Research progress on alternative non-classical mechanisms of PCSK9 in atherosclerosis in patients with and without diabetes.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) acts via a canonical pathway to regulate circulating low-density lipoprotein-cholesterol (LDL-C) via degradation of the LDL receptor (LDLR) on the liver cell surface. Published research has shown that PCSK9 is involved in atherosclerosis via a variety of non-classical mechanisms that involve lysosomal, inflammatory, apoptotic, mitochondrial, and immune pathways. In this review paper, we summarized these additional mechanisms and described how anti-PCSK9 therapy exerts effects through these mechanisms. These additional pathways further illustrate the regulatory role of PCSK9 in atherosclerosis and offer an in-depth interpretation of how the PCSK9 inhibitor exerts effects on the treatment of atherosclerosis.

Transformation of Fe-P Complexes in Bioreactors and P Recovery from Sludge: Investigation by XANES Spectroscopy.

The transformation of Fe-P complexes in bioreactors can be important for phosphorus (P) recovery from sludge. In this research, X-ray absorption near-edge structure analysis was conducted to quantify the transformation of Fe and P species in the sludge of different aging periods and in the subsequent acidogenic cofermentation for P recovery. P was readily removed from wastewater by Fe-facilitated coprecipitation and adsorption and could be extracted and recovered from sludge via acidogenic cofermentation and microbial iron reduction with food waste. The fresh Fe-based sludge mainly contained fresh ferrihydrite and amorphous FePO4 with sufficient accessible surface area, which was favorable for Fe-P mobilization and dissolution via microbial reaction. Ferric iron dosed into wastewater underwent rapid hydrolysis, clustering, aggregation, and slow crystallization to form hydrous iron oxides (HFO) with various complicated structures. With the aging of sludge in bioreactors, the HFO densified into phases with much reduced surface area and reactivity (e.g., goethite), which greatly increased the difficulty of P release and recovery. Thus, aging of P-containing sludge should be minimized in wastewater treatment systems for the purpose of P recovery.

[Mechanism research of curcumin on cancer cells based on cell metabolic profiling].

In this study, gas chromatography coupled with mass spectrometry(GC-MS) was used to analyze the changes of 12 kinds of cancer cells treated by curcumin. The related differential metabolites were screened and the metabolic pathways were analyzed to explore the anti-tumor mechanism of curcumin. Methyl thiazol tetrazolium(MTT) assay was used to detect the 50% inhibiting concentration(IC_(50)) of curcumin on 12 human tumor cells. After treatment with curcumin for 48 h, the cells were collected and analyzed by GC-MS, followed by pathway analysis and multivariate data analysis including principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA) and One-way analysis of variance(ANOVA),etc. Overall, 34 metabolites showed significant concentration changes after intervention for 48 h, mainly involving multiple metabolic pathways, including lysine degradation, glycine, serine and threonine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, lysine biosynthesis. In this study, the anti-tumor mechanisms of curcumin interfering with energy metabolism, amino acid metabolism, microtubule system, protein synthesis and oxidative stress response of tumor cells were analyzed from the perspective of metabolism, providing a new reference for further tumor pharmacology study.

Six New neo-Clerodane Diterpenoids from Aerial Parts of Scutellaria barbata and Their Cytotoxic Activities.

Six new neo-clerodane diterpenoids (1: -6: ), scutebatas X - Z, A1-C1, along with twelve known ones (7: -18: ) were obtained via the phytochemical investigation of the aerial parts of Scutellaria barbata. Their structures were established by detailed spectroscopic analysis. The absolute configurations of 1: and 2: , as the representative members of this type, were identified based on a circular dichroic exciton chirality method. Moreover, in vitro cytotoxicity of compounds 1: -6: were evaluated against three human cancer cell lines (SGC-7901, MCF-7, and A-549) using the MTT method. Compound 6: showed cytotoxic activities against all the three cell lines with IC50 values of 17.9, 29.9, and 35.7 µM, respectively.

Prevalence and Patterns of Insomnia Symptoms Among People Aged 65 and Above in Guangdong Province, China.

