TMEM16A enhances the activity of the Cdc42-NWASP signaling pathway to promote invasion and metastasis in oral squamous cell carcinoma.

OBJECTIVE: We explored the relationship between TMEM16A and metastasis and development in oral squamous cell carcinoma (OSCC). STUDY DESIGN: The University of Alabama at Birmingham and Gene Expression Profiling Interactive Analysis Databases were employed to analyze the relationship between the expression of TMEM16A and the survival of patients with OSCC. TMEM16A was knocked down and overexpressed in CAL27 and SCC-4 cells, respectively, and the malignant behavior and expression of key proteins were detected. The Cdc42-NWASP pathway was inhibited, and the effects of TMEM16A and the Cdc42-NWASP pathway on promoting the malignant behavior of cancer cells were verified. A xenograft tumor model was constructed, and tumor growth, cell proliferation index, apoptosis, and Cdc42-NWASP signal pathway activity were detected. RESULTS: The expression of TMEM16A in oral cancer tissues was significantly higher than in adjacent tissues, and mice with high expression of TMEM16A had shorter survival. Overexpression of TMTM16A could significantly promote the occurrence of cancer and reduce the apoptosis of cancer cells, whereas the activity of the Cdc42 pathway was higher. Knocking down TMEM16A or inhibiting the Cdc42-NWASP pathway could reverse these results. CONCLUSION: The activation of the Cdc42-NWASP pathway by high TMEM16A expression is closely related to OSCC and may become a new therapeutic target to prevent OSCC metastasis.

CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a poor prognosis and growing incidence. In this study, we explored the potential roles of CDK1, CDK2, CDK4, and CDK6 in the progression of early-stage PDAC. Clinicopathologic and mRNA expression data and treatment information of 140 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy were obtained from the Cancer Genome Atlas data set. Our bioinformatic analysis showed that higher CDK1, CDK2, CDK4, or CDK6 expression was associated with a shorter median survival of the early-stage PDAC patients. Of note, in the low-proliferating pancreatic cancer group, CDKs expressions were significantly associated with proteins functioning in apoptosis, metastasis, immunity, or stemness. Among the low-proliferating PDAC, higher expression of CDK1 was associated with the shorter survival of patients, suggesting that CDK1 may regulate PDAC progression through cell cycle-independent mechanisms. Our experimental data showed that CDK1 knockdown/inhibition significantly suppressed the expression levels of AHR and POU5F1, two critical proteins functioning in cancer cell metastasis and stemness, in low-proliferating, but not in high-proliferating pancreatic cancer cells. In all, our study suggests that CDKs regulate PDAC progression not only through cell proliferation but also through apoptosis, metastasis, immunity, and stemness.

Epidemiological and Antimicrobial Resistant Patterns, and Molecular Mechanisms of Carbapenem-Resistant Klebsiella pneumoniae Infections in ICU Patients.

Objective: To study the epidemiological and antimicrobial resistant patterns, clinical characteristics and risk factors of critically ill patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) from intensive care units (ICUs). The potential molecular mechanisms of antimicrobial resistance and virulence of CRKP were investigated through evaluation of associated genes. Methods: Totally, 201 ICU patients infected with K. pneumoniae were recruited from January 2020 through January 2021. K. pneumoniae strains were collected from diverse clinical specimens and identified by microbial cultures and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Antimicrobial resistance was measured through broth micro-dilution or Kirby-Bauer assays. The carbapenemase-, virulence-, and capsular serotype-associated genes of CRKP were individually detected by PCR and sequencing. Demographic and clinical profiles were acquired from hospital databases to evaluate the correlation of CRKP infection incidence with clinical risk factors. Results: Of the 201 K. pneumoniae strains, CRKP accounted for 41.29%. Seasonal bias existed in local prevalence of CRKP infections. CRKP strains mounted significantly strong resistance against major antimicrobial agents except ceftazidime-avibactam, tigecycline and minocycline. Recent exposure to certain antibiotics and prior treatment with invasive interventions were prone to increase CRKP infection risks with worsened infectious outcomes. The local top carbapenemase-encoding and virulence-associated genes of CRKP were blaKPC and irp2, respectively. Nearly half of CRKP isolates harbored a capsular polysaccharide serotype of K14.K64 (wzi-64) which preferentially emerged in the cohort with worse outcomes of infection. Conclusion: Featured epidemiology and typical clinical characteristics existed extensively in K. pneumoniae infections among ICU patients. The CRKP cohort exhibited substantially high antimicrobial resistance. Distinctive carbapenemase-, virulence-, and serotype-associated genes were intensively involved in the spread and pathogenesis of CRKP. These findings supported careful management of critically ill patients potentially infected with virulent CRKP in the ICUs.

Methodological comparison of bronchoalveolar lavage fluid-based detection of respiratory pathogens in diagnosis of bacterium/fungus-associated pneumonia in critically ill patients.

Background: Bacterium/fungus-associated pneumonia (BAP/FAP) is the prominent cause of high mortality and morbidity with important clinical impacts globally. Effective diagnostic methods and proper specimen types hopefully facilitate early diagnosis of pneumonia and prevent spread of drug-resistant bacteria/fungi among critically ill patients. Methods: In the present study, 342 bronchoalveolar lavage fluid (BALF) samples were collected from critically ill patients with pulmonary infections between November 2020 and March 2021. The BALF materials were comparatively employed to screen BAP/FAP through microscopy, culture, antigenic marker and PCR-based methods. The limit of detection (LOD) of cultures and PCR for bacteria/fungi was determined by serial dilution assays. Specimen slides were prepared with Gram staining for microscopic examinations. Microbial cultures and identifications underwent routine clinical protocols with the aid of mass spectrometry. (1,3)-ß-D-glucan and galactomannan tests with BALF were carried out accordingly. Direct detection of pathogens in BALF was achieved through PCR, followed by sequencing and BLAST in GenBank database for pathogenic identification. The subjects' demographic and clinical characteristics were well evaluated. Results: BAP/FAP was identified in approximately 47% of the subjects by the BALF-based PCR. The PCR-based diagnostic methods showed improved detection performance for fungi with good LOD, but performed similarly for bacteria, when compared to the cultures. There was poor agreement among traditional microscopy, culture and PCR assays for bacterial detections (kappa value, 0.184 to 0.277). For overall bacterial/fungal detections, the microscopy showed the lowest detecting rate, followed by the cultures, which displayed a slightly higher sensitivity than the microscopy did. The sensitivity of PCR was much higher than that of the other means of interest. However, the traditional cultures rather than antigenic marker-based approaches were moderately consistent with the PCR-based methods in fungal species identification, particularly for Candida and Aspergillus spp. Our findings further revealed that the age, length of hospital stay, invasive procedures and cerebral diseases were likely considered as main risk factors for BAP/FAP. Conclusion: Screening for BALF in critically ill patients with suspected pneumonia pertaining high risk factors using combined PCR-based molecular detection strategies would hopefully contribute to early diagnosis of BAP/FAP and improved prognosis of the patients.

Screening of periodontitis-related diagnostic biomarkers based on weighted gene correlation network analysis and machine algorithms.

BACKGROUND: Periodontitis is a common oral immune inflammatory disease and early detection plays an important role in its prevention and progression. However, there are no accurate biomarkers for early diagnosis. OBJECTIVE: This study screened periodontitis-related diagnostic biomarkers based on weighted gene correlation network analysis and machine algorithms. METHODS: Transcriptome data and sample information of periodontitis and normal samples were obtained from the Gene Expression Omnibus (GEO) database, and key genes of disease-related modules were obtained by bioinformatics. The key genes were subjected to Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and 5 machine algorithms: Logistic Regression (LR), Random Forest (RF), Gradient Boosting Decisio Tree (GBDT), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM). Expression and correlation analysis were performed after screening the optimal model and diagnostic biomarkers. RESULTS: A total of 47 candidate genes were obtained, and the LR model had the best diagnostic efficiency. The COL15A1, ICAM2, SLC15A2, and PIP5K1B were diagnostic biomarkers for periodontitis, and all of which were upregulated in periodontitis samples. In addition, the high expression of periodontitis biomarkers promotes positive function with immune cells. CONCLUSION: COL15A1, ICAM2, SLC15A2 and PIP5K1B are potential diagnostic biomarkers of periodontitis.

lncRNA OIP5-AS1 knockdown or miR-223 overexpression can alleviate LPS-induced ALI/ARDS by interfering with miR-223/NLRP3-mediated pyroptosis.

BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases and endothelial barrier injury is an important contributor to the pathogenesis of ALI/ARDS. Long non-coding (lncRNA) has been shown to participate in the progression of ALI/ARDS. The present study aimed to investigate the function of lncRNA opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in lipopolysaccharide (LPS)-induced ALI/ARDS. METHODS: OIP5-AS1 and miR-223 levels were detected by a polymerase chain reaction in the serum of ALI/ARDS patients or healthy donors. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was performed to detect the proliferation of human pulmonary microvascular endothelial cells (HPMECs). Flow cytometry were performed to detect the apoptosis of HPMECs. The protein levels of NLRP3, ASC, GSDMD-N and caspase-1 were measured by western blotting to detect the pyroptosis of HPMECs. Interleukin (IL)-1ß, IL-6, IL-18 and IL-10 were detected by an enzyme-linked immunosorbent assay to measure the inflammatory response of HPMECs. The production of reactive oxygen species, superoxide dismutase and malondialdehyde was measured to determine the oxidative stress of HPMECs. Targets of OIP5-AS1 and miR-223 were predicted by StarBase and confirmed by a dual-luciferase reporter assay. RESULTS: We found that OIP5-AS1 was up-regulated and miR-223 was down-regulated in the serum of ALI/ARDS patients and LPS-treated HPMECs. Functionally, knockdown of OIP5-AS1 induced proliferation and inhibited apoptosis, pyroptosis, inflammatory response and oxidative stress of LPS-treated HPMECs. Interestingly, miR-223 was a target of OIP5-AS1 and miR-223 inhibition abolished the effects of si-OIP5-AS1 on LPS-induced HPMECs. More importantly, miR-223 directly targeted NLRP3, and miR-223 overexpression promoted proliferation and inhibited apoptosis, pyroptosis, inflammatory response and oxidative stress of LPS-treated HPMECs, with this being abolished by NLRP3 overexpression. Finally, we found that OIP5-AS1 knockdown and miR-223 overexpression could both alleviate LPS-induced ALI/ARDS in vivo. CONCLUSIONS: Taken together, we find that lncRNA OIP5-AS1 aggravates LPS-induced ALI/ARDS via miR-223/NLRP3 axis and provides new targets for ALI/ARDS therapy.

Effects of low-level light therapy on dentin hypersensitivity: a systematic review and meta-analysis.

OBJECTIVE: To investigate the treatment efficacy of low-level light therapy on dentin hypersensitivity. MATERIALS AND METHODS: Following the PRISMA guideline, six electronic databases supplemented with bibliographies were searched till December 2020. Two reviewers performed the screenings independently with a reliability assessment. Studies fulfilling the pre-registered eligibility criteria were included for risk-of-bias assessment and data synthesis. RESULTS: Thirty-five articles ultimately informed this systematic review based on the eligibility criteria and underwent risk-of-bias assessment (ĸ = 0.86). Quantitative results were deduced by meta-analysis of 20 randomised controlled trials: LLLT showed favourable outcomes compared to placebos for immediate (SMD: 1.09, 95% CI: 0.47 to 1.70), interim (SMD: 1.32, 95% CI: 0.41 to 2.23), and persistent efficacies (SMD: 2.86, 95% CI: 1.98 to 3.74). However, substantial heterogeneity existed among included studies (I2: 64-95%). Regarding comparisons with other desensitising strategies, LLLT showed no significant benefits in DH alleviation over others except fluorides for interim efficacy (SMD: 0.31, 95% CI: 0.10 to 0.52) and persistent efficacy (SMD: 0.45, 95% CI: 0.03 to 0.86). CONCLUSIONS: This systematic review shows that LLLT has positive immediate, interim, and persistent DH-treatment efficacies compared with placebo. No superior treatment effects of LLLT were observed except fluoride agent use. Further studies are warranted-RCTs with low risk of bias, consistent technical settings, comprehensive assessments, and long follow-up periods. CLINICAL RELEVANCE: This systematic review bridges a critical research gap by analysing clinical evidence in the DH-alleviating efficacy of LLLT in comparison with placebo and other in-office desensitising strategies.

