Anti-coronavirus and anti-pulmonary inflammation effects of iridoids, the common component from Chinese herbal medicines for the treatment of COVID-19.

The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC50 of 14.3 µM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1ß and IL-8 at 10 µM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.

Comparison of percutaneous microwave ablation with radiofrequency ablation for hepatocellular carcinoma adjacent to major vessels: A retrospective study.

Purpose: To compare the therapeutic efficacy and safety of percutaneous microwave ablation (MWA) with those of percutaneous radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC) adjacent to major vessels. Methods: From January 2010 to April 2011, 78 patients with a single nodule, no >5 cm, adjacent to major vessels were enrolled in this study. Forty-four patients (forty-one men, three women; age range, 33-72 years) treated by MWA were compared with thirty-four patients (thirty-one men, three women; age range, 33-75 years) treated by RFA. Local tumor progression rate, overall survival rate, and disease-free survival rate were calculated using the Kaplan-Meier method, and differences between groups were estimated by log-rank test. Results: No death related to treatment occurred in the two groups. The 1-, 2-, and 3-year local tumor progression rates were 6.8%, 11.4%, and 15.9%, respectively, in the microwave group versus 17.6%, 20.6%, and 20.6%, respectively in the radiofrequency group (P = 0.544). The rates of major complications associated with microwave and RFA were 2.3% (1/44) versus 0% (0/34; P = 0.376). The microwave group's 1-, 2-, and 3-year disease-free survival rates were 72.7%, 65.9%, and 51.8%, respectively, and those in the radiofrequency were 58.8%, 52.9%, and 47.1%, respectively (P = 0.471). The microwave group's 1-, 2-, and 3-year overall survival rates were 93.2%, 90.9%, and 83.6%, respectively, and those in the radiofrequency group were 91.2%, 88.2%, and 82.4%, respectively (P = 0.808) There was no significant difference in local tumor progression, complications related to treatment, and long-term results between the two modalities. The incidence of peritumoral structure damage on image scan was significantly higher in the microwave group than in the RFA group (P = 0.025). Conclusions: Both RFA and MWA are safe and effective techniques for HCC adjacent to major vessels and have the same clinical value.

Highly Diastereoselective Synthesis of Oxindoles Containing Vicinal Quaternary and Tertiary Stereocenters by a Domino Heck/Decarboxylative Alkynylation Sequence.

A palladium-catalyzed domino Heck/decarboxylative alkynylation reaction of trisubstituted alkenes or enamines is reported. For two different types of substrates, the current domino reaction employing different solvents and bases led to 3,3-disubstituted oxindoles and hydropyrimidinyl spirooxindoles containing vicinal quaternary and tertiary stereocenters in moderate to good yields, respectively. The general applicability of this method was shown by gram-scale syntheses and diverse transformations of the reaction products. The enantioselective version for this domino process was also studied.

Enabling Cyclopropanation Reactions of Imidazole Heterocycles via Chemoselective Photochemical Carbene Transfer Reactions of NHC-Boranes.

Herein we report a site-selective cyclopropanation of N-heterocyclic carbene (NHC)-borane complexes via photochemical carbene transfer reactions. By subtle changes to the reaction conditions, this approach can be further extended toward the difunctionalization of NHC-boranes via cyclopropanation and the B-H insertion reaction. Further investigations in photochemical continuous-flow applications and synthetic transformations proved the utility of the method. Theoretical calculations and control experiments were performed to explain the observed selectivity.

Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as α-glucosidase and α-amylase inhibitors.

Different oleanolic acid (OA) oxime ester derivatives (3a-3t) were designed and synthesised to develop inhibitors against α-glucosidase and α-amylase. All the synthesised OA derivatives were evaluated against α-glucosidase and α-amylase in vitro. Among them, compound 3a showed the highest α-glucosidase inhibition with an IC50 of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest α-amylase inhibitory with an IC50 of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds 3a and 3f were reversible and mixed types towards α-glucosidase and α-amylase, respectively. Molecular docking studies analysed the interaction between compound and two enzymes, respectively. Furthermore, cytotoxicity evaluation assay demonstrated a high level of safety profile of compounds 3a and 3f against 3T3-L1 and HepG2 cells.HighlightsOleanolic acid oxime ester derivatives (3a-3t) were synthesised and screened against α-glucosidase and α-amylase.Compound 3a showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound 3f presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and in silico studies analysed the binding between compounds and α-glucosidase or α-amylase.