Objective: This survey investigated the prevalence, distribution, and correlative factors of insomnia symptoms among people aged 65 and above in Guangdong Province, China. Methods: The Guangdong Mental Health Survey was conducted on the elderly in all 21 cities of Guangdong Province from September to December 2021. Multistage stratified cluster sampling was adopted, and 16 377 adult residents were interviewed face-to-face, from which 4001 elderly participants aged 65 and above were included for this study. Complex weighted adjustment methods were applied to weight the data. Multinomial logistic regression was applied to test the independent associations of clinical insomnia symptoms (CIS) and subthreshold insomnia symptoms (SIS) with the factors. Results: The pooled estimate of insomnia symptoms was 13.44% [95% confidence interval (CI): 12.2 %-14.7%]. The 1-month weighted prevalence of SIS and CIS were 11.15% (95% CI: 10.05%-12.37%) and 2.28% (95%CI: 1.77%-2.94%), respectively. Multinomial logistic regression analysis revealed that urban residence, irregular diet, low body mass index, chronic disease, napping 3-4/week, early changes in dementia, symptoms of subthreshold depression, subthreshold generalized anxiety, and generalized anxiety disorder were positively associated with SIS. Additionally, living in urban areas, having chronic diseases, symptoms of subthreshold depression, major depressive disorder, subthreshold generalized anxiety, generalized anxiety disorder were positively associated with CIS. Conclusion: Insomnia symptoms, including CIS and SIS, were prevalent among the elderly in Guangdong Province. Given the high burden of CIS and SIS, policymakers and healthcare professionals must explore and treat the related factors accordingly.

Depression, anxiety and insomnia in Chinese older adults and their family caregivers during the COVID-19 pandemic: an actor-partner interdependence model approach.

Aims: This study aimed to explore the dyadic effects of depression and anxiety on insomnia symptoms in Chinese older adults and their caregivers living in a community setting. Methods: Data were collected from 1,507 pairs of older adults and their caregivers who were in the Guangdong Mental Health Survey in China. The 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder module 7 (GAD-7), and Insomnia Severity Index (ISI) were used to measure depression, anxiety, and insomnia symptoms. Actor-Partner Interdependence Models (APIM) were used to determine whether anxiety or depression symptoms predicted individual or dyadic insomnia. Results: Older adults' and caregivers' depression and anxiety had significant positive correlations with their own and their caregivers' insomnia symptoms (all P < 0.001). Actor effects were found between depression and insomnia symptoms in both older adults and caregivers (B = 0.695, P < 0.001; B = 0.547, P < 0.001, respectively), with one significant partner effects (B = 0.080, P = 0.007). Actor effects were also found between anxiety and insomnia symptoms in both older adults and caregivers (B = 0.825, P < 0.001; B = 0.751, P < 0.001, respectively), with one significant partner effects (B = 0.097, P = 0.004). However, the caregivers' depression and anxiety were not associated with older adults' insomnia symptoms in the APIM analyses. Conclusions: Older adults and their caregivers had an interrelationship between psychological distress and insomnia. Consequently, healthcare providers might consider involving dyads when designing programs to reduce insomnia and improve psychological distress for family caregivers.

Exploring the Influence of Dysphagia and Tracheostomy on Pneumonia in Patients with Stroke: A Retrospective Cohort Study.