Anthropometric accuracy of three-dimensional average faces compared to conventional facial measurements.

This study aimed to evaluate and compare the accuracy of average faces constructed by different methods. Original three-dimensional facial images of 26 adults in Chinese ethnicity were imported into Di3DView and MorphAnalyser for image processing. Six average faces (Ave_D15, Ave_D24, Ave_MG15, Ave_MG24, Ave_MO15, Ave_MO24) were constructed using "surface-based registration" method with different number of landmarks and template meshes. Topographic analysis was performed, and the accuracy of six average faces was assessed by linear and angular parameters in correspondence with arithmetic means calculated from individual original images. Among the six average faces constructed by the two systems, Ave_MG15 had the highest accuracy in comparison with the conventional method, while Ave_D15 had the least accuracy. Other average faces were comparable regarding the number of discrepant parameters with clinical significance. However, marginal and non-registered areas were the most inaccurate regions using Di3DView. For MorphAnalyser, the type of template mesh had an effect on the accuracy of the final 3D average face, but additional landmarks did not improve the accuracy. This study highlights the importance of validating software packages and determining the degree of accuracy, as well as the variables which may affect the result.

Microemulsion-Assisted Self-Assembly and Synthesis of Size-Controlled Porphyrin Nanocrystals with Enhanced Photocatalytic Hydrogen Evolution.

Design and engineering of highly efficient light-harvesting nanomaterial systems to emulate natural photosynthesis for maximizing energy conversion have stimulated extensive efforts. Here we present a new class of photoactive semiconductor nanocrystals that exhibit high-efficiency energy transfer for enhanced photocatalytic hydrogen production under visible light. These nanocrystals are formed through noncovalent self-assembly of In(III) meso-tetraphenylporphine chloride (InTPP) during microemulsion assisted nucleation and growth process. Through kinetic control, a series of uniform nanorods with controlled aspect ratio and high crystallinity have been fabricated. Self-assembly of InTPP porphyrins results in extensive optical coupling and broader coverage of the visible spectrum for efficient light harvesting. As a result, these nanocrystals display excellent photocatalytic hydrogen production and photostability under the visible light in comparison with the commercial InTPP porphyrin powders.

Multiple Copies in T-Cell Malignancy 1 (MCT-1) Promotes the Stemness of Non-Small Cell Lung Cancer Cells via Activating Interleukin-6 (IL-6) Signaling through Suppressing MiR-34a Expression.

BACKGROUND Although the oncogenic roles of multiple copies in T-cell malignancy 1 (MCT-1) have been revealed in multiple cancers, its effects on non-small cell lung cancer (NSCLC) progression are still uncertain. This study aimed to reveal the effects of MCT-1 on the stem cell-like traits of NSCLC cells. MATERIAL AND METHODS Western blot, real-time quantitative polymerase chain reaction (RT-qPCR), spheroid forming ability, and ALDH1 (aldehyde dehydrogenase 1) activity analysis were carried out to examine the effects of MCT-1/micrRNa-34 (miR-34a)/interleukin-6 (IL-6) on the stem cell-like characteristics of lung cancer cells. RESULTS MCT-1 knockdown reduced the spheroid forming ability, characterized as the decreased spheroid size and number. Additionally, MCT-1 knockdown decreased the expression of the NSCLC stemness markers and the activity of ALDH1. Moreover, MCT-1 knockdown decreased IL-6 secretion that promotes NSCLC cell stemness. Furthermore, MCT-1 knockdown increased the level of miR-34a, which attenuated the stemness of NSCLC cells through targeting IL-6R (IL-6 receptor) expression. CONCLUSIONS These results suggest MCT-1/miR-34a/IL-6/IL-6R axis is responsible for MCT-1-mediated effects on NSCLC cell stemness.

