Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway.

Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.

Early diagnosis of spinal tuberculosis by magnetic resonance: perfusion weighted imaging in a rabbit model.

BACKGROUND: This study aimed to analyze the application value of magnetic resonance (MR)-perfusion weighted imaging (PWI) in the early imaging diagnosis of rabbit spinal tuberculosis. METHODS: Spinal tuberculosis model was established using ATCC25177 Mycobacterium tuberculosis strain in the lumbar spine of rabbits. Forty rabbits were divided into 2 groups: rabbits in the experiment group were injected with 0.2 ml of 5.0 mg/ml tuberculosis suspension (n = 30) and those in the control group were injected with 0.2 ml of normal saline (n = 10) after vertebrae drilling surgery. Routine MRI and MR-PWI were performed at 4, 6, and 8 weeks after surgery. The statistical difference in terms of perfusion parameter values in the early MR-PWI scan of spinal tuberculosis between two groups was analyzed. The receiver operating characteristic (ROC) curve analysis was conducted for the accuracy of MR-PWI parameters in the early diagnosis of spinal tuberculosis. RESULTS: Except time to peak, the other perfusion parameters in the experiment group were all increased with time. In addition, the difference between the two groups, as well as the differences at each time point was statistically significant (all P < 0.05). First-pass enhancement rate (Efirst), early enhancement rate (Ee), peak height (PH), maximum slope of increase (MSI), maximum signal enhancement rate (Emax) and signal enhancement rate (SER) showed high values in early diagnosing spinal tuberculosis. CONCLUSION: The parameters including Efirst, Ee, PH, MSI, Emax and SER may provide valuable imaging evidence for the early diagnosis of spinal tuberculosis in clinical application.

Machine Learning for Evaluating the Cytotoxicity of Mixtures of Nano-TiO2 and Heavy Metals: QSAR Model Apply Random Forest Algorithm after Clustering Analysis.

With the development and application of nanomaterials, their impact on the environment and organisms has attracted attention. As a common nanomaterial, nano-titanium dioxide (nano-TiO2) has adsorption properties to heavy metals in the environment. Quantitative structure-activity relationship (QSAR) is often used to predict the cytotoxicity of a single substance. However, there is little research on the toxicity of interaction between nanomaterials and other substances. In this study, we exposed human renal cortex proximal tubule epithelial (HK-2) cells to mixtures of eight heavy metals with nano-TiO2, measured absorbance values by CCK-8, and calculated cell viability. PLS and two ensemble learning algorithms are used to build multiple QSAR models for data sets, and the test set R2 is increased from 0.38 to 0.78 and 0.85, and RMSE is decreased from 0.18 to 0.12 and 0.10. After selecting the better random forest algorithm, the K-means clustering algorithm is used to continue to optimize the model, increasing the test set R2 to 0.95 and decreasing the RMSE to 0.08 and 0.06. As a reliable machine algorithm, random forest can be used to predict the toxicity of the mixture of nano-metal oxides and heavy metals. The cluster analysis can effectively improve the stability and predictability of the model, and provide a new idea for the prediction of cytotoxicity model in the future.

Benefits of a transtheoretical model-based program on exercise adherence in older adults with knee osteoarthritis: A cluster randomized controlled trial.

AIMS: Benefits of a transtheoretical model-based exercise program on exercise adherence (primary outcome) and secondary outcomes (self-efficacy, decisional balance, knee osteoarthritis symptoms, and physical function) were assessed among older adults with knee osteoarthritis. DESIGN: A two-arm, superiority, assessor-blinded, cluster randomized trial with randomization at the community level. METHODS: Participants were recruited from 14 communities in Beijing between April - October 2018 (N = 189). The intervention was a 24-week transtheoretical model-based exercise program and the control group underwent a non-theory-based exercise program. Exercise adherence was collected every 4 weeks and secondary outcomes were measured at baseline, 12 weeks, and 24 weeks. An independent t test and repeated-measures ANOVA were the main statistical tests. RESULTS: Most participants were women (92.5%), married (81.4%), with high-school education (36.0%), with both knees affected (50.3%), and did not make use of a walker (93.8%). There were no significant differences between groups in any of the outcome measures at baseline. Repeated-measures ANOVA indicated that there was a significant difference in the trend of adherence scores between the two groups from 0-24 weeks. The independent t test showed that scores in the intervention group were significantly better than in the control group at 16, 20, and 24 weeks. Improvements in the intervention group were also significantly greater in all secondary outcomes than in the control group. CONCLUSION: A theory-based exercise program could improve exercise adherence, self-efficacy, decisional balance, knee osteoarthritis symptoms, and physical functioning in older adults with knee osteoarthritis. TRIAL REGISTRATION: Chinese Clinical Trials Registry number ChiCTR1800015458. Registered 31 March 2018. IMPACT: The 24-week theory-based exercise program could improve exercise adherence, self-efficacy, decisional balance, symptoms of knee osteoarthritis, and physical functioning in older adults with knee osteoarthritis. The theory-based exercise program could help older adults with knee osteoarthritis to improve their symptoms and knee function.

