Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene.

Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proof-of-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses.

6PPD-quinone exposure induces neuronal mitochondrial dysfunction to exacerbate Lewy neurites formation induced by α-synuclein preformed fibrils seeding.

The emerging toxicant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) is of wide concern due to its ubiquitous occurrence and high toxicity. Despite regular human exposure, limited evidence exists about its presence in the body and potential health risks. Herein, we analyzed cerebrospinal fluid (CSF) samples from Parkinson's disease (PD) patients and controls. The CSF levels of 6PPD-Q were twice as high in PD patients compared to controls. Immunostaining assays performed with primary dopaminergic neurons confirm that 6PPD-Q at environmentally relevant concentrations can exacerbate the formation of Lewy neurites induced by α-synuclein preformed fibrils (α-syn PFF). Assessment of cellular respiration reveals a considerable decrease in neuronal spare respiratory and ATP-linked respiration, potentially due to changes in mitochondrial membrane potential. Moreover, 6PPD-Q-induced mitochondrial impairment correlates with an upsurge in mitochondrial reactive oxygen species (mROS), and Mito-TEMPO-driven scavenging of mROS can lessen the amount of pathologic phospho-serine 129 α-synuclein. Untargeted metabolomics provides supporting evidence for the connection between 6PPD-Q exposure and changes in neuronal metabolite profiles. In-depth targeted metabolomics further unveils an overall reduction in glycolysis metabolite pool and fluctuations in the quantity of TCA cycle intermediates. Given its potentially harmful attributes, the presence of 6PPD-Q in human brain could potentially be a risk factor for PD.

Genetic Polymorphism of NQO1 Influences Susceptibility to Coronary Heart Disease in a Chinese Population: A Cross-Sectional Study and Meta-Anaylsis.

Objective: The present study is to explore the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. Methods: This research were selected 80 CHD patients as the observation group and 130 healthy people who participated in normal physical examination during the same period as the control group. NQO1 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In addition, we conducted a meta-analysis to summarize the results of three relevant previously published adult population studies on the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. Results: There were three genotypes (CC, CT, and TT) for NQO1 C609T polymorphism. The significant associations were found in TT genotype and T allele (all p<0.05). Specifically, People with the TT genotype have 2.06 times CHD risk as those with the CC genotype. And People with the T allele have 1.62 times CHD risk as those with the C allele. No significant association was found by any genetic models in the meta-analysis (all p >0.05). Conclusion: NQO1 gene polymorphism increased the CHD risk in a Chinese population. Combined with individual gene polymorphism, the accuracy of risk assessment for CHD can be improved and individualized health education can be provided for CHD patients by nurses.

Intact living-cell electrolaunching ionization mass spectrometry for single-cell metabolomics.

While single-cell mass spectrometry can reveal cellular heterogeneity and the molecular mechanisms of intracellular biochemical reactions, its application is limited by the insufficient detection sensitivity resulting from matrix interference and sample dilution. Herein, we propose an intact living-cell electrolaunching ionization mass spectrometry (ILCEI-MS) method. A capillary emitter with a narrow-bore, constant-inner-diameter ensures that the entire living cell enters the MS ion-transfer tube. Inlet ionization improves sample utilization, and no solvent is required, preventing sample dilution and matrix interference. Based on these features, the detection sensitivity is greatly improved, and the average signal-to-noise (S/N) ratio is about 20 : 1 of single-cell peaks in the TIC of ILCEI-MS. A high detection throughput of 51 cells per min was achieved by ILCEI-MS for the single-cell metabolic profiling of multiple cell lines, and 368 cellular metabolites were identified. Further, more than 4000 primary single cells digested from the fresh multi-organ tissues of mice were detected by ILCEI-MS, demonstrating its applicability and reliability.

Evaluation of the safety and efficacy of a Fuling-Zexie decoction for people with asymptomatic hyperuricemia: protocol for a prospective, double-blinded, randomized, placebo-controlled clinical trial.

