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Jian-Jun Wu,1 Ping-An Zhang,1 Ming-Zhe Chen,2 Yi Zhang,1 Wei-Sha Du,1 Xiao-Ning Li,1 Guo-Chao Ji,1 Liang-Duo Jiang,3 Yang Jiao,4,* Xin Li5,* 1Respiratory Department, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Infectious Disease Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 3Respiratory Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Respiratory Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Glaucoma Department, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Li, Glaucoma Department, Eye Hospital, China academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email doudou8295@163.comBackground: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear.Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained.Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated.Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated.Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.Keywords: COPD, GC, GEO database, miRNA-mRNA, DEMs, DEGs

BACKGROUND: Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE: To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING: Eleven hospitals from 4 provinces in China. PATIENTS: 410 young adults aged 15 to 59 years with laboratory-confirmed H1N1 influenza. INTERVENTION: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION: Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE: Beijing Science and Technology Project and Beijing Nova Program. [ABSTRACT FROM AUTHOR]

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is a widely studied plant that shows potential in treating urinary diseases. Previous studies have focused on its chemical composition, pharmacological effects, and clinical applications. This review aims to provide a comprehensive summary and evaluation of the existing literature on CS. It also suggests future research directions to increase our understanding of its medicinal value. 129 pieces of literature were selected from several databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wan-fang Database, and Google Scholar, and were analyzed. Forty-five active compounds of CS have pharmacological effects such as lowering uric acid, anti-inflammation, anti-oxidation, and kidney protection. The potential mechanisms of these effects may be related to inhibiting transforming growth factor β1 (TGF-β1) activation, reducing inflammatory factors such as IL-8, IL-1β, TNF-α, PGE2, IFN-γ, and IL-6 levels, suppressing the activation of NF-κB, JAK/STAT pathway, enhancing the clearance of ROS, MDA DPPH·, and O 2 ̇ - , and regulating the expression of apoptosis-related pathways and proteins. This paper also discusses the quality control of CS and its efficacy and safety in treating urinary diseases. The study concludes that CS has a high potential for treating urinary diseases. Future studies should focus on observing the metabolic changes of CS active compounds in vivo and investigating the effects of CS on key signaling pathways. Additionally, more standardized and reasonable clinical studies and safety evaluation experiments should be conducted to obtain more clinical data., Competing Interests: Declaration of competing interest We confirm that there are no conflicts of interest associated with this publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.

Background: Yujin powder (YJP) is a classic prescription for treating dampness-heat diarrhea (DHD) in Traditional Chinese Medicine (TCM), but the main functional active ingredients and the exact mechanisms have not been systematically studied., Objectives: This study aimed to preliminarily explore the potential mechanisms of YJP for treating DHD by integrating UPLC-MS/MS and network pharmacology methods., Methods: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to determine the ingredients of YJP. And then, the targets of these components were predicted and screened from TCMSP, SwissTargetPrediction databases. The disease targets related to DHD were obtained by using the databases of GeneCards, OMIM, DisGeNET, TTD, and DrugBank. The protein-protein interaction networks (PPI) of YJP-DHD were constructed using the STRING database and Origin 2022 software to identify the cross-targets by screening the core-acting targets and a network diagram by Cytoscape 3.8.2 software was also constructed. Metascape database was used for performing GO and KEGG enrichment anlysis on the core genes. Finally, molecular docking was used to verify the results with AutoDock 4.2.6, AutoDock Tools 1.5.6, PyMOL 2.4.0, and Open Babel 2.3.2 software., Results: 597 components in YJP were detected, and 153 active components were obtained through database screening, among them the key active ingredients include coptisine, berberine, baicalein, etc. There were 362 targets treating DHD, among them the core targets included TNF, IL-6, ALB, etc. The enriched KEGG pathways mainly involve PI3K-Akt, TNF, MAPK, etc. Molecular docking results showed that coptisine, berberine, baicalein, etc., had a strong affinity with TNF, IL-6, and MAPK14. Therefore, TNF, IL-6, MAPK14, ALB, etc., are the key targets of the active ingredients of YJP coptisine, baicalein, and berberine, etc. They have the potential to regulate PI3K-Akt, MAPK, and TNF signalling pathways. The component-target-disease network diagram revealed that YJP treated DHD through the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury., Conclusion: It is demonstrated that YJP treats DHD mainly through the main active ingredients coptisine, berberine, baicalein, etc. comprehensively exerting the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury, which will provide evidence for further in-depth studying the mechanism of YJP treating DHD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Patients with cerebral venous sinus thrombosis (CVST) may die during the acute phase due to increased intracranial pressure and cerebral herniation. The purpose of this study was to assess the role of decompressive craniectomy in the treatment of patients with malignant CVST., Methods: Patients who underwent decompressive craniectomy and were consequently admitted to the Critical Care Unit, Department of Neurosurgery, at Capital Medical University Xuanwu Hospital from March 2010 to January 2021 were retrospectively examined with follow-up data at 12 months., Results: In total, 14 cases were reviewed, including 9 female and 5 male patients, aged 23-63 years (42.7 ± 12.3 years). Prior to surgery, all patients had a GCS score <9. 6 patients had a unilateral dilated pupil, while 4 patients had bilateral dilated pupils. According to the head computed tomography (CT), all patients had hemorrhagic infarction, and the median midline shift was 9.5 mm before surgery. Thirteen patients underwent unilateral decompressive craniectomy, and 1 patient underwent bilateral decompressive craniectomy, among whom, 9 patients underwent hematoma evacuation. Within 3 weeks of surgery, 3 cases (21.43%) resulted in death, with 2 patients dying from progressive intracranial hypertension and 1 from acute respiratory distress syndrome (ARDS). Eleven patients (78.57%) survived after surgery, of whom 4 (28.57%) patients recovered without disability at 12-month follow-up (mRS 0-1), 2 (14.29%) patients had moderate disability (mRS 2-3), and 5 (35.71%) patients had severe disability (mRS 4-5)., Conclusions: Emergent decompressive craniectomy may provide a chance for survival and enable patients with malignant CVST to achieve an acceptable quality of life (QOL)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

