Development and preliminary validation of a PROS scale for Chinese bladder cancer patients with abdominal stoma.

Bladder cancer is a common malignant tumor, and patients who have undergone radical cystectomy and urinary diversion require a lifelong abdominal stoma. This greatly affects their physiological, psychological, and social well-being. However, there is currently a lack of a self-assessment outcome scale specifically designed for bladder cancer patients with abdominal stomas. Therefore, we developed and validated a self-assessment outcome scale (PROS-BCAS) for Chinese bladder cancer patients with abdominal stomas. The scale was initially developed through literature research and expert consultation, and it comprised four dimensions: physiological, psychological, social, and treatment, with a total of 66 items. After item analysis, 44 items were retained. We collected scale data from 382 patients to examine its validity and reliability. The results showed that the PROS-BCAS scale had good content validity (S-CVI/Ave = 0.992), construct validity (KMO > 0.6), and discriminant validity (correlation coefficient 0.404-0.870). The Cronbach's alpha coefficients (0.801-0.954), test-retest reliability (0.778-0.956), and split-half reliability (0.896-0.977) all demonstrated good internal consistency for each dimension and the overall scale. The study demonstrated that the PROS-BCAS scale is a reliable and valid tool for accurately assessing the health-related quality of life of bladder cancer patients with abdominal stomas, providing reference for developing individualized clinical care plans.

Modulation of smoker brain activity and functional connectivity by tDCS: A go/no-go task-state fMRI study.

Background: Transcranial direct current stimulation (tDCS) applied to particular brain areas may reduce a smoker's smoking cravings. Most studies on tDCS mechanisms are performed on brains in the resting state. Therefore, brain activity changes induced by tDCS during tasks need to be further studied. Methods: Forty-six male smokers were randomised to receive anodal tDCS of the left/right dorsolateral prefrontal cortex (DLPFC) or sham tDCS. A go/no-go task was performed before and after stimulation, respectively. Brain activity and functional connectivity (FC) changes during the task state before and after tDCS were used for comparison. Results: This study revealed that the anodal stimulation over one DLPFC area caused decreased activity in the ipsilateral precuneus during the go task state. Right DLPFC stimulation increased the FC between the bilateral DLPFCs and the right anterior cingulate cortex (ACC), which is closely associated with cognition and inhibition of executive functions. Additionally, the study showed variations in brain activity depending on whether the anode was positioned over the right or left DLPFC (R-DLPFC or L-DLPFC). Conclusion: During the go task, tDCS might exert a suppressive effect on some brain areas, such as the precuneus. Stimulation on the R-DLPFC might strengthen the FC between the right ACC and the bilateral DLPFCs, which could enhance the ability of behavioural decision-making and inhibition to solve conflicts effectively. Stimulating the L-DLPFC alone could increase the FC of bilateral DLPFCs with some brain regions associated with response inhibition.

Shoseiryuto Promotes the Formation of a Tight-Junction Barrier in Cultured Human Bronchial Epithelial Cells.

Shoseiryuto (SST) (Xiao-Qing-Long-Tang in Chinese) is an effective treatment for respiratory diseases, such as bronchial asthma and allergic rhinitis, but its effects on the bronchial tight-junction (TJ) barrier have not been clarified. This study aimed to evaluate the effect of SST on TJ-barrier function in human bronchial epithelial (16HBE) cells. The 16HBE cells were cultured in a culture medium without (control) and with SST in the absence and presence of bacterial endotoxin lipopolysaccharide (LPS) in transwell chambers. Transepithelial electrical resistance (TEER) and sodium fluorescein (Na-F) permeability of the cultured-cell monolayer were measured as TJ integrity markers. In addition, immunofluorescence staining and quantitative real-time polymerase chain reaction analysis were used to measure the expression of the TJ protein, occludin. SST increased TEER and decreased Na-F permeability of the 16HBE cell monolayers. Furthermore, SST increased both occludin mRNA and immunostained protein expressions, suggesting that SST has the effect of directly promoting epithelial TJ-barrier function. LPS decreased TEER, increased Na-F permeability, and decreased both occludin mRNA and protein expression. LPS-induced barrier dysfunction was completely blocked by pre/co- and posttreatment with SST. These results suggest that SST has protective and therapeutic effects against LPS-induced TJ-barrier damage. To our knowledge, these are the first results to demonstrate the protective and therapeutic effects conferred by TJ-barrier promoting, which may be a novel mechanism contributing to the efficacy of SST for respiratory diseases.

