A Carbon 21 Steroidal Glycoside with Pregnane Skeleton from Cynanchum atratum Bunge Promotes Megakaryocytic and Erythroid Differentiation in Erythroleukemia HEL Cells through Regulating Platelet-Derived Growth Factor Receptor Beta and JAK2/STAT3 Pathway.

Erythroleukemia is a rare form of acute myeloid leukemia (AML). Its molecular pathogenesis remains vague, and this disease has no specific therapeutic treatments. Previously, our group isolated a series of Carbon 21 (C-21) steroidal glycosides with pregnane skeleton from the root of Cynanchum atratum Bunge. Among them, we found that a compound, named BW18, can induce S-phase cell cycle arrest and apoptosis via the mitogen-activated protein kinase (MAPK) pathway in human chronic myeloid leukemia K562 cells. However, its anti-tumor activity against erythroleukemia remains largely unknown. In this study, we aimed to investigate the anti-erythroleukemia activity of BW18 and the underlying molecular mechanisms. Our results demonstrated that BW18 exhibited a good anti-erythroleukemia activity in the human erythroleukemia cell line HEL and an in vivo xenograft mouse model. In addition, BW18 induced cell cycle arrest at the G2/M phase and promoted megakaryocytic and erythroid differentiation in HEL cells. Furthermore, RNA sequencing (RNA-seq) and rescue assay demonstrated that overexpression of platelet-derived growth factor receptor beta (PDGFRB) reversed BW18-induced megakaryocytic differentiation in HEL cells, but not erythroid differentiation. In addition, the network pharmacology analysis, the molecular docking and cellular thermal shift assay (CETSA) revealed that BW18 could inactivate Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, which might mediate BW18-induced erythroid differentiation. Taken together, our findings elucidated a novel role of PDGFRB in regulating erythroleukemia differentiation and highlighted BW18 as an attractive lead compound for erythroleukemia treatment.

Defining indicators for the scoping stage of health impact assessment to evaluate tobacco control policy in the city of Beijing.

INTRODUCTION: Beijing initiated the nation's most comprehensive tobacco control program that adheres to the WHO Framework Convention on Tobacco Control. This study aimed to identify a set of indicators for the scoping of an Health Impact Assessment (HIA) to assess this policy. METHODS: This study used a modified Delphi process. It proposed a tobacco control health impact framework based on the Driving forces- Pressure- State- Exposure- Effect- Action model and the Determinants of Health Theory. After a review of current surveillance system and literature, a working group of 13 experts with multidisciplinary background was established to formulate indicator evaluation criteria and conduct indicator scoring. Each indicator was scored by experts according to four evaluation criteria chosen. Indicators that obtained a total score above 80% and with standard error less than 5 were selected as the final set of indicators. Kendall's coefficient of concordance was calculated. RESULTS: Twenty-three out of 36 indicators were selected. Smoking prevalence, mortality rate, hospital admission rate, tobacco consumption and hospital admission fees of smoking related diseases achieved more than 90% of total scores and ranked as the top five. Kendall's concordance coefficient was 0.218 for all indicators. For all model composition, Kendall's concordance coefficients were statistically significant. CONCLUSION: This study identified a set of twenty-three indicators for scoping of HIA of a comprehensive tobacco control policy in Beijing based on a tobacco control health impact conceptual framework. The set of indicators achieved high scores and statistically significant consistency and has great potential to promote the evaluation of tobacco control policy in a global city. Further study might use the set of indicators for HIA on tobacco control policy to analyze empirical data.