Background: Pneumonia is common in patients with tracheostomy and dysphagia. However, the influence of dysphagia and tracheostomy on pneumonia in patients with stroke remains unclear. The aim of this study was to explore the risk factors related to pneumonia, and the association between dysphagia, tracheostomy and pneumonia in patients with stroke was investigated. Methods: Patients with stroke who experienced tracheostomy and dysphagia were included and divided into two groups based on record of pneumonia at discharge. Clinical manifestations and physical examination were used to diagnose pneumonia, whereas clinical swallowing examination, and videofluoroscopy swallowing studies (VFSS) were used to evaluate swallowing function. Results: There were significant differences between the pneumonia group and the no pneumonia group in total tracheostomy time (6.3 ± 5.9 vs. 4.3 ± 1.7 months, p = 0.003), number of instances of ventilator support (0.41 ± 0.49 vs. 0.18 ± 0.38, p = 0.007), PAS score (5.2 ± 1.92 vs. 4.3 ± 1.79, p = 0.039), impaired or absent cough reflex (76.4 vs. 55.6%, p = 0.035), oropharyngeal phase dysfunction (60.6 vs. 40.8%, p = 0.047), length of hospital stay (36.0 ± 7.2 vs. 30.5 ± 11.7 days, p = 0.025) and direct medical costs (15,702.21 ± 14,244.61 vs. 10,923.99 ± 7250.14 United States dollar [USD], p = 0.042). Multivariate logistic regression showed that the total tracheostomy time (95% confidence interval [CI], 1.966−12.922, p = 0.001), impaired or absent cough reflex (95% CI, 0.084−0.695, p = 0.008), and oropharyngeal phase dysfunction (95% CI, 1.087−8.148, p = 0.034) were risk factors for pneumonia. Spearman's correlation analysis demonstrated that PAS scores were significantly correlated with cough reflex dysfunction (r = 0.277, p = 0.03), oropharyngeal phase dysfunction (r = 0.318, p < 0.01) and total tracheostomy time (r = 0.178, p = 0.045). The oropharyngeal phase dysfunction was significantly correlated with cough reflex (r = 0.549, p < 0.001) and UES opening (r = 0.643, p < 0.01). Conclusions: Tracheostomy and dysphagia increased the risk of pneumonia in patients with stroke. Total tracheostomy time, duration of ventilator support, degree of penetration and aspiration, and oropharyngeal phase dysfunction are risk factors. Given this, we also found that there may be a correlation between tracheostomy and dysphagia.

[Effect of navel acupuncture on bladder emptying function in patients with urinary retention after stroke].

OBJECTIVE: To observe the effect of navel acupuncture on bladder emptying function in patients with urinary retention after stroke based on the conventional treatment. METHODS: A total of 106 patients with urinary retention after stroke were randomly divided into an observation group (53 cases, 3 cases dropped off) and a control group (53 cases, 3 cases dropped off). Patients in the control group were treated with drugs, catheterization and bladder function rehabilitation training. On the basis of the treatment in the control group, the observation group was treated with navel acupuncture, 30 min each time, once every other day, for 4 weeks. The bladder residual urine volume, spontaneous urination volume and catheterization times before and after treatment were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, in the two groups, the bladder residual urine volume and catheterization times were lower than those before treatment (P<0.01), and the spontaneous urination volume was higher than that before treatment (P<0.01); the bladder residual urine volume and catheterization times in the observation group were less than those in the control group (P<0.05, P<0.01), and the spontaneous urination volume was higher than that in the control group (P<0.01). The effective rate of the observation group was 90.0 % (45/50), which was higher than 72.0 % (36/50) in the control group (P<0.05). CONCLUSION: On the basis of conventional treatment, navel acupuncture can effectively improve the bladder emptying function of patients with urinary retention after stroke.

The characteristics of postprandial glycemic response patterns to white rice and glucose in healthy adults: Identifying subgroups by clustering analysis.

Objectives: Large interpersonal variability in postprandial glycemic response (PGR) to white rice has been reported, and differences in the PGR patterns during the oral glucose tolerance test (OGTT) have been documented. However, there is scant study on the PGR patterns of white rice. We examined the typical PGR patterns of white rice and glucose and the association between them. Materials and methods: We analyzed the data of 3-h PGRs to white rice (WR) and glucose (G) of 114 normoglycemic female subjects of similar age, weight status, and same ethnic group. Diverse glycemic parameters, based on the discrete blood glucose values, were calculated over 120 and 180 min. K-means clustering based on glycemic parameters calculated over 180 min was applied to identify subgroups and representative PGR patterns. Principal factor analysis based on the parameters used in the cluster analysis was applied to characterize PGR patterns. Simple correspondence analysis was performed on the clustering categories of WR and G. Results: More distinct differences were found in glycemic parameters calculated over 180 min compared with that calculated over 120 min, especially in the negative area under the curve and Nadir. We identified four distinct PGR patterns to WR (WR1, WR2, WR3, and WR4) and G (G1, G2, G3, and G4), respectively. There were significant differences among the patterns regard to postprandial hyperglycemia, hypoglycemic, and glycemic variability. The WR1 clusters had significantly lower glycemic index (59 ± 19), while no difference was found among the glycemic index based on the other three clusters. Each given G subgroup presented multiple patterns of PGR to WR, especially in the largest G subgroup (G1), and in subgroup with the greatest glycemic variability (G3). Conclusion: Multiple subgroups could be classified based on the PGR patterns to white rice and glucose even in seemingly homogeneous subjects. Extending the monitoring time to 180 min was conducive to more effective discrimination of PGR patterns. It may not be reliable to extrapolate the patterns of PGR to rice from that to glucose, suggesting a need of combining OGTT and meal tolerance test for individualized glycemic management.

