Objective: To investigate the chemical constituents from the barks of Melia azedarach and their antidiabetes activities. Methods: The constituents were isolated and purified by silica gel, reverse phase silica gel, and Sephadex LH-20 column chromatography, and their structures were identified by spectra and physiochemical characteristic analysis. The agonist activities of the isolated triterpenoids against glucokinase (GK) and SIRT1, and the inhibitory activity against dipeptidyl peptidasesIV (DPPIV), and 11β-hydroxysteroid dehydrogenase (11β-HSD) were tested in vitro. Results: Six triterpenoids and three sterols were obtained from MeOH extract in the barks of M. azedarach and were elucidated as meliastatin 3 (1), kulonic acid (2), kulactone (3), sendanolactone (4), dubione B (5), 20, 24-cyclotirucalla-7(8)-en-16β, 21α, 25-trihydroxy-3-one (6), 3β-hydroxy-5, 8-epidioxy-ergosta-6, 22-diene (7), 2β, 3β, 4β-trihydroxy-pregn-16-one (8), and 3β-hydroxy-pregn-5, 17 (20)-dien-16-one (9). Compound 2 showed the inhibitory activity against 11β-HSD1 with the IC50 value of 54.15 nmol/L. Conclusion: Compounds 6-9 are obtained from this species for the first time. The tested compounds 1-4 are inactive against GK, SIRT1, and DPPIV, but compound 2 shows high selectivity against human 11β-HSD.

Objective: To investigate the effects of glycogen synthase kinase-3β (GSK3β)/eukaryotic extension factor kinase 2 (eEF2K) signaling pathway on the process of pulmonary fibrosis through in vivo experiments, and find new ideas for clinical treatment of pulmonary fibrosis. Methods: The pulmonary fibrosis model of C57BL/6 male mice was induced by bleomycin with intratracheal injection at the dose of 2 mg/kg. After 14 days of modeling, animals were divided into model group, negative inhibition group and inhibition group (n=5 for each group), and control group was not processed. The inhibition group was treated with TDZD-8 (4 mg/kg) after modeling, the negative inhibition group was given DMSO solution after modeling, and the samples were collected after 28 days. Hematoxylin-eosin staining method was used to detect lung fibrosis in mice and scored according to Ashcroft scale. Expression levels of GSK3β, p-GSK3β, eEF2K, p-eEF2K (Ser70, Ser392, Ser470), precursor protein of matrix metalloproteinase-2 (pro-MMP-2), matrix metalloproteinase-2 (MMP-2), collagen I (Col I), collagen Ⅲ (Col Ⅲ) and α-smooth muscle actin (α-SMA) were detected by Western blot. Results: Compared with control group, the fibrosis score was up-regulated, the expression levels of GSK3β, p-GSK3β, p-eEF2K (Ser70, Ser392, Ser470), pro-MMP-2, MMP-2, Col I, Col Ⅲ and α-SMA were increased, while that of eEF2K was decreased in model group (P＜0.05). Compared with model group, the fibrosis score, expression levels of GSK3β, p-GSK3β, p-eEF2K (Ser70, Ser392, Ser470), pro-MMP-2, MMP-2, Col I, Col Ⅲ and α-SMA were decreased, but the expression level of eEF2K was increased in inhibition group (P＜0.05). Conclusion: GSK3β can activate eEF2K by phosphorylation at the sites of Ser70, Ser392 and Ser470, increase the contents of fibrosis indicators, promote the formation of pulmonary fibrosis, and aggravate lung tissue lesions.
Animals ; Collagen ; Collagen Type I ; Elongation Factor 2 Kinase/metabolism* ; Eukaryota/metabolism* ; Fibrosis ; Glycogen Synthase Kinase 3 beta ; Male ; Matrix Metalloproteinase 2/metabolism* ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis/chemically induced* ; Signal Transduction