Inhibitory effects of Jasminum grandiflorum L. essential oil on lipopolysaccharide-induced microglia activation-integrated characteristic analysis of volatile compounds, network pharmacology, and BV-2 cell.

Neuroinflammation is considered to have a prominent role in the pathogenesis of Alzheimer's disease (AD). Microglia are the resident macrophages of the central nervous system, and modulating microglia activation is a promising strategy to prevent AD. Essential oil of Jasminum grandiflorum L. flowers is commonly used in folk medicine for the relief of mental pressure and disorders, and analyzing the volatile compound profiles and evaluating the inhibitory effects of J. grandiflorum L. essential oil (JGEO) on the excessive activation of microglia are valuable for its application. This study aims to explore the potential active compounds in JGEO for treating AD by inhibiting microglia activation-integrated network pharmacology, molecular docking, and the microglia model. A headspace solid-phase microextraction combined with the gas chromatography-mass spectrometry procedure was used to analyze the volatile characteristics of the compounds in J. grandiflorum L. flowers at 50°C, 70°C, 90°C, and 100°C for 50 min, respectively. A network pharmacological analysis and molecular docking were used to predict the key compounds, key targets, and binding energies based on the detected compounds in JGEO. In the lipopolysaccharide (LPS)-induced BV-2 cell model, the cells were treated with 100 ng/mL of LPS and JGEO at 7.5, 15.0, and 30 µg/mL, and then, the morphological changes, the production of nitric oxide (NO) and reactive oxygen species, and the expressions of tumor necrosis factor-α, interleukin-1ß, and ionized calcium-binding adapter molecule 1 of BV-2 cells were analyzed. A total of 34 compounds with significantly different volatilities were identified. α-Hexylcinnamaldehyde, nerolidol, hexahydrofarnesyl acetone, dodecanal, and decanal were predicted as the top five key compounds, and SRC, EGFR, VEGFA, HSP90AA1, and ESR1 were the top five key targets. In addition, the binding energies between them were less than -3.9 kcal/mol. BV-2 cells were activated by LPS with morphological changes, and JGEO not only could clearly reverse the changes but also significantly inhibited the production of NO and reactive oxygen species and suppressed the expressions of tumor necrosis factor-α, interleukin-1ß, and ionized calcium-binding adapter molecule 1. The findings indicate that JGEO could inhibit the overactivation of microglia characterized by decreasing the neuroinflammatory and oxidative stress responses through the multi-compound and multi-target action modes, which support the traditional use of JGEO in treating neuroinflammation-related disorders.

Urate-lowering therapy adherence and the association with medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concern in Chinese gout patients: a cross-sectional study.

This study aims to assess urate-lowering therapy adherence and the relationship with medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concerns in Chinese gout patients during the COVID-19 outbreak. 101 gout patients receiving urate-lowering therapy were involved to evaluate adherence, medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concerns via a mobile app-based questionnaire. Statistical analysis was performed using SPSS 22.0. A total of 101 valid responses were included in the statistical analysis. The results showed that, the rate of adherence to urate-lowering therapy during the COVID-19 outbreak was 22.8% in Chinese patients with gout, higher than that in normal times (9.6%). Compared to the adherent group, non-adherent gout patients had shorter disease duration, lower self-efficacy, lower necessity about urate-lowering therapy score, higher concerns about urate-lowering therapy score, and smaller necessity-concerns differential. Depression and anxiety rates (3.0% and 5.0%, respectively) during the COVID-19 break were lower than that in normal times. Additionally, depression, anxiety, as well as COVID-19 pandemic-related concerns (27.7%) were not related to urate-lowering therapy adherence. In conclusion, adherence rate to urate-lowering therapy in Chinese gout patients during the COVID-19 outbreak was 22.8%, higher than normal times, but still very poor. Except for a little concern about being more susceptible to the virus, patients' mental state is relatively good. While the country puts great efforts into COVID-19 prevention and control, attention must also be paid to the medication management of patients with chronic diseases such as gout.