Methotrexate can prevent cardiovascular events in patients with rheumatoid arthritis: An updated meta-analysis.

AIMS: The incidence of cardiovascular events (CVEs) in patients with rheumatoid arthritis (RA) is higher than that in people without RA. This may be because inflammation promotes the progression of atherosclerosis. Anti-inflammatory drugs might reduce the occurrence of CVEs in patients with RA. Methotrexate (MTX) is a conventional synthetic anti-rheumatic drug that is widely used in the treatment of RA. We performed a meta-analysis to determine whether MTX can prevent CVEs in RA patients. Then, we discussed the possibility of using MTX to prevent recurred CVEs in patients with coronary heart disease (CHD). METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library using the key words "methotrexate," "cardiovascular," "acute coronary syndrome," "coronary heart disease," "myocardial infarction," "angina pectoris," and "rheumatoid arthritis." The efficacy outcome was defined as a composite of CVEs, including stable angina, acute coronary syndrome, stroke, heart failure, and cardiac death. RESULTS: A total of 10 studies and 195,416 RA patients were included in our meta-analysis, and the effect size of relative risk (RR) was pooled using a fixed effect model. The results showed that MTX prevented CVEs in RA patients (RR: 0.798, 95% CI 0.726-0.876, P = .001, I2 = 27. 9%). CONCLUSION: MTX can prevent CVEs in RA patients, but there is not sufficient evidence for using MTX to treat patients with CHD.

[Process comparison of fingerprints of different extracts of Plumbago zeylanica by high performance liquid chromatography].

OBJECTIVE: To optimize the separation conditions of fingerprints of Plumbago zeylanica by high performance liquid chromatography, on this basis, to choose the best way for extracting Plumbago zeylanica by high performance liquid chromatography. METHODS: The investigation of HPLC-FPs of the different extraction samples was by the retention time and the relative area of common peaks in fingerprints. RESULTS: We established the optimum separation conditions of HPLC-FPs for Plumbago zeylanica and there were 4 common peaks in fingerprints. According to the contrast research, the HPLC-FPs of the 90% ethanol extraction and SBE extraction of Plumbago zeylanica were quite similar, and they both had 9 common peaks in fingerprints, It was better to use SBE rather than WE in the extraction of Plumbago zeylanica. CONCLUSION: The SBE may replace the WE and ethanol extraction of Plumbago zeylanica.

[Discussion on ancient theory of acupuncture for post-stroke aphasia from "kidney"].

The relevant articles in the Inner Canon of Yellow Emperor and different physicians' clinical experience regarding acupuncture for post-stroke aphasia were summarized. The etiology, pathogenesis and acupuncture treatment principles for post-stroke aphasia were explored from the perspectives of "treatment based on kidney" "kidney-qi internal exhaustion" of syndrome differentiation of zang-fu and "kidney meridian as core with equal importance to multiple meridians" of syndrome differentiation of meridians, which is aimed to provide reference for clinical treatment.

LC-MS based cell metabolic profiling of tumor cells: a new predictive method for research on the mechanism of action of anticancer candidates.