A comparison of the molecular subtypes of triple-negative breast cancer among non-Asian and Taiwanese women.

BACKGROUND: "Precision medicine" is a concept that by utilizing modern molecular diagnostics, an effective therapy is accurately applied for each cancer patient to improve their survival rates. The treatment of triple-negative breast cancer (TNBC) remains a challenging issue. The aim of this study was to compare the molecular subtypes of triple-negative breast cancer (TNBC) between Taiwanese and Non-Asian women. METHODS: GEO Datasets for non-Asian (12 groups, n = 1450) and Taiwanese (3 groups, n = 465) breast cancer, including 617 TNBC, were acquired, normalized and cluster analyzed. Then, using TNBC cell lines of different subtypes, namely, MDA-MB-468 (basal-like1, BL1), MDA-MB-231 (mesenchymal stem like, MSL), BT-549 (mesenchymal, M), MDA-MB-453 (luminal androgen receptor, LAR), and DU4475 (immunomodulatory, IM), real-time PCR in triplicate for 47 genes signatures were performed to validate the specificity of these subtypes. RESULTS: The results showed that the percentage of TNBC subtypes in non-Asian women, namely, BL1, BL2, IM, M, MSL, and LAR was 13.56, 8.91, 16.80, 20.45, 8.30, and 11.13%, respectively. When data from Taiwanese were normalized and clustered, five TNBC subtypes, namely, BL (8.94%), IM (13.82%), M (22.76%), MSL (30.89%), and LAR (23.58%), were classified. Real-time PCR validated the specificity of these subtypes. Besides, the presence of interaction between IM- and MSL-subtypes suggests the involvement of tumor microenvironment in TNBC subtype classification. CONCLUSION: Our data suggested that there exist different presentations between non-Asian and Taiwanese TNBC subtypes, which provides important information when selection of therapeutic targets or designs for clinical trials for TNBC patients.

Identification, Expression, and Functional Analysis of the Fructokinase Gene Family in Cassava.

Fructokinase (FRK) proteins play important roles in catalyzing fructose phosphorylation and participate in the carbohydrate metabolism of storage organs in plants. To investigate the roles of FRKs in cassava tuber root development, seven FRK genes (MeFRK1-7) were identified, and MeFRK1-6 were isolated. Phylogenetic analysis revealed that the MeFRK family genes can be divided into α (MeFRK1, 2, 6, 7) and ß (MeFRK3, 4, 5) groups. All the MeFRK proteins have typical conserved regions and substrate binding residues similar to those of the FRKs. The overall predicted three-dimensional structures of MeFRK1-6 were similar, folding into a catalytic domain and a ß-sheet ''lid" region, forming a substrate binding cleft, which contains many residues involved in the binding to fructose. The gene and the predicted three-dimensional structures of MeFRK3 and MeFRK4 were the most similar. MeFRK1-6 displayed different expression patterns across different tissues, including leaves, stems, tuber roots, flowers, and fruits. In tuber roots, the expressions of MeFRK3 and MeFRK4 were much higher compared to those of the other genes. Notably, the expression of MeFRK3 and MeFRK4 as well as the enzymatic activity of FRK were higher at the initial and early expanding tuber stages and were lower at the later expanding and mature tuber stages. The FRK activity of MeFRK3 and MeFRK4 was identified by the functional complementation of triple mutant yeast cells that were unable to phosphorylate either glucose or fructose. The gene expression and enzymatic activity of MeFRK3 and MeFRK4 suggest that they might be the main enzymes in fructose phosphorylation for regulating the formation of tuber roots and starch accumulation at the tuber root initial and expanding stages.

Structure, Expression, and Functional Analysis of the Hexokinase Gene Family in Cassava.

