It is unclear which kind of interventional therapies is the best when treating early-stage hepatocellular carcinoma (HCC). We conducted Bayesian network meta-analyses to compare local tumor progression (LTP), total tumor recurrence and survival rates and to rank the best intervention arm.A literature search of Pubmed, Embase, Cochrane library and Clinicaltrials.gov was conducted and randomized controlled trials (RCTs) comparing the outcomes of interventional therapies on early-stage HCC were enrolled. The quality assessment was conducted using Cochrane Collaboration's tool, while the outcome synthesis of the network meta-analysis was conducted using R-3.3.4 software.A total of 35 RCTs were enrolled for further analysis. Using network meta-analysis, it was demonstrated that radiofrequency ablation (RFA) plus adjuvant therapies achieved the best performance in decreasing the LTP rate in early-stage HCC, while hepatic resection ranked as the best arm among all the interventional techniques for LTP at 3 years. Meanwhile, hepatic resection and RFA plus adjuvant therapies were the top two best arms in decreasing total recurrence. Furthermore, RFA plus adjuvant therapeutics ranked the best in achieving overall survival outcome, followed by hepatic resection. For disease-free survival, hepatic resection was the best, while for LTP-free survival, the difference among the included treatments was not significant.Our network meta-analysis showed that RFA-based adjuvant therapies might be the most effective interventions in achieving the best outcomes, while hepatic resection exhibited the best performance in several situations in treating early-stage HCC. More RCTs are needed to draw more solid conclusions.
In order to diagnose and treat papillary thyroid carcinoma (PTC) accurately, phase-transition nanoparticles, P@IP-miRNA (PFP@IR780/PLGA-bPEI-miRNA338-3p), was engineered. The nanoparticles (NPs) can target the tumor cells, realize the multimodal imaging, and provide sonodynamic-gene therapy for PTC.P@IP-miRNA NPs were synthesized through double emulsification method, and miRNA338-3p was attached to the surface of the NPs by electrostatic adsorption. The characterization of NPs was detected to screen out qualified nanoparticles. In vitro, laser confocal microscopy and flow cytometry were used to detect the targeting and subcellular localization of NPs. Western blot, qRT-PCR, and immunofluorescence were used to detect the ability to transfect miRNA. CCK8 kit, laser confocal microscopy and flow cytometry were used to detect the inhibition on TPC-1 cells. In vivo experiments were performed based on tumor-bearing nude mice. The efficacy of combined treatment by NPs was comprehensively evaluated, and the multimodal imaging ability of NPs in vivo and in vitro was detected.P@IP-miRNA NPs were successfully synthesized which have spherical shape, uniform size, good dispersion and positive potential. The encapsulation rate of IR780 was (82.58±3.92) %, the drug loading rate was (6.60±0.32) %, and the adsorption capacity of miRNA338-3p was 41.78 μg/mg. NPs have excellent tumor targeting ability, miRNA transfection ability, ROS production ability and multimodal imaging ability in vivo and in vitro. The antitumor effect of combined treatment group was the best, and the efficacy was better than that of single factor treatment group, and the difference was statistically significant.P@IP-miRNA NPs can realize multimodal imaging and sonodynamic-gene therapy, providing a new idea for accurate diagnosis and treatment of PTC.
As a part of our continuing exploration to discover new potential promising fungicide candidates, eighteen sulfonate derivatives (3a–3r) containing a kakuol moiety were designed and synthesized. Synthetic sulfonate derivatives were tested comprehensively for antifungal activities against four plant pathogenic fungi (Botrytis (B.) cinerea, Valsa (V.) mali, Fusarium (F.) graminearum, Sclerotinia (S.) sclerotiorum), and their structure activity relationships were summarized. Especially, derivatives 3i and 3j exhibited remarkable activity against V. mali, with the inhibition rates of 99.8 and 100%, which were slightly superior to that of carbendazim (98.9%), a reference fungicide. Moreover, derivatives 3a, 3k and 3q possess the broader antifungal spectrum against three tested plant pathogenic fungi with inhibition rates over 60%. Structure–activity relationship (SAR) analysis indicated that the introduction of 2-F or 3-F into the benzene ring would give rise to a remarkable increase of the antifungal activity against V. mali.