BACKGROUND: Hyperuricemia increases the risk of gout and cardiovascular complications, and how to manage asymptomatic hyperuricemia is controversial. Randomized controlled trials and comparative studies are needed to guide management and treatment. Studies show that Chinese medicine can decrease uric acid through multiple targets, but many of these studies have been conducted in animals because of the lack of a consistent prescription and mechanism. Therefore, we designed this research to study whether Chinese medicine is truly effective and which target is essential by using an approved prescription of a Fuling-Zexie decoction to further guide large sample experiments to determine whether Chinese medicine can reduce the long-term incidence of gout and cardiovascular events. METHODS: This pilot study is a prospective, double-blinded, randomized, placebo-controlled clinical trial developed from March 2020 to December 2021. Thirty people with asymptomatic hyperuricemia will be recruited and assigned to either the Chinese medicine group or placebo group, and each group will have 15 subjects. During the 12-week observation period, there will be 4 visits. The decline in uric acid is the main outcome measure, and urinary uric acid, inflammatory biomarkers, and other indices that may be involved in lowering uric acid are the secondary outcome measures. DISCUSSION: This study will probe the effect of Chinese medicine treatment on hyperuricemia and explore possible therapeutic mechanisms. By performing this trial, we hope to provide evidence and data to support further large clinical studies. TRIAL REGISTRATION: ChiCTR2000038575 . Registered on September 24, 2020.

Extension of hydrodynamic chromatography to DNA fragment sizing and quantitation.

Hydrodynamic chromatography (HDC) is a technique originally developed for separating particles. We have recently extended it to DNA fragment sizing and quantitation. In this review, we focus on this extension. After we briefly introduce the history of HDC, we present the evolution of open tubular HDC for DNA fragment sizing. We cover both the theoretical aspect and the experimental implementation of this technique. We describe various approaches to execute the separation, discuss its representative applications and provide a future perspective of this technique in the conclusion section of this review.

Osteogenic differentiation characteristics of hip joint capsule fibroblasts obtained from patients with ankylosing spondylitis.

BACKGROUND: Autoimmune disease are fairly common and one that has an excessive degree of disability is Ankylosing spondylitis (AS). As the main cells in connective tissues, fibroblasts may play important roles in AS ossification. The conducted research aims to establish the osteogenic disparity characteristics of fibroblasts cultured in vitro, obtained via AS patients hip joint capsule, as well as investigating the pathological osteogenic molecular workings of AS. METHODS: AS patients hip joint capsules were acquired and fracture patients as the control with the finite fibroblast line were established by using tissue culture method. AS fibroblast proliferation, cycle and apoptosis, expression of osteogenic marker genes, osteogenic phenotypes, and the activation degree of the bone morphogenetic protein (BMP)/Smads signalling pathway were detected by flow cytometry, western blotting and real-time fluorescent quantitative polymerase chain reaction. RESULTS: Proliferative activity in AS fibroblasts were abnormally high, and the apoptotic rate decreased. Compared with normal fibroblasts, the mRNA expression of osteogenic marker genes, expression of osteogenic phenotypes, protein expression of core-binding factor a1 (Cbfa1), Smad1, Smad4, Smad5, phosphorylated (p) Smad1, and pSmad5 in AS fibroblasts were higher; however, the expression of Smad6 was lower. Moreover, recombinant human bone morphogenetic protein-2(rhBMP-2) stimulated Cbfa1 expression by normal and AS fibroblasts through the BMP/Smads signalling pathway. CONCLUSIONS: The fibroblasts of hip joint capsules in patients with AS cultured in vitro have biologic characteristics of osteogenic differentiation and may be important target cells of AS ossification. The Activated BMP/Smads signalling pathway could potentially be a mechanism relating to fibroblasts differentiating into osteoblasts and an ossification mechanism for AS.

Solid-phase microextraction integrated nanobiosensors for the serial detection of cytoplasmic dopamine in a single living cell.

