Quality appraisal of clinical practice guidelines for the management of Dysphagia after acute stroke.

Objectives: Dysphagia is a common complication in stroke patients, widely affecting recovery and quality of life after stroke. The objective of this systematic review is to identify the gaps that between evidence and practice by critically assessing the quality of clinical practice guidelines (CPGs) for management of dysphagia in stroke. Methods: We systematically searched academic databases and guideline repositories between January 1, 2014, and August 1, 2023. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was used by two authors to independently assess CPG quality. Results: In a total of 14 CPGs included, we identified that three CPGs obtained a final evaluation of "high quality," nine CPGs achieved "moderate quality" and two CPGs received "low quality." The domain of "scope and purpose" achieved the highest mean score (91.1%) and the highest median (IQR) of 91.7% (86.1, 94.4%), while the domain of "applicability" received the lowest mean score (55.8%) and the lowest median (IQR) of 55.4% (43.2, 75.5%). Conclusion: The CPG development group should pay more attention to improving the methodological quality according to the AGREE II instrument, especially in the domain of "applicability" and "stakeholder involvement;" and each item should be refined as much as possible.

Study on the Correlation between Urinary Sodium and Potassium Excretion and Blood Pressure in Adult Hypertensive Inpatients of Different Sexes.

Objective: This study aims to understand the difference in the influence of urinary sodium and potassium excretion on blood pressure in patients of different sexes with hypertension by analyzing the relationship between urinary sodium and potassium excretion and blood pressure. Methods: In this cross-sectional study, 606 hospitalized patients with essential hypertension were recruited from 16 hospitals in the Shanxi Province between June 2018 and December 2019. These patients were grouped by sex, with 368 males and 238 females. Basic information and relevant serum biochemical indexes of patients in the two groups were recorded. The 24-hour urinary sodium and potassium excretion were measured, and 24-hour ambulatory blood pressure monitoring was performed simultaneously. This was done to analyze and compare the relationship between urinary sodium and urinary potassium excretion and blood pressure in adult hospitalized patients of different sexes with hypertension. Results: The 24-hour urinary sodium excretion in male patients with hypertension was significantly higher than that in female patients (P < 0.001). There was no significant difference in 24-hour urinary potassium excretion between male patients with hypertension and female patients. Spearman correlation analysis showed that 24-hour urinary sodium excretion was positively correlated with 24-hour SBP and nSBP in male patients (P < 0.05), while 24-hour urinary potassium excretion was negatively correlated with 24-hour SBP and nSBP in male patients (P < 0.05). The 24-hour urinary sodium in female patients was significantly positively correlated with 24-hour SBP, 24-hour DBP, SBP, dDBP, nSBP, and nDBP (P < 0.01). The 24-hour urinary potassium was significantly negatively correlated with nSBP (P < 0.05). Multiple stepwise linear regression showed that 24-hour urinary sodium excretion was still significantly positively correlated with 24-hour SBP and nSBP in male patients with hypertension after adjusting for various confounding factors. Conclusion: High urinary sodium and low urinary potassium excretion are closely related to elevated blood pressure in adult patients with hypertension, and there are sex differences.

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

The Correlation Between Urinary Sodium Excretion and Blood Pressure in Hospitalized Adult Patients with Hypertension.

INTRODUCTION: This study was designed to understand the baseline salt intake of adult patients with hypertension in Shanxi Province, and to analyze the correlation between urinary sodium excretion and blood pressure. METHODS: From June 2018 to December 2019, 16 hospitals with regional representativeness and experimental conditions in Shanxi Province were selected, and 643 eligible adult inpatients with primary hypertension were enrolled from these hospitals. The ages of patients ranged from 18 to 80 years. A 24-h ambulatory blood pressure monitoring was performed, and morning urine sodium concentration and 24-h urine sodium excretion were measured. The correlation between urinary sodium excretion and blood pressure in adult patients with hypertension was analyzed. RESULTS: The baseline salt intake of the adult patient participants with hypertension in Shanxi Province was 11.51 g/day. The average 24-h urinary sodium excretion of all observed subjects was 191.90 ± 98.18 mmol. The 24-h urinary sodium excretion and morning urinary sodium concentration were significantly positively correlated with systolic and diastolic blood pressure following adjustment of confounding factors, including gender, age, body weight, and smoking. CONCLUSION: The morning urine sodium concentration and 24-h urine sodium excretion were significantly positively correlated with blood pressure. High sodium excretion may be a risk factor for rhythm abnormalities in non-dipper pattern blood pressure. The control of urinary sodium concentration can thus be an important strategy for regulating abnormal blood pressure rhythm.