Hexokinase (HXK) proteins play important roles in catalyzing hexose phosphorylation and sugar sensing and signaling. To investigate the roles of HXKs in cassava tuber root development, seven HXK genes (MeHXK1-7) were isolated and analyzed. A phylogenetic analysis revealed that the MeHXK family can be divided into five subfamilies of plant HXKs. MeHXKs were clearly divided into type A (MeHXK1) and type B (MeHXK2-7) based on their N-terminal sequences. MeHXK1-5 all had typical conserved regions and similar protein structures to the HXKs of other plants; while MeHXK6-7 lacked some of the conserved regions. An expression analysis of the MeHXK genes in cassava organs or tissues demonstrated that MeHXK2 is the dominant HXK in all the examined tissues (leaves, stems, fruits, tuber phloems, and tuber xylems). Notably, the expression of MeHXK2 and the enzymatic activity of HXK were higher at the initial and expanding tuber stages, and lower at the mature tuber stage. Furthermore, the HXK activity of MeHXK2 was identified by functional complementation of the HXK-deficient yeast strain YSH7.4-3C (hxk1, hxk2, glk1). The gene expression and enzymatic activity of MeHXK2 suggest that it might be the main enzyme for hexose phosphorylation during cassava tuber root development, which is involved in sucrose metabolism to regulate the accumulation of starch.

Modeling study for predicting altered cellular activity induced by nanomaterials based on Dlk1-Dio3 gene expression and structural relationships.

Nanomaterials have been widely applied and developed due to its unique physicochemical characteristics, such as their small size. The environmental and biological effects caused by nanomaterials have raised concerns. In particular, some nanometal oxides have obvious biological toxicity and pose a major safety problem. The prediction model established by combining the expression levels of key genes with quantitative structure-activity relationship (QSAR) studies can predict the biotoxicity of nanomaterials by relying on both structural information and gene regulation information. This model can fill the gap of missing mechanisms in QSAR studies. In this study, we exposed A549 cells and BEAS-2B cells to 21 nanometal oxides for 24 h. Cell viability was assessed by measuring absorbance values using the CCK8 assay, and the expression levels of the Dlk1-Dio3 gene cluster were measured. By using the theoretical basis of the nano-QSAR model and the improved principles of the SMILES-based descriptors to combine specific gene expression and structural factors, new models were constructed using Monte Carlo partial least squares (MC-PLS) for the biotoxicity of the nanometal oxides on two different lung cells. The overall quality of the nano-QSAR models constructed by combining specific gene expression and structural parameters for A549 and BEAS-2B cells was better than that of the models constructed based on structural parameters only. The coefficient of determination (R2) of the A549 cell model increased from 0.9044 to 0.9969, and the Root Mean Square Error (RMSE) decreased from 0.1922 to 0.0348. The R2 of the BEAS-2B cell model increased from 0.9355 to 0.9705, and the RMSE decreased from 0.1206 to 0.0874. The model validation proved the proposed models have a good prediction, generalization ability and model stability. This study offers a new research perspective for the toxicity assessment of nanometal oxides, contributing to a more systematic safety evaluation of nanomaterials.

Specific Pandemic-Related Worries Predict Higher Attention-Related Errors and Negative Affect Independent of Trait Anxiety in UK-Based Students.

Background: The COVID-19 pandemic has resulted in many individuals experiencing increased symptoms of anxiety. We predict that this increase may be underpinned by pandemic-related worry (PRW), characterised by repetitive negative thinking about pandemic-specific outcomes; and that this relationship is mediated through reduced attentional capacity required to regulate negative affect. Methods: We developed a novel scale to measure the contents of PRW in an initial sample of 255 participants, and explored its relationship with cognitive functioning and negative affect in a sample of 382 UK-based university students, whilst controlling for recalled pre-pandemic trait anxiety. Results: A five-factor model of PRW was identified, with factors reflecting worry about decline in quality of life (QoL) and probability of infection correlating with attention and memory-related errors. Importantly, attention-related errors partially mediated the positive relationship between PRW and negative affect, even when controlling for pre-pandemic trait anxiety. Conclusion: PRW's relationship with negative affect was partially mediated through attentional function, consistent with models of anxiety and attentional control. In UK-based students PRW may be predominantly focused on the decline in QoL; therefore, interventions targeting worry about the decline in QoL caused by COVID-19 are especially important in this population in the wake of the pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s10608-022-10336-7.

