Drug resistance remains a major challenge for anticancer treatment, and one of the major mechanisms of drug resistance is the overexpression of drug efflux transporters in cancer. A new approach for defeating drug resistance is the use of a co-delivery strategy that utilizes small interfering RNA (siRNA) to silence the expression of efflux transporters together with a suitable anticancer drug for drug-resistant cells. In this work, multifunctional graphene capable of integrating multiple functions in one system was employed as a novel co-delivery system for siRNA and doxorubicin (Dox), as well as for the controlled release of intracellular pH-triggered and heat-triggered Dox. Additionally, it was used as a synergistic therapy based on the photothermal effect of graphene oxide (GO) under near-infrared (NIR) irradiation and the chemotherapeutic effect of Dox. The nanocomplex exhibited high drug and siRNA loading. Furthermore, the dual delivery of siRNA and Dox by folic acid (FA)-conjugated polyethylenimine-modified PEGylated nanographene (PPG-FA/siRNA/Dox) exhibited a satisfactory gene silencing effect as well as efficient intracellular delivery of Dox. Thus, Dox could access the nucleus and induce greater cytotoxicity compared with siRNA-absent delivery systems. Significantly, under irradiation, the combined treatment showed more synergistic effect for overcoming drug resistance compared with chemotherapy effect alone.

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Background:The Wenchuan earthquake in China caused shock and grief worldwide. Sudden bereavement caused by the earthquake led to physical disorders as well as psychological disturbances in the bereaved individuals. The bereaved had a high risk for complicated grief (CG), which may have led to significant distress and impairment in their health. However, there was few available studies on CG among disaster-bereaved individuals in China after the disaster. The aim of this study was to identify factors (demographic characteristics and disaster-related variables) associated with symptoms of CG among the bereaved 18 months after the Wenchuan earthquake.Methods:This study was conducted with a cross-sectional design and a convenience sample of 271 bereaved individuals from three of the hardest hit areas. Data were collected by questionnaires and the instruments used in the study were: General questionnaire and Inventory of CG (ICG). Multivariate linear regression analysis was used to identify factors associated with symptoms of CG.Results:The mean score on ICG was 52.77 (standard deviation: 10.00). Being female and loss of a child were related to higher level of CG while having another child after the disaster and receiving psychological counseling experience were associated with lower level of CG. Forty-nine percent of the variance of CG was explained by these identified factors.Conclusions:Eighteen months after the Wenchuan earthquake, the symptoms of CG among the bereaved were higher than the previous studies with bereaved individuals. This study uncovers a vulnerable population of the bereaved at high risk for CG. Early assessments, targeted interventions, and policy support tailored for the disaster-bereaved individuals are necessary to identify and alleviate symptoms of CG and to improve their well-being.

The predominant mRNA expression of type II and immunosuppressive cytokines in pleural effusion and tumor tissue of NSCLC patients mirrors an immunosuppressive state in the immunological microenvironment. The present study may, therefore, help to elucidate mechanisms of tumor escape and contribute to the development of an effective immunomodulatory treatment of NSCLC.

Background COVID-19 has spread all around the world. Italy is one of the worst affected countries in Europe. Although there is a trend of relief, the epidemic situation hasn’t stabilized yet. This study aims to investigate the dynamics of the disease spread in Italy and provide some suggestions on containing the epidemic. Methods We compared Italy’s status at the outbreak stage and control measures with Guangdong Province in China by data observation and analysis. A modified autonomous SEIR model was used to study the COVID-19 epidemic and transmission potential during the early stage of the outbreak in Italy. We also utilized a time-dependent dynamic model to study the future disease dynamics in Italy. The impact of various non-pharmaceutical control measures on epidemic was investigated through uncertainty and sensitivity analyses. Results The comparison of specific measures implemented in the two places and the time when the measures were initiated shows that the initial prevention and control actions in Italy were not sufficiently timely and effective. We estimated parameter values based on available cumulative data and calculated the basic reproduction number to be 4.32 before the national lockdown in Italy. Based on the estimated parameter values, we performed numerical simulations to predict the epidemic trend and evaluate the impact of contact limitation, detection and diagnosis, and individual behavior change due to media coverage on the epidemic. Conclusions Italy was in a severe epidemic status and the control measures were not sufficiently timely and effective in the beginning. Non-pharmaceutical interventions, including contact restrictions and improvement of case recognition, play an important role in containing the COVID-19 epidemic. The effect of individual behavior changes due to media update of the outbreak cannot be ignored. For policy-makers, early and strict blockade measures, fast detection and improving media publicity are key to containing the epidemic.

Non-alcoholic fatty liver disease (NAFLD) is a series of diseases, involving excessive lipid deposition in the liver and is often accompanied by obesity, diabetes, dyslipidemia, abnormal blood pressure, and other metabolic disorders. In order to more accurately reflect its pathogenesis, an international consensus renamed NAFLD in 2020 as metabolic (dysfunction) associated with fatty liver disease (MAFLD). The changes in diet and lifestyle are recognized the non-drug treatment strategies; however, due to the complex pathogenesis of NAFLD, the current drug therapies are mainly focused on its pathogenic factors, key links of pathogenesis, and related metabolic disorders as targets. There is still a lack of specific drugs. In clinical studies, the common NAFLD treatments include the regulation of glucose and lipid metabolism to protect the liver and anti-inflammation. The NAFLD treatments based on the enterohepatic axis, targeting gut microbiota, are gradually emerging, and various new metabolism-regulating drugs are also under clinical development. Therefore, this review article has comprehensively discussed the research advancements in NAFLD treatment in recent years.

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