A new coumarin and a new norlignan from Ficus tsiangii.

Chemical investigation of the stem bark of Ficus tsiangii led to the isolation of a new coumarin ficuscoumarin (1) and a new norlignan ficuslignan (2) by chromatographic methods. Their structures were elucidated on the basis of spectroscopic analyses.

Three new triterpenoid saponins from Albizia julibrissin.

Three new triterpenoid saponins, julibrosides A5-A7 (1-3), together with five known saponins (4-8), were isolated from the stem bark of Albizia julibrissin. Their structures were elucidated on the basis of extensive spectroscopic data analysis of MS, 1D and 2D NMR, and chemical methods. Compounds 7 and 8 were isolated from the genus Albizia for the first time. The new compounds showed no cytotoxicity and anti-inflammatory activity.

CD44 Deficiency in Mice Protects the Heart Against Angiotensin Ii-Induced Cardiac Fibrosis.

This study tested the hypothesis that CD44 is involved in the development of cardiac fibrosis via angiotensin II (Ang II) AT1 receptor-stimulated TNFα/NFκB/IκB signaling pathways. Study was conducted in C57BL/6 wild type and CD44 knockout mice subjected to Ang II infusion (1,000 ng/kg/min) using osmotic minipumps up to 4 weeks or with gastric gavage administration of the AT1 receptor blocker, telmisartan at a dose of 10 mg/kg/d. Results indicated that Ang II enhances expression of the AT1 receptor, TNFα, NFκB, and CD44 as well as downregulates IκB. Further analyses revealed that Ang II increases macrophage migration, augments myofibroblast proliferation, and induces vascular/interstitial fibrosis. Relative to the Ang II group, treatment with telmisartan significantly reduced expression of the AT1 receptor and TNFα. These changes occurred in coincidence with decreased NFκB, increased IκB, and downregulated CD44 in the intracardiac vessels and intermyocardium. Furthermore, macrophage migration and myofibroblast proliferation were inhibited and fibrosis was attenuated. Knockout of CD44 did not affect Ang II-stimulated AT1 receptor and modulated TNFα/NFκB/IκB signaling, but significantly reduced macrophage/myofibroblast-mediated fibrosis as identified by less extensive collagen-rich area. These results suggest that the AT1 receptor is involved in the development of cardiac fibrosis by stimulating TNFα/NFκB/IκB-triggered CD44 signaling pathways. Knockout of CD44 blocked Ang II-induced cell migration/proliferation and cardiac fibrosis. Therefore, selective inhibition of CD44 may be considered as a potential therapeutic target for attenuating Ang II-induced deleterious cardiovascular effects.

Total saponins of Albiziae Cortex show anti-hepatoma carcinoma effects by inducing S phase arrest and mitochondrial apoptosis pathway activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Albiziae Cortex (AC) is a widely used traditional medicine in China. It is possess various properties to treat insomnia, traumatic injuries, diuresis, sthenia, and confusion. Total saponins of Albiziae Cortex (TSAC) are the most abundant bioactive components of AC, which were reported to show significant anti-tumor effects in vivo and in vitro. But the underlying mechanism of TSAC remained to be revealed. AIM OF STUDY: In this study, we investigated the anti-hepatoma carcinoma effects and the potential mechanism of TSAC in vivo and in vitro. MATERIALS AND METHODS: We first purified TSAC from crude extracts and characterized the major bioactive compounds by high performance liquid chromatography (HPLC). Effects of TSAC on viability of various hepatoma carcinoma cell lines were measured by MTT. Inhibition on cell proliferation was analysed using colony formation assay. Cell cycle distribution was revealed by flow cytometry. The apoptotic cells were observed by Hoechst 33258 staining and acridine orange (AO)/ethidium bromide (EB) double staining. Microstructures of apoptotic cells were examined by Transmission electron microscopy (TEM). The mitochondrial membrane potential were determined by JC-1 staining. Western blot was used to investigate the effects of TSAC on apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), and S-phase related protein cyclin A, cyclin E and cyclin-dependent kinases 2 (CDK2). Effects on tumor growth was assessed by H22-bearing ICR mice. RESULTS: TSAC significantly decreased the hepatoma carcinoma cell viability and inhibited HepG2 cell colony formation in a concentration-dependent manner. We also found that TSAC inhibited HepG2 cell growth via induction of S phase arrest. Further study showed that TSAC significantly down-regulated the expressions of cyclin A, cyclin E and CDK2 in HepG2 cells. Meanwhile, TSAC could effectively induce mitochondria-dependent caspase apoptosis pathway activation. Furthermore, TSAC increased the expression of pro-apoptotic protein Bax and decreased the expression of anti-apoptotic protein Bcl-2. In vivo assay showed that the anti-tumor effects of TSAC were significantly augmented without increasing toxicity in H22-bearing ICR mice. CONCLUSION: TSAC could inhibit cell proliferation through inducing S phase arrest and activate cell apoptosis via mitochondria-dependent apoptosis pathway. Therefore, TSAC could be a promising agent in clinical trials for anti-hepatoma carcinoma treatment.

