Targeting DNA methylation and demethylation in diabetic foot ulcers.

BACKGROUND: Poor wound healing is a significant complication of diabetes, which is commonly caused by neuropathy, trauma, deformities, plantar hypertension and peripheral arterial disease. Diabetic foot ulcers (DFU) are difficult to heal, which makes patients susceptible to infections and can ultimately conduce to limb amputation or even death in severe cases. An increasing number of studies have found that epigenetic alterations are strongly associated with poor wound healing in diabetes. AIM OF REVIEW: This work provides significant insights into the development of therapeutics for improving chronic diabetic wound healing, particularly by targeting and regulating DNA methylation and demethylation in DFU. Key scientific concepts of review: DNA methylation and demethylation play an important part in diabetic wound healing, via regulating corresponding signaling pathways in different breeds of cells, including macrophages, vascular endothelial cells and keratinocytes. In this review, we describe the four main phases of wound healing and their abnormality in diabetic patients. Furthermore, we provided an in-depth summary and discussion on how DNA methylation and demethylation regulate diabetic wound healing in different types of cells; and gave a brief summary on recent advances in applying cellular reprogramming techniques for improving diabetic wound healing.

Effects of ethephon on heartwood formation and related physiological indices of Dalbergia odorifera T. Chen.

Introduction: Dalbergia odorifera T. Chen, known as fragrant rosewood, is a rare and endangered tree species. Studies have shown that plant growth regulators can effectively promote heartwood formation. This study aimed to investigate the effects of ethephon (ETH) on heartwood formation and the influence of ethephon and hydrogen peroxide (H2O2) on the physiological characteristics in D. odorifera. Methods: D. odorifera branches underwent treatment with 2.5% plant growth regulators, including ETH, jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), H2O2, and inhibitors such as ascorbic acid (AsA) to inhibit H2O2 synthesis, and (S) -trans 2-amino-4 - (2-aminoethoxy) -3-butene (AVG) to inhibit ethylene synthesis. After a 14-day period, we conducted an analysis to evaluate the impact of these plant growth regulators on elongation distance, vessel occlusion percentage, and trans-nerol content. Additionally, the effects of ETH and H2O2 on endogenous plant hormones, H2O2 content, soluble protein content, and enzyme activity were investigated within 0-48 h of treatment. Results: After treatment with ETH for 14 days, the extension distance of the heartwood material was 15 cm, while the trans-nerolol content was 15 times that of the ABA group. ETH and H2O2 promoted endogenous ethylene synthesis; Ethylene content peaked at 6 and 18 h. The peak ethylene content in the ETH group was 68.07%, 12.89%, and 20.87% higher than the initial value of the H2O2 group and ddH2O group, respectively, and 29.64% higher than that in the AVG group. The soluble protein content and activity of related enzymes were significantly increased following ETH treatment. Discussion: ETH exhibited the most impact on heartwood formation while not hindering tree growth. This treatment effectively triggered the production of endogenous ethylene in plants and enhanced the activity of essential enzymes involved in heartwood formation. These findings serve as a valuable reference for future investigations into heartwood formation.

[Effect of heat-reinforcing needling on expression of P2X7R, NLRP3 and Caspase-1 in synovial tissues of knee joint in rabbits with cold syndrome rheumatoid arthritis].

