This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

OBJECTIVE: To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism. METHODS: A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24⁺), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups. RESULTS: After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05). CONCLUSION Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.
Humans ; Sleep Initiation and Maintenance Disorders/therapy* ; Transcranial Magnetic Stimulation ; Brain-Derived Neurotrophic Factor ; Treatment Outcome ; Acupuncture Therapy ; Acupuncture Points ; gamma-Aminobutyric Acid ; Depressive Disorder

ObjectiveTo evaluate the safety and comfort of hepatic artery infusion chemotherapy （HAIC） via distal transradial access （dTRA） in patients with liver cancer. MethodsPatients with advanced liver cancer who received HAIC via dTRA or transfemoral access （TFA） at the Department of Interventional Radiology， the First Affiliated Hospital of Sun Yat-sen University， were enrolled. The patients underwent dTRA or TFA for onetime and crossed-over subsequently. The patients received HAIC using FOLFOX4 regimen. Postcatheterization questionaire was used to compare the effects of the two vessel accesses on patients’ quality of life. Procedure-related adverse events were also recorded. ResultsAmong the 18 cases enrolled for HAIC， 9 underwent crossover from dTRA to TFA and the the remaining 9 from TFA to dTRA. During HAIC via dTRA， we only found grade 1 or grade 2 procedure-related adverse events such as 2 access site hematoma， 3 persistent pain at access site and 1 left palm numbness. No grade 3 or grade 4 procedure-related adverse event was found. Post dTRA ultrasound revealed no proximal radial artery occlusion. Significant difference in catheterization time between dTRA and TFA accesses was found （4 min vs. 3 min， P < 0.05）. All comfort scores were higher with dTRA as compared to TFA and patients preferred dTRA （7.89 vs. 2.72， P < 0.001）. The compression time for dTRA access was significantly shorter than TFA access （2 h vs. 7 h， P < 0.05）. ConclusionsdTRA approach is safe and tolerable， which is beneficial to improve the quality of life and comfort of patients with liver cancer when undergoing HAIC.

OBJECTIVE: To observe the effects of Casitas B lymphoma (CBL) protein on proliferation, migration and invasion of breast cancer cells and explore its mechanism of action. METHODS: Cultured breast cancer cell lines MDA-MB-231 and MCF7A were transfected with a CBL-overexpressing plasmid and a specific siRNA targeting CBL (siRNA-CBL), respectively, and the changes in cell proliferation, migration and invasion were examined using colony-forming assay, cell counting kit-8 (CCK-8), scratch test and Transwell assay. Flow cytometry and Western blotting were performed to examine the effects of CBL overexpression on cell cycle and epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells, and the changes in the number of filamentous pseudopodia were observed by rhodamine- labeled phalloidin staining of the cytoskeleton. IP-mass spectrometry identified NCK2 as the interacting proteins of CBL, and their interaction was verified by immunoprecipitation and immunofluorescence co-localization experiments in HEK-293T cells transfected with the plasmids for overexpression of CBL, NCK2, or both. Cycloheximide tracking and ubiquitination assays were used for assessing the effects of CBL on stability and ubiquitination of NCK2 protein in MDA-MB-231 cells; CCK-8 and Transwell assays were used to determine the effect of NCK2 overexpression on CBL-mediated proliferation and migration of the cells. RESULTS: The proliferation, migration and invasion were significantly suppressed in MDA-MB-231 cells overexpressing CBL (P < 0.05) and significantly enhanced in MCF7 cells with CBL silencing (P < 0.01). Silencing of CBL promoted G1/S transition in MCF7 cells (P < 0.05). Overexpression of CBL significantly decreased the expressions of CDK2/4 (P < 0.01), cyclinA2/B1/D1/D3/E2 (P < 0.05), Snail, N-cadherin, claudin-1 (P < 0.05), and upregulated the expression of E-cadherin (P < 0.05). CBL silencing upregulated the expressions of CDK2/4/6 (P < 0.05), cyclin A2/B1/D1/D3/E2 (P < 0.05), Snail, vimentin, and claudin-1 (P < 0.05) and down-regulated E-cadherin expression (P < 0.05). CBL overexpression obviously reduced the number of filamentous pseudopodia in MDA-MB-231 cells, and the reverse changes were observed in MCF7 cells with CBL silencing. In MDA-MB-231 cells, CBL overexpression lowered NCK2 protein stability (P < 0.05) and promoted its ubiquitin-mediated degradation (P < 0.01). Overexpression of NCK2 obviously reversed CBL-mediated inhibition of cell proliferation and migration (P < 0.01). CONCLUSION CBL can inhibit the proliferation, migration and invasion of breast cancer cells through ubiquitination-mediated degradation of NCK2.
Humans ; Sincalide ; Lymphoma ; Cytoskeleton ; Cadherins ; MCF-7 Cells ; Oncogene Proteins ; Adaptor Proteins, Signal Transducing