A Novel Derivative of Curcumol, HCL-23, Inhibits the Malignant Phenotype of Triple-Negative Breast Cancer and Induces Apoptosis and HO-1-Dependent Ferroptosis.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype of breast cancer. Curcumol, as a natural small molecule compound, has potential anti-breast cancer activity. In this study, we chemically synthesized a derivative of curcumol, named HCL-23, by structural modification and explored its effect on and underlying mechanism regarding TNBC progression. MTT and colony formation assays demonstrated that HCL-23 significantly inhibited TNBC cells proliferation. HCL-23 induced G2/M phase cell cycle arrest and repressed the capability of migration, invasion, and adhesion in MDA-MB-231 cells. RNA-seq results identified 990 differentially expressed genes including 366 upregulated and 624 downregulated genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that these differentially expressed genes were obviously enriched in adhesion, cell migration, apoptosis, and ferroptosis. Furthermore, HCL-23 induced apoptosis via the loss of mitochondrial membrane potential and the activation of the caspase family in TNBC cells. In addition, HCL-23 was verified to trigger ferroptosis through increasing cellular reactive oxygen species (ROS), labile iron pool (LIP), and lipid peroxidation levels. Mechanistically, HCL-23 markedly upregulated the expression of heme oxygenase 1 (HO-1), and the knockdown of HO-1 could attenuate ferroptosis induced by HCL-23. In animal experiments, we found that HCL-23 inhibited tumor growth and weight. Consistently, the upregulation of Cleaved Caspase-3, Cleaved PARP, and HO-1 expression was also observed in tumor tissues treated with HCL-23. In summary, the above results suggest that HCL-23 can promote cell death through activating caspases-mediated apoptosis and HO-1-dependent ferroptosis in TNBC. Therefore, our findings provide a new potential agent against TNBC.

Potential roles and molecular mechanisms of bioactive ingredients in Curcumae Rhizoma against breast cancer.

BACKGROUND: Breast cancer is the most prevalent cancer worldwide, with high morbidity and mortality. Despite great advances in the therapeutic strategies, the survival rate in the past decades of patients with breast cancer remains unsatisfactory. Growing evidence has demonstrated that Curcumae Rhizoma, called Ezhu in Chinese, showed various pharmacological properties, including anti-bacterial, anti-oxidant, anti-inflammatory and anti-tumor activities. It has been widely used in Chinese medicine to treat many types of human cancer. PURPOSE: To comprehensively summarize and analyze the effects of active substances in Curcumae Rhizoma on breast cancer malignant phenotypes and the underlying mechanisms, as well as discuss its medicinal value and future perspectives. METHOD: We used "Curcumae Rhizoma" or the name of crude extracts and bioactive components in Curcumae Rhizoma in combination with "breast cancer" as key words. Studies focusing on their anti-breast cancer activities and mechanisms of action were extracted from Pubmed, Web of Science and CNKI databases up to October 2022. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: Crude extracts and 7 main bioactive phytochemicals (curcumol, ß-elemene, furanodiene, furanodienone, germacrone, curdione and curcumin) isolated from Curcumae Rhizoma have shown many anti-breast cancer pharmacological properties, including inhibiting cell proliferation, migration, invasion and stemness, reversing chemoresistance, and inducing cell apoptosis, cycle arrest and ferroptosis. The mechanisms of action were involved in regulating MAPK, PI3K/AKT and NF-κB signaling pathways. In vivo and clinical studies demonstrated that these compounds exhibited high anti-tumor efficacy and safety against breast cancer. CONCLUSION: These findings provide strong evidence that Curcumae Rhizoma acts as a rich source of phytochemicals and has robust anti-breast cancer properties.

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma.

PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities. EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients. RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks. CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

HIV-infected patients rarely develop invasive fungal diseases under good immune reconstitution after ART regardless high prevalence of pathogenic filamentous fungi carriage in nasopharynx/oropharynx.

