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Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NH
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Objective:To investigate the relationship and diagnostic value of serum hepatitis B virus(HBV) RNA on liver significant inflammation in chronic hepatitis B (CHB)patients with normal or mildly elevated alanine transaminase (ALT) levels.Methods:A total of 211 treatment-naive CHB patients with ALT<two times of the upper limit of normal in Shanghai Public Health Clinical Center, Fudan University between January 2016 and June 2019 were retrospectively studied.All of them received liver biopsy. Serum HBV RNA levels were quantified by quantitative reverse transcription polymerase chain reaction. Statistical analyses were performed with t test, Mann-Whitney U test, chi-square test and logistic regression analysis. Results:In 83 hepatitis B e antigen (HBeAg)-positive patients, the serum HBV RNA levels decreased with the increasing severity of liver inflammation ((6.208±1.363) lg copies/mL vs (4.654±0.962) lg copies/mL, t=6.035, P<0.01). In 138 HBeAg-negative patients, the serum HBV RNA levels increased with the increasing severity of liver inflammation ((3.101±0.720) lg copies/mL vs (3.965±0.782) lg copies/mL, t=-5.892, P<0.01). Logistic regression analysis showed that serum HBV RNA level was an independent predictor for significant liver inflammation (odds ratio ( OR)=0.168, P=0.003) in HBeAg-positive patients. Area under receiver operator characteristic curve (AUROC) was 0.82 (95% confidence interval ( CI) 0.73-0.91) of HBV RNA and 0.56(95% CI 0.44-0.69) of ALT for the diagnosis of significant liver inflammation. The difference was statistically significant ( z=2.975, P=0.003). Serum HBV RNA ( OR=4.960, P<0.01), γ-glutamyl transpeptidase ( OR=1.021, P=0.019) and blood platelet (PLT) ( OR=0.987, P=0.008) were independent predictors for significant liver inflammation in HBeAg-negative patients. The AUROC of HBV RNA and ALT was 0.78(95% CI 0.69-0.87) and 0.65(95% CI 0.55-0.75), respectively. The AUROC of combination diagnostic model consisting of HBV RNA, γ-glutamyl transpeptidase and blood platelet was 0.86(95% CI 0.79-0.93) for the diagnosis of significant liver inflammation. Conclusions:The serum HBV RNA levels are significantly different among the different phases of liver inflammation in treatment-naive CHB patients with normal or mildly elevated ALT levels. Inflammation-related serum HBV RNA and combination diagnostic model are expected to be the novel non-invasive diagnostic biomarkers for significant liver inflammation and of great benefit for determining the time for clinical medication of treatment-naive CHB patients.
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In recent years, mesoporous silica nanoparticles (MSNs) have been widely used in the construction of various intelligent drug delivery systems due to their unique and excellent properties. The stimuli-responsive drug delivery system based on mesoporous silica nanoparticles can effectively load anticancer drugs and target them to tumor cells, and then responsively release anticancer drugs under the action of specific stimulation signals. The method of specifically delivering anticancer drugs to target sites not only can greatly improvethe drug efficacy, but also effectively reduce the side effects of anticancer drugs on normal tissues and organs. Thereby the advantages of anticancer drugs in tumor therapy are improved. In this paper, the applications and developments of stimuliresponsive mesoporous silica nano drug delivery systems in tumor therapy were summarized.
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Malignant tumors are the second most important cause of death after cardiovascular and cerebrovascular diseases. Chemotherapeutic drugs for tumor treatment have strong toxic side effects. The common solution is to use nanoparticle as a carrier that can deliver drugs to tumor issues so as to kill the tumor cells. However, most of the current drug-carriers have a serious drug loss before reaching the tumor area, which makes the difficult control of drug release. Multi-stimulus responsive nano-carrier systems can overcome these drawbacks and make drug release controllable. pH/redox dual sensitive nano-carrier systems are currently hot research direction. In this paper, the research progress of pH/redox dual sensitive nano-carrier systems in recent years was reviewed in order to provide reference for relative researches.
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Objective To explore the expression profiles and their clinical significance of serum exosomal microRNA (miRNA ) in the different phases of natural history in chronic hepatitis B (CHB ) patients .Methods A total of 92 treatment-naive CHB patients in Shanghai Public Health Clinical Center between January 2014 and January 2017 were retrospectively studied .The cases in immune tolerant (IT) phase ,immune reactive (IR) phase ,inactive carrier (IC) phase and HBeAg-negative CHB (ENH) phase were 24 ,24 ,24 ,and 20 ,respectively .Exosomes were isolated by ExoQuick solution from 250μL serum . The expressions of the surface protein markers LAMP2 and TSG101 in serum exosomes were determined by Western blotting . The expressions of miRNA-122 , miRNA-125a , miRNA-29c , miRNA-200c in exosomes were detected by real-time fluorescent quantitative PCR .The Kruskal-Wallis H test and Mann-Whitney U test were used to determine intergroup differences . The correlation coeffcients ( r) were calculated using Spearman′s correlation .Receiver operating characteristic (ROC) and the area under the curve (AUC ) were used to calculate the diagnostic values . Results Western blotting showed that exosome-specific markers LAMP2 and TSG101 were positive .The levels of serum exosomal miRNA-122 , miRNA-125a ,miRNA-29c and miRNA-220c were significantly different in CHB patients in different phases (H=41 .06 ,29 .31 ,49 .14 and 31 .73 ,respectively ,all P<0 .05) .Based on the results of liver function test and liver biopsy , serum exosomal miRNA-122 , miRNA-29c and miRNA-200c in inflammation group were down-regulated (U = 804 ,317 and 574 ,respectively ,all P< 0 .05) ,while miRNA-125a was up-regulated (U=279 ,P<0 .01) compared with non-inflammation group .The level of exosomal miRNA-200c was negatively correlated with ALT (r= -0 .3932 ,P<0 .01) ,while the level of miRNA-125a was positively correlated with ALT (r=0 .5981 , P<0 .01) .AUC of the above exosomal miRNA were 0 .6193 ,0 .8396 ,0 .8243 and 0 .6883 ,respectively .The highest AUC was miRNA-125a with the sensitivity of 84 .62％ and the specificity of 74 .47％ .AUC of ALT discrimination for liver inflammation was 0 .7953 ,with the sensitivity of 81 .08％ and the specificity of 70 .97％ .Conclusions The serum exosomal miRNA levels are significantly different among the different phases of natural history in CHB patients .Inflammation-associated exosomal miRNA is expected to be the non-invasive diagnostic biomarkers of liver inflammation and is of great benefit for determining the best time for clinical medication of CHB patients .