Knockdown of lncRNA-UCA1 inhibits cell viability and migration of human glioma cells by miR-193a-mediated downregulation of CDK6.

BACKGROUND: Long noncoding RNA urothelial carcinoma-associated 1 (lncRNA-UCA1) is generally recognized as an oncogenic molecule in several human malignant tumors. However, the available evidence does not necessarily imply an unequivocal causal function of UCA1 in glioblastoma. The current study was aimed to probe the biological function of lncRNA-UCA1 in human glioblastoma cell lines. Besides, we further investigated the potential mechanisms. METHODS: Cell viability, apoptosis, as well as migration and invasion were measured using a commercial cell counting kit-8, flow cytometry, and 24-Transwell assay, respectively. LncRNA-UCA1, microRNA-193a (miR-193a), and CDK6 at messenger RNA levels were evaluated by quantitative real-time polymerase chain reaction method. Protein level was examined by Western blot analysis. RNA immunoprecipitation was utilized to validate lncRNA-UCA1 associated with miR-193a. Luciferase activity assay was used to identify the miR-193a-targeted CDK6 3'-untranslated region. RESULTS: lncRNA-UCA1 knockdown weakened cell viability, augmented apoptosis progression, as well as suppressed migration and invasion behaviors in glioblastoma cells, whereas lncRNA-UCA1 silence exhibited the opposite functions. lncRNA-UCA1 functioned as an endogenous sponge of miR-193a. miR-193a silence reversed the biological function of lncRNA-UCA1 knockdown on U-118 MG cells. miR-193a negatively regulated the expression of CDK6, and it affected the U-118 MG cells through regulating CDK6 expression. CDK6 overexpression abrogated the blockage of PI3K/AKT, mitogen-activated protein kinase (MAPK), and Notch signaling pathways. Furthermore, lncRNA-UCA1 and miR-193a could affect these signaling cascades through regulating CDK6 expression. The regulatory mechanisms of lncRNA-UCA1 were further consolidated in clinical specimens. CONCLUSION: lncRNA-UCA1 silence reduced cell viability, promoted apoptosis progression, while impeding the migration and invasion of glioblastoma cells by miR-193a-mediated silence of CDK6, with blockage of PI3K/AKT, MAPK, and Notch pathways.

Strong evidence supports the use of estradiol therapy for the treatment of vaginal inflammation: a two-way Mendelian randomization study.

OBJECTIVE: Nowadays, there has been limited Mendelian randomization (MR) research focusing on the causal relationship between estradiol and vaginitis. Therefore, this study conducted a two-way MR study to clarify the causal effect and related influencing factors between them. METHODS: All genetic datasets were obtained using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. MR analysis was performed using MR-Egger, weighted median (WM) and inverse variance weighted (IVW) methods to assess the causal relationship between exposure and outcome and to validate the findings by comprehensively evaluating the effects of pleiotropic effects and outliers. RESULTS: MR analysis revealed no significant causal relationship between estradiol and vaginitis risk. There was a negative correlation between estradiol and age at menarche (IVW, OR: 0.9996, 95% CI: 0.9992-1.0000, P = 0.0295; WM, OR: 0.9995, 95% CI: 0.9993-0.9998, P = 0.0003), and there was a positive correlation between age at menarche and vaginitis (IVW, OR: 1.5108, 95% CI: 1.1474-2.0930, P = 0.0043; MR-Egger, OR: 2.5575, 95% CI: 1.7664-9.6580, P = 0.0013). Estradiol was negatively correlated with age at menopause (IVW, OR: 0.9872, 95% CI: 0.9786-0.9959, P = 0.0041). However, there was no causal relationship between age at menopause and vaginitis (P > 0.05). In addition, HPV E7 Type 16, HPV E7 Type 18, and Lactobacillus had no direct causal effects on estradiol and vaginitis (P > 0.05). Sensitivity analyses revealed no heterogeneity and horizontal pleiotropy. CONCLUSION: When estrogen levels drop, it will lead to a later age of menarche, and a later age of menarche may increase the risk of vaginitis, highlighting that the longer the female reproductive tract receives estrogen stimulation, the stronger the defense ability is formed, and the prevalence of vaginitis is reduced. In conclusion, this study indirectly supports an association between reduced level of estrogen or short time of estrogen stimulation and increased risk of vaginitis.

Anlotinib Inhibits Ovarian Cancer and Enhances Cisplatinum Sensitivity via Suppressing NOTCH2 Expression and Stemness.