Purpose: We aimed to investigate the prevalence and risk factors of filamentous fungi (FF) carriage in human immunodeficiency virus (HIV)-infected patients in Guangdong province, along with its subsequent incidence of invasive fungal disease (IFD). Methods: Seven hundred and sixteen HIV-infected individuals from the outpatient clinic and 293 sex-matched healthy controls were recruited prospectively from May 1 to August 31, 2017. Fungi were isolated from oropharyngeal and nasopharyngeal swabs, then identified by morphological and molecular biological techniques. Logistic regression analysis was used to identify risk factors of pathogenic FF carriage. Pathogenic FF carriers were followed up through the end of 2019. Results: Of the 716 included HIV-infected patients, 602 (84.1%) were male, the median age was 34 (27-42) years, and the median CD4+ count was 385 (254-542) cells/µl. Pathogenic FF were isolated in 119 (16.6%) cases with HIV infection and 40 (13.7%) healthy controls. Mucorales were found in 3 HIV-infected individuals and Talaromyces marneffei in 2 HIV-infected individuals, but not in healthy controls. History of cured opportunistic infections (OIs; OR, 1.97; 95% CI, 1.23-3.13, p = 0.004), and smoking (OR, 1.55; 95%CI, 1.03-2.32, p = 0.035) were independent risk factors of pathogenic FF carriage in HIV-infected individuals. A total of 119 pathogenic FF carriers with HIV infection were followed. During follow-up, 119 (100%) cases received antiretroviral therapy (ART) for at least 28 months, 107 (90%) cases had CD4+ counts>200 cells/µl, and none developed IFD. Discussion: Pathogenic FF carriage is common in HIV-infected individuals but may not develop IFD in those who achieved immune reconstitution. Smoking and cured OIs history increase the risk of pathogenic FF carriage. Smoking abstinence and ART adherence are especially important for these patients.

Protection motivation theory and smoking quitting intention: findings based on structural equation modelling and mediation analysis.

OBJECTIVE: Although many smoking cessation strategies have been implemented, only a few strategies at the population level are grounded in theory. Even in those interventions based on specific theories, most studies have focused only on the outcome. The main objective of this study was to demonstrate the utility of protection motivation theory (PMT) in explaining smoking quitting behaviour among adults, with the goal of providing valuable evidence for further intervention strategies. METHOD: This was a cross-sectional study. Participants were randomly selected on the street from 26 provinces in mainland China. Data were collected via face-to-face interviews. Cronbach's alpha coefficient and the interclass correlation coefficient (ICC) were used to assess the reliability of the individual PMT constructs. We applied structural equation modelling (SEM) to test how well the PMT constructs predicted intention. A bootstrap test was performed to test the potential mediators. RESULTS: The Cronbach's alpha coefficients of all the subscales ranged from 0.71 to 0.74. Greater intentions were significantly associated with higher threat appraisal (Coef. = 0.18, P < 0.01) and coping appraisal (Coef. = 0.24, P < 0.01). Threat appraisal was significantly associated with higher perceived severity and vulnerability but inversely associated with extrinsic rewards and intrinsic rewards. Coping appraisal was significantly associated with higher self-efficacy and response efficacy but inversely associated with response cost. The R2 of quitting intention was 0.12, which means that 12% of quitting intention was predicted by PMT constructs. For threat appraisal, approximately 19.8% of the effects on lower threat appraisal were mediated by higher extrinsic rewards. For coping appraisal, approximately 42.8% of the effects on higher coping appraisal were mediated by higher response efficacy. CONCLUSION: This study finds that PMT is a sound theoretical framework for predicting smoking quitting intention among adults. Coping appraisal has a stronger effect than threat appraisal for predicting quitting intention. Mediation analyses confirmed that extrinsic rewards and response efficacy mediated the relationship between PMT constructs and quitting intention. Our findings are essential for understanding quitting behaviour among adults and support more effective smoking cessation activities.

The characteristics and patterns of e-cigarette use and its association with cigarette cessation intention in a Chinese smoking population: A mediation analysis.