Dopamine participates in many physiological and pathological processes. Dynamic monitoring of dopamine levels in the cytoplasm of a single living cell reflects not only the functional state of dopamine synthesis factors but also the processes of related neurodegenerative diseases. Due to the low content of cytoplasmic dopamine and the difficulty to keep cells alive during the operating process, the detection of cytoplasmic dopamine is still challenging. Herein, a solid-phase microextraction (SPME) technique integrated nanobiosensor was employed to trace and quantify dopamine concentration fluctuations in the cytoplasm of a single living cell. We designed a polypyrrole modified carbon fiber nanoprobe as a bifunctional nanoprobe that can extract cytoplasmic dopamine and then perform electrochemical detection. This bifunctional nanoprobe can detect 10 pmol/L extracted dopamine and detected a 60% decrease of the cytoplasmic dopamine concentration in a single living cell by K+ stimulation. This study allowed for the first time serially detecting cytoplasmic dopamine while keeping the target cell alive, which might yield a new method for research on dopamine neurotoxicity and the related drug action mechanisms for neurodegenerative disease.

Controllable fabrication of pico/femtoliter pipette sampling probes and visual sample volume determination.

We propose a hydraulically assisted eddy-current etching method for the controllable fabrication of pico/femtoliter sampling probes with equal inner diameters along the length of the probe. The relative standard deviations of the outer and inner diameters (O.D. and I.D., respectively) of several 1.07-µm-I.D. sampling probe tips fabricated in a single batch using this method were 2.2% and 2.8%, respectively, and the average O.D./I.D. ratio of these probes was 1.17. The probe fabrication method has high reproducibility, and sharp tips are produced, which is advantageous for the transfer of ultra-small sample volumes. Further, the narrow, equal diameter, cylindrical inner bore allows the online, visual determination of the pipetted sample volume by utilizing a microscopic imaging system to measure the liquid length. This value is converted linearly to the pipetted volume, whose measurement error is on a sub-pixel level. Image-based sampling using the fabricated probes was achieved by connecting the probe to an electroosmotic pump, which allowed the controlled pipetting of pico/femtoliter samples. Because the pipette allows samples of the same volume to be measured accurately, the pipette was applied for the semiquantitative mass spectrometry analysis of the metabolites in individual epidermal cells sampled from different parts of Portulaca oleracea plants. The results show that different types of cells have distinct metabolite profiles. Further, the experiments showed that, in dopamine-rich leaves, the content of dopamine in the petioles is higher than that in the foliage. The probe fabrication strategy opens new avenues for the controllable pipetting of ultra-small volume samples and the realization of the visual pipetting of pico/femtoliter samples.

miR-21-5p promotes lung adenocarcinoma cell proliferation, migration and invasion via targeting WWC2.

OBJECTIVE: Studies have suggested that miR-21-5p and WWC2 are key players in most cancer types, yet the underlying mechanisms in lung adenocarcinoma (LUAD) remain elusive. This study made in-depth research on the two factors-dependent mechanisms underlying LUAD occurrence and development. METHODS: Bioinformatics methods were employed to identify the miRNA and its target gene of interest. In all, 20 pairs of LUAD tumor tissue samples and matched adjacent normal samples along with 5 LUAD cell lines were collected for evaluating the aberrant expression of miR-21-5p and WWC2. Dual-luciferase reporter assay was performed to validate the targeted relationship between miR-21-5p and WWC2. A series of in vitro experiments including colony formation assay, EdU, wound healing assay and Transwell were conducted for assessment of the LUAD cell biological behaviors. In addition, Western blot was carried out to determine the protein expression of epithelial-mesenchymal transition (EMT)-related proteins. RESULTS: miR-21-5p was found to be considerably increased in LUAD tissue and cells relative to that in the adjacent tissue and the human bronchial epithelial cells, whereas WWC2 was significantly decreased. Dual-luciferase reporter assay revealed that miR-21-5p targeted WWC2 and down-regulated its expression. Besides, silencing miR-21-5p or overexpressing WWC2 played an inhibitory role in PC-9 cancer cell proliferation, migration and invasion, but such effect was suppressed when miR-21-5p was overexpressed. Furthermore, Western blot uncovered that WWC2 overexpression impeded the EMT process in LUAD cells. CONCLUSION: miR-21-5p facilitates LUAD cell proliferation, migration and invasion through targeting WWC2, which provides a novel therapeutic target for LUAD treatment.

A scalable synthesis of ternary nanocatalysts for a high-efficiency electrooxidation catalysis by microfluidics.

Microfluidic synthesis has attracted extensive attention due to the ability for the multistep precise control of the synthesis parameters, continuous and reproducible preparation, and its ease of integration. However, its commercial application is still affected by its low production efficiency. In this case, we report a high-throughput continuous flow synthesis of highly dispersed PtFeCu/C nanocatalysts using a metal microchip setup with four parallel channels. The high flow rate and integrated channels enabled improving the throughput, whereby 1.33 g h-1 of catalysts could be achieved with the flow rate of 1200 mL h-1 under the experimental conditions. The as-prepared PtFeCu/C exhibited excellent performance, 1.94 times higher than Pt/C for methanol oxidation. More importantly, the yield of the PtFeCu/C nanocatalysts could be further increased through designing numerous parallel channels, which might provide a promising approach for large-scale commercialization of the catalysts. Such a high-throughput fabrication pathway is significant for the large-scale industrial production of nanomaterials.

Single-particle-frit-based packed columns for microchip chromatographic analysis of neurotransmitters.

The fabrication of effective microchip liquid chromatography (LC) systems tends to be limited by the availability of suitable chromatographic columns. Herein, we developed a glass microchip LC system in which porous single-particle silica was adopted as frits and a freeze-thaw valve was utilized to achieve sample injection without interfering with sampling. The fabrication of single-particle-frit-based packed columns did not require an additional packing channel, thus avoiding dead volumes within the channel interface that can influence chromatographic separation. Further, the length of the packed column could be adjusted using the location of single-particle frits within the column channel. The fabricated frits exhibited high mechanical strength, good permeability, and tolerance for high pressures during chromatographic separation. In particular, the developed microchip LC system was able to withstand high separation pressures of more than 5000 psi. The microchip LC system was applied to the separation of neurotransmitters. Three different monoamine neurotransmitters were completely separated within 5 min with theoretical plate numbers on the order of 100,000 plates m-1. The microchip LC system has a potential for application in a variety of fields including environmental analysis, food safety, drug analysis, and biomedicine.

Quantitative knowledge presentation models of traditional Chinese medicine (TCM): A review.

Modern computer technology sheds light on new ways of innovating Traditional Chinese Medicine (TCM). One method that gets increasing attention is the quantitative research method, which makes use of data mining and artificial intelligence technology as well as the mathematical principles in the research on rationales, academic viewpoints of famous doctors of TCM, dialectical treatment by TCM, clinical technology of TCM, the patterns of TCM prescriptions, clinical curative effects of TCM and other aspects. This paper reviews the methods, means, progress and achievements of quantitative research on TCM. In the core database of the Web of Science, "Traditional Chinese Medicine", "Computational Science" and "Mathematical Computational Biology" are selected as the main retrieval fields, and the retrieval time interval from 1999 to 2019 is used to collect relevant literature. It is found that researchers from China Academy of Chinese Medical Sciences, Zhejiang University, Chinese Academy of Sciences and other institutes have opened up new methods of research on TCM since 2009, with quantitative methods and knowledge presentation models. The adopted tools mainly consist of text mining, knowledge discovery, technologies of the TCM database, data mining and drug discovery through TCM calculation, etc. In the future, research on quantitative models of TCM will focus on solving the heterogeneity and incompleteness of big data of TCM, establishing standardized treatment systems, and promoting the development of modernization and internationalization of TCM.

Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment.