EGFR transcriptionally upregulates UTX via STAT3 in non-small cell lung cancer.

BACKGROUND: Histone demethylase UTX has been reported to participate in the occurrence and development of many cancers in tissue-specific manners. However, the role of UTX in non-small cell lung cancer (NSCLC) and exactly what regulates the expression of UTX remains unclear. Here, we analyzed the role of UTX in NSCLC in association with the widely recognized tumor driver epidermal growth factor receptor (EGFR). METHODS: UTX levels in clinical samples were detected by immunohistochemistry staining, western blotting and real-time quantitative PCR. The expression of UTX in tumor tissue was correlated with the phosphorylation of EGFR. Cell proliferation and migration were evaluated by MTT and wound-healing assays. The impact of EGFR and its downstream pathways on UTX was explored with corresponding inhibitors, and examined by western blotting and real-time quantitative PCR. RESULTS: In this study, we found that the expression of UTX in cancer tissues of patients with NSCLC was significantly higher than that in paracancerous tissues, and positively associated with EGFR phosphorylation levels. In addition, in NSCLC cell lines, UTX can promote proliferation and migration, while inhibition of its enzyme activity suppressed cell growth. Moreover, UTX expression was significantly upregulated when EGFR signaling pathway was activated, and vice versa when EGFR pathway was inhibited by tyrosine kinase inhibitor. Further mechanistic studies suggested that the activation of EGFR activated its downstream JAK/STAT3 signaling pathway and promoted STAT3 phosphorylation; the phosphorylated STAT3 transcriptionally promoted the levels of UTX. CONCLUSIONS: These results suggest an "EGFR-STAT3-UTX" axis that plays an oncogenic role in NSCLC.

Store-operated calcium entry-associated regulatory factor regulates airway inflammation and airway remodeling in asthma mice models.

Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can downregulate SOCE. We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the SARAF gene + GFP (green fluorescence protein) or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA (siRNA) or SARAF-specific siRNA, respectively. The proliferation, migration rate, hypertrophy, and SOCE activity of hASMCs were examined with Cell Counting Kit-8, wound healing test, bright field imaging, and Ca2+ fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time PCR. Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance, and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy, and SOCE activity in hASMCs. SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.

Efficacy and safety of aliskiren combination therapy: a protocol for an umbrella review.

INTRODUCTION: Efficacy of aliskiren combination therapy with other antihypertensive has been evaluated in the treatment of patients with hypertension in recent systematic reviews. However, most previous reviews only focused on one single health outcome or one setting, none of them made a full summary that assessed the impact of aliskiren combination treatment comprehensively. As such, this umbrella review based on systematic reviews and meta-analyses is aimed to synthesise the evidences on efficacy, safety and tolerability of aliskiren-based therapy for hypertension and related comorbid patients. METHODS AND ANALYSIS: A comprehensive search of PubMed, EMBASE, Cochrane Library, CNKI published from inception to August 2020 will be conducted. The selected articles are systematic reviews which evaluated efficacy, safety and tolerability of aliskiren combination therapy. Two reviewers will screen eligible articles, extract data and evaluate quality independently. Any disputes will be resolved by discussion or the arbitration of a third person. The quality of reporting evidence will be assessed using the Assessment of Multiple Systematic Reviews V.2 tool tool. We will take a mixed-methods approach to synthesising the review literatures, reporting summary of findings tables and iteratively mapping the results. ETHICS AND DISSEMINATION: Ethical approval is not required for the study, as we would only collect data from available published materials. This umbrella review will be also submitted to a peer-reviewed journal for publication after completion. PROSPERO REGISTRATION NUMBER: CRD42020192131.

Clinical characteristics on admission predict in-hospital fatal outcome in patients aged ≥75 years with novel coronavirus disease (COVID-19): a retrospective cohort study.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) has become a worldwide pandemic and precise fatality data by age group is needed urgently. This study to delineate the clinical characteristics and outcome of COVID-19 patients aged ≥75 years and identify the risk factors of in-hospital death. METHODS: A total of 141 consecutive patients aged ≥75 years who were admitted to the hospital between 12th and 19th February 2020. In-hospital death, clinical characteristics and laboratory findings on admission were obtained from medical records. The final follow-up observation was on the 31st March 2020. RESULTS: The median age was 81 years (84 female, 59.6%). Thirty-eight (27%) patients were classified as severe or critical cases. 18 (12.8%) patients had died in hospital and the remaining 123 were discharged. Patients who died were more likely to present with fever (38.9% vs. 7.3%); low percutaneous oxygen saturation (SpO2) (55.6% vs. 7.3%); reduced lymphocytes (72.2% vs. 35.8%) and platelets (27.8% vs. 4.1%); and increased D-dimer (94.4% vs. 42.3%), creatinine (50.0% vs. 22.0%), lactic dehydrogenase (LDH) (77.8% vs. 30.1%), high sensitivity troponin I (hs-TnI) (72.2% vs. 14.6%), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (72.2% vs. 6.5%; all P < 0.05) than patients who recovered. Male sex (odds ratio [OR] = 13.1, 95% confidence interval [CI] 1.1 to 160.1, P = 0.044), body temperature > 37.3 °C (OR = 80.5, 95% CI 4.6 to 1407.6, P = 0.003), SpO2 ≤ 90% (OR = 70.1, 95% CI 4.6 to 1060.4, P = 0.002), and NT-proBNP> 1800 ng/L (OR = 273.5, 95% CI 14.7 to 5104.8, P < 0.0001) were independent risk factors of in-hospital death. CONCLUSIONS: In-hospital fatality among elderly COVID-19 patients can be estimated by sex and on-admission measurements of body temperature, SpO2, and NT-proBNP.

Clinical efficacy, safety and tolerability of Aliskiren Monotherapy (AM): an umbrella review of systematic reviews.

BACKGROUND: Aliskiren is a newly developed drug. Its role in lowering BP has been recognized. However, the role of aliskiren in treating heart and renal diseases are still controversial. OBJECTIVE: To evaluate the existing evidence about clinical efficacy, safety and tolerability of aliskiren monotherapy (AM). METHODS: An umbrella review of systematic reviews of interventional studies. We searched Pubmed, Embase and Cochrane Library up to June 2019. Two reviewers applied inclusion criteria to the select potential articles independently. The extract and analyze of accessible data were did by two reviewers independently too. Discrepancies were resolved with discussion or the arbitration of the third author. RESULTS: Eventually, our review identified 14 eligible studies. Results showed that for essential hypertension patients, aliskiren showed a great superiority over placebo in BP reduction, BP response rate and BP control rate. Aliskiren and placebo, ARBs or ACEIs showed no difference in the number or extent of adverse events. For heart failure patients, AM did not reduce BNP levels (SMD -0.08, - 0.31 to 0.15) or mortality rate (RR 0.76, 0.32 to 1.80), but it decreased NT-proBNP (SMD -0.12, - 0.21 to - 0.03) and PRA levels (SMD 0.52, 0.30 to 0.75), increased PRC levels (SMD -0.66, - 0.8 to - 0.44). For patients who are suffered from hypertension and diabetes and/or nephropathy or albuminuria at the same time, aliskiren produced no significant effects (RR 0.97, 0.81 to 1.16). CONCLUSION: We found solid evidence to support the benefits of aliskiren in the treatment of essential hypertension, aliskiren can produce significant effects in lowering BP and reliable safety. However, the effects of aliskiren in cardiovascular and renal outcomes were insignificant. TRIAL REGISTRATION: Study has been registered in PROSPERO (CRD42019142141).

Comprehensive analysis of the compound profiles of Folium Camelliae Nitidissimae extract by ultrafast liquid chromatography with quadrupole-time-of-flight mass spectrometry and hepatoprotective effect against CCl4 -induced liver injury in mice.

