esophageal carcinoma by a meta-analysis. METHODS: PubMed and manual searches were done to identify all published randomized controlled trials (RCTs) that compared neoadjuvant chemoradiotherapy plus surgery (CRTS) with surgery alone (S) for esophageal cancer. According to the test of heterogeneity, a fixed-effect model or a random effect model was used and the odds ratio (OR) was the principal measure of effects. RESULTS: Fourteen RCTs that included 1737 patients were selected with quality assessment ranging from A to C (Cochrane Reviewers' Handbook 4.2.2). OR (95% CI, P value), expressed as CRTS vs S (values > 1 favor CRTS arm), was 1.19 (0.94-1.48, P = 0.28) for 1-year survival, 1.33 (1.07-1.65, P = 0.69) for 2-year survival, 1.76 (1.42-2.19, P = 0.11) for 3-year survival, 1.41 (1.06-1.87, P = 0.11) for 4-year survival, 1.64 (1.28-2.12, P = 0.40) for 5-year survival, 0.82 (0.39-1.73, P < 0.0001) for rate of resection, 1.53 (1.33-2.84, P = 0.007) for rate of complete resection, 1.78 (1.14-2.78, P = 0.79) for operative mortality, 1.12 (0.89-2.48, P = 0.503) for all treatment mortality, 1.33 (0.94-1.88, P = 0.04) for the rate of adverse treatment, 1.38 (1.23-1.63, P = 0.0002) for local-regional cancer recurrence, 1.28 (0.85-1.58, P = 0.60) for distant cancer recurrence, and 1.27 (0.86-1.65, P = 0.19) for all cancer recurrence. A complete pathological response to chemoradiotherapy occurred in 10%-45.5% of patients. The 5-year survival benefit was most pronounced when chemotherapy and radiotherapy were given concurrently (OR: 1.45, 95% CI: 1.26-1.79, P = 0.015) instead of sequentially (OR: 0.85, 95% CI: 0.64-1.35, P = 0.26). CONCLUSION: Compared with surgery alone, neoadjuvant chemoradiotherapy can improve the long-term survival and reduce local-regional cancer recurrence. Concurrent administration of neoadjuvant chemoradiotherapy was superior to sequential chemoradiotherapy.