In the process of anticancer drug development, research on the mechanism of action remains a major obstacle. In the present study, a cell metabolic profiling based discriminatory model was designed to give general direction on anticancer candidate mechanisms. Firstly, ultra-performance liquid chromatography in tandem with high-definition mass spectrometry was applied to obtain a comprehensive metabolic view of 12 human tumor cells. Secondly, multivariate data analysis was used to assess the metabolites' variations, and 42 metabolites were identified as the main contributors to the discrimination of different groups. Then a metabolite-based prediction model was constructed for the first time and verified by cross validation (R 2 = 0.909 and Q 2 = 0.869) and a permutation test (R 2 = 0.0871 and Q 2 = -0.4360). To validate if the model can be applied for mechanism prediction, 4 independent sample sets were used to train the model and the data dots of different drugs were located in different regions. Finally, the model was applied to predict the anticancer mechanism of two natural compounds and the results were consistent with several other studies. Overall, this is the first experimental evidence which reveals that a metabolic profiling based prediction model has good performance in anticancer mechanism research, and thus it may be a new method for rapid mechanism screening.

Efficacy and safety of statins and exercise combination therapy compared to statin monotherapy in patients with dyslipidaemia: A systematic review and meta-analysis.

Background Statin treatment in association with physical exercise can substantially reduce mortality in dyslipidaemic individuals. However, the available data to compare the efficacy and safety of statins and exercise combination therapy with statin monotherapy are limited. Design Systematic review and meta-analysis. Methods We systematically searched PubMed, Embase and the Cochrane Library from database inception until December 2016. We included randomised and non-randomised studies that compared the efficacy and safety of statins and exercise combination therapy with statin monotherapy in patients with dyslipidaemia. Standardised mean differences were calculated and pooled by means of fixed effects models. The risk of bias and heterogeneity among trials was also assessed. Seven articles were assessed in terms of the efficacy of therapy and 13 from the viewpoint of therapeutic safety. Results In terms of efficacy, statins and exercise combination decreased the incidence of diabetes mellitus, improved insulin sensitivity and inflammation, but caused no change in lipid profile compared to statins alone. In terms of safety, statins and exercise combination increased peak oxygen uptake (standardised mean difference 1.01, 95% confidence interval 0.46 to 1.57) compared to statins alone. In contrast to statin-induced myopathy, chronic exercise training prior to statin treatment could counteract statin-induced adverse effects in skeletal muscle. Conclusion Statins and exercise combination therapy is more effective than statin monotherapy in terms of insulin sensitivity, inflammation and exercise capacity. The small number of studies warrants the need for more randomised controlled trials evaluating the efficacy and safety of combination therapy.

Soluble epoxide hydrolase inhibitors, t-AUCB, regulated microRNA-1 and its target genes in myocardial infarction mice.

PURPOSE: Soluble epoxide hydrolase inhibitors (sEHIs) had been demonstrated to produce cardioprotective effects against ischemia-induced lethal arrhythmias, but the exact mechanisms remain unknown. The present study was designed to investigate whether the beneficial effects of sEHIs are related to regulation of microRNA-1, which was a proarrhythmic factor in the ischemic heart. METHODS: A mousemyocardial infarction (MI) model was established by ligating the coronary artery. sEHI t-AUCB (0.2, 1, 5 mg/L in drinking-water) was administered daily seven days before MI. The incidence of arrhythmias was assessed by in vivo electrophysiologic studies. miR-1, KCNJ2 (encoding the K+ channel subunit Kir2.1), and GJA1 (encoding connexin 43 [Cx43]) mRNA were measured by real-time PCR; Kir2.1 and Cx43 protein were assessed by western blotting and immunohistochemistry. RESULTS: We demonstrated that sEHIs reduced the myocardium infarct size and incidence of inducible arrhythmias in MI mice. Up-regulation of miR-1 and down-regulation of KCNJ2/Kir2.1 and GJA1/Cx43 mRNA/protein were observed in ischemic myocaridum, whereas administration of sEHIs produced an opposite effect. In addition, miR-1 overexpression inhibited expression of the target mRNA and their corresponding proteins, whereas t-AUCB reversed the effects. Our results further revealed that PI3K/Akt signaling pathway might participate in the negatively regulation of miR-1 by sEHi. CONCLUSIONS: We conclude that sEHIs can repress miR-1, thus stimulate expression of KCNJ2/Kir2.1 and GJA1/Cx43 mRNA/protein in MI mice, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmias.