[Prediction of quality markers of Angong Niuhuang Pills based on LC-MS and pull-down with SPR chips].

Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 µmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.

Giant Serpentine Middle Cerebral Artery Aneurysm.

Giant serpentine aneurysms are rare entity, which have unique presentations and distinct angiographic features, with poor prognosis if not treated. In this paper, a patient with a giant serpentine aneurysm originated from right middle cerebral artery was reported. A 38-year-old woman suffered from progressively headache and vision declined. The computed tomography and magnetic resonance image revealed a partially calcified, large mass (approximately 80 × 70 × 60 mm sized) in the right frontal-temple lobe. On computed tomography angiography, an unruptured, giant, partially thrombosed, serpentine aneurysm was confirmed. After treatment by craniotomy, the patient was rehabilitation. Operation is an effective method for the treatment of giant serpentine aneurysms. In addition, cerebral angiography and balloon test occlusion are the crucial way of preoperative assessment.

Decreased serum bilirubin is associated with silent cerebral infarction.

OBJECTIVE: The presence of silent cerebral infarction (SCI) increases the risk of transient ischemia attack, symptomatic stroke, cardiovascular disease, and dementia. Total bilirubin (TB) levels were demonstrated to be decreased in carotid intima-media thickness, cardiovascular disease, stroke, and peripheral arterial disease. However, little information is available concerning the correlation between TB and SCI. APPROACH AND RESULTS: A cross-sectional study was conducted to evaluate the association between TB and SCI in 2865 subjects (1831 men and 1034 women) undergoing medical checkup. The participants with SCI had lower TB levels than those without SCI. The subjects with a low TB had a higher prevalence of SCI. Moreover, partial correlation showed that TB levels were tightly correlated with brachial-ankle pulse wave velocity after adjusting for confounding covariates (r=-0.149; P<0.001). Multivariate logistic regression analysis revealed that higher TB was associated with a lower risk of SCI (odds ratio, 0.925; 95% confidence interval, 0.897-0.954; P<0.001). CONCLUSIONS: TB is a novel biochemical indicator for SCI regardless of classical cardiovascular risk factors. Early measurement of TB may be useful to assess the risk of SCI.

Synthesis and evaluation of N-analogs of 1,2-diarylethane as Helicobacter pylori urease inhibitors.

Therapies based on urease inhibition are now seriously considered as the first line of treatment for infections caused by Helicobacter pylori. However, the present inhibitors are ineffective or unstable in highly acidic gastric juice. Here, we report a series of benzylanilines as effective inhibitors of H. pylori urease. Out of the obtained twenty-one compounds, N-(3,4-dihydroxybenzyl)-4-nitroaniline (4) was evaluated in detail and shows promising features for development as anti-H. pylori agent. Excellent potency against urease in both cell-free extract and intact cell was observed at low concentrations of 4 (IC50=0.62 ± 0.04 and 1.92 ± 0.09 µM), which showed over 29- and 54-fold increase in potency with respect to the positive control AHA. The SAR analysis revealed that protection of 3,4-dihydroxy group of 4 as methoxy or changes of 4-NO2 will result in a moderate to dramatic decrease in potency.

Adenosine analogs as inhibitors of tyrosyl-tRNA synthetase: Design, synthesis and antibacterial evaluation.

Herein we describe the synthesis and evaluation of a series of adenosine analogs for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Out of these compounds, compound c6 has much stronger antibacterial potency against Pseudomonas aeruginosa than ciprofloxacin, and was determined to target tyrosyl-tRNA synthetase with IC50 of 0.8±0.07 µM. Structure-activity relationship analysis suggested that introduction of a fluorine atom at the 3'-position of benzene ring of the phenylacetyl moiety significantly increased affinities to the enzyme. In comparison with isopropylidene analogs, 2',3'-deprotected compounds displayed higher inhibitory activity. Molecular dockings provided an explanation for observations in biological assays.

A decreased mean platelet volume is associated with stable and exacerbated asthma.

BACKGROUND: Systemic inflammation is related to disease progression in asthma. Activated platelets play a critical role in atherogenesis, inflammation, and atherothrombosis. The mean platelet volume (MPV) is an early marker of platelet activation. OBJECTIVES: The aim of this study is to clarify the relevance of MPV levels in patients with stable and exacerbated asthma. METHODS: We investigated the peripheral blood cell count parameters, C-reactive protein (CRP), lung function parameters, and arterial blood gas in patients with asthma and control subjects. Eighty-five stable asthma patients and 85 asthmatics with exacerbations were investigated. Eighty-five controls matched for age, gender, body mass index (BMI), and smoking status were recruited. RESULTS: Patients with exacerbated asthma had lower MPV and higher CRP levels and white blood cell (WBC) counts compared to patients with stable asthma and control subjects. Furthermore, the MPV was reduced in patients with stable asthma compared to control subjects. Negative correlations between MPV and CRP were present in stable and exacerbated asthma. Although there was no relationship between MPV and WBC count in stable asthma, there was an inverse relationship between MPV and WBC count in exacerbated asthma. CONCLUSIONS: These findings show that patients with stable asthma had a lower MPV compared to controls and the MPV levels in asthmatic patients with exacerbations were lower compared to those in patients with stable asthma. Further investigations regarding the role of MPV in asthma may be beneficial in the search for therapeutic targets.