Asymmetric Domino Heck/Dearomatization Reaction of ß-Naphthols to Construct Indole-Terpenoid Frameworks.

A palladium-catalyzed enantioselective Heck cyclization/dearomatization cascade via capturing the cyclized Heck π-allylpalladium intermediate by ß-naphthols is reported, which provides a new strategy for the construction of chiral indole-terpenoid frameworks. This method affords indole-functionalized ß-naphthalenone compounds bearing an all-carbon-substituted quaternary chiral center in excellent yields (up to 92%) and enantioselectivities (up to 94% ee). In addition, the utility of this method is showcased by the gram-scale syntheses and diverse transformations of the dearomatized products.

Novel cinnamic acid magnolol derivatives as potent α-glucosidase and α-amylase inhibitors: Synthesis, in vitro and in silico studies.

In this study, twenty novel cinnamic acid magnolol derivatives were synthesized, and screened for their anti-hyperglycemic potential. All synthesized compounds exhibited good to moderate α-glucosidase and α-amylase inhibitory activities with IC50 values: 5.11 ± 1.46-90.26 ± 1.85 µM and 4.27 ± 1.51-49.28 ± 2.54 µM as compared to the standard acarbose (IC50: 255.44 ± 1.89 µM and 80.33 ± 2.95 µM, respectively). Compound 6j showed the strongest inhibitory activity against α-glucosidase (IC50 = 5.11 ± 1.46 µM) and α-amylase (IC50 = 4.27 ± 1.51 µM). Kinetic study indicated that compound 6j was reversible and a mixed type inhibitor against α-glucosidase and α-amylase. In silico studies revealed the binding interaction between 6j and two enzymes, respectively. Finally, cells cytotoxicity assay revealed that compound 6j showed low toxicity against 3 T3-L1 cells and HepG2 cells.

Synergistic anti-inflammatory effects of silibinin and thymol combination on LPS-induced RAW264.7 cells by inhibition of NF-κB and MAPK activation.

BACKGROUND: Combination drug therapy has become an effective strategy for inflammation control. The anti­inflammatory capacities of silibinin and thymol have each been investigated on its own, but little is known about the synergistic anti-inflammatory effects of these two compounds. PURPOSE: This study aims to investigate the synergistic anti-inflammatory effects of silibinin and thymol when administered in combination to lipopolysaccharide (LPS)-induced RAW264.7 cells. METHODS: RAW264.7 cells were pre-treated with silibinin and thymol individually or in combination for 2 h before LPS stimulation. Cell viability was detected by the MTT assay. Nitric oxide (NO) production was measured by Griess reagent. Reactive oxygen species (ROS) was evaluated by 2',7'-dichlorofluorescein-diacetate. ELISA was used to detect tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Western blot was performed to analyse the protein expression of LPS-induced RAW264.7 cells. RESULTS: We observed a synergistic anti-inflammatory effect of silibinin and thymol when administered in combination to LPS-induced RAW264.7 cells. Silibinin combined with thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) had more potent effects on the inhibition of NO, TNF-α, and IL-6 than those exerted by individual administration of these compounds in LPS-induced RAW264.7 cells. The combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) strongly inhibited ROS and cyclooxygenase-2 (COX-2). More importantly, the combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) was also successful in inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activities. Our results suggest that the synergistic anti-inflammatory effects of silibinin with thymol were associated with the inhibition of NF-κB and MAPK signalling pathways. CONCLUSION: The combination of silibinin and thymol (40 µM and 120 µM, respectively, with the molar ratio 1:3) could inhibit inflammation by suppressing NF-κB and MAPK signalling pathways in LPS-induced RAW264.7 cells.

[Difference in intra- and inter-specific competition of two endangered plant species (Toona ciliate var. pubescens and Taxus chinensis var. mairei)in the middle subtropical zone of China]. / ä¸­äºšçƒ­å¸¦æ¿’å±æ¤ç‰©æ¯›çº¢æ¤¿å’Œå—æ–¹çº¢è±†æ‰ç§å† ä¸Žç§é—´ç«žäº‰å·®å¼‚.