INTRODUCTION: The use of e-cigarettes has become more common in China, but the research on e-cigarettes in China, while growing, is still limited. This study examined the characteristics and patterns of e-cigarette use, and analyzed the possible mediators between cigarette cessation intention and e-cigarette use in a Chinese smoking population. METHODS: This was a cross-sectional study conducted in mainland China. By convenience sampling method, the participants were recruited from 85 major commercial streets of several large cities in China. The study interviewers completed face-to-face interviews and uploaded the completed questionnaires into the online survey platform. The participants were contacted for clarification if any problems were detected. Logistic regression yielded adjusted odds ratios (ORs) for ever use of e-cigarettes. We further conducted a mediation analysis to estimate the effect of possible mediators. RESULTS: From July to August 2020, a total of 738 smokers were invited to participate in this study; 613 smokers were identified as eligible and 609 smokers were included in this analysis. Of them, 24 (3.94%) participants were currently using e-cigarettes, and 165 (27.09%) participants have ever used e-cigarettes. The participants with younger age were more likely to have ever used e-cigarettes, ranging from 37.5% in the 18-29 years age group to 6.5% in the 60-69 years age group. After controlling for demographic characteristics and nicotine dependence, the ever use of e-cigarettes was significantly associated with younger age, higher education level, higher monthly income, previous smoking cessation attempts and quitting intention. With the mediation analysis, the education level is confirmed as a mediating factor, and approximately 42.86% of the effects were mediated through the channel of higher socioeconomic status. CONCLUSIONS: This is the first study to examine the possible mediators between cigarette cessation intention and e-cigarette use in a Chinese smoking population. The findings revealed that high socioeconomic status, particularly higher education level, was a major mediating factor.

The association of workplace smoke-free policies on individual smoking and quitting-related behaviours.

BACKGROUND: Our study aims to provide information about workplace smoke-free (SF) policy coverage in mainland China and to assess the relationship between workplace SF policies and secondhand smoke (SHS) exposure, current smoking, smoking harm awareness and quitting intention among smokers. METHOD: Data from the 2018 Asia Best Workplace Mainland China programme were used to address these aims. This cross-sectional study included 14,195 employees from the 2018 survey and 14,953 employees from the 2019 survey. Logistic regression with year-fixed effects was applied to these data. The dependent variables were SHS exposure, smoking or smoking harm awareness. The explanatory variable was the SF workplace policy. RESULTS: A total of 21,275 participants (73.0%) reported working under SF policies. The overall prevalence of smoking and SHS exposure were 20.3% and 52.5%, respectively. The workplace SF policy was significantly associated with lower SHS exposure (OR: 0.48, 95% CI: 0.45-0.51), lower current smoking employees (OR: 0.81, 95% CI: 0.76-0.87) and higher awareness of smoking harm (OR: 1.76, 95% CI: 1.61-1.91). However, workplace SF policy was not significantly associated with quitting intention (OR: 0.99, 95% CI: 0.84-1.16). CONCLUSION: Our study identified that although most companies had established workplace SF policies, the overall prevalence of SHS exposure remained very high. Workplace SF policy is associated with lower SHS exposure, lower overall current smoking and higher awareness of smoking harm. These findings provide valuable evidence to promote such policies in all workplaces.

Tobacco dependence affects determinants related to quitting intention and behaviour.

This study uses protection motivation theory (PMT) to examine the quitting intentions and behaviours of smokers who have varying levels of nicotine dependence. Our goals are to identify the psychological factors that influence smoking cessation and to provide valuable evidence to promote theory-guided interventions. This is a cross-sectional study that was conducted from July to August 2020. Participants were randomly selected on the streets of 26 provinces on mainland China. Data were collected via face-to-face interviews. Our analysis was conducted in three steps. First, we employed descriptive statistics to present the overall characteristics of our sample. Second, we analysed the association between PMT constructs and quitting intentions stratified by nicotine dependence. Third, we tested how quitting intentions were associated with quitting behaviours in each subgroup using logistic regression models. For intention, almost all the PMT constructs were significantly associated with quitting intention in the low-dependence group. For the moderate- and high-dependence groups, only perceived vulnerability (coefficient = 0.35, P = 0.04) was positively associated with quitting intention. For behaviour, we found a stronger association between quitting intention and behaviour in the low-dependence group (Coef. = 1.67, P = 0.00) than for the other groups. We found a significant association between e-cigarette use and quitting behaviour only in the low-dependence group (Coef. = 1.34, P = 0.00). Coefficients for the moderate- and high-dependence groups were not statistically significant. Smokers at various levels of nicotine dependence have different psychological factors that influence their intentions to stop smoking. Quitting intention was more significantly associated with quitting behaviour for the low nicotine-dependence group than for the other groups. More convincing research is necessary to determine how e-cigarette use affects quitting behaviour in the long term.