Introduction. Ankylosing spondylitis (AS) is a systemic progressive disease with an unknown etiology that may be related to the gut microbiome. Therefore, a more thorough understanding of its pathogenesis is necessary for directing future therapy.Aim. We aimed to determine the differences in intestinal microbial composition between healthy individuals and patients with AS who received and who did not receive treatment interventions. In parallel, the pathology of AS in each patient was analysed to better understand the link between AS treatment and the intestinal microbiota of the patients.Methodology. Sixty-six faecal DNA samples, including 37 from healthy controls (HCs), 11 from patients with untreated AS (NM), 7 from patients treated with nonsteroidal anti-inflammatory drugs (e.g. celecoxib; WM) and 11 from patients treated with Chinese herbal medicine (CHM), such as the Bushen-Qiangdu-Zhilv decoction, were collected and used in the drug effect analysis. All samples were sequenced using Illumina HiSeq 4000 and the microbial composition was determined.Results. Four species were enriched in the patients with AS: Flavonifractor plautii, Oscillibacter, Parabacteroides distasonis and Bacteroides nordii (HC vs. NM, P<0.05); only F. plautii was found to be significantly changed in the NM-HC comparison. No additional species were found in the HC vs. CHM analysis, which indicated a beneficial effect of CHM in removing the other three strains. F. plautii was found to be significantly increased in the comparison between the HC and WM groups, along with four other species (Clostridium bolteae, Clostridiales bacterium 1_7_47FAA, C. asparagiforme and C. hathewayi). The patients with AS harboured more bacterial species associated with carbohydrate metabolism and glycan biosynthesis in their faeces. They also had bacterial profiles less able to biodegrade xenobiotics or synthesize and transport vitamins.Conclusion. The gut microbiota of the patients with AS varied from that of the HCs, and the treatment had an impact on this divergence. Our data provide insight that could guide improvements in AS treatment.

MiR-520f acts as a biomarker for the diagnosis of lung cancer.

Lung cancer is a malignant tumor with high morbidity and mortality. Early diagnosis remains a great challenge for the cancer. In this study, we aimed to explore diagnostic performance of serum microRNA-520f (miR-520f) in lung cancer.Serum specimens were collected from 139 lung cancer patients and 76 healthy volunteers. Relative expression level of serum miR-520f was detected adopting quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was applied to evaluate the association of miR-520f with clinical parameters of the patients. Additionally, receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic value of miR-520f in lung cancer.Serum miR-520f was down-regulated in lung cancer patients compared with healthy group (P <.001). Moreover, the expression of miR-520f was significantly associated with advanced TNM stage (P = .031) and metastasis (P = .002). The area under the curve (AUC) value of ROC curve was 0.888, suggesting that miR-520f could be a diagnostic biomarker for lung cancer. The cut-off value of serum miR-520f for lung cancer diagnosis was 1.815, with a sensitivity of 79.9% and a specificity of 84.2%.Serum miR-520f was down-regulated in lung cancer patients, and may be a candidate biomarker for non-invasive screening of the disease.

Comparison of combination therapy with methotrexate and sinomenine or leflunomide for active rheumatoid arthritis: A randomized controlled clinical trial.

BACKGROUND: A combination of conventional disease-modifying anti-rheumatic drugs improves the treatment of rheumatoid arthritis but with high side-effects. Methotrexate (MTX) combination therapy that with high therapeutic efficacy and low toxicity is in demand in many countries to replace the use of expensive biological agents. STUDY DESIGN: This study was an open-label, 24-week, parallel randomized controlled trial conducted between November 2015 and December 2017. METHODS: Patients were randomly assigned at a 3:2 ratio to receive MTX combined with sinomenine (SIN) at a dose of 120 mg twice daily, or leflunomide (LEF) at a dose of 20 mg once daily. Efficacy and safety were assessed at weeks 4, 12 and 24. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology (ACR)50 response and a European League Against Rheumatism (EULAR) good response at week 24. RESULTS: A total of 101/120 (84.2%) patients completed 24 weeks of observation. In the intention-to-treat (ITT) analysis, 65.3% of patients treated with MTX + SIN showed improved disease activity as determined by the ACR50 response at week 24 compared to 69.6% of patients treated with MTX + LEF. A similar insignificant pattern was found for the ACR20 and ACR70 responses, as well as the clinical disease activity index, EULAR response, and remission and low disease activity rates between these two treatment groups. The per-protocol analysis showed results consistent with those of the ITT analysis. Notably, significant reductions in gastrointestinal adverse reactions and liver toxicity were found in patients treated with MTX + SIN compared to patients treated with MTX + LEF (p < 0.05). CONCLUSION: Considering the balance of efficacy and toxicity, the current study provides evidence that MTX + SIN combination therapy is probably one of the choices for treating patients with active rheumatoid arthritis in addition to MTX + LEF combination therapy.