Folium Camelliae Nitidissimae (jinhuacha in Chinese, JHC) is a kind of caffeine-less tea with antioxidant, antitumor and antibacterial effects. Studies on the chemical profiles and hepatoprotective effects of JHC extracts have not been systematically conducted so far. This study comprehensively investigated the compound profiles of JHC extract by ultrafast liquid chromatography with quadrupole time-of-flight tandem mass spectrometry. We also determined JHC's hepatoprotective effects against CCl4 -induced liver injury in mice. A JHC extract was administered orally to mice at 1.95 and 7.80 g/kg body weight once daily for 14 consecutive days prior to CCl4 treatment. Eighty-four compounds including flavonoids, organic acids, catechins, coumarins, phenylpropanol, amino acids, anthraquinones, saponins and nucleosides in JHC extract were authentically identified or tentatively identified by comparing MS information and retention times with those of authentic standards or available references. JHC administration significantly decreased elevated levels of aspartate aminotransferase and alanine aminotransferase in mouse serum, inhibited hepatic malondialdehyde formation and enhanced glutathione and superoxide dismutase activities in the liver of CCl4 -treated mice. The histological observations also further supported the results. These results demonstrate that JHC contains various chemical compounds and its hepatoprotective effects against CCl4 -induced liver injury correlated with decreasing lipid oxidation are significant.

Clinical efficacy, safety and tolerability of aliskiren monotherapy: a protocol for an umbrella review.

INTRODUCTION: Aliskiren is a newly developed medicine. As one of the effective renin-angiotensin-aldosterone system inhibitors, its role in lowering blood pressure has been recognised. However, its safety and tolerability still remain controversial. The aim of the paper is to systematically summarise the published studies about the clinical efficacy and side effects of aliskiren monotherapy. METHODS AND ANALYSIS: A comprehensive review of PubMed, Embase and Cochrane Library databases published from inception until June 2019 will be conducted. The selected articles are meta-analyses that integrated the randomised controlled studies, which evaluated efficacy, safety and tolerability of aliskiren monotherapy. Two people will select eligible articles and extract data independently. Any disputes will be resolved by discussion or the arbitration of a third person. The quality of reporting evidence will be assessed using the AMSTAR 2 tool. Study selection process will be presented using a flowchart. We will re-analyse each outcome with the random effect methods if necessary. If possible, we will also calculate 95% prediction intervals for each random effect estimate, by using Egger's test to evaluate if the reporting bias existed. ETHICS AND DISSEMINATION: Ethical approval is not required for the study, as we only collected data from available published materials. This umbrella review will be also submitted to a peer-reviewed journal for publication after completion. PROSPERO REGISTRATION NUMBER: CRD42019142141.

Aquivion-Carbon Composites with Tunable Amphiphilicity for Pickering Interfacial Catalysis.

A key demand in biomass conversion is how to achieve high reactivity with immiscible reagents with the use of neither cosolvents nor additives. Pickering interfacial catalysis encompassing the design of amphiphilic catalysts behaving concomitantly as emulsifiers offers an elegant solution. In this study, we prepared a systematic series of amphiphilic Aquivion-carbon composites by the hydrothermal carbonization of guar gum with Aquivion perfluorosulfonic superacid. By tuning the Aquivion-carbon composition, materials with tunable hydrophilic-lipophilic properties could be prepared, showing high versatility for conducting biphasic reactions without stirring. In particular, an optimal formulation based on 5:1 Aquivion-carbon could be developed, showing high activity in the transesterification reaction of glyceryl trioleate with methanol at 100 °C with good reusability due to the genesis of stable Pickering emulsions.

Photonic crystal materials and their application in biomedicine.

Photonic crystal (PC) materials exhibit unique structural colors that originate from their intrinsic photonic band gap. Because of their highly ordered structure and distinct optical characteristics, PC-based biomaterials have advantages in the multiplex detection, biomolecular screening and real-time monitoring of biomolecules. In addition, PCs provide good platforms for drug loading and biomolecule modification, which could be applied to biosensors and biological carriers. A number of methods are now available to fabricate PC materials with variable structure colors, which could be applied in biomedicine. Emphasis is given to the description of various applications of PC materials in biomedicine, including drug delivery, biodetection and tumor screening. We believe that this article will promote greater communication among researchers in the fields of chemistry, material science, biology, medicine and pharmacy.

Whole Exome Sequencing Identifies Frequent Somatic Mutations in Cell-Cell Adhesion Genes in Chinese Patients with Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy.