Five new flavan-4-ol glycosides jixueqiosides A-E (1-5) and two new flavan glycosides jixueqiosides F and G (6 and 7), along with twelve known flavan-4-ol glycosides (8-19), were isolated from the roots of Pronephrium penangianum. Comprehensive spectral analyses, X-ray single-crystal diffraction, and theoretical electronic circular dichroism (ECD) calculations established structures and absolute configurations. A single crystal structure of flavan-4-ol glycoside (14) was reported for the first time, while the characteristic ECD and NMR data for all isolated flavan-4-ol glycosides (1-5 , 8-19) were analyzed, establishing a set of empirical rules. Activity screening of these isolates showed that 8 and 9 could inhibit the proliferation of MDA-MB-231 and MCF-7 cells with IC₅₀ values of 7.93 ? 2.85 ?mol?L^-1 and 5.87 ? 1.58 ?mol?L^-1 (MDA-MB-231), and 2.21 ? 1.38 ?mol?L^-1 and 3.52 ? 1.55 ?mol?L^-1 (MCF-7), respectively. Western blotting and flow cytometry analyses demonstrated that 8 and 9 dose-dependently induced apoptosis in MDA-MB-231 cells by up-regulating BAX, activating caspase-3 and down-regulating BCL-2. Additionally, compound 8 affected autophagy-related proteins, increasing the ratio of LC3-II/LC3-I and Beclin-1 levels to inhibit MDA-MB-231 cell proliferation. Moreover, anti-inflammatory studies indicated that 2, 3, 7, 13, 14, and 18 moderately inhibited tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and nitric oxide (NO) release.
Humans ; Plant Roots/chemistry* ; Glycosides/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Flavonoids/isolation & purification* ; Cell Proliferation/drug effects* ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Molecular Structure ; Apoptosis/drug effects* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6/immunology* ; Animals ; Mice

Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE^-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg^-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.
Animals ; Mice ; Atherosclerosis/drug therapy* ; Diet, High-Fat ; Endothelial Cells ; Inflammation/drug therapy* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Reactive Oxygen Species

BACKGROUND: The change of the axial angle of the lower limb is related to the occurrence and development of osteoarthritis.OBJECTIVE: To analyze the correlation between the change of lower limb power line and pain area in the knee osteoarthritis patients.METHODS: Totally 65 knee osteoarthritis patients were selected as pain group and 30 healthy people were selected as control group. All the participants took anteroposterior and lateral knee radiographs through PACS imaging systems to collect six imaging indexes, including install index, the degree of tibiofemoral joint subluxation, tibiofemoral inside and outside joint clearance ratio, femoral angle, tibial angle and tibiofemoral angle. Knee osteoarthritis patients in pain group were divided into two common clinical pain areas which were proparea and medial area.RESULTS AND CONCLUSION: (1) The insall index, the degree of tibiofemoral joint subluxation, tibiofemoral inside andoutside joint clearance ratio between knee osteoarthritis patients in pain group and people in healthy control group hadsignificant differences. There was no statistical significance in the femoral angle, tibial angle and tibiofemoral angle. (2) In terms of the comparison between proparea and medial area in knee osteoarthritis patients in pain group, tibiofemoral joint subluxation degree was statistically different. (3) These findings suggest that there was a higher patella in knee osteoarthritis patients who were in pain, more severe in the degree of tibiofemoral joint subluxation, and more limited in tibiofemoral inside and outside joint clearance ratio. The degree of tibiofemoral joint subluxation of proparea was more severe than medial area in pain group.

Objective To evaluate the effect of minimally invasive therapy for treating intraventricular hemorrhage.Methods The minimally invasive therapy with unilateral or bilateral drainage were received according to quantity and shape of intraventricular hemorrhage.Results It was operated 22 cases with unilateral drainage and 28 cases with bilateral drainage in the 50 cases intraventricular hemorrhage.Death was 3 cases and mortality rate was 6% in the minimally invasive therapy.ADL1 15 cases(30%),ADL2 18 CRSeS(36%),ADL3 8 cases(16%),ADLA4 cases(8%),ADL5 2 cases(4%)in leave hospital.Conclusion Minimal invasive therapy of intraventrieular hemorrhage has great superiority,such as it can operate simple,trauma mild,decrease complications and enhance curative effect.It can generalize in the basic hospital.

Objective - To analyze the relation between classes and prognosis of the brain.stem hemorrhage.Methods 37 patients with spontaneous brainstem hemorrhage were divided into three groups according to con-sciousness and breathing function: Ⅰ group 13 cases with consciousness; Ⅱ group 11 cases without consciousness; Ⅲgroup 13 cases without consciousness and respiration, according to the classes, using different ways and means. Re-suits Ⅰ group 13 cases survival in 13 cases; Ⅱ group 10 cases survival and 1 case death in 11 cases; Ⅲ group 1 case survival and 12 cases death in 13 eases. Conclusion The classes of the brain.stem hemorrhage is propitious to select therapeutic measure and prognostic estimate. The intensive care and the surgery can reduce mortality rate.

Objective To study the characteristics of ? cell function change and to explore the predictive value of glutamic acid decarboxylase (GAD)-Ab and other factors for ? cell function in the patients with latent autoimmune diabetes of adults (LADA). Methods Sixteen LADA patients (positive GAD-Ab) and 24 type 2 diabetic patients (negative GAD-Ab) were followed-up at 0, 6th, 12th, 30th, 36th, 42th and 48th months respectively. Their fasting and postprandial 2h C-peptide and glycemic control were measured. GAD-Ab was determined by radioimmunoprecipitation assay and C-peptide by RIA. Results Decreased fasting C peptide (FCP) levels (Month 30, 36, 42, 48 compared with Month 0, P