The effect of cardiovascular risk factors on the carotid intima-media thickness in an old-aged cohort with hypertension: a longitudinal evolution with 4-year follow-up of a random clinical trial.

Hypertension is a generally accepted atherogenic risk factor. The aim of this prospective longitudinal study was to evaluate changes in carotid intima-media thickness (c-IMT) and explore the association of cardiovascular risk factors and the carotid intima thickness in adults with hypertension using standardized methods. We used data from a subgroup of Beijing Vascular Disease Patients Evaluation Study (BEST), a population-based study of community-dwelling adults. The c-IMT, biomarkers, and carotid-femoral-pulse wave velocity (PWV) were measured at baseline, and lifestyles such as smoking status, sleeping habits, and oil or salt intake level were determined with the use of a validated questionnaire in the follow-up. We reevaluated c-IMT in all the initial 1284 (540 female and 744 male) patients with hypertension after 4 years. At reevaluation, mean (± SD) age was 66 ± 1.2 years, systolic blood pressure was 138 ± 19 mmHg, and diastolic blood pressure was 91 ± 10 mmHg. The results showed that mean c-IMT z-scores increased significantly during 4 years (0.002 ± 0.003, p < 0.001) as well as carotid-femoral PWV (13.99 ± 2.74, p < 0.01) and total cholesterol (6.97 ± 1.08, p < 0.001). Linear regression showed statistically significant associations between systolic blood pressure, diastolic blood pressure, C-reactive protein, lip-line, and heart rate with c-IMT z-scores of >1.5SD in the fully adjusted models and the p values were 0.000, 0.000, 0.017, 0.001, and 0.044, respectively . There were significant predictors for the mean effect on c-IMT z-score. In a full-model logistic regression, significant risk factors for an increase in IMT of ≥1.5 z-scores were carotid-femoral PWV (odds ratio: 1.119, confidence interval: 1.018, 1.230, p = 0.020 < 0.05) at first measurement. The conclusion of the study was that longitudinal c-IMT measurements revealed progression in subclinical atherosclerosis during a four-year period in a hypertensive old-aged cohort. Systolic or diastolic blood pressure, homocysteine, carotid-femoral PWV, and waistline were significantly related to c-IMT increment. By lifestyle and medical intervention to control these risk factors may prevent progression of c-IMT in old-aged cohort with hypertension. Clinical trial registration: Clinical trials. Gov. Identifier: NCT02569268.

The Effectiveness and Safety of Tripterygium wilfordii Hook. F Extracts in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Objective: To conduct a meta-analysis of the effectiveness and safety of Tripterygium wilfordii Hook. F (TwHF) extracts for the treatment of rheumatoid arthritis (RA). Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane, Medline, CNKI, SinoMed and WanFang Library till 12 July 2017. All included studies were analyzed with the use of the Review Manager 5.2 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Results: Fourteen randomized controlled trials (RCTs) were identified. TwHF extracts provided a statistically significant improvement in grip strength (GS), swelling joint count (SJC) and morning stiffness (MS) compared with placebo (P < 0.001). The meta-analysis showed significant differences between TwHF extract-treated group and the DMARDs group in GS, MS, C-reactive protein (CRP), and tender joint count (TJC) (P < 0.05), aside from ESR and SJC (P > 0.05). The pooled results also displayed significant differences between the combination of TwHF extracts with DMARDs and the DMARDs alone group in ESR, CRP, SJC, and TJC (P ≤ 0.05). For the safety analysis, two trials favored TwHF extract-treatment and one trial favored non-TWHF extract-treatment in AEs (P < 0.05). Eleven trials showed no statistically significant differences between TwHF extract-treated group and the DMARDs group (P > 0.05). Conclusions: The findings of this systematic review with meta-analysis indicate that TwHF extracts provides statistically significant and clinically important improvement in RA symptoms and has an acceptable safety profile.