[Anti-tumor target identification and molecular mechanism study of total saponins from Albizia julibrissin].

Dried stem bark from Albizia julibrissin(AJ) is a common traditional Chinese herb with several therapy effects including insomnia, anxiety and anti-tumor. Recently, the anti-tumor effect and mechanism studies of AJ have drawn much attention; however, there are still some troubles in chemical composition separation, which leads to the difficulties in pharmacological research of AJ. In this study, we firstly confirmed the proliferation inhibitory effect of total saponins from AJ(TSAJ)on human hepatocarcinoma(HepG2) cells, and also tested the apoptosis induction effect of TSAJ. Then, we successfully captured the potential target proteins from HepG2 lysates by using TSAJ-modified solid beads, and identified the target proteins by LC-MS/MS. Finally, we confirmed 5 target proteins including Exportin-2, Beta-actin-like protein 2, Myosin-9, Protein transport protein Sec61 subunit beta,and Cytochrome c oxidase copper chaperone, which are responsible forcell apoptosis, proliferation, differentiation andmigration. In summary, our findings elucidate the potential anti-tumor mechanism of TSAJ from the direct target proteins, and provide a new insight for exploring the pharmacological mechanism of traditional Chinese medicine.

(±)-Torreyunlignans A-D, rare 8-9' linked neolignan enantiomers as phosphodiesterase-9A inhibitors from Torreya yunnanensis.

(±)-Torreyunlignans A-D (1a/1b-4a/4b), four pairs of new 8-9' linked neolignan enantiomers featuring a rare (E)-2-styryl-1,3-dioxane moiety, were isolated from the trunk of Torreya yunnanensis. The structures were determined by combined spectroscopic and chemical methods, and the absolute configurations were elucidated by ECD calculations. The compounds were screened by using tritium-labeled adenosine 3',5'-cyclic monophosphate ([(3)H]-cGMP) as a substrate for inhibitory affinities against phosphodiesterase-9A (PDE9A), which is a potential target for the treatment of diabetes and Alzheimer's disease. All of the enantiomers exhibited inhibition against PDE9A with IC50 values ranging from 5.6 to 15.0 µM. This is the first report of PDE9A inhibitors from nature.

Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi.

Ten new prostaglandin derivatives (PGs), sarcoehrendins A-J (1-10), together with five known analogues (11-15) were isolated from the soft coral Sarcophyton ehrenbergi. Compounds 4-8 represented the first examples of PGs featuring an 18-ketone group. The structures including the absolute configurations were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates and six synthetic analogues (3a, 3b, 4a, and 11a-11c) were screened for inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 2, 10, 11a, 11b, and 13-15 exhibited inhibition with IC50 values less than 10 µM, and compound 15 (IC50 = 1.4 µM) showed comparable activity to the positive control rolipram (IC50 = 0.60 µM). The active natural PGs (2, 10, and 13-15) represent the first examples of PDE4 inhibitors without an aromatic moiety, and a preliminary structure-activity relationship is also proposed.

Determination of the absolute stereochemistry of two new aristophyllene sesquiterpenes: a combined theoretical and experimental investigation.

Aristoyunnolins G (1) and H (2), two new diastereoisomeric sesquiterpenes featuring a rare aristophyllene skeleton, were isolated from the traditional Chinese medicine Aristolochia yunnanensis. Their absolute stereochemistry involving three chiral centers was determined by combined chemical, spectral, and Density Functional Theory (DFT) calculation methods.

ß3-Adrenergic receptor antagonist improves exercise performance in pacing-induced heart failure.

