Absorption, metabolism, and pharmacokinetic profile of xanthohumol in rats as determined via UPLC-MS/MS.

Xanthohumol, a natural isoflavone from Humulus lupulus L., possesses biological activities. However, the biological fate of xanthohumol in vivo remains unclear. The aim of this study was to investigate the absorption and metabolism of xanthohumol in rats through UPLC-MS/MS. The plasma, urine and fecal samples were collected after oral administration of xanthohumol (25, 50, 100 mg/kg) in SD rats. The contents of xanthohumol and its metabolites were determined by UPLC-MS/MS. A total of 6 metabolites of xanthohumol were identified in rats, including methylated, glucuronidated, acid-catalyzed cyclization and oxidation, indicating xanthohumol underwent phase I and II metabolism. Besides, isoxanthohumol was the major metabolites of xanthohumol. Xanthohumol was rapidly absorbed, metabolized, and eliminated in rats. The pharmacokinetics results showed the Tmax of xanthohumol and isoxanthohumol were 3 and 2.33 h, respectively. The AUC0-t of xanthohumol and isoxanthohumol were 138.83 ± 6.03 and 38.77 ± 4.46 ng/ml·h, respectively. Furthermore, xanthohumol was mainly excreted in the form of prototype through feces and a small amount of xanthohumol was excreted through urine. These results illustrated the absorption, metabolism, and pharmacokinetics process of xanthohumol in rats, and provided a reference for the further rational applications.

Altered spontaneous brain activity patterns in dysthyroid optic neuropathy: a resting-state fMRI study.

This research investigates the characteristics of spontaneous brain activity in dysthyroid optic neuropathy patients using the regional homogeneity technique. Sixteen patients with dysthyroid optic neuropathy and 16 thyroid-associated ophthalmopathy patients without dysthyroid optic neuropathy were recruited, matched for weight, height, age, sex, and educational level. All participants underwent resting-state functional nuclear resonance imaging, and the characteristics of spontaneous brain activity were evaluated using the regional homogeneity technique. Each participant in the dysthyroid optic neuropathy group also completed the Hospital Anxiety and Depression scale. Receiver operating characteristic curves were used to compare brain activity between the two groups. Pearson correlation analysis evaluated the relationship between regional homogeneity and clinical manifestations in dysthyroid optic neuropathy patients. In addition, we analyzed the correlation between Hospital Anxiety and Depression scale and regional homogeneity. We found that the regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus significantly decreased in dysthyroid optic neuropathy patients. Regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus were negatively correlated with Hospital Anxiety and Depression scale and disease duration. It was found that the regional homogeneity signal values were significantly lower than in thyroid-associated ophthalmopathy without in dysthyroid optic neuropathy, which may indicate a risk of regional brain dysfunction in dysthyroid optic neuropathy. The results show that regional homogeneity has the potential for early diagnosis and prevent dysthyroid optic neuropathy. In addition, the findings suggest possible mechanisms of dysthyroid optic neuropathy optic nerve injury. They may provide a valuable basis for further research on the pathological mechanisms of dysthyroid optic neuropathy.

The abnormal fractional amplitude of low-frequency fluctuation changes in patients with diabetic optic neuropathy: a steady-state fMRI study.

The spontaneous changes in brain activity in patients with diabetic optic neuropathy using steady-state fMRI. The fractional amplitude of the low-frequency fluctuation method was applied to evaluate neural activity changes. The Hospital Anxiety and Depression Scale was used to assess the anxiety and depression status of participants. The independent sample t-test and chi-squared test were applied to analyze the demographics of diabetic optic neuropathy patients and healthy controls. Receiver operating characteristic curves were applied to analyze the variation in mean fractional amplitude of low-frequency fluctuation values between diabetic optic neuropathy patients and healthy controls. Pearson's correlation analysis analyzed the relationships between the fractional amplitude of low-frequency fluctuation values of brain regions and clinical behaviors in the diabetic optic neuropathy group. The fractional amplitude of low-frequency fluctuation value of diabetic optic neuropathy patients was significantly higher than healthy controls in the right precentral gyrus. However, the fractional amplitude of low-frequency fluctuation values in the right anterior cingulate gyrus and left middle cingulate gyrus were markedly decreased in diabetic optic neuropathy patients. The area under the curve of receiver operating characteristics for each brain region showed high accuracy. Pearson's correlation analysis showed that fractional amplitude of low-frequency fluctuation values of the right anterior cingulate gyrus and left middle cingulate gyrus was negatively correlated with Hospital Anxiety and Depression Scale scores. The fractional amplitude of low-frequency fluctuation values of the left middle cingulate gyrus was negatively correlated with diabetic optic neuropathy disease duration. In conclusion, we found abnormal spontaneous brain activities in regions related to cognitive and emotional dysfunction, eye movement disorder, and vision loss in patients with diabetic optic neuropathy. These results may indicate the underlying neuropathological mechanisms of diabetic optic neuropathy and show that fractional amplitude of low-frequency fluctuation may be an effective method to distinguish patients with diabetic optic neuropathy from healthy individuals.

Pretreatment risk management of a novel nomogram model for prediction of thoracoabdominal extrahepatic metastasis in primary hepatic carcinoma.

BACKGROUND: Extrahepatic metastasis is the independent risk factor of poor survival of primary hepatic carcinoma (PHC), and most occurs in the chest and abdomen. Currently, there is still no available method to predict thoracoabdominal extrahepatic metastasis in PHC. In this study, a novel nomogram model was developed and validated for prediction of thoracoabdominal extrahepatic metastasis in PHC, thereby conducted individualized risk management for pretreatment different risk population. METHODS: The nomogram model was developed in a primary study that consisted of 330 consecutive pretreatment patients with PHC. Large-scale datasets were extracted from clinical practice. The nomogram was based on the predictors optimized by data dimension reduction through Lasso regression. The prediction performance was measured by the area under the receiver operating characteristic (AUROC), and calibrated to decrease the overfit bias. Individualized risk management was conducted by weighing the net benefit of different risk population via decision curve analysis. The prediction performance was internally and independently validated, respectively. An independent-validation study using a separate set of 107 consecutive patients. RESULTS: Four predictors from 55 high-dimensional clinical datasets, including size, portal vein tumor thrombus, infection, and carbohydrate antigen 125, were incorporated to develop a nomogram model. The nomogram demonstrated valuable prediction performance with AUROC of 0.830 (0.803 in internal-validation, and 0.773 in independent-validation, respectively), and fine calibration. Individual risk probability was visually scored. Weighing the net benefit, threshold probability was classified for three-independent risk population, which was < 19.9%, 19.9-71.8% and > 71.8%, respectively. According to this classification, pretreatment risk management was based on a treatment-flowchart for individualized clinical decision-making. CONCLUSIONS: The proposed nomogram is a useful tool for pretreatment risk management of thoracoabdominal extrahepatic metastasis in PHC for the first time, and may handily facilitate timely individualized clinical decision-making for different risk population.

[Research progress of chemical constituents and pharmacological activities in Humulus lupulus].

Hops, the female inflorescences of the hop plant (Humulus lupulus), are widely used in the brewing industry to add bitterness and aroma to beer. Combining with the relevant literature, the chemical composition(resinae, volatile oil, polyphenol and polysaccharide) in hops and their pharmacological effects are reviewed in this paper so as to present some sights for further application research and development.

Silencing of ACO decreases reproduction and energy metabolism in triazophos-treated female brown plant hoppers, Nilaparvata lugens Stål (Hemiptera: Delphacidae).

The brown plant hopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacidae), is a major pest affecting rice in Asia, and outbreaks of this pest are closely linked to pesticide-induced stimulation of reproduction. Therefore, the BPH is a classic example of a resurgent pest. However, the effects of different genes on the regulation of pesticide-induced reproductive stimulation in the BPH are unclear. In this study, the regulatory effects of acyl-coenzyme A oxidase (ACO) on the reproduction and biochemistry of the BPH were investigated with gene silencing. The number of eggs laid per female by triazophos (TZP)+dsACO BPH females was significantly lower than those of TZP-treated (without ACO silencing) or TZP+GFP females (negative control), with the number of eggs decreasing by 30.8% (from 529.5 to 366.3) and 32.0% (from 540.5 to 366.3), respectively. The preoviposition period, oviposition period, and longevity of the TZP-treated females were also influenced by dsACO treatment. Additionally, the amounts of crude fat, protein, and some fatty acids (oleic acid, palmitic acid, linoleic acid, stearic acid, and myristoleic acid) in TZP+dsACO females were significantly lower than in TZP-treated females. Thus, ACO is one of the key genes regulating the TZP-induced stimulation of reproduction in BPH females.