Mean platelet volume is negatively associated with bone mineral density in postmenopausal women.

Osteoporosis (OP) has been associated with cardiovascular disease. More specifically, osteoporosis was found to be an independent predictor of cardiovascular mortality. Recent studies revealed that platelets play a critical role in bone remodeling. Mean platelet volume (MPV) is an early marker of platelet activation, which is involved in the pathophysiology of coronary heart disease. However, little research has been conducted to investigate the relationship between MPV and OP. In this cross-sectional study, we investigated the relationship between platelet count, MPV, and bone mineral density (BMD) in 410 subjects in the geriatric department of the Second Affiliated Hospital, Harbin, China. Different biochemical parameters, platelet count, and MPV were determined, and bone mineral density (BMD) (g/cm(2)) was measured in the osteoporosis, osteopenia, and normal BMD groups. Mean age, systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and MPV increased gradually, and body mass index (BMI), decreased as BMD decreased. A negative correlation was present between MPV and the lumbar spine (L2-L4) and femoral neck BMD after adjusting other risk factors. Univariate analysis and multivariate analysis showed that MPV was significantly associated with lumbar spine L2-L4 BMD and femoral neck BMD (ß = -0.285, P < 0.001 for lumbar spine L2-L4 BMD; ß = -0.207, P < 0.001 for femoral neck BMD in multivariate model). The findings show that MPV is negatively correlated with BMD. Further studies on the involvement of MPV in osteoporosis may contribute to the evaluation of thrombotic risk in elderly patients with osteoporosis.

Relationship between platelet activation markers and spontaneous abortion: A meta-analysis.

Numerous studies have indicated that mean platelet volume (MPV) and platelet distribution width (PDW) were correlated with spontaneous abortion (SAB), but the results were contradictory. Hence, we performed a meta-analysis to assess the association of MPV and PDW with SAB. We systematically searched on China National Knowledge Internet, PubMed, and Embase up to May 2022 to retrieve eligible studies. The synthesized standard mean difference (SMD) with a 95% confidence interval (CI) was used to evaluate the correlation of MPV and PDW with SAB. A total of 20 studies were finally included in this meta-analysis. The pooled analysis results showed that PDW was markedly increased in patients with SAB versus women with a healthy pregnancy (SMD = 1.03; 95% CI: 0.51-1.54; p = 0.0001), while there were no significant differences in MPV between women with SAB and those with healthy pregnancy (SMD = 0.19; 95% CI: -0.26 to 0.65; p = 0.40). Therefore, PDW may serve as a potential marker for predicting SAB. However, homogeneous and multiethnic studies with larger sample sizes are warranted to validate our findings due to several limitations in this meta-analysis.

Squamous cell carcinoma antigen, platelet distribution width, and prealbumin collectively as a marker of squamous cell cervical carcinoma.

BACKGROUND: Squamous cell cervical carcinoma is the most common gynecological malignant disorder worldwide. Early detection of squamous cell cervical carcinoma is needed for proper clinical management. Squamous cell carcinoma antigen (SCCA) is commonly used as a tumor marker for squamous cell cervical carcinoma. Platelet distribution width (PDW) is an indicator of platelet activation. Prealbumin is a negative acute-phase protein. OBJECTIVE: The aim of this study was to investigate the ability of SCCA, PDW, and prealbumin individually or in combination, to distinguish between cervical carcinoma and control subjects. MEHTODS: Two hundred and twenty patients with squamous cell cervical carcinoma and 211 control subjects were included in the study. Patients' characteristics and hematologic tests data at initial diagnosis were collected. RESULTS: Our results showed that SCCA and PDW were higher, and prealbumin was lower in cervical carcinoma patients than in control subjects. Single biomarker had AUC value ranging from 0.753 for SCCA to 0.845 for PDW. The combination of SCCA and PDW increased the AUC to 0.900 (p< 0.0001). In addition, the combination of SCCA, PDW and prealbumin exhibited a significantly larger AUC of 0.917 (0.887-0.942), significantly higher than those of any single marker. CONCLUSIONS: The combined use of SCCA, PDW and prealbumin can accurately distinguish squamous cell cervical carcinoma from control subjects. This promising approach could be helpful in early detection of squamous cell cervical carcinoma.