In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. We have previously shown that in HF at rest stimulation of ß3-adrenergic receptors by endogenous catecholamine depresses LV contraction and relaxation. ß3-Adrenergic receptors are activated at higher concentrations of catecholamine. Thus exercise may cause increased stimulation of cardiac ß3-adrenergic receptors and contribute to this abnormal response. We assessed the effect of L-748,337 (50 µg/kg iv), a selective ß3-adrenergic receptor antagonist (ß3-ANT), on LV dynamics during exercise in 12 chronically instrumented dogs with pacing-induced HF. Compared with HF at rest, exercise increased LV end-systolic pressure (PES), minimum LV pressure (LVPmin), and the time constant of LV relaxation (τ) with an upward shift of early diastolic portion of LV pressure-volume loop. LV contractility decreased and arterial elastance (EA) increased. LV arterial coupling (EES/EA) (0.40 vs. 0.51) was impaired. Compared with exercise in HF preparation, exercise after ß3-ANT caused similar increases in heart rate and PES but significantly decreased τ (34.9 vs. 38.3 ms) and LVPmin with a downward shift of the early diastolic portion of LV pressure-volume loop and further augmented dV/dtmax. Both EES and EES/EA (0.68 vs. 0.40) were increased. LV mechanical efficiency improved from 0.39 to 0.53. In conclusion, after HF, ß3-ANT improves LV diastolic filling; increases LV contractility, LV arterial coupling, and mechanical efficiency; and improves exercise performance.

Unusual 9,19 : 24,32-dicyclotetracyclic triterpenoids from Lygodium japonicum.

Lygodipenoids A (1) and B (2), two novel C33 tetracyclic triterpenoids with a new 9,19 : 24,32-dicyclopropane skeleton, were isolated from the whole grass of Lygodium japonicum. Their structures were elucidated by spectroscopic and chemical means. Compounds 1 and 2 were tested in transfected cultured human embryonic kidney 293 HEK293 cells for an agonist assay, and compound 1 was identified as a partial agonist for liver X receptor α.

[Evaluation of shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation: a randomized, double-blind and controlled multicenter trial].

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicinal shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation. METHODS: From August 2007 to July 2008, Beijing Chaoyang Hospital conducted a multicenter study, select the eleven hospital's outpatient subjects, aged 18 to 75 years old, male or female, paroxysmal atrial fibrillation (at least one electrocardiogram diagnosis) seizure frequency ≥ 2 times/month, according to the ratio 1:1:1, subjects were randomly divided into three groups: a. shensongyangxin group, taking shensongyangxin capsule 4 + propafenone analogues 150 mg, 3 times a day; b. propafenone group, taking propafenone tablets 150 mg + 4 shensongyangxin analogues, 3 times a day; shensongyangxin capsule + propafenone group, taking shensongyangxin capsule 4 + propafenone 150 mg, 3 times a day. The treatment course is 8 weeks, with 3 times of follow-up. RESULTS: Total of 349 cases of paroxysmal atrial fibrillation, which 117 cases in shensongyangxin group, 115 cases in propafenone group; 117 cases in shensongyangxin + propafenone group. The baseline data analysis showed that there were no significantly difference (P > 0.05) among the three groups of atrial fibrillation seizure frequency, vital signs, general condition, medical history, 24-hour ambulatory ECG, 12-lead normal electrocardiogram, cardiac ultrasound and symptoms. The comparison before and after (8 weeks) treatment showed that the frequency (from 6 times/m to 2 times/m in each group, P < 0.01), number of cases [from 46 (43.3%) to 22 (20.8%), 43 (43.4%) to 25 (25.3%), and 40 (40.6%) to 31 (29.2%), respectively P < 0.01] and duration time of attack of atrial fibrillation (from 4 h to 0.5 h, 4 h to 0.5 h, and 4.25 h to 0.5 h, respectively P < 0.01) all decreased in three groups. No significant difference among the three groups comparing the overall effect (62.3%, 58.6%, and 58.5%, respectively, P > 0.05), while the efficacy of TCM symptoms in shensongyangxin group (80.2%) was better than that of propafenone group (67.7%) (P < 0.05). Safety evaluation showed that adverse reaction rate was 1.8% in shensongyangxin group, and 8.2% and 5.4% in propafenone group and shensongyangxin + propafenone group. CONCLUSION: Shensongyangxin capsules and propafenone have comparable efficacies in the treatment of PAF. The efficacy of TCM symptoms is better than propafenone. Shensongyangxin capsules have an excellent profile of safety.