Objective: To evaluate the 4-year clinical outcomes of patients following Firesorb bioresorbable scaffold (BRS) implantation. Methods: The study reported the 4-year follow-up results of the FUTURE I study. FUTURE I was a prospective, single-center, open-label, first-in-man study which evaluated the feasibility, preliminary safety, and efficacy of Firesorb stent in the treatment of coronary artery stenosis. A total of 45 patients with single de novo lesions in native coronary arteries ,who hospitalized in Fuwai Hospital from January to March 2016 were enrolled. After successfully stent implantation these patients were randomized in a 2∶1 ratio into cohort 1 (n=30) or cohort 2 (n=15). The patients in cohort 1 underwent angiographic, IVUS or OCT examination at 6 months and 2 years; and cohort 2 underwent angiographic, IVUS or OCT at 1 and 3 years. All patients underwent clinical follow-up at 1, 6 months and 1 year and annually thereafter up to 5 years. The primary endpoint was target lesion failure (TLF, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization). Secondary endpoints included patient-oriented composite endpoint (PoCE, defined as composite of all death, all miocardial infarction, or any revascularization). Results: A total of 45 patients were enrolled and implanted with Firesorb BRS, including 35 males (77.8%), and the age was (54.4±9.3) years. At 4 years, 10 patients in cohort 1 were reexamined by coronary angiography and OCT examination. Among them, 2 patients' stents were completely degraded and absorbed. Compared with the OCT images of the other 8 patients in cohort 2 at 3 years, the degree of stent degradation was increased, and no stent adherence was found. The 4-year clinical follow-up rate was 100%. In 4-year clinical following up, 2 patients suffered PoCE (4.4%): 1 patient underwent non-target vessel revascularization the day after index procedure and target vessel revascularization (Non-target lesion revascularization) at 2-year imaging follow-up; the other patient underwent target lesion revascularization during imaging follow-up at 4 years but not due to ischemic driven. There was no scaffold thrombosis or TLF events through 4 years. Conclusions: Four years after the implantation, complete degradation and absorption of the Firsorb stent are evidenced in some patients. Firesorb stent is feasible and effective in the treatment of patients with non-complex coronary lesions.
Absorbable Implants ; Cardiovascular Agents ; Coronary Artery Disease/surgery* ; Drug-Eluting Stents ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Prospective Studies ; Sirolimus ; Treatment Outcome

【Objective】 Evaluate the efficacy of stent placement in the treatment of superior mesenteric artery dissection(SMAD) . 【Methods】 Data of 14 cases with SMAD treated with stent placement in our center between January 2009 and December 2018 were retrospectively analyzed. All lesions were treated with bare stent or covered stent deployment. The numeric rating scales(NRS) and diameter of superior mesenteric artery true lumen before and after the procedure were compared and analyzed. The success rate of technique and the primary patency rate of stent within one year were also analyzed. 【Results】 The success rate of procedure was 100% technically. There was significant difference in numeric rating scales between before and after procedure(5.9 vs. 1.9, P < 0.05). Diameter of superior mesenteric artery true lumen was significantly improved compared with those before procedure(6.6 mm vs. 2.6 mm, P < 0.05). The primary patency rates of stents in 12 months were 100%. 【Conclusion】 Endovascular stent placement is an effective treatment of SMAD with symptoms improved.