Prevalence of gingival recession after orthodontic treatment of infraversion and open bite.

PURPOSE: Aim of the present study was to investigate the prevalence of gingival recession and related factors in teeth with low occlusal function (open bite and infraversion) after orthodontic treatment. METHODS: From January 2014 to December 2017, 403 patients received orthodontic treatment. Their gingival recession and related factors before and after treatment were retrospectively analyzed. RESULTS: The prevalence of gingival recession in patients with infraversion and open bite after orthodontic treatment were 80.6 and 75.0%, respectively; these values were 43.4 and 47.5% before treatment, respectively. Notably, the Miller index of gingival recession increased after orthodontic treatment (P < 0.05). The risk of gingival recession in patients with infraversion or open bite after orthodontic treatment was remarkably higher than the risk in other patients (odds ratio [OR] = 16.712 and 5.073, respectively); the gingival recession rate was related to treatment with tooth extraction (OR = 2.043), as well as gingival biotype (OR = 0.341) and gingival index (GI) before orthodontic treatment (OR = 97.404; P < 0.05). CONCLUSIONS: Patients with these two types of low occlusal function are more likely to exhibit gingival recession after orthodontic treatment. Moreover, the prevalence of gingival recession after orthodontic treatment is higher among patients who have undergone tooth extraction during orthodontic treatment, and among those who exhibit thin gingival biotype and high gingival index before orthodontic treatment.

Fabrication of Large-Area Arrays of Vertically Aligned Gold Nanorods.

Anisotropic nanoparticles, such as nanorods and nanoprisms, enable packing of complex nanoparticle structures with different symmetry and assembly orientation, which result in unique functions. Despite previous extensive efforts, formation of large areas of oriented or aligned nanoparticle structures still remains a great challenge. Here, we report fabrication of large-area arrays of vertically aligned gold nanorods (GNR) through a controlled evaporation deposition process. We began with a homogeneous suspension of GNR and surfactants prepared in water. During drop casting on silicon substrates, evaporation of water progressively enriched the concentrations of the GNR suspension, which induces the balance between electrostatic interactions and entropically driven depletion attraction in the evaporating solution to produce large-area arrays of self-assembled GNR on the substrates. Electron microscopy characterizations revealed the formation of layers of vertically aligned GNR arrays that consisted of hexagonally close-packed GNR in each layer. Benefiting from the close-packed GNR arrays and their smooth topography, the GNR arrays exhibited a surface-enhanced Raman scattering (SERS) signal for molecular detection at a concentration as low as 10-15 M. Because of the uniformity in large area, the GNR arrays exhibited exceptional detecting reproducibility and operability. This method is scalable and cost-effective and could lead to diverse packing structures and functions by variation of guest nanoparticles in the suspensions.

The correlation between growth hormone receptor (GHR) polymorphism and obstructive sleep apnea syndrome among the Han and Hani population in China.