OBJECTIVE: To observe the effects of heat-reinforcing needling on the expression of purinergic ligand-gated ion channel 7 receptor(P2X7R)，Nodlike receptor protein 3(NLRP3) and Caspase-1 in synovium tissues of knee joint of rabbits with cold syndrome rheumatoid arthritis(RA)，so as to explore the anti-inflammatory mechanism of heat reinforcing needling in the treatment of RA. METHODS: Thirty male New Zealand white rabbits were randomly divided into normal group, model group, reinforcing-reducing needling group(RRG), heat-reinforcing needling group(HRG), and antagonist group(AG), with 6 rabbits in each group.The model of cold syndrome RA was established by ovalbumin combined with Freund's adjuvant and cryogenic freezing. Rabbits of RRG and HRG were treated with corresponding acupuncture techniques on both sides of "Zusanli"(ST36) for 30 min, once a day for 7 days; Rabbits of the AG was intraperitoneally injected with A438079(2.5 mg/kg), once a day for 7 days. After intervention, color Doppler ultrasound was used to observe the joint cavity effusion, synovial thickness and internal blood flow signal.The histomorphological changes of synovial tissues were observed by HE staining. Quantitative real-time PCR method was used to detect the mRNA expression levels of P2X7R, NLRP3, and Caspase-1 in synovial tissues. Western blot was used to detect the protein expression of interleukin(IL)-1ß, IL-6 and tumor necrosis factor(TNF)-α in synovial tissues. RESULTS: Compared with the normal group, the synovial tissues in the model group was thickened, linear and punctate blood flow signals were increased, joint effusion was obvious, synovial coating cells were enlarged, the synovial matrix was severely hyperplasia, inflammatory cells infiltration was obvious.The mRNAs expression levels of P2X7R, NLRP3, Caspase-1 and IL-1ß, IL-6, TNF-α proteins in synovial tissues were significantly increased(P<0.01). Compared with model group, abnormal blood flow signals, synovial thickness, joint effusion, proliferation of synovial matrix, inflammatory cell infiltration and synovial coating cells in the RRG, HRG and AG were improved. The mRNAs expression levels of P2X7R, NLRP3, Caspase-1 and IL-1ß, IL-6, TNF-α proteins in synovial tissues were decreased in the RRG, HRG and AG (P<0.05, P<0.01). Compared with the RRG, the above indexes were lower in the HRG and AG (P<0.05, P<0.01).There was no significant difference in all indexes above between the HRG and AG (P<0.01, P<0.05). CONCLUSION: Heat reinforcing needling can improve synovial inflammation of RA, which may be related to regulating the expressions of P2X7R/NLRP3/Caspase-1 signaling pathway.

Are preoperative phase-contrast CSF flow parameters ideal for predicting the outcome of shunt surgery in patients with idiopathic normal pressure hydrocephalus?

Purpose: Phase-contrast magnetic resonance (PC-MR) is widely used in patients with idiopathic normal pressure hydrocephalus (iNPH), but its role in predicting prognosis remains controversial. To evaluate the effectiveness of preoperative PC-MR CSF flow measurement in predicting the clinical response to shunt surgery in patients with iNPH. Methods: Forty-six patients with definite iNPH were included between January 2018 and January 2022. PC-MR was used to evaluate CSF peak velocity (PV), average velocity, aqueductal stroke volume (ASV), net ASV, and net flow. The modified Rankin Scale (mRS), iNPH grading scale (iNPHGS), Mini-Mental State Examination (MMSE), and Timed 3-m Up and Go Test (TUG) were used for clinical assessment. The primary endpoint was the improvement in the mRS score 1 year after surgery, and the secondary endpoints were the iNPHGS, MMSE, and TUG scores at 1 year. Differences between shunt improvement and non-improvement groups, based on the clinical outcomes, were compared using the Mann-Whitney U-test, logistic regression models, and receiver operating characteristic curves. Correlations between CSF flow parameters and the baseline clinical outcomes were assessed using Spearman's correlation coefficient. Results: No CSF parameters significantly differed between shunt improvement and non-improvement groups based on mRS and secondary outcomes. And all CSF parameters showed significant overlap in both shunt improvement and non-improvement groups based on mRS and secondary outcomes. Significant correlations between the mRS and iNPHGS scores, and PV, ASV, and net ASV were observed. Conclusion: While some preoperative PC-MR CSF flow parameters reflected the symptom severity of iNPH to a certain extent, they alone might not be ideal markers of shunt responsiveness.

[Anti-inflammation mechanism of electro-scalp acupuncture in treatment of ischemic stroke based on IL-12 mediated JAK/STAT signaling pathway].