Cow milk consumption (CMC) and alterations of gut bacterial composition are proposed to be closely related to human health and disease. Our research aims to investigate the changes in human gut microbial composition in Chinese peri-/postmenopausal women with different CMC habits. A total of 517 subjects were recruited and questionnaires about their CMC status were collected; 394 subjects were included in the final analyses. Fecal samples were used for studying gut bacterial composition. All the subjects were divided into a control group ( n = 248 ) and a CMC group ( n = 146 ) according to their CMC status. Non-parametric tests and LEfSe at different taxonomic levels were used to reveal differentially abundant taxa and functional categories across different CMC groups. Relative abundance (RA) of one phylum ( p&#95;Actinobacteria ), three genera ( g&#95;Bifidobacterium , g&#95;Anaerostipes , and g&#95;Bacteroides ), and 28 species diversified significantly across groups. Specifically, taxa g&#95;Anaerostipes ( p < 0.01 ), g&#95;Bacteroides ( p < 0.05 ), s&#95;Anaerostipes&#95;hadrus ( p < 0.01 ), and s&#95;Bifidobacterium&#95;pseudocatenulatum ( p < 0.01 ) were positively correlated with CMC levels, but p&#95;Actinobacteria ( p < 0.01 ) and g&#95;Bifidobacterium ( p < 0.01 ) were negatively associated with CMC levels. KEGG module analysis revealed 48 gut microbiome functional modules significantly ( p < 0.05 ) associated with CMC, including Vibrio cholerae pathogenicity signature, cholera toxins ( p = 9.52e-04 ), and cephamycin C biosynthesis module ( p = 0.0057 ), among others. In conclusion, CMC was associated with changes in gut microbiome patterns including beta diversity and richness of some gut microbiota. The alterations of certain bacteria including g&#95;Anaerostipes and s&#95;Bifidobacterium&#95;pseudocatenulatum in the CMC group should be important for human health. This study further supports the biological value of habitual cow milk consumption., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Yao, Lin, Lv, Jiang, Wang, Shen, Xiao, Xu, Xu, Cheng, Shen, Qiu, Luo, Zhao, Yan, Deng and Zhang.)

Takayasu's arteritis (TAK) mainly involves the aorta and its major branches, which is characterized as a chronic, progressive and inflammatory disease. China belongs to one of the regions with a high prevalence of TAK referring to its global distribution. However, it is insufficient for the spread and update of standardized diagnosis and treatment of TAK. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed the standardized diagnosis and treatment of TAK in China. The purpose is to standardize the methods for diagnosis of TAK, assessment of disease activity and disease severity, strategies of internal treatment and timing of surgical intervention, and further leading to protect the function of important organs and improve the disease prognosis.

Objective: To investigate the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in assessing disease activity in Takayasu arteritis (TA)., Methods: Ninety-one patients with TA were recruited from a Chinese cohort. Clinical data, acute-phase reactants and 18F-FDG-PET/CT findings were simultaneously recorded. The value of using 18F-FDG-PET/CT to identify active disease was evaluated, using ESR as a reference. Disease activity assessment models were constructed and concordance index (C-index), net reclassification index (NRI), and integrated discrimination index (IDI) were evaluated to compare the benefits of the new modes with ESR and the Kerr score., Results: In total, 64 (70.3%) cases showed active disease. Higher levels of ESR and CRP, and lower IL-2 receptor (IL-2R) levels were observed in active cases. 18F-FDG-PET/CT parameters measured by determining the standard uptake value (SUV), including SUVmean, SUVratio1, SUVratio2, sum of SUVmean and sum of SUVmax, were significantly higher in active disease groups. The C-index threshold of ESR to indicate active disease was 0.78 (95% CI: 0.69, 0.88). The new activity assessment model combining ESR, sum of SUVmean and IL-2R showed significant improvement in C-index over the ESR method (0.96 vs 0.78, P < 0.01; NRI 1.63, P < 0.01; and IDI 0.48, P < 0.01). The new model also demonstrated modest superiority to the Kerr score assessment (0.96 vs 0.87, P = 0.03; NRI 1.19, P < 0.01; and IDI 0.33, P < 0.01)., Conclusions: A novel 18F-FDG-PET/CT-based method that involves combining the sum of SUVmean with ESR score and IL-2R levels demonstrated superiority in identifying active TA compared with conventional methods., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Several studies have indicated metabolic function disruption effects of bisphenol analogues through peroxisome proliferator-activated receptor (PPAR) alpha and gamma pathways. In the present study, we found for the first time that PPARβ/δ might be a novel cellular target of bisphenol analogues. By using the fluorescence competitive binding assay, we found seven bisphenol analogues could bind to PPARβ/δ directly, among which tetrabromobisphenol A (TBBPA, 18.38-fold) and tetrachlorobisphenol A (TCBPA, 12.06-fold) exhibited stronger binding affinity than bisphenol A (BPA). In PPARβ/δ-mediated luciferase reporter gene assay, the seven bisphenol analogues showed transcriptional activity toward PPARβ/δ. Bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol B (BPB) even showed higher transcriptional activity than BPA, while TBBPA and TCBPA showed comparable activity with BPA. Moreover, in human liver HL-7702 cells, the bisphenol analogues promoted the expression of two PPARβ/δ target genes PDK4 and ANGPTL4. Molecular docking simulation indicated the binding potency of bisphenol analogues to PPARβ/δ might depend on halogenation and hydrophobicity and the transcriptional activity might depend on their binding affinity and hydrogen bond interactions. Overall, the PPARβ/δ pathway may provide a new mechanism for the metabolic function disruption of bisphenol analogues, and TBBPA and TCBPA might exert higher metabolic disruption effects than BPA via PPARβ/δ pathway., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China., Methods: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world., Results: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million., Conclusions: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: We aimed to construct and validate a risk assessment model to identify risk factors for heart failure (HF) in patients with Takayasu's arteritis (TAK)., Methods: Three hundred sixty-five patients with TAK were recruited in the East China Takayasu Arteritis Cohort from January 2012 to December 2019. Patients were assigned into training and validation sets following a 2:1 ratio according to the date of enrollment. Clinical characteristics were compared between heart failure (HF) and non-HF subgroups in the training set, and a risk assessment model for HF and its scoring algorithm was established based on logistic regression, which was tested in the validation set., Results: Among total of 74 (20.27%) TAK patients exhibited HF, and 55 cases (74.32%) were in the training set. The risk factors for HF of TAK patients included onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension. We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients in the training set with the score ≥ 3 appeared to be associated with an increased risk of HF with an area under curve (AUC) of 0.88 and 0.90 in Model 1 and Model 2 respectively. The AUC reached to 0.88 and 0.89 in the validation set that proved the accuracy of the model., Conclusions: We presented a risk assessment model of HF in TAK, which may help clinicians alert the complication of HF in the patients with specifically cardiac impairments. Key Points • Heart failure was not rare in Chinese Takayasu's arteritis patients, and there were approximately 20% of patients with heart failure in ECTA cohort. • Cardiac involvements on echocardiography include pathological valvular and atrioventricular abnormalities. • The onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension were risk factors for heart failure in Takayasu's arteritis patients. • We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients with the risk assessment model score of ≥ 3 appeared to be associated with an increased risk of heart failure., (© 2021. International League of Associations for Rheumatology (ILAR).)