Phytochemical and Pharmacological Profiles of Three Fagopyrum Buckwheats.

The genus Fagopyrum (Polygonaceae), currently comprising 15 species of plants, includes three important buckwheat species: Fagopyrum esculentum (F. esculentum) Moench. (common buckwheat), Fagopyrum tataricum (F. tataricum) (L.) Gaertn. (tartary buckwheat) and Fagopyrum dibotrys (F. dibotrys) (D. Don) Hara. (perennial buckwheat), which have been well explored due to their long tradition of both edible and medicinal use. This review aimed to present an up-to-date and comprehensive analysis of the phytochemistry and pharmacology of the three Fagopyrum buckwheats. In addition, the scope for future research was also discussed. All available references included in this paper were compiled from major databases, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. A total of 106 compounds isolated from three Fagopyrum buckwheats can be mainly divided into six classes: flavonoids, phenolics, fagopyritols, triterpenoids, steroids and fatty acids. Flavonoids and phenolic compounds were considered to be the major active components. Considerable pharmacological experiments both in vitro and in vivo have validated that Fagopyrum buckwheats possess antitumor, anti-oxidant, anti-inflammatory, hepatoprotective, anti-diabetic activities, etc. All reported data lead us to conclude that Fagopyrum buckwheats have convincing medicinal potential. However, further research is needed to explore its bioactive constituents, the relationship to their structural activities and the molecular mechanisms of action.

Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses.

To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1ß, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1ß, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.

Anti-inflammatory constituents from the root of Litsea cubeba in LPS-induced RAW 264.7 macrophages.

Context Litsea cubeba (Lour.) Pers. (Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) for the treatment of rheumatic diseases. Previous studies from our laboratory indicated that L. cubeba extract showed anti-arthritic activity in rats. Objective To study L. cubeba chemically and biologically and to find the potential constituents responsible for its anti-arthritic effect. Materials and methods The compounds were isolated from the root of L. cubeba by column chromatography which eluted with PE:EtOAc gradient system, and the structures were elucidated by detailed spectroscopic data analysis; the anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide (LPS)-induced RAW 264.7 cells and the TNF-α and NO level were measured by ELISA (commercial kit); The iNOS and COX-2 mRNA expression were measured by RT-PCR and the phosphorylation of IκBα, IKKß, P38 and Akt were determined by western blots. Results A novel 9-fluorenone, 1-ethoxy-3,7-dihydroxy-4,6-dimethoxy-9-fluorenone (1), together with 4 known compounds, namely pinoresinol (2), syringaresinol (3), 9,9'-O-di-(E)-feruloyl-meso-5,5'-dimethoxysecoisolariciresinol (4) and lyoniresinol (5) were isolated from the root of L. cubeba for the first time. The IC50 for NO inhibition on compounds 1 and 4 were 56.1 ± 1.2 and 32.8 ± 2.3 µM, respectively. The IC50 for TNF-α inhibition were 28.2 ± 0.9 and 15.0 ± 1.0 µM, respectively. Both 1 and 4 suppress mRNA expression of iNOS, COX-2 and protein phosphorylation of IκBα, IKKß in LPS-induced RAW 264.7 cells. Discussion and conclusion Compounds 1 and 4 isolated from L. cubeba exhibited potent anti-inflammatory activity through the NF-κB signal pathway.

[Research on immune-modulation effects and its mechanisms of Guizhi Fuling capsule and its active ingredient combination].

The effects of Guizhi Fuling capsule and its active ingredient combination within different concentration on SPL proliferate were observed by MTT method. The ratio of CD80/86, CD3CD25 and CD3CD69 was used to evaluate cell activation effects of Guizhi Fuling capsule and its active ingredient combination by FCM. Guizhi Fuling capsule with concentration of 400 mg · L(-1)can promote spleen lymphocyte proliferation, as well as the active ingredient combination, which showed the obvious dose-effect relationship. Compared with control group, the difference has statistical significance (P≤0.01). The result of FCM showed that Guizhi Fuling capsule and its active ingredient combination can promote CD80 and CD86 expression on spleen lymphocyte, and also can increase CD25 and CD69 ratio between spleen CD3+ cells. Compared with control group, the difference has statistical significance (P≤0.01). Thus, Guizhi Fuling capsule and its active ingredient combination may have immune-modulate effects, and the mechanism may have a close relationship with the lymphocyte activation.