The association of workplace health education with smoking-related behaviour and unequal gains by job position in China: ABWMC programme findings.

BACKGROUND: Although the Chinese government has introduced a series of regulations to promote tobacco-related health education in workplaces, their implementation has been far from satisfactory. The aim of the present study was to explore the association of company-level tobacco-related health education and employee smoking behaviour. METHODS: Data from the 2018 Asia Best Workplace Mainland China programme were used to address these aims. This was a cross-sectional study that included 14,195 employees from 79 companies in mainland China. Spearman correlation tests were used to examine unadjusted correlations between the study variables, and binary logistic regression was used for multivariable analysis. The dependent variables included smoking-related variables or health information-seeking behaviour. The explanatory variable was the company-level tobacco-related health education. RESULTS: Tobacco-related health education was associated with better smoking harm awareness (OR = 2.23; 95% CI = 1.94-2.56), lower second-hand smoke exposure (OR = 0.73; 95% CI = 0.66-0.81), better perception of the workplace environment (OR = 2.04; 95% CI = 1.84-2.26) and positive health information-seeking behaviour (OR = 2.07; 95% CI = 1.86-2.30). Job position interacted with health education, suggesting that the positive association of health education was lower for general employees than employees who held an administrative position. CONCLUSIONS: Tobacco-related health education is not only associated with lower SHS exposure but also related to more positive environmental perceptions and health attitudes, and these effects are significant for higher-ranking employees. Policy makers should recognize and reduce these potential health disparities.

4-Hydroxyl-oxoisoaporphine, one small molecule as theranostic agent for simultaneous fluorescence imaging and photodynamic therapy as type II photosensitizer.

Oxoisoaporphine (OA) is a plant phototoxin isolated from Menispermaceae, however, its weak fluorescence and low water solubility impede it for theranostics. We developed here 4-hydroxyl-oxoisoaporphine (OHOA), which has good singlet oxygen-generating ability (0.06), strong fluorescence (0.72) and improved water solubility. OHOA displays excellent fluorescence for cell imaging and exhibits light-induced cytotoxicity against cancer cell. In vitro model of human cervical carcinoma (HeLa) cell proved that singlet oxygen generated by OHOA triggered photosensitized oxidation reactions and exert toxic effect on tumor cells. The MTT assay using HeLa cells verified the low cytotoxicity of OHOA in the dark and high phototoxicity. Confocal experiment indicates that OHOA mainly distributes in mitochondria and western blotting demonstrated that OHOA induces cell apoptosis via the mitochondrial pathway in the presence of light. Our molecule provides an alternative choice as a theranostic agent against cancer cells which usually are in conflict with each other for most traditional theranostic agents.

Mutation landscape of TSC1/TSC2 in Chinese patients with tuberous sclerosis complex.

Genetic testing of TSC1 and TSC2 is important for the diagnosis of tuberous sclerosis complex (TSC), an autosomal dominant neurocutaneous disease. This study retrospectively reviewed 347 samples from patients with clinically suspected TSC being tested for mutations in TSC1 and TSC2 genes using next-generation sequencing and multiplex ligation-dependent probe amplification. Two hundred eighty-one patients (80.98%) were classified as definite/possible/uncertain diagnosis of TSC and the mutational spectrum of TSC1/TSC2 was described. Two hundred eighteen unique nonsynonymous SNVs/Indels (64 in TSC1, 154 in TSC2) and 13 copy number variants (CNVs) were identified in 241 samples (85.77%), including 82 novel variants. CNVs involving 12 large deletions and one duplication were detected exclusively in TSC2. Both TSC1 and TSC2 mutations were nearly uniformly distributed in their protein-coding regions. Furthermore, a string of non-TSC1/TSC2 deleterious variants in 12 genes was identified in the patients, especially overwhelmingly present in the patients with no mutation identified (NMI) in TSC1/TSC2. Our study provides a comprehensive TSC1/TSC2 mutation landscape and reveal some potential risk non-TSCs variants present in patients with NMI.