BACKGROUND/AIM: The prognosis of ovarian cancer (OC) patients is especially poor for patients with chemotherapy resistance. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor, has shown encouraging clinical efficacy in several tumor types. The aim of the present study was to examine the inhibitory efficacy and mechanism of anlotinib on the proliferation and chemosensitivity of OC cells. MATERIALS AND METHODS: The inhibitory effects of Anlotinib on SKOV3 and OVCAR3 OC cells were examined using CCK-8 cell-viability, colony-formation, flow-cytometry, transwell-migration and sphere-formation assays. A xenograft mouse model was used for in vivo studies. RT-qPCR and western blotting were used to detect gene expression. RESULTS: Molecular targets of anlotinib were elevated in OC patient tumors. Anlotinib significantly inhibited ovarian cancer cell proliferation and migration in vitro. Anlotinib enhanced the sensitivity of ovarian cancer cells to cisplatinum both in vitro and in vivo. Anlotinib suppressed sphere formation and the stemness phenotype of OC cells by inhibiting NOTCH2 expression. CONCLUSION: Anlotinib inhibits ovarian cancer and enhances cisplatinum sensitivity, suggesting its future clinical promise.

The power and the promise of synthetic lethality for clinical application in cancer treatment.

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.

Preoperative prediction of Lauren classification in gastric cancer: a radiomics model based on dual-energy CT iodine map.

OBJECTIVE: To investigate the value of a radiomics model based on dual-energy computed tomography (DECT) venous-phase iodine map (IM) and 120 kVp equivalent mixed images (MIX) in predicting the Lauren classification of gastric cancer. METHODS: A retrospective analysis of 240 patients undergoing preoperative DECT and postoperative pathologically confirmed gastric cancer was done. Training sets (n = 168) and testing sets (n = 72) were randomly assigned with a ratio of 7:3. Patients are divided into intestinal and non-intestinal groups. Traditional features were analyzed by two radiologists, using logistic regression to determine independent predictors for building clinical models. Using the Radiomics software, radiomics features were extracted from the IM and MIX images. ICC and Boruta algorithm were used for dimensionality reduction, and a random forest algorithm was applied to construct the radiomics model. ROC and DCA were used to evaluate the model performance. RESULTS: Gender and maximum tumor thickness were independent predictors of Lauren classification and were used to build a clinical model. Separately establish IM-radiomics (R-IM), mixed radiomics (R-MIX), and combined IM + MIX image radiomics (R-COMB) models. In the training set, each radiomics model performed better than the clinical model, and the R-COMB model showed the best prediction performance (AUC: 0.855). In the testing set also, the R-COMB model had better prediction performance than the clinical model (AUC: 0.802). CONCLUSION: The R-COMB radiomics model based on DECT-IM and 120 kVp equivalent MIX images can effectively be used for preoperative noninvasive prediction of the Lauren classification of gastric cancer. CRITICAL RELEVANCE STATEMENT: The radiomics model based on dual-energy CT can be used for Lauren classification prediction of preoperative gastric cancer and help clinicians formulate individualized treatment plans and assess prognosis.

Development and validation of real-time recombinase polymerase amplification-based assays for detecting HPV16 and HPV18 DNA.

IMPORTANCE: HPV DNA screening is an effective approach for the prevention of cervical cancer. The novel real-time recombinase polymerase amplification-based HPV detection systems we developed constitute an improvement over the HPV detection methods currently used in clinical practice and should help to extend cervical cancer screening in the future, particularly in point-of-care test settings.

Evaluation of the Rapid Antigen Detection Test for Diagnosing SARS-CoV-2 during the COVID-19 Pandemic: Experience from a Centralized Isolation Site in Shanghai, China.