OBJECTIVE: To observe the impact of electro-scalp acupuncture (ESA) on the neural function and inflammatory response of ischemic cortex in the model rats with ischemic stroke and explore the anti-inflammation mechanism of ESA in treatment of ischemic stroke from the perspective of modulating the interleukin 12 (IL-12) mediated JAK (Janus kinase)/STAT (signal transduction and transcription activator) signal pathway. METHODS: Ninety male SD rats were randomized into a normal group (n =16) and a model preparation group (n=74). In the model preparation group, the model of middle cerebral artery occlusion (MCAO) was duplicated with suture-occlusion method. After modeled successfully, 48 rats with neurological deficit score of 1-3 were divided into a model group, an inhibitor group and an ESA group, 16 rats in each one. In the inhibitor group, IL-12 inhibitor (apilimod, 5 mg/kg) was used via intragastric administration. In the ESA group, the anterior oblique line of vertex-temporal (MS6) was stimulated bilaterally with electric acupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in current intensity. The needles were retained for 30 min. The treatment was given once daily and for 7 days in above two intervention groups. Before and after intervention, the neurological deficit score (NDS) and neurobehavioral score (NBS) were assessed in each group. HE staining method was adopted to observe the morphological manifestations of ischemic cortical lesion; the concentrations of IL-12 and IL-12R of the brain tissue in the ischemic cortical lesion were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of STAT4 and Tbx21 were detected by real-time PCR technique; and the protein expression of IL-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-4 were detected using immunohistochemistry. RESULTS: NDS and NBS in the model group, the inhibitor group and the ESA group were all higher than those in the normal group before intervention (P<0.01). After intervention, NDS and NBS in the model group were higher than the normal group (P<0.01); the two scores were all reduced when compared with those before intervention in the inhibitor group and the ESA group (P<0.01), and lower than those of the model group (P<0.01). NDS in the ESA group was lower than the inhibitor group (P<0.05). In the model group, the cells were shrunk and vacuolated in the ischemic cortical lesion. Many normal cells were visible in the ESA group and the inhibitor group. Compared with the normal group, the concentrations of IL-12 and IL-12R , the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in brain tissue of ischemic cortical lesion were all increased in the model group (P<0.01), while the protein expression level of IL-4 decreased (P<0.01). The concentrations of IL-12 and IL-12R, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ were all reduced (P<0.01), while the protein expression level of IL-4 increased (P<0.01) in the ESA group and the inhibitor group when compared with the model group. The concentration of IL-12, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in the ESA group were all higher than those of the inhibitor group (P<0.05); while the concentration of IL-12R and the protein expression level of IL-4 were lower than the inhibitor group (P<0.05). CONCLUSION: Electro-scalp acupuncture may improve the neurological function of the rats with ischemic stroke. The modulation to IL-12 mediated JAK/STAT signaling pathway is the potential molecular mechanism of this therapy for the inflammatory response in ischemic cortical lesion.

Social support status and associated factors among people living with HIV/AIDS in Kunming city, China.

BACKGROUND: People living with HIV/AIDS not only require effective treatment for the alleviation of physical discomfort but also require social support to help them address difficulties in life and relieve their psychological anxiety and uneasiness. The social support network is of tremendous importance in helping people living with HIV/AIDS maintain good physical and mental health. This study aims to analyse the social support status among people living with HIV/AIDS in Kunming and explore associated factors. METHOD: The Social Support Rating Scale (SSRS) was used, and a questionnaire survey was conducted using convenience sampling to select people living with HIV/AIDS from 14 counties of Kunming. It collected information on general demographic information and social support status. Univariate and multivariate linear regression models were used to explore the associated factors. RESULTS: A total of 990 valid questionnaires were completed. Data from all participants were analysed. Univariate analysis suggested that the factors associated with social support may include marital status, monthly income, and antiretroviral therapy. On the other hand, factors including monthly income and antiretroviral therapy accounted for the social support total score in the multivariate analysis. CONCLUSION: Social support among people living with HIV/AIDS in Kunming was generally low. This study identified a number of factors associated with social support among people living with HIV/AIDS. Based on our findings, appropriate interventions should be introduced to provide social support for those living with HIV/AIDS.