Discovery of a Highly Potent and Novel Gambogic Acid Derivative as an Anticancer Drug Candidate.

BACKGROUND AND PURPOSE: Gambogic Acid (GA), a promising anti-cancer agent isolated from the resin of Garcinia species in Southeast Asia, exhibits high potency in inhibiting a wide variety of cancer cells' growth. Moreover, the fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anti-cancer agents. METHODS: Gambogic acid-3-(4-pyrimidinyloxy) propyl ester (compound 4) was derived from the reaction between 4-hydroxypropoxy pyrimidine and GA. Its structure was elucidated by comprehensive analysis of ESIMS, HRESIMS, 1 D NMR data. Anti-tumor activities of compound 4 and GA in vitro against HepG-2, A549 and MCF-7 cells were investigated by MTT assay. FITC/PI dye was used to test apoptosis. The binding affinity difference of compound 4 and GA binding to IKKß was studied by using Discovery Studio 2016. RESULTS: Compound 4 was successfully synthesized and showed strong inhibitory effects on HepG-2, A549 and MCF-7 cells lines with an IC50 value of 1.49±0.11, 1.37±0.06 and 0.64±0.16µM, respectively. Molecular docking study demonstrated that four more hydrogen bonds were established between IKKß and compound 4, compared with GA. CONCLUSION: Our results suggested that compound 4 showed significant effects in inducing apoptosis. Further molecular docking study indicated that the introduction of pyrimidine could improve GA's binding affinity to IKKß. Compound 4 may serve as a potential lead compound for the development of new anti-cancer drugs.

Using betaxolol for the prevention of paronychia induced by epidermal growth factor receptor inhibitors: a case-control cohort study.

BACKGROUND: High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)-induced paronychia, which may even interrupt the course of treatment for EGFR-TKI therapy. Thus, we conducted this study to determine how effectively a topical ß-blocker, betaxolol, prevents EGFR-TKI-induced paronychia. METHODS: This case-control cohort study included a total of 131 non-small-cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR-TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR-TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. RESULTS: In terms of the cumulative incidence of paronychia, significant differences (P < 0.01) were noted at both the 2nd and 3rd months after starting EGFR-TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively (P < 0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively (P < 0.01). The average numbers of involved digits were 2.25 (range: 1-5 digits) in the prevention group and 3.03 (range: 1-7) in the control group (P = 0.07). CONCLUSIONS: Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR-TKI-induced paronychia.

Inferring Disease-Associated Microbes Based on Multi-Data Integration and Network Consistency Projection.

Plenty of microbes in our human body play a vital role in the process of cell physiology. In recent years, there is accumulating evidence indicating that microbes are closely related to many complex human diseases. In-depth investigation of disease-associated microbes can contribute to understanding the pathogenesis of diseases and thus provide novel strategies for the treatment, diagnosis, and prevention of diseases. To date, many computational models have been proposed for predicting microbe-disease associations using available similarity networks. However, these similarity networks are not effectively fused. In this study, we proposed a novel computational model based on multi-data integration and network consistency projection for Human Microbe-Disease Associations Prediction (HMDA-Pred), which fuses multiple similarity networks by a linear network fusion method. HMDA-Pred yielded AUC values of 0.9589 and 0.9361 ± 0.0037 in the experiments of leave-one-out cross validation (LOOCV) and 5-fold cross validation (5-fold CV), respectively. Furthermore, in case studies, 10, 8, and 10 out of the top 10 predicted microbes of asthma, colon cancer, and inflammatory bowel disease were confirmed by the literatures, respectively.