Aims: Osteosarcoma (OS) is an extremely malignant bone cancer with high incidence and rapid progression. This study aims to investigate the role and underlying mechanisms of MALAT1 and miR-485-3p in OS., Materials and Methods: qRT-PCR and Western blotting were utilized to measure the levels of miR-485-3p, MALAT1, c-MET, AKT3, p-mTOR, mTOR, glycolysis-related proteins or migration-related proteins. Colony formation and transwell assay were used to test the roles of miR-485-3p, MALAT1, c-MET and AKT3 in cancer cell proliferation, migration and invasion. Dual luciferase assay was used to validate the interactions of miR-485-3p/c-MET, miR-485-3p/AKT3, and MALAT1/miR-485-3p. Glucose uptake assay and measurement of lactate production were employed to determine the glycolysis process. Mouse tumour xenograft model was used to determine the effect of shMALAT1 and miR-485-3p mimics on tumour growth and metastasis in vivo., Key Findings: miR-485-3p was decreased while c-MET, AKT3, and MALAT1 were increased in human OS tissues and cells. miR-485-3p bound directly to c-MET and AKT3 mRNAs and repressed OS cell glycolysis, proliferation, migration, and invasion through decreasing glycolysis-related proteins and migration-related proteins via inhibiting c-MET and AKT3/mTOR pathway. In addition, MALAT1 interacted with miR-485-3p and disinhibited c-MET and AKT3/mTOR signalling. Knockdown MALAT1 or overexpression of miR-485-3p restrained OS tumour growth and lung metastasis in vivo., Significance: miR-485-3p suppresses OS glycolysis, proliferation, and metastasis via inhibiting c-MET and AKT3/mTOR signalling and MALAT1 acts as a sponge of miR-485-3p. MALAT1 and miR-485-3p may be the key regulators in OS progression, and potential molecular targets for future OS therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To identify valuable ultrasonography findings combined with clinical markers for predicting carotid progression of Takayasu's arteritis (TAK) on imaging during a 1-year follow-up period., Methods: From May 2016 to June 2019, 77 Chinese TAK patients with carotid artery involvement were enrolled in the present study. The patients' clinical characteristics and serological test and carotid ultrasonography results were recorded at baseline and each visit. Carotid progression was evaluated by ultrasonography every 3 months during the 1-year follow-up. Baseline clinical characteristics and ultrasonography results for predicting progression on imaging were identified., Results: Sixteen (20.8%) patients presented with carotid progression on imaging during the 1-year follow-up period. The patients in the progressive group were younger (23.4±3.7 vs. 32.3±9.8 years, p<0.01) than those in the non-progressive group. At baseline, the vessel wall was thicker in the progressive group than in the non-progressive group (2.4±0.8 vs. 1.9±0.5 mm, p=0.041). Furthermore, the proportion of patients with refractory disease (87.5% vs. 16.4%, p<0.01) was higher in the progressive group than in the non-progressive group. Patients with a thickened carotid wall (≥1.9 mm), refractory disease, and younger age (≤30 years) might be at a high risk of carotid progression on imaging (75%, AUC: 0.93, sensitivity: 75%, specificity: 93.4%)., Conclusions: Younger patients with early vascular structural changes at baseline as well as refractory disease seemed more likely to show carotid progression on imaging.

Introduction: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate., Methods: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively., Results: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks., Conclusions: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE., Trial Registration: ClinicalTrials.gov identifier, NCT02265705.

Background: Clinical studies have shown that hyperuricemia is associated with many cardiovascular diseases; however, the mechanisms involved remain unclear. In this study, we investigated the effect of uric acid on cardiomyocytes and the underlying mechanism., Methods and Results: H9c2 cardiomyocytes were treated with various concentrations of uric acid. 3-Methyladenine (3-MA) or Compound C was added before treatment with uric acid. The expression of myocardial hypertrophy-related genes was measured using polymerase chain reaction (PCR). The cell surface area was calculated using ImageJ Software. Western blotting was used to measure the protein levels. Uric acid increased the gene expression of Nppa , Nppb , and Myh5 , which are involved in myocardial hypertrophy, and the relative cell surface area of cardiomyocytes in a dose-dependent manner. Consistently, the ratio of LC3II/I, which is a biomarker of autophagy, increased dose-dependently, whereas the protein level of p62, a protein that is degraded by autophagy, decreased. 3-MA, an autophagy inhibitor, rescued uric acid-induced myocardial hypertrophy. Treatment with uric acid increased the level of phosphorylated adenosine monophosphate kinase (AMPK), as well as its downstream effector unc-51-like kinase (ULK1). Pharmacological inhibition of AMPK by Compound C attenuated the uric acid-induced activation of autophagy and myocardial hypertrophy., Conclusions: Uric acid induces myocardial hypertrophy by activating autophagy via the AMPK-ULK1 signaling pathway. Decreasing the serum uric acid level may therefore be clinically beneficial in alleviating cardiac hypertrophy., Competing Interests: None., (AJTR Copyright © 2020.)