The study reported the synthesis and antifungal activities in vitro against six phytopathogenic fungi of 17 novel N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives. All the target compounds were synthesized and elucidated by means of MS, high resolution (HR)-MS, IR, (1)H- and (13)C-NMR analysis. The results showed that almost all the derivatives exhibited good activities against each of the tested fungi at the concentration of 50 µg/mL. Among them, 6h displayed excellent activity against Alternaria alternata with the median effective concentration value (EC50) of 1.77 µg/mL, superior to myclobutanil (EC50=6.23 µg/mL), a commercial fungicide with broad-spectrum bioactivities for plant protection and high-efficiency. Compound 6k showed the broadest antifungal spectrum, demonstrating positive activities against the corresponding fungi with EC50 values ranging from 0.98 to 6.71 µg/mL. Furthermore, 6e to 6i revealed good activities against Alternaria solani with EC50 values of 1.90, 4.51, 7.07, 2.00 and 5.44 µg/mL, respectively. The preliminary analysis of structure-activity relationship (SAR) demonstrated that the presence of F or Cl on the benzene ring remarkably improved the activity, while the introduction of 4-OMe or CF3 group decreased the activity in varying degrees. Thus, the present results strongly suggest that N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives should be promising candidates for the development of novel antifungal agents in the effective control of phytopathogenic fungi.
Objective: Through comparing and analyzing the clinical effect, adverse reaction rate, changes of postoperative hepatic function and blood routine examination polycinnamol and anhydrous alcohol in the treatment of hepatic cyst by percutaneous puncture sclerosing under the guidance of ultrasound, evaluate the advantages and disadvantages of two sclerosing agents in the treatment of simple hepatic cysts. Methods: Eighty-six patients with hepatic cyst collected from Department of Ultrasonic Puncture and Sclerosing Agent of Third Hospital of Jilin University during April, 2015 to April, 2017 were randomly divided into polycinnamol group and anhydrous alcohol group They will separately receive two kinds of sclerosing treatment under the guidance of ultrasound to compare the adverse reaction rate, the cure rate, the changes of TBil, ALT and AST before and after treatment, and the changes of blood routine 24 hours after operation. T test was used among the data groups, and the comparison between the count data groups was compared with the X2 test. Results: The concentration of blood ethanol in polycinnamol group was significantly lower than that in anhydrous alcohol group (P < 0.05). There was no significant difference between the two groups in the cure rate (1 month after operation and 6 months after operation), the changes of blood routine at 24 h after operation and the occurrence of adverse reactions (Average P > 0.05). There was no significant difference in ALT and AST between the poly-cinnamol group and the anhydrous alcohol group 1 week after operation. Conclusion: Ultrasound-guided polycinnamol and anhydrous ethanol sclerosing for simple hepatic cysts are safe, effective, less injured and have a higher clinical cure rate, but the adverse reactions caused by polycinnamol are less than those caused by anhydrous ethanol. The adverse effects on liver function were also lighter than that of anhydrous ethanol. The appropriate sclerosing agent should be selected in combination with the clinical data of the patients.
As a part of our ongoing program for the development of analogues of kakuol drugs, 27 α, β-unsaturated ketones compounds with a terminal C=C bond, were synthesized and characterized by spectroscopic analysis.Their antifungal activity was evaluated at the concentration of 50 μg/mL against seven plant pathogenic fungi, and their structure-activity relationships (SAR) were also discussed.Especially compounds 9c, 9g, 10a exhibited more potent antifungal activity against A. solani than that of thiabendazole (a positive control).SAR analysis demonstrated that the conjugated terminal C=C bond is necessary for improvement of the activity.
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