Gallstone disease is associated with arterial stiffness progression.

Gallstones have been linked to dyslipidemia, metabolic syndrome and cardiovascular disease. Arterial stiffness is an indicator of subclinical atherosclerosis. The aim of this study was to prospectively examine the relationship between gallstone disease and arterial stiffness progression in 347 men and 454 women. These subjects were followed for 7 years. Arterial stiffness progression was measured based on increases in brachial-ankle pulse wave velocity. Changes in brachial-ankle pulse wave velocity during the study period were significantly greater in patients with gallstones than in subjects without gallstones. After adjusting for multiple risk factors, gallstone disease was found to be a significant and independent predictor of brachial-ankle pulse wave velocity progression (ß=0.189; P<0.001). In conclusion, gallstone disease is an independent predictor of arterial stiffness progression, even after adjusting for other cardiovascular risk factors.

Reduced prealbumin is associated with bone mineral density in women with osteoporosis.

OBJECTIVES: Poor nutritional status is associated with osteoporosis (OP) in postmenopausal women. Moreover, recent studies documented that prealbumin is the best and most widely used parameter to monitor nutrition intervention and is a sensitive predictor of short-term outcome compared with albumin. Therefore, the aim of this study was to examine the association of prealbumin levels with bone mineral density (BMD) in patients with OP. METHODS: This cross-sectional study recruited 664 women. Prealbumin levels and BMD at femoral neck and lumbar spine were measured. Multiple linear regression analysis was performed to assess the correlation between prealbumin and BMD. RESULTS: Results of this study found that prealbumin levels dropped gradually as BMD decreased. Furthermore, partial correlation analysis revealed that prealbumin was correlated with BMD after adjusting for confounders. Multiple linear regression analysis showed that prealbumin is a significant factor for reduced BMD in women (for BMD at spine L2-4, ß = 0.186, P < 0.001; for BMD at femoral neck, ß = 0.180, P < 0.001). CONCLUSION: Prealbumin was significantly correlated with BMD after adjusting for traditional cardiovascular risk factors. Further prospective research is warranted to further enhance our understanding of the important role of prealbumin in OP.

Bone mineral density is associated with left ventricular diastolic function in women.

BACKGROUND: Low bone mineral density (BMD) and left ventricular (LV) diastolic function are associated with heart failure. However, little is known about the association between BMD and LV diastolic function. HYPOTHESIS: BMD is independently related to LV diastolic function in women. METHODS: We conducted a cross-sectional study of 432 women. Brachial-ankle pulse wave velocity (baPWV) and BMD measurements were performed. LV diastolic function and structure were assessed by echocardiographic examination. RESULTS: BaPWV and the percentage of LV diastolic dysfunction increased with progressive bone loss. Moreover, partial correlation analysis demonstrated that BMD at spine L2-4 and at femoral neck were correlated with baPWV and LV diastolic function parameters after adjusting covariates. Multivariate logistic regression analysis revealed that osteoporosis was independently associated with LV diastolic dysfunction in women. CONCLUSIONS: Osteoporosis is independently associated with LV diastolic dysfunction in women. A prospective study is needed to elucidate the effects of BMD on cardiac function in women.

Neutrophil-Lymphocyte ratio is associated with arterial stiffness in diabetic retinopathy in type 2 diabetes.

AIMS: Diabetic retinopathy (DR) is the most common complication of type 2 diabetes mellitus (T2DM). Inflammation plays a considerable role in the pathogenesis of T2DM and DR. Emerging evidence revealed that the neutrophil-lymphocyte ratio (NLR) may be a useful marker of cardiovascular disease. The brachial-ankle pulse wave velocity (baPWV) is an indicator for early atherosclerotic changes. Therefore, this study aimed to investigate the association of NLR with baPWV in patients with DR. METHODS: In this cross-sectional study, we investigated the relationship between NLR and baPWV in 402 participants. Participants were divided into the following three groups: 133 control subjects without T2DM; 138 diabetic subjects without DR; and 131 patients with DR. RESULTS: NLR and baPWV were elevated both in T2DM and in DR. Moreover, compared to T2DM, NLR and baPWV were higher in DR. There was a positive correlation between NLR and baPWV in patients with T2DM and DR after adjusting confounding factors. Multiple linear regression analysis further revealed that NLR was an independent and significant determinant for elevated baPWV (for T2DM, ß=0.170; p=0.041; for DR, ß=0.188; p=0.022, respectively). CONCLUSIONS: The findings showed that NLR and baPWV are elevated both in T2DM and in DR. In addition, NLR is independently associated with baPWV. Early detection of abnormal NLR levels may be helpful for the search of subclinical atherosclerosis in patients with T2DM and DR.