Antiinflammatory effects and chemical constituents of Veronicastrum axillare.

Our study aims to ascertain the antiinflammatory activity of Veronicastrum axillare and characterize the bioactive constituents. Antiinflammatory activity of the total extract and different fractions from V. axillare was investigated by employing the xylene-induced mouse ear edema model. As a result, the ethyl acetate (EtOAc) fraction showed the highest antiinflammatory activity in vivo. From the EtOAc fraction and the inactive dichloromethane fraction, a total of five new compounds, axillasides A-C and axillactones A and B, together with four known compounds, procumboside A, buergeriside C1 , indole-3-carboxylic acid and apigenin, were isolated and identified. Their structures were elucidated on the basis of spectroscopic analysis and by comparison of their nuclear magnetic resonance data with those reported in the literature. Procumboside A, a major constituent in EtOAc fraction, showed significant antiinflammatory activity in vivo. Further studies revealed that procumboside A was a potent COX-2 inhibitor, significantly reducing the COX-2 protein level in lipopolysaccharide-stimulated RAW 264.7 macrophages.

Gene cloning, protein expression, and enzymatic characterization of a double-stranded RNA degrading enzyme in Apolygus lucorum.

RNA interference (RNAi) is a powerful tool that post-transcriptionally silences target genes in eukaryotic cells. However, silencing efficacy varies greatly among different insect species. Recently, we met with little success when attempting to knock down genes in the mirid bug Apolygus lucorum via dsRNA injection. The disappearance of double-stranded RNA (dsRNA) could be a potential factor that restricts RNAi efficiency. Here, we found that dsRNA can be degraded in midgut fluids, and a dsRNase of A. lucorum (AldsRNase) was identified and characterized. Sequence alignment indicated that its 6 key amino acid residues and the Mg2+ -binding site were similar to those of other insects' dsRNases. The signal peptide and endonuclease non-specific domain shared high sequence identity with the brown-winged green stinkbug Plautia stali dsRNase. AldsRNase showed high salivary gland and midgut expression and was continuously expressed through the whole life cycle, with peaks at the 4th instar ecdysis in the whole body. The purified AldsRNase protein obtained by heterologously expressed can rapidly degrade dsRNA. When comparing the substrate specificity of AldsRNase, 3 specific substrates (dsRNA, small interfering RNA, and dsDNA) were all degraded, and the most efficient degradation is dsRNA. Subsequently, immunofluorescence revealed that AldsRNase was expressed in the cytoplasm of midgut cells. Through cloning and functional study of AldsRNase, the enzyme activity and substrate specificity of the recombinant protein, as well as the subcellular localization of nuclease, the reason for the disappearance of dsRNA was explained, which was useful in improving RNAi efficiency in A. lucorum and related species.

[Chemical constituents from the roots of Ilex pubescens].

OBJECTIVE: To study the chemical constituents from the roots of Ilex pubescens. METHODS: The 95% ethanol extract of the plant was separated by silica gel, Sephadex LH-20 and preparative HPLC chromatography. The structures were elucidated based on the physiochemical properties and spectroscopic analysis. RESULTS: Fifteen compounds were isolated and identified as oleuropein(1), oleoside dimethyl ester(2),8 (Z)-nuezhenide(3),3,4-dicaffeoylquinic acid methyl ester(4),3,4,5-tricaffeoylquinic acid methyl ester (5), isovanillic acid(6), syringic acid(7), 3beta-acetyloleanolic acid (8), 3beta-acetylursolic acid(9), uvaol(10), asiatic acid(11), 2alpha-hydroxyursolic acid(12), oleanolic acid (13), ursolic acid (14), stigmasterol-3-O-beta-D-glucopyranoside (15). CONCLUSION: Compounds 2,3,8,9 are obtained from this genus for the first time,compounds 5-7,10-12 are isolated from this plant for the first time.

Curative effects of oleanolic Acid on formed hypertrophic scars in the rabbit ear model.

