Objective: To study the steroidal saponins from Allii Macrostemonis Bulbus. Methods The silica gel and ODS column chromatographies were used for the isolation and purification of compounds from Allii Macrostemonis Bulbus. Their structures were identified through comparing with references and spectral analyses. Results: Three steroidal saponins were isolated from the 70% ethanol extract from Allii Macrostemonis Bulbus and identified as 5β-spirostane-25(27)-en-3β, 12β-diol-3-O-β-D-glucopyranosyl- (1→2)-β-D-galactopyranoside (1), (25R)-5β-spirostane-3β, 12β-diol-3-O-β-D-glucopyranosyl- (1→2)-β-D-galactopyranoside (2), and 5β-spirostane-25(27)-en-2β, 3β-diol-3-O-β-D-glucopyranosyl- (1→2)-β-D-galactopyranoside (3). Conclusion: Compound 1 is a new compound named macrostemonoside S. Compound 2 is isolated from Allii Macrostemonis Bulbus for the first time.

BACKGROUND: Dysfunction of endothelial cells is independently associated with coronary atherosclerotic heart disease. Correlation of dysfunction of endothelial cells to restenosis after stent implantation is not yet clearly determined.OBJECTIVE: To evaluate the correlation of vascular endothelial dysfunction to restenosis after stent implantation. DESIGN, TIME AND SETTING: A case control study was performed at the Department of Cardiology and Department of Heart Ultrasound, Sichuan People's Hospital from March 2005 to January 2007.PARTICIPANTS: After review, coronary angiography showed that 11 patients who occurred restenosis at the lesion region after stent implantation were included in a restenosis group, and an additional 15 patients who did not develop in-stent restenosis were included in a control group. Patients in the following conditions were excluded: over 70 years old, histories of long-term smoking, diabetes mellitus, multivessel disease, long coronary lesion and chronic total occlusion, heart failure (Killip's class Ⅲ or above), severe hepatic and/or renal insufficiency.METHODS: High-resolution ultrasound was used to assess the percentage of flow-mediated dilatation of brachial artery. Differences in endothelial function were compared between both groups.MAIN OUTCOME MEASURES: Ultrasound parameter of the brachial artery in both groups; Partial correlation analysis on control variable including sex, age, blood lipid level, diseased region and stent type.RESULTS: No significant difference was found in basic diameter of brachial artery in both groups. During reactive hyperemia, inner diameter and its absolute variation of brachial artery were smaller in the restenosis group than in the control group (P<0.01). The percentage of brachial artery flow-mediated dilatation was lower in the restenosis group compared with the control group (P=0.013). The partial correlation coefficient between the percentage of flow-mediated dilatation of brachial artery and in-stent restenosis was 0.47 (P=0.04).CONCLUSION: The endothelial dysfunction significantly decreases in patients with restenosis compared with controls following stent implantation. There is a correlation between endothelial dysfunction and restenosis.

OBJECTIVETo investigate the role of C-type natriuretic peptide receptor (NPR-C) and large-conductance calcium-activated potassium channels (BK(Ca)) in brain natriuretic peptide (BNP) induced porcine coronary artery dilation.

METHODSPorcine coronary artery rings were obtained and treated with BNP (10(-6) mol/L), BNP + NPR-C antagonist cANF4-28 (10(-6) mol/L) and BNP + BK(Ca) blocker tetraethylammonium (TEA, 1 mmol/L). The vascular tone experiments were observed on 10 vessel segments. BK(Ca) current density was measured by the whole-cell patch clamp technique.

RESULTSThe maximum diastolic rate was similar between BNP group (68.51% ± 11.50%) and cANF4-28 + BNP group (65.67% ± 11.90%, P > 0.05) while significantly reduced in TEA + BNP group (28.87% ± 4.55%, all P < 0.05). When the holding potential was set at +60 mV, the BK(Ca) current density of BNP group was (78.48 ± 5.86) pA/pF, which was significantly higher than control group [(53.84 ± 4.55) pA/pF, P < 0.05], which was equally reduced in the TEA group and TEA + BNP group [(28.80 ± 2.76) pA/pF and (30.60 ± 3.88) pA/pF respectively, all P < 0.05 vs. control group].

CONCLUSIONBNP could relax the porcine coronary arterial smooth muscles by increasing BK(Ca) current, and this effect is not mediated by NPR-C.

Animals ; Coronary Vessels ; drug effects ; physiology ; Large-Conductance Calcium-Activated Potassium Channels ; physiology ; Natriuretic Peptide, Brain ; pharmacology ; Patch-Clamp Techniques ; Receptors, Atrial Natriuretic Factor ; physiology ; Swine

OBJECTIVETo investigate if the increased incidence of atrial fibrillation with age was associated with changes of Na(+) channel in atrial myocytes.