Rapid and reliable diagnosis is important for the management of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid antigen detection test (RADT) is a rapid, inexpensive, and easy method. Several studies have reported that RADTs performed well in many countries; however, very few studies have been reported in China. In this study, we assessed the performance of the RADT (Ediagnosis COVID-19 antigen test kit). This study was conducted in a centralized isolation site in Shanghai and enrolled 716 patients with COVID-19 and 203 noninfected participants. Nasopharyngeal swabs from all participants were collected on the same day and tested using the RADT and real-time reverse transcription-PCR (RT-PCR). The performance of the RADT was evaluated in different scenarios, such as threshold cycle (CT) values, symptomatic phase, and symptoms on the day of testing. The results demonstrated that the sensitivity for patients with CT values lower than 20 was 96.55% (95% confidence interval [CI], 87.05 to 99.4). The sensitivities were 78.4% (95% CI, 69.96 to 85.05) for participants within 5 days after the first RT-PCR-positive result and 90.77% (95% CI, 80.34 to 96.19) within 5 days after symptom onset. Moreover, the sensitivity of the RADT was more than 80% for patients with symptoms on the day of testing, including fever (89.29%), cough (86.84%), stuffy nose (92.59%), runny nose (92%), sore throat (81.25%), and muscle pain (80.77%), especially for those with upper respiratory tract symptoms. The specificity of the RADT was good in all scenarios. During the SARS-CoV-2 epidemic, Ediagnosis performed excellently in individuals with a higher viral load (evidenced by lower CT values), individuals in the early symptomatic phase, and especially those with upper respiratory tract symptoms. IMPORTANCE RADTs have demonstrated excellent performance in many counties for screening SARS-CoV-2 infection, but very few studies have been conducted in China. The performance of RADTs is largely related to different real-life scenarios. In our study, the performance of the RADT was evaluated in different scenarios, such as CT values, symptomatic phase, and symptoms on the day of testing. The results demonstrated that Ediagnosis (an RADT made in China) performed excellently for individuals with a higher viral load (evidenced by lower CT values), individuals in the early symptomatic phase, and especially those with upper respiratory tract symptoms.

Chinese herbal medicine Yanghe decoction for knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) has been widely used to treat knee osteoarthritis (KOA), among which Yanghe decoction (YHD) is one of the commonly used prescriptions. The purpose of this study is to evaluate the effectiveness and safety of YHD in the treatment of KOA. METHODS: Six databases, including Embase, PubMed, the Cochrane Library, the China National Knowledge Infrastructure, Wanfang Database and Chinese Science and Technology Periodical Database will be searched from their inception to July 2020. Two researchers will independently select studies, collect data and evaluate the quality of included studies. Statistical analysis will be processed by RevMan V.5.3 software. RESULTS: This study will provide an assessment of the current state of YHD in the treatment of KOA, aiming to show the efficacy and safety of YHD. CONCLUSION: This study will provide evidence to judge whether YHD is an effective intervention for KOA.

Chinese herbal medicine Yanghe decoction for ankylosing spondylitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine is a commonly used traditional treatment for ankylosing spondylitis (AS). Among them, Yanghe decoction (YHD) has an obvious effect in relieving the symptoms of AS, but its efficacy is still controversial. The purpose of this study is to systematically evaluate the effectiveness and safety of YHD in the treatment of AS patients. METHODS: From the establishment to September 2020, we will search a total of 7 electronic databases including PubMed, Cochrane Library, Embase, CNKI, VIP, WanFang, and the Chinese SinoMed Database. Two independent reviewers will search the database for relevant randomized controlled trials (RCTs), extract data, and evaluate the quality of the included RCTs. Data analysis will be processed by RevMan V.5.4 software. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: This study will provide evidence for the effectiveness of YHD in treating patients with AS.

Safety of tumor necrosis factor-alpha inhibitors for treatment of ankylosing spondylitis: A meta-analysis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic immune-mediated disease affecting the sacroiliac joints and the spine, manifesting with new bone formation and osteopenia. Five tumor necrosis factor-alpha (TNF-α) inhibitors (infliximab, etanercept, adalimumab, certolizumab, and golimumab) are available for the treatment of AS, however, the results for the safety of TNF-α inhibitors in the treatment of AS are not consistent. METHODS: In this study, we conducted a meta-analysis to determine the safety of TNF-α inhibitors compared with placebo in reducing pain, swelling, and inflammation of AS patients. Eight relevant articles including 2049 patients were included for this meta-analysis study. We observed that the incidence of adverse events (RR  =  1.22, 95% CI: 1.12-1.33; P  =  .501, I  =  0%) and injection-site reaction (RR  =  2.93, 95% CI: 2.02-4.23; P  =  .691, I  =  0%) in AS patients' treatment with TNF-α inhibitors was significantly higher than that with placebo. RESULTS: However, there was no significant difference in the incidence of serious adverse event, infection, serious infection, and discontinuations due to adverse event. TNF-α inhibitors may be a promising treatment for AS, but carries an increased incidence rate of adverse events and injection-site reaction. CONCLUSION: Due to the existence of the unstable factors, further studies need to be done to verify the result of this study.