Intermittent androgen blockade or continuous androgen blockade in advanced prostate cancer: a meta-analysis of efficacy, quality of life and side effects.

PURPOSE: To compare the efficacy, quality of life (QoL) and side effects of intermittent androgen blockade (IAB) vs. continuous androgen blockade (CAB) as treatment of advanced prostate cancer (PCA). METHODS: Using the search terms "advanced prostate cancer", "prostate cancer", "intermittent androgen blockade", "continuous androgen blockade", "randomized controlled trial" (RCT), the literature in Chinese and English language was searched in several databases to see for any difference between IAB and CAB concerning the effectiveness, QoL and side effects. Then, the studies to be included were identified according to previously established inclusion criteria, and those selected were assessed by methodological quality. Finally, the data of the studies included were extracted using self-tabulate tables, and the criteria of RCTs were studied. At the same time, odds ratio (OR) and weighted mean difference (WMD) of random effects model and fixed effects model were calculated to evaluate sensitivity. RESULTS: There were 16 RCTs that compared IAB with CAB with a total of 3264 patients (1624 with IAB and 1640 with CAB). Pooled effects indicated no significant difference between IAB and CAB groups in terms of death and progression rate (OR=0.99, 95% CI 0.80-1.23, and OR=1.03, 95% CI 0.84-1.26 respectively). Calculated results indicated that QoL on sexual activity was significantly higher in the IAB group (OR=0.24, 95% Cl 0.17-0.33, p<0.00001). Moreover, IAB could effectively reduce side effects. CONCLUSION: The therapeutic efficacy (progression and death rate) was not significantly different between the IAB and CAB groups. However, IAB can effectively preserve the QoL (sexual life) and reduce the side effects. With analysis of more RCTs with strict design stronger evidence of the superiority of IAB could be proven.

Factorial validity, reliability, and measurement invariance of the Negative Physical Self Scale in a sample of men residing in North America.

The Negative Physical Self Scale (NPSS) is a measure of body dissatisfaction that was developed for administration within an Asian sample and has recently been translated to English and validated for use in North American female samples. The aim of the present study was to examine the factor structure and measurement invariance of the English-translated version of the NPSS across three ethnic groups (i.e., Caucasian, Asian, and other) using a sample of men residing in North America. Additionally, the internal consistency, convergent validity, and incremental validity of the NPSS were examined. A sample of 534 young (aged between 18 and 25) North American men completed self-report measures of the NPSS, the Body Shape Questionnaire, the Eating Disorder Examination Questionnaire, and the Male Body Attitudes Scale. Confirmatory factor analysis was conducted on two hypothesized models. The results supported the second-order factor structure (four factors with three subdimensions). Overall, we found that the factor structure and factor loadings of the NPSS were equal in participants across three broad ethnic categories (i.e., Caucasian, Asian, and other). Likewise, the NPSS displayed first-order scalar invariance. Further, the NPSS test scores demonstrated high internal consistency, strong convergent validity, and incremental validity over and above the existing measures of body dissatisfaction, body attitudes, and disordered eating. In sum, the English version of the NPSS is a valid and appropriate measure to assess body dissatisfaction in men residing in North America. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

MeNINV1: An Alkaline/Neutral Invertase Gene of Manihot esculenta, Enhanced Sucrose Catabolism and Promoted Plant Vegetative Growth in Transgenic Arabidopsis.

Alkaline/neutral invertase (A/N-INV) is an invertase that irreversibly decomposes sucrose into fructose as well as glucose and plays a role in plant growth and development, starch synthesis, abiotic stress, and other plant-life activities. Cassava is an economically important starch crop in tropical regions. During the development of cassava tuber roots, A/N-INV activity is relatively high, which indicates that it may participate in sucrose metabolism and starch synthesis. In this study, MeNINV1 was confirmed to function as invertase to catalyze sucrose decomposition in yeast. The optimal enzymatic properties of MeNINV1 were a pH of 6.5, a reaction temperature of 40 °C, and sucrose as its specific catalytic substrate. VB6, Zn2+, and Pb2+ at low concentrations as well as EDTA, DTT, Tris, Mg2+, and fructose inhibited A/N-INV enzymic activity. In cassava, the MeNINV1 gene was mainly expressed in the fibrous roots and the tuber root phloem, and its expression decreased as the tuber root grew. MeNINV1 was confirmed to localize in chloroplasts. In Arabidopsis, MeNINV1-overexpressing Arabidopsis had higher A/N-INV activity, and the increased glucose, fructose, and starch content in the leaves promoted plant growth and delayed flowering time but did not change its resistance to abiotic stress. Our results provide new insights into the biological function of MeNINV1.