METHODSTwenty-three patients underwent valve replacement operations were divided into adult [< 60 years, n = 15, 9 males, mean age (42.1 +/- 7.1) years] and aged group [> or = 60 years, n = 8, 5 males, mean age (63.3 +/- 3.1) years]. All patients were in normal sinus rhythm. Whole cell patch clamp techniques were used to record the Na(+) currents (I(Na)) of right auricle myocytes.

RESULTSBoth current density and time-dependent recovery of I(Na) were similar in the cells from the 2 groups. Voltage-dependent inactivation of I(Na) of myocytes in the aged atria was shifted to more positive voltages.

CONCLUSIONCurrent density of I(Na) was similar between the 2 age groups, and Na(+) channel might not be an important determinant for the increased incidence of atrial fibrillation in aged patients.

Adult ; Age Factors ; Atrial Fibrillation ; Female ; Heart Atria ; cytology ; physiopathology ; Heart Valve Diseases ; physiopathology ; Humans ; Male ; Middle Aged ; Myocytes, Cardiac ; metabolism ; Patch-Clamp Techniques ; Sodium Channels ; analysis

OBJECTIVETo understand the infection status and epidemiological features of HBV in permanent residents of Shenzhen city.

METHODSA multi-stage stratified random sampling method was performed for questionnaire survey to permanently-registered residents of 1-59 years old in Luohu and Baoan district of Shenzhen in 2010, and blood samples of the subjects were collected. Hepatitis B virus-related surface antigen (HBsAg) and hepatitis B virus surface antibody (anti-HBs) were detected with ELISA.

RESULTSThe total 3771 studied population showed 252 HBsAg positive and 2712 anti-HBs positive residents with the standardization prevalence as 9.73% and 72.83% , respectively. The difference of the prevalence of HBsAg and anti-HBs between males and females were not statistically significant (P > 0.05). The prevalence of HBsAg was reduced with increasing age. The differences of the prevalence of HBsAg between Shenzhen permanent registered and non-permanent registered population were not significant, but the prevalence of anti-HBs in Permanent registered residents (78.32%) was higher than in non-permanent (66.03%, χ(2) = 41.613, P < 0.001). The prevalence of HBsAg was significantly different in various occupational and educational levels. Peasants had the highest prevalence (24.13%) and medical workers had the highest prevalence of anti-HBs (89.10% ). People with junior high school education had the highest prevalence of HBsAg (12.76%) and the lowest of anti-HBs (62.45%). Population with high-level education had the highest prevalence of anti-HBs(81.00% average). The prevalence of HBsAg was over 10% in people who were born in Shenzhen and Guangdong province, and the anti-HBs was the highest in Shenzhen population with the prevalence as 74.48% and 76.47% , respectively.

CONCLUSIONIn the Shenzhen resident population, the overall prevalence of HBV was lower than the average level of Guangdong province, but higher than the national wide.

Adolescent ; Adult ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Hepatitis B ; blood ; epidemiology ; Humans ; Infant ; Male ; Middle Aged ; Seroepidemiologic Studies ; Surveys and Questionnaires

Cholesterol Ester Storage Disease/genetics* ; Humans ; Mutation ; Sterol Esterase/genetics*

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

OBJECTIVE: To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD). METHODS: Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins. RESULTS: In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa. CONCLUSION Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.
Humans ; Mice ; Animals ; Caco-2 Cells ; beta Catenin/metabolism* ; Culture Media, Conditioned/pharmacology* ; Tight Junctions/metabolism* ; Intestinal Mucosa ; Inflammatory Bowel Diseases ; Tight Junction Proteins/metabolism* ; Inflammation/metabolism* ; Fibroblasts/metabolism* ; Mice, Inbred C57BL ; Glycoproteins/metabolism* ; Wnt Proteins/pharmacology* ; Frizzled Receptors/metabolism*

Schistosomiasis is a modern disease name, but it has been widespread in ancient China and exists in a specific form in traditional Chinese medicine (TCM) . The purpose of the paper is to make clear the existing form of schistosomiasis in TCM and infer the prevalence of schistosomiasis in ancient China. The paper focuses on the period when great progress was made on schistosomiasis by TCM, and sums up the understanding of TCM toward schistosomiasis in this period. By studying and analyzing the literature of schistosomiasis in this period, the paper tries to find out the representative Chinese medicine symptom description and TCM "other name" of schistosomiasis, so as to accurately judge whether the relevant description in ancient TCM books and historical documents can provide scientific basis for schistosomiasis. It is important to understand the prevalence and cognition of schistosomiasis in ancient China.