Diffusion Spectrum Imaging of Corticospinal Tracts in Idiopathic Normal Pressure Hydrocephalus.

Purpose: The purpose of this study was to measure the diffusion spectrum imaging (DSI) parameters of corticospinal tracts (CSTs) and evaluate diffusional changes in CSTs in patients with idiopathic normal pressure hydrocephalus (iNPH) by DSI. Methods: Twenty-three iNPH patients and twenty-one healthy controls (HCs) were involved in this study. Brain DSI data for all participants were collected through the same MR scanning procedure. The diffusion parameters measured and analyzed included quantitative anisotropy (QA), the isotropic diffusion component (ISO), general fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of corticospinal tracts. Results: The QA and ISO values of corticospinal tracts in iNPH patients were significantly lower than those in HCs (PLQA = 0.008, PRQA = 0.016, PLISO = 0.024, PRISO = 0.016). The mean MD, AD, and RD values in iNPH patients were significantly higher than those in HCs (PMD = 0.032, PAD = 0.032, PRD = 0.048,). No significant differences in GFA and FA values were noted between iNPH patients and HCs. Conclusion: Decreased QA and ISO values of corticospinal tracts were found in iNPH patients. Quantitative CST evaluation using DSI may lead to information that can improve the present understanding of the disease mechanism.

Idiopathic Normal Pressure Hydrocephalus and Elderly Acquired Hydrocephalus: Evaluation With Cerebrospinal Fluid Flow and Ventricular Volume Parameters.

PURPOSE: To investigate differences in cerebrospinal fluid (CSF) flow through the aqueduct and to determine whether there is a relationship between CSF flow and ventricular volume parameters in idiopathic normal pressure hydrocephalus (iNPH) patients, elderly acquired hydrocephalus patients and age-matched healthy volunteers by phase-contrast MR (PC-MR). METHODS: A total of 40 iNPH patients and 41 elderly acquired hydrocephalus patients and 26 age-matched healthy volunteers in the normal control (NC) group were included between November 2017 and October 2019 in this retrospective study. The following CSF flow parameters were measured with PC-MR: peak velocity, average velocity (AV), aqueductal stroke volume (ASV), net ASV, and net flow. The following ventricular volume parameters were measured: ventricular volume (VV), brain volume, total intracranial volume, and relative VV. Differences between the iNPH and acquired hydrocephalus groups were compared Mann-Whitney U test and correlations between CSF flow and ventricular volume parameters were assessed using the Spearman correlation coefficient. RESULTS: Aqueductal stroke volume was significantly higher in the iNPH and acquired hydrocephalus groups than in the NC group, but did not differ significantly between the iNPH group and acquired hydrocephalus group. The AV, net ASV, and net flow in the iNPH and acquired hydrocephalus groups were significantly higher than those in the NC group (P < 0.0001), and those in the acquired hydrocephalus group were significantly higher than those in the iNPH group (P = 0.01, P = 0.007, P = 0.002, respectively). The direction of the AV and net ASV significantly differed among the three groups. There were no associations between the volume parameters and CSF flow according to PC-MR among the three groups. CONCLUSION: Compared with iNPH, elderly acquired hydrocephalus demonstrated higher CSF hyperdynamic flow. Although increased CSF flow may contribute to further changes in ventricular morphology, there is no linear relationship between them. These findings might help increase our understanding of flow dynamics in iNPH and elderly acquired hydrocephalus.

A protocol of systematic review and meta-analysis of neuromuscular electrical stimulation for interstitial cystitis.