In physiology-related books, there are many relationship curves about blood flow rate in arteries and blood pressure changes with time, but there are not much explanation about such relationship. This is the very the question that the present article tries to answer. We clarified the relations between blood flow rate and blood pressure gradient using the experimental curves as the basis, using Poiseuille Law and relative knowledge of phisics and mathematics, and using analysis and reasoning. Based on the study, it can be concluded that in every course of cardiac cycle, the blood flow rate of any section in artery blood vessel is roughly synchronized with changing rate of space and time of the blood pressure, but blood flow rate is not synchronized with blood pressure.
Arterial Pressure ; physiology ; Arteries ; physiology ; Blood Flow Velocity ; physiology ; Humans ; Time

All physiologic textbooks deal with pleural cavity pressure, alveolar wall pressure and pressure inside the lung, but they have not stated these ideas clearly. The present study reveals production and Law of variation of the intrinsic pressure of pleural cavity, the pressure of alveolar wall and the intrinsic pressure in the alveoli. Pleural cavity intrinsic pressure is produced by the pressure from pleura expanding or compressing force of the lungs. When the lungs calmly inhale, the thorax expands, pleural cavity negative pressure increase. When the lungs calmly exhale, thorax reduces, but thorax and lungs are still in the extended state, pleural cavity is still in negative pressure. With thorax reducing, negative pressure decreases. When the lungs are at the forced expiration, the lung pleura and wall pleura extrude pleural cavity, only to produce positive pressure. The pressure of alveolar wall is the algebraic sum of the intrinsic pressure of pleural cavity, the intrinsic pressure of pulmonary tissue and the additional pressure of alveolar wall. We did the calculation of additional pressure on the alveolar wall by using Laplace formula of spherical elastic membrane. The intrinsic pressure of alveoli depends on the moving speed or slowness of expansion or compression of alveolar wall and the size of trachea resistance.
Humans ; Pleural Cavity ; physiology ; Pressure ; Pulmonary Alveoli ; physiology ; Respiration ; Respiratory Mechanics ; physiology

From the standpoint of training mode,the paper makes an effort to analyze the present situation on Sino-Foreign cooperation in nnning schools in mode of nursing personnel training in Hubei Province,find out the existing problems and put forward the corresponding proposals in order to ensure sustainable development of the Sino-Foreign cooperation in running schools in mode of nursing personnel training.

OBJECTIVETo observe the therapeutic effect of parthenolide (PTL) on rabbit knee arthritis (KOA) and its effects on serum expression of interleukin-1beta (IL-1beta) and contents of tumor necrosis factor-alpha (TNF-alpha).

METHODSEight rabbits were randomly selected from 40 healthy pure-bred New Zealand rabbits as the normal control group. The KOA model was established in the rest 32 rabbits by plaster cast fixation of the right hind limb extension position. After modeling they were randomly divided into 4 groups, i.e., the model control group, the high dose PTL group, the middle dose PTL group, and the low dose PTL group, 8 in each group. Serum contents of IL-1beta and TNF-alpha were detected using enzyme-linked immunosorbent assay.

RESULTSCompared with the model group, IL-1beta and TNF-alpha concentration decreased in the 3 PTL groups (P < 0.01). The decrement was positively correlated with PTL concentrations (IL-1beta: r = 0.55, P < 0.01; TNF-alpha: r = 0.56, P < 0.01). The inhibition reached the peak when the PTL concentration arrived at 20 micromol/L.

CONCLUSIONSPTL could down-regulate the blood IL-1beta and TNF-alpha concentrations of KOA rabbits. Besides, the decrement was positively correlated with the PTL concentration.

Animals ; Female ; Interleukin-1beta ; blood ; Male ; Osteoarthritis, Knee ; blood ; drug therapy ; Phytotherapy ; Rabbits ; Sesquiterpenes ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood

Diabetic retinopathy is the most common disease of microvascular diseases caused by diabetes. It is harmful to vision in the late stage. If not treated in time, it can cause blindness. The diagnosis, treatment and follow-up of diabetic retinopathy were mainly based on fundus fluorescein angiography. There are some limitations in the clinical application because of the side effects of its operation, such as invasive, allergic and adverse reactions. Recently, optical coherence tomography has become more and more popular among ophthalmologists for its noninvasive, rapid and high resolution fundus angiography. It cannot only display the choroidal vascular network information in layers, but also quantitatively analyze the changes of blood flow in the macular region. For the first time, the blood flow analysis of optic disc and macular area in vivo has reached the level of tissue anatomy. It has wide application prospect and is more and more favored by ophthalmologists. In this paper, the clinical application of octa in diabetic retinopathy was reviewed.