Endangered plant species are an important part of global biodiversity. To understand the competition patterns and mechanisms of endangered tree species from plant growth forms in the middle subtropical forest ecosystems, we examined the differences in intra- and inter-specific competitions between Toona ciliate var. pubescens (an intolerant of shade, deciduous species) and Taxus chinensis var. mairei (a tolerant of shade, evergreen species) in the Jiulingshan National Nature Reserve, Jiangxi Province. The results showed that intra-specific competition was dominant in the T. ciliate var. pubescens population, accounting for 66.4% of the total competition intensity. In contrary, the competitive intensity of T. chinensis var. mairei was dominated by the inter-specific competition, which accounted for 68.7% of the total competition intensity. The intra- and inter-specific competition intensity of both species decreased gradually with increasing tree diameter, indicating that competitive pressure was prevalent in small trees. T. ciliate var. pubescens was mainly affected by self-thinning due to intra-specific competition, whereas T. chinensis var. mairei was dominated by alien-thinning due to inter-specific competition. The small individuals of both species could develop into mature stage only after experiencing intense competitive selection during stand regeneration. Considering the substantial difference in the sources of competition pressures, different biodiversity conservation measures should be taken for the two endangered species with contrasting growth forms in the middle subtropical regions.

Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors.

In this study, two series of coumarin derivatives 5a∼i and 6a∼i were synthesized, and their inhibitory activity against α-glucosidase was determined. The results indicated that most of the synthesized derivatives exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 5a and 5b showed the strongest inhibition with the IC50 values of 19.64 µM and 12.98 µM, respectively. Enzyme kinetic studies of compounds 5a and 5b proved that their inhibition was reversible and a mixed type. The KI and KIS values of compound 5a were calculated to be 27.39 µM and 13.02 µM, respectively, and the corresponding values for compound 5b being 27.02 µM and 13.65 µM, respectively. The docking studies showed that compound 5b could be inserted into the active pocket of α-glucosidase and form hydrogen bonds with LYS293 to enhance the binding affinity.

Ultrafast 2,7-Naphthyridine-Based fluorescent probe for detection of thiophenol with a remarkable Stokes shift and its application In vitro and in vivo.

2,7-Naphthyridine derivatives were developed as fluorophores for the first time to design two fluorescence probes, AND-DNP and ND-DNP, which can be applied for detecting thiophenol in aqueous media. Comparing with ND-DNP, AND-DNP showed more favorable properties such as lower background, larger Stokes shift, and higher fluorescence quantum yield for detecting thiophenol. Moreover, the experimental results were verified by theoretical calculations. Hence, AND-DNP was selected as the superior fluorescence probe to detect thiophenol because of its high sensitivity and selectivity. Based on the experimental results, AND-DNP showed a remarkably larger Stokes shift (225 nm), faster response speed (30 s) and higher fluorescence enhancement (240-fold) than most other fluorescent probes for thiophenol reported in the literature. For an extended application, AND-DNP was applied to detect thiophenol quantitatively in real water samples. Meanwhile, AND-DNP also detected thiophenol via red emission in living A549 cells and zebrafish. All these results proved AND-DNP's potential value as an accurate probe for imaging thiophenol in different environments.

Synthesis and biological evaluation of novel oleanolic acid analogues as potential α-glucosidase inhibitors.

Considerable interest has been attracted in oleanolic acid and its analogues because of their hypoglycemic activity. In this study, a series of novel oleanolic acid analogues against α-glucosidase were synthesized and their biological activities were evaluated in vitro and in vivo. In vitro α-glucosidase inhibition activity results indicated that most of the designed analogues exhibited prominent inhibition activities, especially compounds 10, 15, 16 and 26 which with the IC50 values of 0.33 ±â€¯0.01, 0.98 ±â€¯0.06, 0.69 ±â€¯0.01 and 0.72 ±â€¯0.21 µM, respectively. Enzyme kinetic studies on the most potent compounds reveled that derivatives 10, 15, 16 and 26 were noncompetitive inhibitors. Moreover, the docking studies were carried out to prove that the four compounds could interact with the hydrophobic region of the active pocket and form hydrogen bonds to enhance the binding affinity of them with the α-glucosidase. Cytotoxicity evaluation assay demonstrated a high level of safety profile of the active compounds (10, 15, 16 and 26) against normal 3T3 cell line. Furthermore, the in vivo actual pharmacological potential studies on derivatives 10, 15, 16 and 26 showed that the hypoglycemic effects of them were comparable to that of positive control, acarbose.