Mechanism and modeling of human disease-associated near-exon intronic variants that perturb RNA splicing.

It is estimated that 10%-30% of disease-associated genetic variants affect splicing. Splicing variants may generate deleteriously altered gene product and are potential therapeutic targets. However, systematic diagnosis or prediction of splicing variants is yet to be established, especially for the near-exon intronic splice region. The major challenge lies in the redundant and ill-defined branch sites and other splicing motifs therein. Here, we carried out unbiased massively parallel splicing assays on 5,307 disease-associated variants that overlapped with branch sites and collected 5,884 variants across the 5' splice region. We found that strong splice sites and exonic features preserve splicing from intronic sequence variation. Whereas the splice-altering mechanism of the 3' intronic variants is complex, that of the 5' is mainly splice-site destruction. Statistical learning combined with these molecular features allows precise prediction of altered splicing from an intronic variant. This statistical model provides the identity and ranking of biological features that determine splicing, which serves as transferable knowledge and out-performs the benchmarking predictive tool. Moreover, we demonstrated that intronic splicing variants may associate with disease risks in the human population. Our study elucidates the mechanism of splicing response of intronic variants, which classify disease-associated splicing variants for the promise of precision medicine.

RNA-Seq Profiling of Circular RNAs and the Oncogenic Role of circPVT1 in Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is associated with a poor 5-year survival rate. circRNAs have an important role in a number of physiological and pathological processes. However, the relationship between circRNAs and cutaneous squamous cell carcinoma (CSCC) is unclear. PURPOSE: The aim of the present study was to investigate the expression of circRNAs in cutaneous squamous cell carcinoma (CSCC) and its effect on CSCC proliferation and metastasis. METHODS: We used high-throughput sequencing (RNA-seq) to identify circRNAs that were differentially in CSCC tissue and their paracarcinoma tissue. Quantitative real-time PCR results confirm deep-sequencing findings in CSCC tissue and cell lines. CCK-8 assay and flow cytometry were used to detect the effect of circPVT1 on the proliferation and migration of CSCC cells. RESULTS: We identified 449 circRNAs that were differentially expressed between CSCC and normal adjacent tissue samples. circPVT1 (hsa_circ_0001821) was further researched to confirm its oncogene role in CSCC. CONCLUSION: Differentially expressed circular RNA plays an important role in the development of CSCC, and circPVT1 may be an important target for the treatment of CSCC.

The effect of transtheoretical model-lead intervention for knee osteoarthritis in older adults: a cluster randomized trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common joint disease in people over 60 years old. Exercise therapy is one of the most effective non-pharmacological treatments for KOA, but low exercise adherence needs to be improved. The present study aimed to evaluate the effect of the transtheoretical model-lead home exercise intervention (TTM-HEI) program on exercise adherence, KOA symptoms, and knee function in older adults with KOA. METHODS: A two-arm, superiority, assessor-blinded, cluster randomized trial was conducted. Community-dwelling older adults with KOA were recruited from 14 community centers in Beijing, China, via print and social media advertisements from April to October 2018. The present study lasted 48 weeks, with an intervention duration of 0-24 weeks and follow-up time of 24-48 weeks. The intervention was a two-stage and 24-week TTM-based exercise program, and the control group underwent a same-length exercise program guidance without any exercise adherence interventions. The primary outcome was exercise adherence to the prescribed home exercise program and was measured using an 11-point numerical (0 = not at all through and 10 = completely as instructed) self-rating scale at weeks 4, 12, 24, 36, and 48 after the program started. KOA symptoms (pain intensity and joint stiffness) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and knee function (lower limb muscle strength and balance) was measured using the Five-Times-Sit-to-Stand Test (FTSST) and the Timed Up and Go Test (TUG) at baseline, week 24, and week 48. Latent growth model (GLM), repeated measures ANOVA, and independent t test were the main statistical tests used. RESULTS: A total of 189 older adults (intervention group: n = 103, control group: n = 86) were enrolled. Differences of any outcome measures at baseline were not significant between groups. The growth rate of exercise adherence in the intervention group increased 2.175 units compared with that in the control group (unstandardized coefficient of slope on group B2 = 2.175, p < 0.001), and the intervention program maintained participants' exercise adherence with 5.56 (SD = 1.00) compared with 3.16 (SD = 1.31) in the control group at week 48. In addition, the TTM-HEI program showed significant effects on relieving KOA symptoms and improving knee function. CONCLUSION: Over time, TTM-HEI could improve participants' exercise adherence, KOA symptoms, and knee function. TRIAL REGISTRATION: This study was approved by the ethics committee (IRB00001052-17066) in July 2017 and was registered at the Chinese Clinical Trial Registry (website: www.chictr.org.cn, registry number: ChiCTR1800015458).