Background: Chronic obstructive pulmonary disease (COPD) patients with different phenotypes show different clinical characteristics. Therefore, we conducted a meta-analysis to explore the clinical characteristics between the non-exacerbator (NE) phenotype and the frequent exacerbator with chronic bronchitis (FE-CB) phenotype among patients with COPD., Methods: CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases were searched from the times of their inception to April 30, 2019. All studies that reported the clinical characteristics of the COPD phenotypes and which met the inclusion criteria were included. The quality assessment was analyzed by Cross-Sectional/Prevalence Study Quality recommendations. The meta-analysis was carried out using RevMan5.3., Results: Ten cross-sectional observation studies (n = 8848) were included. Compared with the NE phenotype, patients with the FE-CB phenotype showed significantly lower forced expiratory volume in 1 s percent predicted (FEV 1 %pred) (mean difference (MD) -8.50, 95% CI -11.36--5.65, P < 0.001, I 2  = 91%), forced vital capacity percent predicted (FVC%pred) [MD - 6.69, 95% confidence interval (CI) -7.73--5.65, P < 0.001, I 2  = 5%], and forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC) (MD -3.76, 95% CI -4.58--2.95,P < 0.001, I 2  = 0%); in contrast, Charlson comorbidity index (MD 0.47, 95% CI 0.37-0.58, P < 0.001, I 2  = 0], COPD assessment test (CAT) score (MD 5.61, 95% CI 4.62-6.60, P < 0.001, I 2  = 80%), the quantity of cigarettes smoked (pack-years) (MD 3.09, 95% CI 1.60-4.58, P < 0.001, I 2  = 41%), exacerbations in previous year (2.65, 95% CI 2.32-2.97, P < 0.001, I 2  = 91%), modified Medical British Research Council (mMRC) score (MD 0.72, 95% CI 0.63-0.82, P < 0.001, I 2  = 57%), and body mass index (BMI), obstruction, dyspnea, exacerbations (BODEx) (MD 1.78, 95% CI 1.28-2.28, P < 0.001, I 2  = 91%), I 2  = 34%) were significantly higher in patients with FE-CB phenotype. No significant between-group difference was observed with respect to BMI (MD-0.14, 95% CI -0.70-0.42, P = 0.62, I 2  = 75%)., Conclusion: COPD patients with the FE-CB phenotype had worse pulmonary function and higher CAT score, mMRC scores, frequency of acute exacerbations, and the quantity of cigarettes smoked (pack-years) than those with the NE phenotype.

Background: Takayasu arteritis-induced renal arteritis (TARA), commonly seen in Takayasu arteritis (TA), has become one of the main causes of poor prognosis and early mortality in patients with TA. TARA progressing into Takayasu arteritis-induced renal artery stenosis (TARAS), could lead to severe complications including malignant hypertension, cardiac-cerebral vascular disease, and ischemic nephropathy. Since there existed no guidelines on treatments, this study aimed to review the comprehensive treatments for TARA., Methods: We searched systematically in databases including PubMed, Ovid-Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and SinoMed, from inception to May 2018. Literature selection, data extraction, and statistical analysis were performed., Results: Eighty-two literatures were recruited focusing on medical treatments (n = 34) and surgical treatments (n = 48). We found that combined medical treatments of glucocorticoids and conventional synthetic disease-modifying anti-rheumatic drugs could reach high rates of remission in patients with TARA, and biological disease-modifying anti-rheumatic drugs were preferred for refractory patients. After remission induction, surgical treatment could help reconstruct renal artery and recover renal function partly. Percutaneous transluminal angioplasty was the first choice for patients with TARAS, while open surgery showed a good long-term survival., Conclusions: Patients with TARA should benefit both from medical treatments and from surgical treatments comprehensively and sequentially. Multidisciplinary team coordination is recommended especially in patients with severe complications.

Background: The development of chronic obstructive pulmonary disease (COPD) is related to the T lymphocyte mediated inflammatory immune response and immune imbalance. The purpose of this systematic review was to evaluate the clinical efficacy and safety of acupoint application on T lymphocyte subsets in patients with COPD., Methods: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, the Cochrane Library, and EMBASE for studies published as of Oct. 31, 2019. All randomized controlled trials of acupoint application on COPD patients that met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan5.3 software was used for meta-analysis., Results: Eight studies (combined n = 524) qualified based on the inclusion criteria. Compared with routine treatment alone, acupoint application combined with routine treatment can significantly increase the T lymphocyte CD4/CD8 ratio (MD 0.12, 95% CI 0.03-0.21, P < .01, I = 49%), reduce CD8 T-cells (MD-0.99, 95% CI-1.70-0.28, P < .001, I = 37%), reduce the times of acute exacerbations (MD-0.28, 95% CI-0.35-0.21, P < .001, I = 0), and improve the clinical efficacy (MD 1.30, 95% CI 1.14-1.48, P < .001, I = 39%)., Conclusion: Acupoint application can improve the CD4/CD8 ratio and CD8 T-cells in patients with COPD and has an auxiliary effect in reducing the times of acute exacerbations and improving clinical efficacy.

Background: Patients with head trauma may have concomitant orbital floor fractures (OFFs). The objective of our study was to determine the specific CT findings and investigate the diagnostic performance of head CT in detecting OFFs., Methods: We analyzed 3534 head trauma patients undergoing simultaneous head and facial CT over a 3-year period. The clinical data and specific head CT findings between patients with and without OFFs were compared., Results: In our cohort, 198 patients (5.6%) had OFFs visible on CT. On head CT, orbital floor discontinuity, gas bubbles entrapped between floor fragments, inferior extraconal emphysema, and maxillary hemosinus (MHS) were more commonly observed among patients with OFFs ( p < 0.001). The absence of MHS had a high negative predictive value (99.7%) for excluding OFFs. Among the different types of MHS, the pattern showing high-attenuation opacity mixed with mottled gas had the highest positive predictive value (69.5%) for OFFs and was the only independent predictor of OFFs after adjusting for the other CT variables in all patients with MHS., Conclusion: Head CT may serve as a first-line screening tool to detect OFFs in head trauma patients. Hence, unnecessary facial CT and additional radiation exposure may be reduced.

Objectives: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis., Methods: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses., Results: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