【Objective】To evaluate the safety and effects of transcatheter arterial chemoembolization using Drug-eluted beads（DEB-TACE）plus apatinib in patients with hepatocellular carcinoma（HCC）.【Methods】A retrospective analysis was performed，which included 11 HCC patients treated with DEB- TACE and followed by a target therapy of apatinib（500 mg QD）in our clinical research center. Radiograph evaluation and tumor biomarker，alpha- fetoprotein（AFP）， were recorded before the procedure and during the follow-up of the first cycle after 4~8 weeks. Adverse events induced by apatinib were recorded. 【Results】 According to the response evaluation criteria in solid tumors （RECIST），modified response evaluation criteria in solid tumors （mRECIST） and European Association for the study of the liver （EASL） criteria，the objective response rate （ORR） was 36.4% ，63.6% ，72.7% respectively，and the disease control rate（DCR）was 90.7% ，72.7% ，81.8% respectively. AFP levels were 44 251.7 μg/L which significantly decreased after the procedure ，compared to 366 336 μ g/L ，the levels before the treatment. Four reversible grade III adverse events were recorded and no grade IV adverse events found in these cases. 【Conclusion】According to the short-term treatment response and safety，DEB- TACE combined with apatinib could be considered as a promising treatment for intermediate and advanced stage hepatoma.

【Objective】 To investigate the safety and benefit of doxorubicin loaded hydrophobic linear alkyl modified graphene oxide （DOX@GO- C18） served as vectors in transcatheter arterial chemoembolization （TACE）. 【Methods】 Doxorubicin loaded hydrophobic linear alkyl modified graphene oxide was manufactured and characterized. VX2 liver carcinoma was established in rabbits and the hepatic lesions were treated with TACE using DOX@GO- C18 which was dissolved in lipiodol. Pre- and post- CT scans were performed to evaluate the treatment response. Liver function was assessed via blood samples drawn on day 0（preoperative），1，3，7，and day 14. The animals were sacrificed on day 14 and tissue samples collected to stain for pathology（hematoxylin-eosin staining），lipiodol（oil red O staining）and DOX（fluorescent）.【Results】The dispersion of DOX@GO-C18 in lipiodol was highly stable. Pre-and post-CT scan revealed that the diameter of the VX2 lesions barely varied and enhancements were decreased after the treatment. Target lesions gained stable disease（SD）as the treatment response based on Response Evaluation Criteria in Solid Tumors 1.1（RECIST 1.1）. Histological examination revealed that DOX@GO-C18 was located within the tumor tissue along with the lipiodol. The release of DOX may contribute to the necrosis in tumor.【Conclusions】DOX@GO-C18［CC2］may proved to be a safe and effective vectors in TACE treatment for liver carcinoma.

Metabolomics data contains multiple variables usually processed and evaluated by means of principal components analysis. The statistical analysis of the multivariate data is involved in abstract, elusory fitting for the model of hyperspace, complicated theoretical arithmetic and sophisticated transformation of the data matrix. It is crucially important to understand the arithmetic mechanism and the properties of the models fully. In this article, we reviewed the key and puzzling issues in principal components analysis of the metabolomics data, including the principal components, the scores and loadings of a principal components, scaling and weighting, partial least square projection to latent structures, partial least squares discriminant analysis, orthogonal projection to latent structure, orthogonal bidirectional projections to latent structures, S-plot, shared and unique structure plot, and the validation of the model. Hopefully, this article provides a better understanding of data processing mode, model selection, procedure standardization, and data interpretation for a reliable conclusion.

OBJECTIVETo investigate whether plasma from patients with systemic lupus erythematosus (SLE) inhibits the suppressive effects of mesenchymal stem cells (MSCs) on lupus B lymphocytes.

METHODSMSCs isolated and expanded from the bone marrow of healthy donors were co-cultured with B cells purified from the peripheral blood of SLE patients in the presence of fetal bovine serum or pooled plasma from SLE patients, and the proliferation and maturation of the B lymphocytes were analyzed.

RESULTSs Co-culture with normal MSCs obviously inhibited the proliferation of lupus B cells and suppressed the maturation of B lymphocytes, which showed lowered expressions of CD27 and CD38. The pooled plasma from SLE patients significantly inhibited the suppressive effects of normal MSCs on B cell proliferation and maturation.

CONCLUSIONPlasma from SLE patients negatively modulates the effects of normal MSCs in suppressing lupus B cell proliferation and maturation to affect the therapeutic effect of MSC transplantation for treatment of SLE. Double filtration plasmapheresis may therefore prove beneficial to enhance the therapeutic effects of MSC transplantation for SLE.

B-Lymphocytes ; pathology ; Cell Proliferation ; Coculture Techniques ; Humans ; Lupus Erythematosus, Systemic ; blood ; Lymphocyte Activation ; Mesenchymal Stromal Cells ; cytology ; Plasma