The biological evaluation of fusidic acid and its hydrogenation derivative as antimicrobial and anti-inflammatory agents.

BACKGROUND: Fusidic acid (FA) (WU-FA-00) is the only commercially available antimicrobial from the fusidane family that has a narrow spectrum of activity against Gram-positive bacteria. METHODS: Herein, the hydrogenation derivative (WU-FA-01) of FA was prepared and both compounds were examined against a panel of six bacterial strains. In addition, their anti-inflammatory properties were evaluated using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model. RESULTS: The results of the antimicrobial assay revealed that both WU-FA-00 and WU-FA-01 displayed a high level of antimicrobial activity against Gram-positive strains. Moreover, killing kinetic studies were performed and the results were in accordance with the minimum inhibitory concentration and minimum bactericidal concentration results. We also demonstrated that the topical application of WU-FA-00 and WU-FA-01 effectively decreased TPA-induced ear edema in a dose-dependent manner. This inhibitory effect was associated with the inhibition of TPA-induced upregulation of proinflammatory cytokines IL-1ß, TNF-α, and COX-2. WU-FA-01 significantly suppressed the expression levels of p65, IκB-α, and p-IκB-α in the TPA-induced mouse ear model. CONCLUSION: Overall, our results showed that WU-FA-00 and WU-FA-01 not only had effective antimicrobial activities in vitro, especially to the Gram-positive bacteria, but also possessed strong anti-inflammatory effects in vivo. These results provide a scientific basis for developing FA derivatives as antimicrobial and anti-inflammatory agents.

Synthesis and biological evaluation of novel ursolic acid analogues as potential α-glucosidase inhibitors.

Ursolic acid (UA) is a major pentacyclic triterpenoid in plants, vegetables and fruits, which has been reported to have a potential anti-diabetic activity. Despite various semi-synthetic ursolic acid derivatives already described, new derivatives still need to be designed and synthesized to further improve the anti-diabetic activity. In the present study, two series of novel UA derivatives, were synthesized and their structures were confirmed. The enzyme inhibition activities of semi-synthesized analogues against α-glucosidase were screened in vitro. The results indicated that most of UA derivatives showed a significant inhibitory activity, especially analogues UA-O-i with the IC50 values of 0.71 ± 0.27 µM, which was more potential than other analogues and the positive control. Furthermore, molecular docking studies were also investigated to verify the in vitro study. Structure modification at the C-3 and C-2 positions of UA was an effective approach to obtain the desired ligand from UA, whose structure was in accordance with the active pocket. Besides, suitable hydrophobic group at the position of C-2 might play an important role for the docking selectivity and binding affinity between the ligand and the homology modelling protein. These results could be helpful for designing more potential α-glucosidase inhibitors from UA in the future.

Microwave ablation is as effective as radiofrequency ablation for very-early-stage hepatocellular carcinoma.

BACKGROUND: Percutaneous radiofrequency ablation (RFA) is a first-line treatment for very-early-stage hepatocellular carcinoma (HCC), whereas the efficacy of percutaneous microwave ablation (MWA) for very-early-stage HCC remains unclear. The purpose of this study was to clarify this issue by comparing the safety and efficacy of percutaneous MWA with percutaneous RFA in treating very-early-stage HCC. METHODS: Clinical data of 460 patients who were diagnosed with very-early-stage HCC and treated with percutaneous MWA or RFA between January 2007 and July 2012 at the Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, in Shanghai, China were retrospectively analyzed. Of these 460 patients, 159 received RFA, 301 received MWA. Overall survival (OS), recurrence-free survival (RFS), local tumor progression (LTP), complete ablation, and complication occurrence rates were compared between the two groups, and the prognostic factors associated with survival were analyzed. RESULTS: No significant differences were observed between the two groups in terms of the 1-, 3-, or 5-year OS rates (99.3%, 90.4%, and 78.3% for MWA vs. 98.7%, 86.8%, and 73.3% for RFA, respectively; P = 0.331). Furthermore, no significant differences were observed between the two groups in terms of the corresponding RFS rates (94.4%, 71.8%, and 46.9% for MWA vs. 89.9%, 67.3%, and 54.9% for RFA, respectively; P = 0.309), the LTP rates (9.6% vs. 10.1%, P = 0.883), the complete ablation rates (98.3% vs. 98.1%, P = 0.860), or the occurrence rates of major complications (0.7% vs. 0.6%, P = 0.691). By multivariate analysis, LTP, antiviral therapy, and treatment of recurrence were independent risk factors for OS (P < 0.001), and the alpha-fetoprotein level was an independent prognostic factor for RFS (P = 0.002). CONCLUSIONS: MWA is as safe and effective as RFA in treating very-early-stage HCC, supporting MWA as a first-line treatment option for this disease.