To investigate the difference of clinical characteristics between chronic obstructive pulmonary disease (COPD) patients with the frequent exacerbators with chronic bronchitis (FE-CB) phenotype and those with the asthma-COPD overlap syndrome (ACO) phenotype.We searched CNKI, Wan Fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases for studies published as of April 30, 2019. All studies that investigated COPD patients with the FE-CB and ACO phenotypes and which qualified the inclusion criteria were included. Cross-sectional/prevalence study quality recommendations were used to measure methodological quality. RevMan5.3 software was used for meta-analysis.Ten studies (combined n = 4568) qualified the inclusion criteria. The FE-CB phenotype of COPD was associated with significantly lower forced vital capacity percent predicted (mean difference [MD] -9.05, 95% confidence interval [CI] [-12.00, -6.10], P < .001, I = 66%), forced expiratory volume in 1 second (FEV1) (MD -407.18, 95% CI [-438.63, -375.72], P < .001, I = 33%), forced expiratory volume in 1 second percent predicted (MD -9.71, 95% CI [-12.79, -6.63], P < .001, I = 87%), FEV1/forced vital capacity (MD -5.4, 95% CI [-6.49, -4.30], P < .001, I = 0%), and body mass index (BMI) (MD -0.81, 95% CI [-1.18, -0.45], P < .001, I = 44%) as compared to the ACO phenotype. However, FE-CB phenotype was associated with higher quantity of cigarettes smoked (pack-years) (MD 6.45, 95% CI [1.82, 11.09], P < .001, I = 73%), COPD assessment test score (CAT) (MD 4.04, 95% CI [3.46, 4.61], P < .001, I = 0%), mMRC score (MD 0.54, 95% CI [0.46, 0.62], P < .001, I = 34%), exacerbations in previous year (1.34, 95% CI [0.98, 1.71], P < .001, I = 68%), and BMI, obstruction, dyspnea, exacerbations (BODEx) (MD 1.59, 95% CI [1.00, 2.18], P < .001, I = 86%) as compared to the ACO phenotype.Compared with the ACO phenotype, COPD patients with the FE-CB phenotype had poorer pulmonary function, lower BMI, and higher CAT score, quantity of cigarettes smoked (pack-years), exacerbations in previous year, mMRC score, and BODEx.This study is an analysis of published literature, which belongs to the second study. Therefore, this study does not require the approval of the ethics committee. The findings will be disseminated through a peer-reviewed journal publication or conference presentation.

Background: Previous studies have reported an increased risk of cavities in diabetic patients with pulmonary tuberculosis (PTB), which may be associated with poor glycemic control. Cavities have a negative impact on PTB treatment outcomes; however, the possible interaction of other potentially confounding diabetes-related variables regarding pulmonary cavities have not been fully evaluated., Methods: We conducted a retrospective cohort study of diabetic patients with culture-proven PTB. The patients' chest X-rays (CXRs) and computed tomography (CT) scans were reviewed to assess the effects of clinical factors, glycosylated hemoglobin (HbA1c) levels, and antidiabetic agents on cavitary lesions., Results: Among 128 diabetic PTB patients, those with pulmonary cavities on CXRs and CT scans presented younger ages, lack of metformin treatment, and significantly higher HbA1c levels than those without cavities. Multivariate logistic regression analysis revealed significantly higher HbA1c levels in patients with cavities than in those without cavities on CXRs (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.12-1.61) and CT scans (OR, 1.36; 95% CI, 1.13-1.64). Patients with multiple cavities had significantly higher HbA1c levels than those with a single cavity on CT scans (p = 0.002). No significant differences in other variables, including metformin treatment, were noted between the groups., Conclusion: This study suggests that despite multiple potential confounding variables, including metformin use, poor glycemic control is still the dominant risk factor for cavitary lesions in diabetic patients with PTB. Efforts to improve glycemic control in diabetic PTB patients may be of considerable value in facilitating antimycobacterial treatment.

Objective: To explore the clinical efficacy and safety of Qigong in reducing the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients with chronic obstructive pulmonary disease (COPD)., Methods: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE for studies published as of Dec 31, 2018. All randomized controlled trials of Qigong in COPD patients, which met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan 5.3 software was used for meta-analysis., Results: Six studies (combined n = 415 patients) met the inclusion criteria. Compared with conventional therapy alone, Qigong in combination with conventional therapy significantly improved the following outcome measures: SDS score [mean difference (MD) -3.99, 95% CI (-6.17, -1.82), P < .001, I = 69%]; SAS score[MD -4.57, 95% CI (-5.67, -3.48), P < .001, I = 15%]; forced expiratory volume in one second/prediction (FEV1% pred) [MD 3.77, 95% CI (0.97,6.58), P < .01, I = 0]; forced expiratory volume in one second (FEV1) [MD 0.21, 95% CI (0.13, 0.30), P < .001, I = 0%]; forced vital capacity (FVC) [MD 0.28, 95% CI (0.16, 0.40), P < .001, I = 0]; 6-minute walk test (6MWT) distance [MD 39.31, 95% CI (18.27, 60.34), P < .001, I = 32%]; and St. George's Respiratory Questionnaire (SGRQ) total score [MD -11.42, 95% CI (-21.80, -1.03), P < .05, I = 72%]., Conclusion: Qigong can improve the SDS and SAS scores of COPD patients, and has auxiliary effects on improving lung function, 6MWT distance, and SGRQ score.

Objective: To investigate the sex- and age-specific association between serum uric acid level and body mass index (BMI). Methods: A total of 144,856 subjects aged 20 to 79 years were enrolled in this cross-sectional study. Serum uric acid level, renal function, hepatic function, and lipid profile were investigated. Results: The prevalence of hyperuricemia decreased with age in men but increased in women. In men, the correlation coefficient between the serum urate level and BMI declined steadily with age. Underweight was associated with a 53 to 68% and a 66% lower prevalence of hyperuricemia in men aged 20 to 69 years and in women aged 20 to 29 years, respectively. Overweight and obesity were correlated with a higher odds ratio (OR) (95% confidence interval [CI]) for hyperuricemia in both genders. In individuals with overweight or obesity, younger subjects had a higher OR (95% CI) for hyperuricemia than older subjects. Among subjects aged 20 to 59 years, as they gained weight, the OR (95% CI) for hyperuricemia increased faster in women than in men compared with their respective normal-weight controls. Conclusion: Underweight was associated with a lower prevalence of hyperuricemia in men aged ≤69 years. In individuals with overweight or obesity, younger subjects were more likely to develop hyperuricemia than older subjects. With active weight gain, the likelihood for developing hyperuricemia increased faster in women than in men compared with their respective normal-weight controls. Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMI = body mass index; CI = confidence interval; eGFR = estimated glomerular filtration rate; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OR = odds ratio.