Relationship between Serum Uric Acid and Vascular Function and Structure Markers and Gender Difference in a Real-World Population of China-From Beijing Vascular Disease Patients Evaluation Study (BEST) Study.

AIM: The study was done to establish the relationship between serum uric acid (UA) and vascular function and structure parameters including carotid femoral pulse wave velocity (CF-PWV), carotid radial pulse wave velocity (CR-PWV), cardio ankle vascular index (CAVI), ankle brachial index (ABI), and carotid intima-media thickness (CIMT), and the gender difference in a real-world population from China. METHODS: A total of 979 subjects were enrolled (aged 60.86±11.03 years, male 416 and female 563). Value of UA was divided by 100 (UA/100) for analysis. RESULTS: Body mass index (BMI), diastolic blood pressure (DBP), fasting plasma glucose (FPG), UA, and UA/100 were significantly higher in males compared with females (all p＜0.05); pulse pressure (PP), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were lower in males than females (all p＜0.05). All vascular parameters including CF-PWV, CR-PWV, CAVI, ABI, and CIMT were higher in males than females (all p＜0.05). Multiple linear regression analysis showed that UA/100 was independently positively linearly correlated with CAVI (B=0.143, p=0.001) and negatively correlated with ABI in the male population (B=－0.012, p=0.020). In people with higher UA, the risk of higher CF-PWV was 1.593 (p＜0.05). CONCLUSIONS: 1. All vascular parameters were higher in males than females. There was no gender difference in the relationship between UA and vascular markers except in ABI. 2. UA was independently linearly correlated with CAVI. 3. In people with higher UA level, the risk of higher CF-PWV increased. Therefore, higher UA may influence the vascular function mainly instead of vascular structure.

Cardio-ankle vascular index value in dyslipidemia patients affected by cardiovascular risk factors.

BACKGROUND: Increased arterial stiffness is an independent cardiovascular risk factor in smokers or patients with diabetes mellitus and hypertension. Cardio-ankle vascular index (CAVI) is an index of arterial stiffness and atherosclerosis. One of the most important risk factors of the causes of atherosclerosis is dyslipidemia(DLP). However, there was a little research about which influence factors such as: hypertension, diabetes mellitus, and smoking could contribute to the atherosclerosis in the subjects withDLP. METHODS: A total of 649 subjects with DLP (Male328/Female321) from Vascular Medicine of Peking University Shougang Hospital were examined, with a median age of 66 and 5-95 percentile range 47.0-83.5 years. Fasting plasma glucose (FPG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG) were analyzed by colorimetric enzymatic assays with the use of an auto analyzer (HITACHI-7170, Hitachi, Tokyo, Japan).CAVI was measured by VS-1000 apparatus. RESULTS: CAVI correlated significantly with age (p<0.001), Systolic (p<0.001) blood pressure(BP), Total cholesterol (p<0.001), LDL-cholesterol (p<0.001),Triglycerides (p<0.001) . There was no significant difference in CAVI between smokers and non-smokers (p = 0.08) and between statin-treated subjects than in those without statins (p = 0.247). CAVI was significantly higher in subjects with hypertension than in the normotensive group (p<0.001) and in mellitus subjects than in those without mellitus (p<0.001);however, CAVI values adjusted for age was higher only in hypertension than in the normotensive group (p<0.001). CONCLUSIONS: Our study demonstrated that CAVI value in DLP patients is not significantly affected by diabetes mellitus and smoking, but is increased by hypertension.