Hepatitis B, hepatitis C, and type 2 diabetes mellitus (T2DM) are serious public health issues worldwide. This article analyzes the association of hepatitis B and hepatitis C with T2DM. The analysis shows that on the one hand, both hepatitis B and hepatitis C promote the pathogenesis of T2DM, which involves viral infection inhibiting insulin signal transduction as well as glucose uptake and glycogen synthesis in insulin target cells; on the other hand, patients with T2DM are prone to hepatitis B and hepatitis C, which may be associated with multiple organ dysfunction caused by diabetes.

Objective: The effect of total flavonoids of litchi (TFL) on nuclear translocation of nuclear factor-kappa B (NF- kappa B) in rat hepatic stellate cell line (HSC-T6) induced by transforming growth factor - beta 1 (TGF- beta 1) in vitro was studied to explore the mechanism of action of anti-hepatic fibrosis drugs. Methods: HSC-T6 was cultured in vitro, induced by TGFβ1 for 24 h, and then treated with TFL at 125, 250 and 500 μg/ml for 48 h. The effect of TFL on NF-κB nuclear translocation in HSC-T6 was observed by confocal laser microscopy. The effects of TFL on the expression of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and Collagen I protein were detected by western blot. The expressions of TLR4 and p-NF-κB p65 were detected by immunofluorescence. Data were presented as mean±SEM. Homogeneity test of variance was performed and then followed by one-way analysis of variance (ANOVA). The multiple comparisons between groups were performed by LSD test. P < 0.05 was considered statistically significant. Results: Confocal laser scanning microscopy showed TFL inhibited the nuclear translocation of NF-κB in activated HSC-T6 in a concentration-dependent manner and TFL down regulated the protein expression levels of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and collagen I protein in HSC-T6 in a concentration-dependent manner. Conclusion The mechanism of TFL against hepatic fibrosis may be related to the inhibition of nuclear translocation of NF-κb in the activated HSC-T6 and the expression of TLR4, P-iκbɑ, P-nf-κb p65, NF-κb and collagen I protein in HSC-T6.

AIM: To investigate the effect of d-δ-tocopherol on the growth of human lens epithelial SRA cells and its related molecular mechanism, and to provide experimental basis for the treatment and prevention of posterior cataract with d-δ-tocopherol.

METHODS: The experiment was divided into 6 groups, blank control group and experimental group, that is, five different concentrations of d-δ-tocopherol(40, 60, 80, 100, 120)μmoL/L. The proliferation inhibition rate of each group was detected by thiazolam(MTT)assay. The morphology of human lens epithelial SRA cells was observed under inverted microscope. Cell cycle was detected by flow cytometry and the expression of bcl-2, bax, Cyclin D1, P21 protein was detected by Western Blot(WB).

RESULTS: With the increase of d-δ-tocopherol concentration, the SRA cells decreased significantly compared with the control group; the MTT results showed that with the increase of d-δ-tocopherol concentration, the inhibition rate of cell proliferation increased gradually, the difference was statistically significant(P<0.05); cell cycle: with the increase of the concentration of tocopherol drugs in the experimental group, the proportion of cells in the S phase increased gradually compared with the control group, the cells were blocked in the S phase, the difference was statistically significant(P<0.05); Western blotting: after 48h of d-δ-tocopherol intervention human lens epithelial SRA cells, the P21, Cyclin D1 and bcl-2 expression of human lens epithelial cells gradually decreased, and the expression of bax gradually increased, which was statistically significant(P<0.01).

CONCLUSION: d-δ-tocopherol can significantly inhibit the proliferation of human lens epithelial SRA cells and block the cell cycle in S phase. d-δ-tocopherol can inhibit the proliferation of human lens epithelial cells. The proliferation of human lens epithelial SRA cells may be achieved by inhibiting the expression of bcl-2, P21, Cyclin D1 and inducing the expression of bax.