Obstructive sleep apnea syndrome (OSAS) is a common health problem that is associated with abnormality in craniofacial morphology. The growth hormone receptor (GHR) belongs to the cytokine receptor superfamily and mediates the majority of growth hormone signaling, which, among other functions, determines mandibular growth and development. The aim of this study was to determine if correlations exist between single nucleotide polymorphisms (SNPs) in the GHR gene and OSAS in the Han or Hani ethnic groups in China. A total of 274 Han subjects (106 with OSAS and 168 without OSAS) and a total of 270 Hani subjects (64 with OSAS and 206 without OSAS) were enrolled in our study. Genomic DNA was extracted from peripheral blood obtained from all subjects. Genotyping was undertaken for eight SNPs in the GHR gene (rs3756416, rs7727047, rs2910875, rs12153009, rs2972781, rs12518414, rs4410646, and rs6451620) using PCR amplification and Sanger sequencing. The genotype frequency of rs12518414 was associated with OSAS in both the Han and Hani groups, and the A allele frequency was remarkably lower in Hani OSAS patients compared with Hani controls (16.7 vs 29.9%). In addition, the G allele frequency of the rs3756416 SNP was significantly lower in OSAS patients compared with normal controls in the Hani ethnic group (12.5 vs 24.6%). In a comparison between ethnic groups, genotype frequencies of four SNPs (rs2972781, rs6451620, rs12518414, and rs7727047) differed between Han and Hani OSAS patients, with the A allele frequency of the rs12518414 and G allele frequency of the rs7727047 were significantly higher in the Han OSAS patients. In conclusion, significant associations were detected between some SNPs in the GHR gene and OSAS occurrence while others appeared to be ethnicity-dependent.

miR-944 inhibits cell migration and invasion by targeting MACC1 in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common disease in Southern China with high prevalence. miR-944 has been reported to play a vital role in progression of a variety of cancers. The present study aimed to investigate the potential role of miR-944 in NPC cell migration and invasion through elucidating the interaction with its target genes, MACC1. Expression of miR-944 in NPC tissues and cell lines was examined with quantitative RT-PCR. Overexpressed miR-944 and suppressed miR-944 were established with miR-944 mimics and miR-944 inhibitor, respectively. The effect of miR-944 on cell migration and invasion was determined using Transwell cell migration and Matrigel invasion assay. Luciferase assay was used to determine the target of miR-944. Knocked down of MACC1 was done by MACC1 siRNA. Expression of MET related-markers was examined using Western blot analysis. The expression level of miR-944 was downregulated in NPC tissues and cell lines. Overexpression of miR-944 significantly inhibited the cell migration and invasion in NPC 6-10B cells. In contrast, suppression of miR-944 promoted cell migration and invasion in NPC C-6661 cells. MACC1 is a direct target of miR-944. MACC1 expression was repressed in miR-944 mimic transfected cells while it was enhanced in miR-944 inhibitor transfected cells. MACC1 knock down inhibited cell migration and invasion. Either miR-944 restoration or MACC1 knockdown caused enhanced E-cadherin, reduced N-cadherin, and vimentin expression. In conclusion, miR-944 could inhibit MET and metastasis of NPC by targeting MACC1. This study suggests that miR-944 has anti-tumor and anti- metastatic properties and could thus be a novel therapeutic agent for NPC treatment.

Preoperative lymphocyte-to-monocyte ratio predicts survival in primary hepatitis B virus-positive hepatocellular carcinoma after curative resection.

BACKGROUND: Both inflammation and immunity are associated with the development of malignancy. The lymphocyte-to-monocyte ratio (LMR) has been confirmed as a prognostic factor for several malignant diseases. The purpose of our study was to analyze prognostic significance of preoperative LMR in hepatitis B virus (HBV)-related hepatocellular carcinoma after curative resection. PATIENTS AND METHODS: A total of 253 patients with primary HBV-positive hepatocellular carcinoma who underwent a curative operation were enrolled in this retrospective study. The relationship between preoperative LMR and survival outcomes was analyzed through Kaplan-Meier curves and multivariate Cox regression analyses. RESULTS: Patients with a high LMR had a significantly higher mean overall survival than those with a low LMR (67 months vs 55 months, P=0.023), and high LMR remained significant for longer survival in the multivariate analysis (hazard ratio, 0.147; 95% confidence interval [CI]: 0.085-0.253; P=0.021). Furthermore, patients with a high LMR also had a higher median recurrence-free survival than those with a low LMR in univariate analyses (60 months vs 48 months, P=0.026) and multivariate analyses (hazard ratio, 0.317; 95% CI: 0.042-1.023; P=0.032). However, the survival benefit was limited to patients with advanced cancer. CONCLUSION: LMR was confirmed as an independent prognostic biomarker for primary HBV-positive hepatocellular carcinoma after curative resection.