[Changes of Main Syndromes of Gan Failing to Maintain Normal Flow of Qi in Premenstrual Dysphoric Disorder].

Objective To observe the changes of Chinese medicine (CM) symptoms, the distri- bution characteristics of CM syndromes, and related neuroendocrine levels in premenstrual dysphoric disorder (PMDD) patients. Methods Totally 3 541 female outpatients (18 -45 years old) were inter- viewed by clinical epidemiological questionnaire. According to PMDD diagnostic criteria in DSM-IV , PMDD patients' CM syndromes were identified. Their scores of main symptoms and CM symptoms of common CM syndromes were compared. Contents of 8 neuroendocrine indicators in serum were detected [5- hydroxytryptamine (5-HT) , adrenocorticotropic hormore (ACTH) , angiotensin-II (Ang-II ) , glucocorti- coid (GC), homocysteine (Hcy), melatonin (MLT), nitrogen monoxide (NO), neuropeptide Y (NPY)]. Results Totally 258 PMDD were detected in 3 541 female outpatients (18 -45 years old). The main syn- drome and common syndromes of PMDD patients were reversed invasion of Gan qi syndrome [40.3% (104/258)] and stagnation of Gan qi syndrome [34. 9% (90/258) ], followed by Gan stagnation Pi deficiency syndrome [7.8%(20/258)], Gan stagnation blood stasis syndrome [7.4% (19/258)], Gan stagnation induced fire hyperactivity syndrome [ 6.2% ( 16258 )], Gan stagnation Shen deficiency syndrome [3.1%(8/258)], and Pi-Shen yang deficiency syndrome [0.4%(1258)]. Compared with reversed invasion of Gan qi syndrome, emotional depression and low spirits were main symptoms of stagnation of Gan qi syndrome. Scores for the two symptoms increased (P <0.05). Compared with stagnation of Gan qi syn- drome, irritability, upset, abdominal distension, anxiety, headache, dizziness, insomnia, head distension, bitter mouth, unclear vision were main symptoms of reversed invasion of Gan qi syndrome. Scores for the 10 symptoms increased (P <0.05). Compared with stagnation of Gan qi syndrome, the Hcy level in serum obviously decreased in reversed invasion of Gan qi syndrome (P <0.05). There was no statistical difference in the rest indices (P >0. 05). Conclusions PMDD is closely related to Gan failing to maintain normal flow of qi. Reversed invasion of Gan qi syndrome and stagnation of Gan qi syndrome have different scientif- ic connotations and biological bases. So regulating Gan should be considered as the first choice.

Origin and Evolution of Allopolyploid Wheatgrass Elymus fibrosus (Schrenk) Tzvelev (Poaceae: Triticeae) Reveals the Effect of Its Origination on Genetic Diversity.

Origin and evolution of tetraploid Elymus fibrosus (Schrenk) Tzvelev were characterized using low-copy nuclear gene Rpb2 (the second largest subunit of RNA polymerase II), and chloroplast region trnL-trnF (spacer between the tRNA Leu (UAA) gene and the tRNA-Phe (GAA) gene). Ten accessions of E. fibrosus along with 19 Elymus species with StH genomic constitution and diploid species in the tribe Triticeae were analyzed. Chloroplast trnL-trnF sequence data suggested that Pseudoroegneria (St genome) was the maternal donor of E. fibrosus. Rpb2 data confirmed the presence of StH genomes in E. fibrosus, and suggested that St and H genomes in E. fibrosus each is more likely originated from single gene pool. Single origin of E. fibrosus might be one of the reasons causing genetic diversity in E. fibrosus lower than those in E. caninus and E. trachycaulus, which have similar ecological preferences and breeding systems with E. fibrosus, and each was originated from multiple sources. Convergent evolution of St and H copy Rpb2 sequences in some accessions of E. fibrosus might have occurred during the evolutionary history of this allotetraploid.