BACKGROUND: This study will examine the effectiveness and safety of neuromuscular electrical stimulation (NMES) for the treatment of patients with interstitial cystitis (IC). METHODS: We will retrieve the following electronic databases from their commencements to the March 1, 2020 to discover all related potential studies: MEDLINE, EMBASE, Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and WANFANG Database. Randomized controlled trials related to the NMES for the treatment of patients with IC will be included, regardless publication status and language. Literature selection, data collection, and study quality assessment will be independently performed by 2 authors. The extracted data will be expressed as risk ratio and 95% confidence intervals for dichotomous data, and mean difference or standard mean difference and 95% confidence intervals for continuous data. RevMan V.5.3 software will be employed for statistical analysis. RESULTS: This study will summarize current high quality randomized controlled trials to appraise the effectiveness and safety of NMES for the treatment of patients with IC. CONCLUSION: The findings of this study will provide helpful evidence to determine whether NMES is an effective treatment for patients with IC or not. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020170495.

Efficacy of pirarubicin for nonmuscle invasive bladder cancer: A protocol of systematic review and meta-analysis.

BACKGROUND: This study will aim to appraise the efficacy and safety of pirarubicin for the treatment of patients with nonmuscle invasive bladder cancer (NMIBC). METHODS: We will perform a comprehensive literature search in MEDLINE, EMBASE, Cochrane Library, Scopus, PsycINFO, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from their beginning to the February 29, 2020. All randomized controlled trials of pirarubicin for NMIBC will be included regardless limitations related to the language and publication time. Two researchers will independently select studies from searched records, extract data from included randomized controlled trials, and assess study quality using Cochrane risk of bias tool. Any differences between them will be solved with the help of another researcher. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will provide a synthesis of current evidence to investigate the efficacy and safety of pirarubicin for NMIBC using overall survival, progression-free survival, recurrence-free survival, quality of, rates of recurrence, and adverse events. CONCLUSION: This study will explore whether or not pirarubicin can be used as an effective and safety treatment for patients with NMIBC. REGISTRATION NUMBER: INPLASY202040113.

Clinicopathological significance of Ki67 expression in colorectal cancer: A protocol of systematic review and meta-analysis.

BACKGROUND: This study will investigate the diagnostic accuracy of Ki67 expression in colorectal cancer (CC). METHODS: A comprehensive search in electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) will be performed from inception to the February 29, 2020 with no restrictions to the language and publication status. Two authors will examine the collected studies, extract essential data, and appraise study quality separately. If possible, we will estimate receiver operating characteristic (ROC), sensitivity and specificity by utilizing bivariate random effects and hierarchical summary ROC models. RESULTS: This study will summarize present evidence to explore the diagnostic accuracy of Ki67 expression in CC. CONCLUSION: The findings of this study will clarify the diagnostic accuracy of Ki67 expression in CC. SYSTEMATIC REVIEW REGISTRATION: INPLASY202030009.

Infection Control against COVID-19 in Departments of Radiology.

The COVID-19 epidemic, which is caused by the novel coronavirus SARS-CoV-2, has spread rapidly to become a world-wide pandemic. Chest radiography and chest CT are frequently used to support the diagnosis of COVID-19 infection. However, multiple cases of COVID-19 transmission in radiology department have been reported. Here we summarize the lessons we learned and provide suggestions to improve the infection control and prevention practices of healthcare workers in departments of radiology.

DSC and DCE Histogram Analyses of Glioma Biomarkers, Including IDH, MGMT, and TERT, on Differentiation and Survival.