Identification of a five-miRNA signature predicting survival in cutaneous melanoma cancer patients.

BACKGROUND: Cutaneous melanoma (CM) is the deadliest form of skin cancer. Numerous studies have revealed that microRNAs (miRNAs) are expressed abnormally in melanoma tissues. Our work aimed to assess multiple miRNAs using bioinformatic analysis in order to predict the prognoses of cutaneous melanoma patients. METHODS: The microarray dataset GSE35579 was downloaded from the Gene Expression Omnibus (GEO) database to detect the differential expression of miRNAs (DEMs), including 41 melanoma (primary and metastatic) tissues and 11 benign nevi. Clinical information and miRNA sequencing data of cutaneous melanoma tissues were downloaded from the Cancer Genome Atlas database (TCGA) to assess the prognostic values of DEMs. Additionally, the target genes of DEMs were anticipated using miRanda, miRmap, TargetScan, and PicTar. Finally, functional analysis was performed using selected target genes on the Annotation, Visualization and Integrated Discovery (DAVID) website. RESULTS: After performing bioinformatic analysis, a total of 185 DEMs were identified: 80 upregulated miRNAs and 105 downregulated miRNAs. A five-miRNA (miR-25, miR-204, miR-211, miR-510, miR-513c) signature was discovered to be a potential significant prognostic biomarker of cutaneous melanoma when using the Kaplan-Meier survival method (P = 0.001). Univariate and multivariate Cox regression analyses showed that the five-miRNA signature could be an independent prognostic marker (HR = 0.605, P = 0.006) in cutaneous melanoma patients. Biological pathway analysis indicated that the target genes may be involved in PI3K-Akt pathways, ubiquitin-mediated proteolysis, and focal adhesion. CONCLUSION: The identified five-miRNA signature may serve as a prognostic biomarker, or as a potential therapeutic target, in cutaneous melanoma patients.

Trichostatin A­induced miR­30a­5p regulates apoptosis and proliferation of keloid fibroblasts via targeting BCL2.

Keloids are benign fibrous overgrowths that occur as a result of abnormal wound healing following cutaneous injury. MicroRNAs (miRNAs/miRs) are short non­coding RNAs that serve critical roles in numerous important biological processes, such as cell proliferation, differentiation and apoptosis. However, their role in keloid development remains largely unknown. In the present study, the role of miR­30a­5p, a miRNA regulated by Trichostatin A (TSA), in apoptosis within cultured keloid fibroblasts was investigated. An MTT assay was used to detect the proliferation of cultured keloid fibroblasts treated with TSA. Cell apoptosis and cell cycle phases were analyzed using flow cytometry. In addition, an miRNA microarray was performed to compare expression profiles between cultured keloid fibroblasts treated with or without 1,000 nM TSA. Reverse transcription­quantitative polymerase chain reaction analysis was conducted to estimate miRNA expression levels. The direct target of miR­30a­5p was identified using a dual­luciferase reporter assay. Western blotting was employed to assess protein expression levels in keloid fibroblasts. The results demonstrated that TSA inhibited the proliferation of keloid fibroblasts in a time­ and dose­dependent manner. The miRNA microarray revealed alterations in the expression of numerous miRNA sequences in response to TSA when compared with controls. Notably, the expression of miR­30a­5p was downregulated in keloid tissues. In addition, overexpression of miR­30a­5p induced apoptosis by targeting B­cell lymphoma 2, which was similar to that observed in response to TSA. These results provide important information regarding a novel miR­30a­5p­mediated signaling pathway induced by TSA treatment, and suggest a potential use for TSA and miR­30a­5p as effective therapeutic strategies for keloids.

Analysis of Risk Factors in Patients With Peripheral Vertigo or Central Vertigo.