[Effect of danshen chuanxiongqin injection on the myocardial damage of unstable angina patients undergoing percutaneous coronary intervention].

OBJECTIVE: To observe the effect of Danshen Chuanxiongqin Injection (DCI) on the myocardial damage of unstable angina (UA) patients undergoing percutaneous coronary intervention (PCI). METHODS: 76 UA patients were randomly assigned to the test group (39 cases) and the control group (37 cases). Routine treatment of Western medicine and PCI were given to all patients. But 10 mL DCI was intravenously dripped to patients in the test group by adding in 250 mL normal saline three to five days before PCI, once daily, lasting for 7 to 10 days. Changes of platelet P-selectin positive expressions before and after medication, the thrombolysis in myocardial infarction (TIMI), myocardial perfusion (TMP) score, levels of creatine kinase-myocardial band (CK-MB) and troponin I (TnI) after PCI were observed in the two groups. RESULTS: After medication the P-selectin positive expressions was lower in the test group than in the control group (2.45% +/- 1.42% vs 4.43% +/- 1.79%, P<0.05). After PCI the incidence of TMP 0/1, the levels of CK-MB and TnI were lower in the test group than in the control group at the same phase, showing statistical difference (P<0.05). No cardiac event occurred in the two groups during the hospital stay. CONCLUSION: Administration of DCI before PCI could effectively inhibit the activation of platelets, improve post-operative myocardial blood perfusion, and lower the incidence of the myocardial damage.

Up-regulation and functional effect of cardiac ß3-adrenoreceptors in alcoholic monkeys.

BACKGROUND: Recent studies link altered cardiac beta-adrenergic receptor (AR) signaling to the pathology of alcoholic cardiomyopathy (ACM). However, the alteration and functional effect of beta(3)-AR activation in ACM are unknown. We tested the hypothesis that chronic alcohol intake causes an up-regulation of cardiac beta(3)-AR, which exacerbates myocyte dysfunction and impairs calcium regulation, thereby directly contributing to the progression of ACM. METHODS: We compared myocyte beta(3)- and beta(1)-AR expression and myocyte contractile ([Ca(2+)](i)), transient ([Ca(2+)](iT)), and Ca(2+) current (I(Ca,L)) responses to beta- and beta(3)-AR stimulation in myocytes obtained from left ventricle (LV) tissue samples obtained from 10 normal control (C) and 16 monkeys with self-administered alcohol for 12 months prior to necropsy: 6 moderate (M) and 10 heavy (H) drinkers with group average alcohol intakes of 1.5 +/- 0.2 and 3.3 +/- 0.2 g/kg/d, respectively. RESULTS: Compared with control myocytes (C), in alcoholic cardiomyocytes, basal cell contraction (dL/dt(max), -39%, H: 69.8 vs. C: 114.6 microm/s), relaxation (dR/dt(max), -37%, 58.2 vs. 92.9 microm/s), [Ca(2+)](iT) (-34%, 0.23 vs. 0.35), and I(Ca,L) (-25%, 4.8 vs. 6.4pA/pF) were all significantly reduced. Compared with controls, in moderate and heavy drinkers, beta(1)-AR protein levels decreased by 23% and 42%, but beta(3)-AR protein increased by 46% and 85%, respectively. These changes were associated with altered myocyte functional responses to beta-AR agonist, isoproterenol (ISO), and beta(3)-AR agonist, BRL-37344 (BRL). Compared with controls, in alcoholic myocytes, ISO (10(-8) M) produced significantly smaller increases in dL/dt(max) (H: 40% vs. C: 71%), dR/dt(max) (37% vs. 52%), [Ca(2+)](iT) (17% vs. 37%), and I(Ca,L) (17% vs. 27%), but BRL (10(-8) M) produced a significantly greater decrease in dL/dt(max) (H: -23% vs. C: -11%), [Ca(2+)](iT) (-30% vs. -11%), and I(Ca,L) (-28% vs. -17%). CONCLUSIONS: Chronic alcohol consumption down-regulates cardiac beta(1)- and up-regulates beta(3)-ARs, contributing to the abnormal response to catecholamines in ACM. The up-regulation of cardiac beta(3)-AR signaling enhances inhibition of LV myocyte contraction and relaxation and exacerbates the dysfunctional [Ca(2+)](i) regulation and, thus, may precede the development of ACM.