RATIONALE AND OBJECTIVES: The World Health Organization 2016 classification of central nervous system tumors added the molecular classification of gliomas and has guiding significance for the operation and prognosis of glioma patients. At present, the perfusion technique plays an important role in judging the malignant degree of glioma. To evaluate the performance of dynamic susceptibility contrast (DSC)- and dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) histogram analyses in discriminating the states of molecular biomarkers and survival in glioma patients. MATERIALS AND METHODS: Forty-three glioma patients who underwent DCE- and DSC-MRI were enrolled. Relevant molecular test results, including those on isocitrate dehydrogenase (IDH), O6-methylguanine-DNA methyltransferase (MGMT) and telomere reverse transcriptase (TERT), were collected. The mean relative cerebral blood volume of DSC-MRI and histogram parameters derived from DCE-MRI (volume transfer coefficient (Ktrans), fractional volume of the extravascular extracellular space (Ve), fractional blood plasma volume (Vp), rate constant between the extravascular extracellular space and blood plasma (Kep) and area under the curve (AUC)) were calculated. Differences in each parameter between gliomas with different expression states (IDH, MGMT, and TERT) were evaluated. The diagnostic efficiency of each parameter was analyzed. The overall survival of all patients was assessed. RESULTS: The 10th percentile AUC (AUC = 0.830, sensitivity = 0.78, specificity = 0.80), the 90th percentile Ve (AUC = 0.816, sensitivity = 0.84, specificity = 0.79), and the mean Kep (AUC = 0.818, sensitivity = 0.76, specificity = 0.78) provided the highest differential efficiency for IDH, MGMT, and TERT, respectively. Kaplan-Meier curves showed a significant difference between subjects with a 10th percentile AUC higher or lower than 0.028 (log-rank = 7.535; p = 0.006) for IDH and between subjects with different 90th percentile Ve values (log-rank = 6.532; p = 0.011) for MGMT. CONCLUSION: Histogram DCE-MRI demonstrates good diagnostic performance in identifying different molecular types and for the prognostic assessment of glioma.

Differential diagnosis of central lymphoma and high-grade glioma: dynamic contrast-enhanced histogram.

BACKGROUND: In clinical diagnosis, some central nervous system lymphomas (CNSL) are difficult to distinguish from high-grade gliomas (HGG). PURPOSE: To evaluate the diagnostic efficacy of the histogram analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in the identification of CNSL and HGG. MATERIAL AND METHODS: In all, 43 patients diagnosed with HGG (n = 28) and CNSL (n = 15) by histopathology underwent DCE-MRI scanning. Differences in histogram parameters based on DCE-MRI between HGG and CNSL were analyzed by Mann-Whitney U test. In addition, receiver operating characteristic (ROC) analysis was performed. Short-term follow-up of patients was performed using Kaplan-Meier analysis to explore the survival rates of HGG and CNSL. RESULTS: For the ROC curve analysis, we demonstrate that the 10th percentile of Ktrans (area under the curve [AUC] = 0.912, sensitivity = 86.7%, specificity = 92.9%), Kep (AUC = 0.940, sensitivity = 93.3%, specificity = 79.6%), Ve (AUC = 0.907, sensitivity = 86.7%, specificity = 89.3%), and AUC (AUC = 0.904, sensitivity = 86.7%, specificity = 92.9%) were significantly different between the CNSL and HGG groups (P < 0.001), with high diagnostic efficiency. Table 2 shows that the histogram features based on AUC maps (10th, 25th, median, 75th, 90th, and mean) were always significantly higher in the CNSL group than in the HGG group (P < 0.001). There was no significant difference in Vp or in the 75th, 90th and mean of Ktrans, Kep, and Ve between the CNSL and HGG groups (P > 0.05). CONCLUSION: A histogram analysis of DCE-MRI identified significant differences between HGG and CNSL, and this will help in the clinical differential diagnosis of these conditions.

Analysis of factors associated with dropping-out from HIV antiretroviral therapy in Kunming City, China.

BACKGROUND: The implementation of national antiretroviral therapy (ART) and expanded ART policies results in that more and more HIV-infected patients receive ART in Kunming, Yunnan province, China. At the same time, however, the number of patients, who drop-out from ART, are also increasing. In this study, we explored the factors that may account for drop-out. METHODS: Four hundred and thirty-nine HIV-infected patients, who received or used to receive ART, were recruited in this study. Their age is among 18 and 75. All patients were divided into two group: ART group (187 patients) and drop-out group (252 patients). Appropriate bio-statistics analysis, including univariate analysis and Multivariate analysis, were used to identify factors associated with drop-out. RESULTS: Data from all patients were analyzed. Univariate analysis suggested that the factors associated with drop-out may include age, residential area, educational level, occupation, monthly income, the access to minimum living allowance, HIV transmission route, and living status. On the other hand, factors including area, monthly income, the access to minimum living allowance, and referral methods of follow-up institutions account for drop-out in multivariate analysis. CONCLUSIONS: This study identified a number of factors associated with drop out from ART. Based on our findings,appropriate interventions should be introduced decrease drop-out.