Prognostic value of preoperative lymphocyte-to-monocyte ratio in pancreatic adenocarcinoma.

BACKGROUND: Inflammation and immunity have an important role in the development of cancer. The lymphocyte-to-monocyte ratio (LMR) has been shown to be of prognostic value in several malignant forms. The purpose of this study was to analyze the prognostic significance of preoperative LMR in post-curative resection of pancreatic adenocarcinoma. METHODS: A total of 144 patients with primary pancreatic adenocarcinoma who underwent curative operation were enrolled in this retrospective study. The correlation between preoperative LMR and survival was analyzed using Kaplan-Meier curves and multivariate Cox regression analyses. RESULTS: In the univariate analysis, an elevated preoperative LMR was significantly associated with an increased overall survival (OS) (19 months vs 12 months, P=0.000), and this result remained significant in the multivariate analysis (hazard ratio [HR]: 0.148; 95% confidence interval [CI]: 0.085-0.252; P=0.000). Furthermore, patients with high LMR also had higher median recurrence-free survival (RFS) than patients with low LMR in univariate (18 months vs 10 months, P=0.000) and multivariate analyses (HR: 0.148; 95% CI: 0.085-0.252; P=0.000). Subgroup analyses showed that both patients with stage III cancer and patients with stage I+II cancer can obtain OS and RFS benefits from high LMR. CONCLUSION: LMR can be considered as an independent prognostic biomarker for operable pancreatic adenocarcinoma.

Epigenetic silencing of miR-181b contributes to tumorigenicity in colorectal cancer by targeting RASSF1A.

Aberrant microRNA expression is common in colorectal cancer and DNA methylation is believed to be responsible for this alteration. In this study, we performed evaluation in vivo and in vitro to determine the role of miR-181b as a potential diagnostic and prognostic biomarker in colorectal cancer. Ninety-seven pairs of colorectal cancer tissues and adjacent normal tissues were collected. The expression level and methylation status of miR-181b was determined in tissue samples and multiple colorectal cancer cell lines. RASSF1A, a predicted target gene of miR-181b, was investigated in vitro. Further mechanistic explorations were conducted. It was found that miR-181b expression was frequently downregulated in cancer samples. This lower expression level resulted from higher hypermethylation in cancer tissue and was closely related to TNM stage. Following artificial synthesis of miR-181b stimulation, colorectal cancer cell proliferation was greatly inhibited in CRC cells while apoptosis percentage markedly increased. miR-181b achieved the tumor suppressive effects via direct targeting of the RASSF1A gene. This study indicated the clinical significance of miR-181b and the influence of miR-181b promoter region in epigenetic silencing of tumorigenicity in colorectal cancer, and implied the possible usage of miR-181b as a diagnostic and prognostic biomarker in colorectal cancer.

[Preparation and properties of chitosan film as a drug sustained-release system].

OBJECTIVE: To develop a best chitosan film for using as a drug sustained-release system through the evaluation of the sustained-release property, degradation property, and cytotoxicity to osteoblast. METHODS: Orthogonal experiments were designed to determine the best combination of chitosan film preparations. Drug release rate was determined with Coomassie brilliant blue G250. In a separate study, chitosan films were placed into the test tubes with buffer solution and 10(7) U/L lysozyme. The degradation rate was calculated. Osteoblasts derived from fetal rat calvarial were cultured on chitosan films. Cell proliferation was tested by methyl thiazolyl tetrazolium (MTT) assay. The relative growth rate was calculated and the cytotoxicity was graded. RESULTS: The best processing condition was 1% acetic acid, chitosan concentration of 2 mg/mL, 6% sodium tripolyphosphate (STPP) concentration, and cross-linking time of one hour. The resulting chitosan film released 33.13% of bovine serum albumin (BSA) within 8 d, 36.73% of BSA within four weeks and the cytotoxicity grade was 0 or 1. CONCLUSION: This chitosan film possesses good sustained release property, and a good degradation rate.