[Evaluation on quitting intervention in health professionals of six cities].

OBJECTIVE: To evaluate the impact of quitting intervention in health professionals of six cities, developing smoking cessation models in China. METHODS: All community directors and health professionals in Seven communities were selected in six cities of Beijing, Shanghai, Tianjin, Changsha, Shenzhen and Puyang were surveyed for smoking cessation using cross-sectional study. RESULTS: There were 25 hospitals that kept on providing smoking cessation service after the intervention. The percent of the awareness about "the harm of smoking is public health problem" has improved 12.8%. The percent of getting some smoking cessation methods and actively providing smoking cessation have improved 9.2% and 7.3% respectively. CONCLUSION: Training the health professionals can not only increase their knowledge but also provide them smoking cessation service actively. It is a effective way to obtain methods and skills of quitting.

Reduction in placental growth factor impaired gestational beta-cell proliferation through crosstalk between beta-cells and islet endothelial cells.

Reduced placental growth factor (PLGF) during pregnancy is known to be a reason for developing preeclampsia (PE) and gestational diabetes mellitus (GDM), but the underlying mechanisms remain unclear. Recently, it has been shown that reduced PLGF may induce GDM through suppressing beta-cell mass growth in a PI3k/Akt signalling-dependent manner. Here, we dissected the interaction between beta-cells and islet endothelial cells in this model. We analysed proliferation of beta-cells and islet endothelial cells at different time points of gestation in mice. We cultured mouse islet endothelial cells (MS1), with or without PLGF. We cultured primary mouse beta-cells in conditioned media from PLGF-treated MS1. We cultured MS1 cells in conditioned media from proliferating beta-cells that were activated with conditioned media from PLGF-treated MS1 cells. We analysed cell proliferation by BrdU incorporation. We analysed cell growth by a MTT assay. We found that during mouse gestation, the increases in cell proliferation occurred earlier in beta-cells than in islet endothelial cells. In vitro, PLGF itself failed to induce proliferation of MS1 cells. However, conditioned media from the PLGF-treated MS1 cells induced beta-cell proliferation, resulting in increases in beta-cell number. Moreover, proliferation of MS1 cells significantly increased when MS1 cells were cultured in conditioned media from proliferating beta-cells activated with conditioned media from PLGF-treated MS1 cells. Thus, our data suggest that gestational PLGF may stimulate islet endothelial cells to release growth factors to promote beta-cell proliferation, and proliferating beta-cells in turn release endothelial cell growth factor to increase proliferation of endothelial cells. PE-associated reduction in PLGF impairs these processes to result in islet growth impairment, and subsequently the onset of GDM.

Predictors of Ibandronate Efficacy for the Management of Osteoporosis: A Meta-Regression Analysis.

BACKGROUND: Aim of the present study was to identify the predictors of ibandronate efficacy in subjects with osteoporosis or decreased bone mineral density (BMD). METHOD: Several electronic databases were searched by using specific keywords for the acquisition of research articles reporting the efficacy of ibandronate in subjects with osteoporosis or decreased BMD. Metaregression analyses were carried out by using changes in the BMD of lumbar spine and total hip following ibandronate treatment as dependent (outcome) variables against several independent (explanatory) variables. RESULTS: Data were extracted from 34 studies (11,090 ibandronate treated subjects) which fulfilled eligibility criteria. A history of previous fracture/s was reported by 46% of these subjects. In overall population, longer treatment duration from 1 to 5 years, increasing age, history of previous fractures, lower baseline T score, and higher baseline levels of C-terminal telopeptide of type 1 collagen (CTX) predicted higher ibandronate efficacy in improving BMD of the lumbar spine as well as of the total hip. Lower baseline levels of vitamin D and higher baseline levels of bone specific alkaline phosphatase (BSAP) predicted higher efficacy of ibandronate for lumbar spine only. In postmenopausal women with osteoporosis or decreased BMD, in addition to above-mentioned predictors, better efficacy of ibandronate was also associated with increasing time since menopause for both lumbar spine and total hip and lower body weight for lumbar spine only. CONCLUSION: Longer treatment duration from 1 to 5 years, increasing age, lower baseline T scores, and higher serum CTX levels are identified as the predictors of better efficacy of ibandronate in the study subjects with osteoporosis or decreased BMD.