MiR-125b regulates the proliferation and metastasis of triple negative breast cancer cells via the Wnt/ß-catenin pathway and EMT.

BACKGROUND/AIM: MiR-125b plays an important role in breast cancer. The current study was to explore the expression and function of miR-125b in triple negative breast cancer cells. MATERIALS AND METHODS: The expression of miR-125b in human TNBC samples and cell lines were examined by qRT-PCR. MTT, scratch assays and transwell assays were utilized to observe the proliferation, migration and invasion ability. MiR-125b's target gene and downstream signaling pathways were investigated by Luciferase Reporter Assays, qRT-PCR, immunofluorescence assays and western bolt. RESULTS: MiR-125b was highly expressed in human TNBC tissues and cell lines. Inhibiting miR-125b expression suppressed the proliferation, cell migration and invasion. The three-prime untranslated region (3´-UTR) of adenomatous polyposis coli (APC) mRNA contains miR-125b binding sites, and inhibiting miR-125b expression suppressed the activity of the intracellular Wnt/ß-catenin pathways and EMT. CONCLUSION: Inhibiting miR-125b regulates the Wnt/ß-catenin pathway and EMT to suppress the proliferation and migration of MDA-MB-468 TNBC cells.

Radiotherapy concurrent versus sequential with endocrine therapy in breast cancer: A meta-analysis.

INTRODUCTION: This study compared treatment outcomes of radiotherapy concurrent with endocrine therapy and radiotherapy sequential with endocrine therapy in breast cancer. MATERIALS AND METHODS: Eligible studies of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were retrieved through extensive searches of the PubMed, Medline, Embase, Cochrane library, FEBM, FMJS, Web of science, Wiley, CBM, CNKI, Wang fang, Cqvip databases from 2000 to 2014. Original English and Chinese publications of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were included. The primary endpoint was radiation-induced toxicity including upper than grade 2 skin related toxicity, radiation pneumonia and pulmonary fibrosis; the second endpoint was survival date, including local recurrence, distant metastasis, 5-year OS, 10-year OS. RESULTS: Eleven eligible trials were identified, six in English and five in Chinese. Totally, there were 1291 women in concurrent groups, and 1179 in sequential groups. Statistical analysis showed that there was no statistical difference between concurrent and sequential groups in skin related toxicity (RR 1.20, 95% CI 0.92-1.56, P = 0.17), radiation pneumonia (RR 1.11, 95% CI 0.46-2.70, P = 0.81) and pulmonary fibrosis (RR 1.35, 95% CI 0.75-2.41, P = 0.32). Meanwhile, no statistical difference was found in survival data, (RR 0.97, 95% CI 0.79-1.28, P = 0.26), (RR 0.86, 95% CI 0.66-1.12, P = 0.27) in local recurrence and distant metastasis respectively, (RR 1.01, 95% CI 0.96-1.06, P = 0.65), (RR 0.98, 95% CI 0.93-1.02, P = 0.32) in 5-year and 10-year overall survival respectively. Stratification analysis was proceeded, grouped by tamoxifen and AI in different treatment timing, however, no statistical difference was found in radiation-induced toxicity and survival outcomes. CONCLUSION: Radiotherapy concurrent with endocrine therapy didn't increase or decrease neither the incidence of radiation-induced toxicity nor the survival rate compared with that of sequential group; Endocrine therapy drugs didn't influence outcomes in different treatment timing.

[Pharmacokinetics and brain distribution of NMD/TMP-nanoparticles].