Application of a UPLC-MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma.

TM-2 known as a potential antitumor drug is a novel semi-synthetic taxane derivative. As drug-protein interactions contribute to insights into pharmacokinetic and pharmacodynamic properties, we elucidated the binding of TM-2 to plasma protein. In this study, a simple, rapid and reliable method was developed and validated employing equilibrium dialysis for the separation of bound and unbound drugs and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the quantitation. Protein binding reached equilibrium within 24 h of incubation at 37 °C. After liquid-liquid extraction with methyl tert-butyl ether, the samples were separated on Thermo Syncronis UPLC® C18 (2.1 mm×50 mm, 1.7 µm), and acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization. The assay was linear over the concentration rang of 5-2000 ng/mL. The intra- and inter-day precisions were 0.1%-14.8%, and the accuracy was from -6.4% to 7.0%. This assay has been successfully applied to a protein binding study of TM-2 in rat, human and beagle dog plasma. TM-2 showed high protein binding of 81.4%±6.5% (rat), 87.9%±3.6% (human) and 79.4%±4.0% (beagle dog). The results revealed that there was an insignificant difference among the three species.

Clinical outcome of medium-sized hepatocellular carcinoma treated with microwave ablation.

AIM: To evaluate the outcomes of patients with medium-sized hepatocellular carcinoma (HCC) who underwent percutaneous microwave ablation (MWA). METHODS: We retrospectively reviewed all patients with a single medium-sized HCC who underwent percutaneous MWA from January 2010 to January 2013. Technical success, technical effectiveness and complications were subsequently observed. Survival curves were constructed using the Kaplan-Meier method. The Cox proportional hazards model was fitted to each variable. The relative prognostic significance of the variables for predicting overall survival rate, recurrence-free survival rate and local tumor recurrence(s) was assessed using univariate analysis. All variables with a P value < 0.20 were subjected to multivariate analysis. RESULTS: The study included 182 patients (mean age, 58 years; age range: 22-86 years) with a single HCC (mean size, 3.72 ± 0.54 cm; range: 3.02-5.00 cm). The estimated technical effectiveness rate was 93% in 182 patients. The major complication rate was 2.7% (5/182), including liver abscess in 4 cases, and abdominal bleeding at the puncture site in 1 case. Thirty-day mortality rate was 0.5% (1/182). One patient died due to liver abscess-related septicemia. Cumulative recurrence-free survival and overall survival (OS) rates were 51%, 36%, 27% and 89%, 74%, 60% at 1, 2, and 3 years, respectively. Age (P = 0.017) and tumor diameter (P = 0.029) were independent factors associated with local tumor recurrence. None of the factors had a statistically significant impact on recurrence-free survival. Serum albumin level (P = 0.009) and new lesion(s) (P = 0.029) were independently associated with OS. CONCLUSION: Percutaneous MWA is a relatively safe and effective treatment for patients with medium-sized HCC.

In vitro and in vivo evaluation of the antidiabetic activity of ursolic acid derivatives.

In this study, a series of ursolic acid derivatives were synthesized, and their structures were confirmed. The activity of the synthesized compounds against α-glucosidase was determined in vitro. The results suggested that all compounds have significant inhibitory activity, especially compounds 3-5 and 8, the IC50 values of which were 2.66 ± 0.84, 1.01 ± 0.44, 3.26 ± 0.22, and 3.24 ± 0.21 µM. These compounds were more potent than acarbose (positive control) against α-glucosidase. Kinetic studies were performed to determine the mechanism of inhibition by compounds 3-5 and 8. The kinetic inhibition studies indicated that compound 3 was a non-competitive inhibitor, and the inhibition constant Ki was calculated to be 2.67 ± 0.19 µM. Moreover, the kinetic inhibition studies of compounds 4, 5 and 8 demonstrated that they were mixed-type inhibitors. Furthermore, the actual pharmacological potentials of synthesized compounds 3 and 4 were demonstrated by the reduction of postprandial blood glucose levels in normal Kunming mice. The hypoglycemic effects of these compounds were more evident 30 and 60 min after maltose ingestion (P < 0.05), which was similar to the effect displayed by the positive control, acarbose.