Aims: To assess the value of contrast-enhanced ultrasonography (CEUS) for monitoring disease activity of Takayasu arteritis (TA)., Methods: TA patients were recruited in a Chinese TA clinical center from January 2016 to September 2017. The physician global assessment was used as the referential standard for disease activity. Clinical data, acute phase reactants, and CEUS scans were simultaneously recorded at baseline and after a 3-month therapy., Results: A total of 84 TA patients were enrolled, and 47 (55.95%) cases were active at baseline. Macaroni sign and entire artery involvement were characteristic findings of CEUS in TA. The average vascular full thickness of the carotid artery in active TA patients was significantly higher than that in inactive patients (2.36 ± 0.86 vs. 1.79 ± 0.49 mm; p = 0.001). Severe neovascularization (grade 2) was observed in 29 active cases (61.70%) and in 9 inactive cases (24.32%) (p = 0.001). Receiver operating characteristic analysis showed that the combination of CEUS parameters (cutoff of thickness was 1.75 mm or neovascularization grade 2) and erythrocyte sedimentation rate (ESR) (cutoff of 20 mm/H) could help differentiate between active and inactive TA patients with a sensitivity and specificity of 81.1% and 81.5%, respectively. Youdon's index was 0.626. Furthermore, our study found that patients with decreased ESR and C-reactive protein (CRP) still had a progression of vascular wall inflammation at 3 months of follow-up., Conclusions: The evaluation of vascular inflammation by CEUS is more sensitive than acute phase reactants. Neovascularization can still be observed in the vascular lesion sites of those who have reached clinical remission after treatment. Thus, CEUS can be used as an alternative method to assess disease activity for TA patients.

Objective: to investigate the clinical characteristics and disease activity in ankylosing spondylitis (AS) patients with hyperuricemia. Method: Laboratory tests, magnetic resonance imaging, disease activity and functional index of AS patients from Fudan University Zhongshan Hospital were collected. T test, square test were applied to investigate the difference between AS patients with hyperuricemia and AS patients with normal serum uric acid in clinical characteristics and disease activity in AS patients. Result: Among all the AS patients, 23.4% (22/94) patients accompanied with hyperuricemia. AS patients accompanied with hyperuricemia showed significant younger age (28.9±7.9 vs 35.8±11.1, P =0.002); higher serum alanine aminotransferase (33.6±23.6 vs 19.8±12.4, P =0.014), aspartate aminotransferase (23.8±8.7 vs 18.6±9.6, P =0.025) and creatinine (78.4±12.5 vs 69.8±13.3, P =0.009), lower Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (11.2±8.8 vs 17.9±12.0, P =0.027) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.7±0.9 vs 1.8±2.2, P =0.002) compared with AS patients whose serum uric acid level is normal. Conclusion: AS Patients with younger age, impaired hepatic and renal funtion and lower scores in BASDAI and BASFI tend to accompany with hyperuricemia.

In the clinical practice, Professor Jiang Liangduo, a national senior Chinese medicine doctor, has created the theory of "sanjiao meridian stasis" from the theory of meridian dialectics and from the overall state. In this paper, the traditional Chinese medicine and Western medicine clinical characteristics of sanjiao meridian stasis theory which is often used by Professor Jiang Liangduo in the treatment of out-patient syndrome differentiation, were first studied and summarized to investigate its inherent regularity. First, the source of data and research methods were introduced, and then the Traditional Chinese Medicine Inheritance Support System was used with the method of data mining to retrospectively analyze the disease characteristics of Chinese and Western medicine in 279 patients with sanjiao meridian stasis diagnosed by Professor Jiang in 2014. Then the following main conclusions were made after research: sanjiao meridian stasis was more common in women as well as young and middle-aged population. Often manifested by prolonged treatment course, red tongue with yellowishfur, with good correlation between modern Western medicine diagnosis and TCM differentiation syndrome. The symptoms of sanjiao meridian stasis syndrome are mostly of heat syndromes, and middle-aged patients are the most common patients with stasis and stasis of sanjiao. Related information of Western medicine diagnosis can help to diagnose the "sanjiao meridian stasis"., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background: Approximately 15-20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric-onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult-onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database., Methods: We made a prospective study of 225 cSLE patients (aged Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI], 0.470-0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512-2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053-2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170-0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log-rank test (0.557, P = 0.455)., Conclusions: cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5- year survival between cSLE and aSLE groups.

Oligopeptides are one of the the key pharmaceutical effective constituents of traditional Chinese medicine(TCM). Systematic study on composition and efficacy of TCM oligopeptides is essential for the analysis of material basis and mechanism of TCM. In this study, the potential anti-hypertensive oligopeptides from Glycine max and their endothelin receptor A (ETA) antagonistic activity were discovered and predicted based on in silico technologies.Main protein sequences of G. max were collected and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then, the pharmacophore of ETA antagonistic peptides was constructed and included one hydrophobic feature, one ionizable negative feature, one ring aromatic feature and five excluded volumes. Meanwhile, three-dimensional structure of ETA was developed by homology modeling methods for further docking studies. According to docking analysis and consensus score, the key amino acid of GLN165 was identified for ETA antagonistic activity. And 27 oligopeptides from G. max were predicted as the potential ETA antagonists by pharmacophore and docking studies.In silico proteolysis could be used to analyze the protein sequences from TCM. According to combination of in silico proteolysis and molecular simulation, the biological activities of oligopeptides could be predicted rapidly based on the known TCM protein sequence. It might provide the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Acyl-coenzyme A cholesterol acyltransferase (ACAT) plays an important role in maintaining cellular and organismal cholesterol homeostasis. Two types of ACAT isozymes with different functions exist in mammals, named ACAT-1 and ACAT-2. Numerous studies showed that ACAT-2 selective inhibitors are effective for the treatment of hypercholesterolemia and atherosclerosis. However, as a typical endoplasmic reticulum protein, ACAT-2 protein has not been purified and revealed, so combinatorial ligand-based methods might be the optimal strategy for discovering the ACAT-2 selective inhibitors. In this study, selective pharmacophore models of ACAT-1 inhibitors and ACAT-2 inhibitors were built, respectively. The optimal pharmacophore model for each subtype was identified and utilized as queries for the Traditional Chinese Medicine Database screening. A total of 180 potential ACAT-2 selective inhibitors were obtained, which were identified using an ACAT-2 pharmacophore and not by our ACAT-1 model. Selective SVM model and bioactive SVR model were generated for further identification of the obtained ACAT-2 inhibitors. Ten compounds were finally obtained with predicted inhibitory activities toward ACAT-2. Hydrogen bond acceptor, 2D autocorrelations, GETAWAY descriptors, and BCUT descriptors were identified as key structural features for selectivity and activity of ACAT-2 inhibitors. This study provides a reasonable ligand-based approach to discover potential ACAT-2 selective inhibitors from Chinese herbs, which could help in further screening and development of ACAT-2 selective inhibitors.