An NIR-light-responsive surface molecularly imprinted polymer for photoregulated drug release in aqueous solution through porcine tissue.

The application of photoresponsive surface molecularly imprinted polymers based on azobenzene is limited by the UV light source required and their poor water solubility. Reducing the phototoxicity and solvent toxicity of the polymers therefore presents a challenge. In this work, an NIR-light-responsive surface molecularly imprinted polymer was fabricated by atom transfer radical polymerization using up-conversion nanoparticles as the core, a hydrophilic green-light-responsive azobenzene derivative as the functional monomer, and a drug as the template. The up-conversion nanoparticles core emitted green fluorescence in the range of 520-550 nm upon NIR irradiation (980 nm, 5 W cm-2), which was absorbed by the azobenzene containing molecularly imprinted polymers layer on the up-conversion nanoparticles surface. This caused the azobenzene chromophores to undergo trans→cis isomerization in phosphate buffered solution (pH = 7.4), thus resulting in NIR-light-induced drug release. The up-conversion fluorescence spectra were used to study the interaction mechanism between the azobenzene monomer and NIR light. Compared with structural analogues of the template (antifebrin and phenacetin), the NIR-light-responsive surface molecularly imprinted polymer showed excellent specificity of recognition for the template drug (paracetamol). The maximum adsorption capacity of the NIR-light-responsive surface molecularly imprinted polymer for loading of paracetamol was 16.80 µmol g-1. The NIR-light-responsive surface molecularly imprinted polymer was applied for NIR-light-induced paracetamol release in phosphate buffered solution (pH = 7.4) through porcine tissue. This work demonstrates the potential of drug delivery systems based on molecularly imprinted polymers for application in deep tissue delivery.

Prediction of the Prognosis Based on Chromosomal Instability-Related DNA Methylation Patterns of ELOVL2 and UBAC2 in PTCs.

Papillary thyroid carcinoma (PTC) is the most common malignant tumor of endocrine systems. Chromosomal instability (CIN) is crucial to the clinical prognoses of tumor patients. DNA methylation plays an important role in the regulation of gene expression and CIN. Based on PTC samples from The Cancer Genome Atlas database, we used multiple regression analyses to identify methylation patterns of CpG sites with the strongest correlation with gene expression. A total of 4,997 genes were obtained through combining the CpG sites, which were represented as featured DNA methylation patterns. In order to identify CIN-related epigenetic markers of PTC survival, we developed a method to characterize CIN based on DNA methylation patterns of genes using the Student's t statistics. We found that 1,239 genes were highly associated with CIN. With the use of the log-rank test, univariate Cox regression analyses, and the Kaplan-Meier method, DNA methylation patterns of UBAC2 and ELOVL2, highly correlated with CIN, provided potential prognostic values for PTC. The higher these two genes, risk scores were correlated with worse PTC patient prognoses. Moreover, the ELOVL2 risk score was significantly different in the four stages of PTC, suggesting that it was related to the progress of PTC. The DNA methylation pattern associated with CIN may therefore be a good predictor of PTC survival.

Pyridone-containing phenalenone-based photosensitizer working both under light and in the dark for photodynamic therapy.

Photosensitizer attracts great attentions and has potential applications in cancer treatment. We developed here a novel pyridone-containing phenalenone-based (PPN-PYR) photosensitizer with excellent singlet oxygen generating ability. Upon light irradiation, PPN-PYR can produce singlet oxygen and transform to its endoperoxide form which in turn release singlet oxygen via thermal cycloreversion at dark. The ability of PPN-PYR to generate reactive oxygen species (ROS) in cell culture and induce corresponding apoptosis both at dark and under light was demonstrated. The efficient PDT performance of PPN-PYR was further verified on cancer cell in vitro. Our study indicate that PPN-PYR can alleviate tumor hypoxia problem and enhance the availability of intermittent photodynamic therapy.