Hypertrophic scarring is a common proliferative disorder of dermal fibroblasts characterized by collagen overproduction and excessive deposition of extracellular matrix (ECM). There is no consensus about the best therapeutics to produce complete and permanent improvement of scars with few side effects. To investigate the therapeutic effects of oleanolic acid (OA) on hypertrophic scars and explore the possible mechanism of action involved, a rabbit ear model with hypertrophic scars was established. OA (2.5%, 5%, and 10%) was given once daily to the scars for 28 consecutive days. As a result, OA significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-ß(1), MMP-1, TIMP-1, and collagens I and III were notably decreased, and the number of apoptosis cells and mRNA expression of MMP-2, caspase-3, and caspase-9 were markedly increased in the scar tissue. The scar elevation index (SEI) was also evidently reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that OA has the favorable curative effects on formed hypertrophic scars in the rabbit ear model, and the possible mechanism of action is that OA decreases HSFs proliferation and increases HSFs apoptosis by reduction of P311 gene expression and TGF-ß(1) production, inhibition of TIMP-1 secretion, enhancement of MMP-2 activity, and subsequently facilitation of degradation of collagen types I and III.

Systematic evaluation and meta-analysis of Chinese medicine in the treatment of centrally mediated abdominal pain syndrome.

BACKGROUND: This study aimed to evaluate the clinical efficacy of Chinese medicine for the treatment of centrally mediated abdominal pain syndrome (CAPS) using a meta-analysis system. METHODS: Six databases, including China National Knowledge Infrastructure, Vendor Information Pages, Chinese Biomedical Database, Wanfang, PubMed, and Embase were searched for randomized controlled trials related to the treatment of CAPS with traditional Chinese medicine. The bias risk assessment tool and RevMan5.3 software (Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration) were used to conduct quality assessment and meta-analysis, and the GRADE grading system was used to evaluate the quality of evidence for outcome indicators. RESULTS: Fifteen articles were included in this study. Meta-analysis results showed that the treatment group was more effective in terms of the total effective rate (relative risk = 1.27; 95% confidence interval [CI], 1.19-1.34; P < .00001), Behavioral Rating Scale-6 pain score (mean difference [MD] = -0.79; 95% CI, -0.99 to -0.59; P < .00001), and traditional Chinese medicine (TCM) symptom score (MD = -1.74; 95% CI, -2.23 to -1.26; P < .00001) than the control group (P < .05). However, in terms of numerical rating scale pain score (MD = 0.79; 95% CI, -1.70 to 0.12; P = .09), the efficacy was comparable between the 2 groups, and the difference was not statistically significant (P > .05). In terms of verbal rating scale pain, depression, and anxiety scores, the data could not be combined due to inconsistent scoring criteria, and only descriptive analysis was performed. The results showed that the treatment group was slightly better than the control group in terms of relieving verbal rating scale pain and improving anxiety and depression (P < .05). CONCLUSION: Chinese medicine can effectively improve the pain and TCM clinical symptoms of patients with CAPS and relieve patients' anxiety and depression with fewer adverse effects, which has certain therapeutic advantages. However, because of the low methodological quality assessment of the included literature, the quality of GRADE evidence for outcome indicators is of mostly low and very low quality, the strength of recommendation is weak, and the credibility of the conclusion is average. More rigorous, larger sample, and higher-quality clinical trials are required to provide a higher level of evidence-based medicine for the development of TCM treatment standards for CAPS.

Corrigendum: ErHuang Formula Improves Renal Fibrosis in Diabetic Nephropathy Rats by Inhibiting CXCL6/JAK/STAT3 Signaling Pathway.

[This corrects the article DOI: 10.3389/fphar.2019.01596.].

Humulus lupulus L. Extract Prevents Ovariectomy-Induced Osteoporosis in Mice and Regulates Activities of Osteoblasts and Osteoclasts.