The objective of the study was to evaluate the efficacy and safety of etanercept (Anbainuo) treatment in Chinese moderate to severe rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); 600 patients (360 in phase III-1 and 240 in phase III-2) poorly responding to MTX were enrolled in the study and randomized at a ratio of 2:1 into an Anbainuo treatment or control group. The study was designed as a 12-week double-blind, placebo-controlled period followed by a 12-week open-label study. The primary endpoint was the ACR20 response rate at week 12. Secondary endpoints included the ACR50, ACR70, ACR-N, and safety. At week 12, ACR20 response was observed in 60.9 % of the Anbainuo group-significantly higher than that of the control group (20.6 %). At week 24, the ACR20 response in the Anbainuo group increased to 70.2 %; there was no significant difference compared with that of the control group (61.8 %, P > 0.05). At week 12, the ACR50 and ACR70 responses of the Anbainuo group increased to 25.6 and 6.8 %, compared to 4 and 1 % in the control group (P < 0.001, P = 0.002). The ACR-N was 2.85 ± 6.73 vs. -3.24 ± 8.78 % in the control group (P < 0.001). During the first 12 weeks of treatment, 66 adverse events (AE) were reported in the Anbainuo group (15.6 %) and 21 AEs (10.5 %) occurred in the control group, whereby the rate of the Anbainuo group was slightly higher than the control group (P = 0.042). Severe adverse events (SAEs) occurred in the Anbainuo group (1.3 %) and one (SAE) occurred in the control group (0.5 %) (P = 0.19). Anbainuo displays a rapid onset of efficacy as well as good tolerance and safety in MTX-IR patients having moderate to severe RA.

Background: Dopamine receptor 2 (DR2) expressions on B cells from Rheumatoid arthritis (RA) patients has been found to be negatively correlated with disease activity and can potentially predict the response to treatment. This study aimed to investigate the role of B cell DR2 expression on bone remodeling in RA., Methods: Patients with RA (n = 14) or osteoarthritis (OA; n = 12), and healthy controls (n = 12) were recruited for this study. Dopamine receptor (DR) 2 expression was assessed using flow cytometry. Pro-inflammatory cytokines, including interleuin(IL)-1β, IL-6, IL-17, and tumor necrosis factor(TNF)-α, and bone turnovers, including osteocalcin (OC),serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (β-CTX), collagen type I cross-linked telopeptide (ICTP), as well as matrix metalloproteinase-3 (MMP-3) and osteoprotegerin (OPG) were measured by electrochemiluminescence, chemiluminescence, or enzyme-linked immunosorbent assay. DR2 expression on synovial B cells from 4 RA patients and 3 OA patients was detected by immunofluorescence., Results: There were more DR2(+)CD19(+) B cells in synovial tissues from RA patients than in those from OA patients. The frequency of peripheral B cells that expressed DR2 was positively correlated with plasma TNF-α level. Levels of ICTP and MMP-3 were significantly higher, and OPG were lower in RA patients compared to those in the OA group and healthy controls (all P < 0.05)., Conclusion: The frequency of B cells that expressed DR2 showed a correlation with levels of the pro-inflammatory cytokine TNF-α. DR2(+)CD19(+) B cells in synovial tissues might have a role in bone metabolism and TNF-α production.

Objective: This study aimed to analyze and evaluate the diagnostic efficacy of Ishikawa's, the modified Ishikawa's criteria, 1990 American College of Rheumatology (ACR ) classification criteria and the diagnostic model based on Chinese population in Chinese TA patients., Methods: One hundred and forty-nine patients with Takayasu arteritis and 126 patients with other vascular disorders which involved aorta or its branches were recruited in this study.All the patients were admitted to the Department of rheumatism and Immunology clinic or inpatient department of Zhongshan Hospital affiliated to Fudan University from January 1(st), 2008 to June 31(st), 2015.General characteristics, clinical manifestations, laboratory results and imaging data of all the patients were collected.Sensitivity, specificity, accuracy and area under receiver operating characteristics (ROC) curve of different criteria were analyzed., Results: Sensitivity, specificity, accuracy and area under ROC curve of Chinese diagnostic model were 90.60%, 80.95%, 86.18%, and 85.80%, respectively, while those of Ishikawa criteria were 34.23%, 99.21%, 64.00%, and 66.70%, respectively.These four indicators of the modified Ishikawa criteria were 84.13%, 79.87%, 81.82%, and 82.00%, respectively and that of ACR criteria were 83.89%, 83.33%, 83.64%, and 83.60%, respectively.No significant difference was found between any two of Chinese diagnostic model, the modified Ishikawa criteria and ACR criteria in all the indicators.Sensitivity of Chinese diagnostic model was highest, while specificity of Ishikawa criteria was the highest.Among these four criteria, the diagnostic efficacy of Chinese model was the best and that of Ishikawa criteria was the worst., Conclusion: Chinese diagnostic model, which is based on Chinese population and adopts advanced imaging modality, has better diagnostic efficacy.

Inhibition of cytochrome P450 (CYP450) enzymes is the most common reasons for drug interactions, so the study on early prediction of CYPs inhibitors can help to decrease the incidence of adverse reactions caused by drug interactions.CYP450 2E1(CYP2E1), as a key role in drug metabolism process, has broad spectrum of drug metabolism substrate. In this study, 32 CYP2E1 inhibitors were collected for the construction of support vector regression (SVR) model. The test set data were used to verify CYP2E1 quantitative models and obtain the optimal prediction model of CYP2E1 inhibitor. Meanwhile, one molecular docking program, CDOCKER, was utilized to analyze the interaction pattern between positive compounds and active pocket to establish the optimal screening model of CYP2E1 inhibitors.SVR model and molecular docking prediction model were combined to screen traditional Chinese medicine database (TCMD), which could improve the calculation efficiency and prediction accuracy. 6 376 traditional Chinese medicine (TCM) compounds predicted by SVR model were obtained, and in further verification by using molecular docking model, 247 TCM compounds with potential inhibitory activities against CYP2E1 were finally retained. Some of them have been verified by experiments. The results demonstrated that this study could provide guidance for the virtual screening of CYP450 inhibitors and the prediction of CYPs-mediated DDIs, and also provide references for clinical rational drug use., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

P2Y1 receptor (P2Y1R), which belongs to G protein-coupled receptors (GPCRs), is an important target in ADP-induced platelet aggregation. The crystal structure of P2Y1R has been solved recently, which revealed orthosteric and allosteric ligand-binding sites with the details of ligand-protein binding modes. And it suggests that P2Y1R antagonists, which recognize two distinct sites, could potentially provide an efficacious and safe antithrombotic profile. In present paper, 2D similarity search, pharmacophore based screening, and molecular docking were used to explore the potential natural P2Y1R antagonists. 2D similarity search was used to classify orthosteric and allosteric antagonists of P2Y1R. Based on the result, pharmacophore models were constructed and validated by the test set. Optimal models were selected to discover potential P2Y1R antagonists of orthosteric and allosteric sites from Traditional Chinese Medicine (TCM). And the hits were filtered by Lipinski's rule. Then molecular docking was used to refine the results of pharmacophore based screening and analyze the binding mode of the hits and P2Y1R. Finally, two orthosteric and one allosteric potential compounds were obtained, which might be used in future P2Y1R antagonists design. This work provides a reliable guide for discovering natural P2Y1R antagonists acting on two distinct sites from TCM.