INTRODUCTION: This study was aimed to determine risk factors for central vertigo (CV) in patients with isolated vertigo accompanied by hearing loss or not. PATIENTS AND METHODS: Patients with CV or peripheral vertigo (PV) who were admitted to our hospital between January 2014 and July 2016 were retrospectively reviewed. All patients underwent thorough physical examination with detailed medical histories recorded, including smoking, hypertension, diabetes, cardiovascular disease, and stroke history. Logistic regression estimated odds ratio (OR) of the risk factors. RESULTS: Eighty-seven patients were enrolled into the study, including 41 cases of CV and 46 cases of PV. There was significant difference in sex, age above 60, hypertension, diabetes, smoking, and stroke history between the 2 groups. The patients without any risk factors did not have CV. The risk for CV in the patients with ≥3 risk factors was greater (OR, 11.43; 95% confidence interval, 3.27-39.93; P<0.001) than the patients with 1 risk factor. The risk for CV in the patients with 2 risk factors was similar (OR, 0.833; 95% confidence interval, 0.17-4.28; P=0.825) to the patients with 1 risk factor. CONCLUSION: The patients with isolated vertigo (accompanied by hearing loss or not) and 3 or more risk factors are at higher risk for CV. They should have a comprehensive neurological examination and be closely followed up.

Lack of coordination between partners: investigation of Physician-Preferred and Patient-Preferred (4P) basal insulin titration algorithms in the real world.

BACKGROUND: Patient-centered care is respectful to a patient's preference. All prior clinical trials on patient self-titration algorithms for basal insulin were decided by physicians. We hypothesized that patients and physicians have different preferences. PATIENTS AND METHODS: Physicians and diabetes patients were asked to choose their preferred insulin glargine self-titration algorithm among 5 algorithms. Algorithm 1, 1 U increase once daily; algorithm 2, 2 U increase every 3 days; algorithm 3, 3 U increase every 3 days; algorithm 4, titration every 3 days according to fasting blood glucose, and algorithm 5, weekly titration 2-8 U based on 3-day mean fasting blood glucose levels. RESULTS: Eleven (5.2%) out of 210 physicians and 180 (90.9%) out of 198 patients preferred algorithm 1 (χ2=300.4, p=0.000). In contrast, 195 (92.9%) physicians and 18 (9.1%) patients preferred algorithm 2 (χ2=286.6, p=0.000). In addition, 4 (1.9%) physicians but no patients preferred algorithm 3 (χ2=2.099, p=0.124). Neither physicians nor patients chose algorithms 4 or 5. Most physicians preferred algorithm 2 since it is recommended by guidelines, but most patients preferred algorithm 1 for its simplicity. CONCLUSION: Patients had different preferences compared with physicians. Attention should be given to patients' preferences to increase adherence and improve glycemic control.

Isolation and Characterization of Ftsz Genes in Cassava.

The filamenting temperature-sensitive Z proteins (FtsZs) play an important role in plastid division. In this study, three FtsZ genes were isolated from the cassava genome, and named MeFtsZ1, MeFtsZ2-1, and MeFtsZ2-2, respectively. Based on phylogeny, the MeFtsZs were classified into two groups (FtsZ1 and FtsZ2). MeFtsZ1 with a putative signal peptide at N-terminal, has six exons, and is classed to FtsZ1 clade. MeFtsZ2-1 and MeFtsZ2-2 without a putative signal peptide, have seven exons, and are classed to FtsZ2 clade. Subcellular localization found that all the three MeFtsZs could locate in chloroplasts and form a ring in chloroplastids. Structure analysis found that all MeFtsZ proteins contain a conserved guanosine triphosphatase (GTPase) domain in favor of generate contractile force for cassava plastid division. The expression profiles of MeFtsZ genes by quantitative reverse transcription-PCR (qRT-PCR) analysis in photosynthetic and non-photosynthetic tissues found that all of the MeFtsZ genes had higher expression levels in photosynthetic tissues, especially in younger leaves, and lower expression levels in the non-photosynthetic tissues. During cassava storage root development, the expressions of MeFtsZ2-1 and MeFtsZ2-2 were comparatively higher than MeFtsZ1. The transformed Arabidopsis of MeFtsZ2-1 and MeFtsZ2-2 contained abnormally shape, fewer number, and larger volume chloroplasts. Phytohormones were involved in regulating the expressions of MeFtsZ genes. Therefore, we deduced that all of the MeFtsZs play an important role in chloroplast division, and that MeFtsZ2 (2-1, 2-2) might be involved in amyloplast division and regulated by phytohormones during cassava storage root development.