OBJECTIVE: To systematically evaluate the protective effects of Humulus lupulus L. extract (HLE) on osteoporosis mice. METHODS: In vivo experiment, a total of 35 12-week-old female ICR mice were equally divided into 5 groups: the sham control group (sham); the ovariectomy with vehicle group (OVX); the OVX with estradiol valerate [EV, 0.2 mg/(kg•d)] the OVX with low- or high-dose HLE groups [HLE, 1 g/(kg•d) and 3 g/(kg•d)], 7 in each group. Treatment began 1 week after the ovariectomized surgery and lasted for 12 weeks. Bone mass and trabecular bone mircoarchitecture were evaluated by micro computed tomography, and bone turnover markers in serum were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. In vitro experiment, osteoblasts and osteoclasts were treated with HLE at doses of 0, 4, 20 and 100 µg/mL. Biomarkers for bone formation in osteoblasts and bone resorption in osteoclasts were analyzed. RESULTS: Compared with the OVX group, HLE exerted bone protective effects by the increase of estradiol (P<0.05), the improvement of cancellous bone structure, bone mineral density (P<0.01) and the reduction of serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), bone gla-protein, c-terminal telopeptides of type I collagen (CTX-I) and deoxypyridinoline levels (P<0.01 for all). In vitro experiment, compared with the control group, HLE at 20 µg/mL promoted the cell proliferation (P<0.01), and increased the expression of bone morphogenetic protein-2 and osteopontin levels in osteoblasts (both P<0.05). HLE at 100 µg/mL increased the osteoblastic ALP activities, and HLE at all dose enhanced the extracellular matrix mineralization (both P<0.01). Furthermore, compared with the control group, HLE at 20 µg/mL and 100 µg/mL inhibited osteoclastic TRAP activity (P<0.01), and reduced the expression of matrix metalloproteinase-9 and cathepsin K (both P<0.05). CONCLUSION: HLE may protect against bone loss, and have potentials in the treatment of osteoporosis.

Arthrobacter woluwensis Bacteremia: A Clinical and Genomic Report.

Arthrobacter woluwensis is a Gram-positive, aerobic Actinobacteria that is widely distributed in the environment worldwide. Little is known about A. woluwensis infection and it is commonly mis-identified by culturing with commercial kits. To date, only six cases of bacteremia caused by A. woluwensis have been reported in the literature. Herein, we report a case of Arthrobacter woluwensis bacteremia in an immunocompromised host. In this case report, the results of antimicrobial susceptibility testing showed that this clinical isolate of A. woluwensis is sensitive to vancomycin, teicoplanin, but resistant to penicillin, cephalosporin and ciprofloxacin. Additionally, whole genome sequencing analysis identified common subunits of the urease system.

[Changes of eye signs in chronic hepatitis B patients with blood stasis syndrome].

OBJECTIVE: To study the characteristics of eye signs in chronic hepatitis B patients with blood stasis syndrome and the association between blood stasis syndrome and eye signs. METHODS: A total of 126 patients with chronic hepatitis B were randomly divided into four groups: non-blood stasis group, and mild, moderate and severe blood stasis groups. The changes of eye signs in the four groups were tested and compared. RESULTS: There were significant differences in scores of blood stasis and eye signs among the four groups (P<0.05 or P<0.01). The changes of eye signs in chronic hepatitis B patients with blood stasis syndrome were different with those with non-blood stasis syndrome. There were no significant differences in each item of the eye signs among the four groups (P>0.05). CONCLUSION: The eye signs of blood stasis syndrome are applicable, objective and convenient for diagnosing blood stasis syndrome in patients with chronic hepatitis B.

Monotropein attenuates oxidative stress via Akt/mTOR-mediated autophagy in osteoblast cells.

Oxidative stress is a crucial pathogenic factor in osteoporosis. Autophagy is a cellular self-digestion process that can selectively remove damaged organelles under oxidative stress, and thus presents a potential therapeutic target against osteoporosis. Monotropein is an iridoid glycoside which can increase osteoblastic bone formation and be applied for medicinal purpose in China. The aim of this work is to investigate whether autophagy participates the protection effects of monotropein in osteoblasts under oxidative stress and the possible mechanism of such involvement. Here, monotropein was capable of inhibiting the H2O2-induced reactive oxygen species generation in osteoblasts. Monotropein induced autophagy and protected osteoblasts from cytotoxic effects of H2O2, as assessed by viability assays, apoptosis and western blotting. Moreover, it significantly attenuated H2O2-evoked oxidative stress as measured by malondialdehyde, catalase, and superoxide dismutase levels. Importantly, monotropein reduced the phosphorylation of protein kinase B (Akt), mammalian target of rapamycin (mTOR) and its two downstream proteins (p70S6K and 4EBP1). The autophagy level increased in osteoblasts treated with monotropein as represented by an increased in both Beclin1 expression and the LC3-II/LC3-I ratio. However, the Akt activator (SC79) and mTOR activator (MHY1485) suppressed the autophagy level induced by monotropein in H2O2-treated cells. Consequently, the antioxidant effects of monotropein were mediated, at least in part, by enhancing autophagy through the Akt/mTOR pathway. These results suggested that monotropein might be a promising candidate for osteoporosis treatment.