In this research, a combined method of ligand-based pharmacophore (LBP), structure-based pharmacophore (SBP), and molecular docking was applied for virtual screening potential ATP-sensitive potassium channel (KATP) openers from Chinese herbs. LBP models were generated by 3D-QSAR pharmacophore(hypogen) program, based on the training set composed of 48 KATP agonists. The best LBP model consisted of one hydrogen-bond acceptor, one hydrogen-bond donor, one hydrophobic feature, one aromatic ring and five excluded volumes. Besides, the correlation coefficient of training set and test set, N, and CAI value of the model were 0.876 4, 0.705 8, 3.304, and 2.616 respectively. Meanwhile, SBP models were also generated based on a 3D structure of KATP (PMID: PM0079770). The best SBP model consisted of six hydrogen-bond acceptors, eight hydrogen-bond donors, seven hydrophobic features and eighteen excluded volumes. The corresponding N and CAI value were 2.200 and 2.017. Then, the best LBP model and SBP model were applied to identify potential KATP openers from Traditional Chinese Medicine Database(TCMD), respectively. 349 hits were obtained after analyzed by drug-likeness rules. Moreover, 12 compounds with high docking scores were reserved after molecular docking evaluation. Interestingly, part of the results had been verified as hypotensive active ingredients by literatures. Therefore, this study uncovers a specific target effect contained in TCMD, and provides candidates for new KATP openers' research., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible.

The prevalence of coronary artery disease (CAD) is growing in the young population. We aimed to investigate the association between serum uric acid (SUA) levels and cardiovascular involvement in individuals under 45 years old diagnosed with early-onset CAD (EOCAD). Seven hundred eighty-six EOCAD patients were recruited and stratified into four groups by SUA levels. General information, serum indicators, and results of coronary angiography and echocardiography were recorded. The associations between SUA levels were explored by univariate and multivariate logistic regressions. With the increasing of SUA levels, the prevalence of hypertension and hyperlipidemia, triple branches involved, heart failure, and cardiac enlargement of left ventricle (LV), left atrium (LA), and right ventricle (RV) were significantly higher (all P < 0.05). The fourth group (SUA >8 mg/dl) had the highest proportions than other groups (all P < 0.05). After controlling potential confounders, multiple logistic regression analysis showed that odds ratios of SUA >8 mg/dl were 2.345 for triple branches involved (95 % confidence interval (CI) 1.335-4.119), 4.168 for heart failure (95 % CI 1.599-10.862), and 4.122 for LV enlargement (95 % CI 1.874-9.065) (P < 0.05). SUA >8 mg/dl was independently associated with triple branches involvement, heart failure and LV enlargement in Chinese EOCAD patients. Higher SUA level might play an important role in cardiac dysfunction and severity of EOCAD.

Background: We investigated the efficacy of annular ligament reconstruction by suture anchor in the treatment of radial head dislocation (RHD) in children., Method: A total of 20 RHD children nderwent annular ligament reconstruction surgery using suture anchor. Preoperative and postoperative elbow functions were evaluated according to Broberg and Morrey 100-point scale. Recovery of radial nerve function was assessed using the Chinese Medical Association of Hand Surgery Branch of Upper Limb Functional Assessment Standard. All statistical analyses were performed using SPSS version 17.0 software., Results: All 20 RHD children who underwent the procedure were followed up for a median duration of 24 months. At the last follow-up, the average Broberg-Morrey score was 94.3, with 12 children (60.0%) showing excellent outcomes (score range, 95 to 100), 7 children (35.0%) showing good outcomes (score range, 80 to 94), 1 child (5.0%) displayed a fair outcome (score range, 60 to 79), and 0 (0%) poor outcome. A significant difference in the excellent-good rate was observed when the elbow function before surgery was compared to after surgery (χ(2)  = 5.559, P = 0.018). The radial nerve function of the 13 RHD children with radial nerve injury also recovered to normal. Among these 13 RHD children, nine exhibited excellent outcomes, 3 showed good outcomes, 1 displayed a fair outcome, and no patient showed a poor outcome. A significant difference in the excellent-good rate of radial nerve function was also observed when before surgery was compared to after surgery in these RHD children (χ(2)  = 4.887, P = 0.027)., Conclusion: Our results strongly indicated that suture anchor is highly effective for reconstruction of the annular ligament and to promote full functional recovery in RHD children, demonstrating that the procedure is an excellent treatment choice in RHD children.

Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors.

Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.

Objective: Dopamine receptor (DR) signaling is involved in the pathogenesis of autoimmune diseases. We aimed to measure the expression levels of DR1-5 on B cells from patients with rheumatoid arthritis (RA) and to analyze the relationship between DRs and clinical manifestations, inflammatory biomarkers, functional status and disease activity., Methods: A total of 29 patients with RA, 12 healthy donors and 12 patients with osteoarthritis (OA) were recruited in this study. Flow cytometry was used to measure the levels of DR1-5 expressed on B cells. The relationships between B cell DR expressions and clinical features in RA patients were analyzed using the Spearman correlation test., Results: The expression levels of B cell DR1-5 in both the RA and OA groups were lower than those in healthy controls. After 3 months of medication, all five receptors were elevated in RA patients, with DR2 and DR3 being significantly increased from the baseline. DR2 expression on B cells was negatively correlated with inflammatory biomarkers and disease activity., Conclusion: RA patients had lower expression level of DR2 on B cells compared to the healthy controls, and the level of DR2 negatively correlated with the disease activity. DR2 and DR3 might be novel predictors of patient responses to disease modifying antirheumatic drug therapy., (Copyright © 2014 Elsevier GmbH. All rights reserved.)