This study aims to prepare nimodipine/tetramethylpyrazine-loaded poly(D, L-lactide-co-glycolide) dual-drug nanoparticles (NMD/TMP-NPs) and investigate pharmacokinetics and brain distribution to evaluate the possibility of enhancing the drug effect of dual-drug nanoparticles. NMD/TMP-NPs were prepared via W/O/W emulsion solvent evaporation. Entrapment efficiency and drug loading of NMD/TMP-NPs were investigated by ultracentrifugation, and drug release behavior in vitro was studied by dialysis method. The pharmacokinetic and brain distribution were studied in SD mice administered intravenously with NMD/TMP-NPs in comparison with NMD-suspension, NMD/TMP-suspension and NMD-NPs, (NMD-NPs+TMP)-suspension. According to the results, the entrapment efficiency and drug loading of NMD were (79.71±0.73)%, (1.74±0.02)%, those of TMP were (40.26±1.51)% and (4.38±0.16)%. The nanoparticles showed the property of sustained release. On the basis of the major parameters for in vivo pharmacokinetic and brain distribution, t1/2ß of NMD-suspension, NMD/TMP-suspension and NMD-NPs, (NMD-NPs+TMP)-suspension, NMD/TMP-NPs were (1.097±0.146), (1.055±0.06), (1.950±0.140), (1.860±0.096), (2.497±0.475） h, CL were (0.778±0.098), (1.133±0.111), (0.247±0.023), (0.497±0.040), (0.297±0.024) h•L-1, AUC0-t in rat plasma were (514.218±60.383), (352.916±33.691), (1 618.429±240.198), (804.110±75.804), (1 349.058±215.497) µg•h•L⁻¹, respectively, and AUC0-t in brain were 0.301 9, 0.624 8, 1.068 6, 1.313 0, 1.046 5 mg•h•L⁻¹, respectively. According to the in vivo study, the pharmacokinetic behavior of NMD were markedly prolonged by adding TMP or prepared dual-drug nanoparticles.

MicroRNAs level as an initial screening method for early-stage lung cancer: a bivariate diagnostic random-effects meta-analysis.

Accumulating studies suggested that microRNAs (miRNAs) can have high diagnostic value as a non-invasive and cost-effective procedure with high sensitivity and specificity in the detection of early-stage lung cancer. However, there is inconsistency observed in the results of relevant studies. Therefore, we performed this meta-analysis to evaluate diagnostic value of miRNAs based on all related studies. A total of 38 studies from 13 included articles were used for the analysis, consisting of 510 patients and 465 healthy controls. All analyses were performed on the R 3.2.0 software. The bivariate random-effects meta-analysis model was applied to obtain the following pooled parameters: sensitivity, 0.797 (95% CI: 0.756-0.832); false positive rate, 0.296 (95% CI: 0.250-0.346); and AUC, 0.818. In addition, subgroup analyses were conducted, showing not only that a combination of multiple miRNAs as biomarkers have greater diagnostic value for early-stage lung cancer (sensitivity, false positive rate and AUC of 83%, 25.2% and 0.858, respectively) had a higher diagnostic accuracy than single miRNA (sensitivity, false positive rate and AUC of 78.3%, 31.6% and 0.799, respectively), but also that specimen from circulating system (sensitivity, false positive rate and AUC of 82.5%, 30.5% and 0.836, respectively) provide better biomarkers than specimen from non-circulating system (sensitivity, false positive rate and AUC of 73.8%, 26.5% and 0.796, respectively). In summary, the current meta-analysis suggests that miRNAs as biomarkers, particularly a combination of multiple tumor-specific miRNAs from circulating system, have moderately high clinical diagnostic value in the detection of early-stage lung cancer. However, the clinical diagnostic utilization and additional improvements of miRNAs as biomarkers for early-stage lung cancer detection still remain to be further validated by more future studies.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.

BACKGROUND: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. MATERIALS AND METHODS: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. RESULTS: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak- STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. CONCLUSIONS: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.