Blood-nourishing and Hard-softening Capsule Costs Less in the Management of Osteoarthritic Knee Pain: A Randomized Controlled Trial

The blood-nourishing and hard-softening (BNHS) capsule is a traditional Chinese formula used in the symptomatic treatment of inflammation and pain. We conducted this randomized controlled trial to compare the efficacy of BNHS with other commonly prescribed drugs. We recruited 120 patients from two teaching hospitals; 30 patients in each hospital were randomly assigned to receive BNHS. In one hospital, the 30 controls were given another traditional Chinese drug; whereas a Western medicine (chondroprotection drug/Viartril-s) was used as the control in the other hospital. Intervention was carried out over a period of 4 weeks. Primary outcome measures included self-reported pain level, and changes in stiffness and functional ability as measured by the Western Ontario McMaster Universities Osteoarthritis (WOMAC) index. Mixed models were used for statistical analysis. Substantial improvements in disease-specific symptoms were observed, after 4 weeks of treatment, in patients taking BNHS capsules. As assessed by the WOMAC index, pain level of the BNHS group decreased by 57% [95% confidence interval (CI) = 50, 63], stiffness by 63% (95% CI = 55, 71) and functional ability increased by 56% (95% CI = 50, 63). No significant differences were found in any of the outcome measures between the BNHS group and either of the comparison groups. No severe adverse effects were reported. However, this study lacked a placebo group; therefore, we conclude that BNHS appears to be as effective as commonly prescribed medicines for the relief of pain and dysfunction in knee osteoarthritis patients, but costs a lot less than other Western and herbal drugs in the study

Stability analysis of two-terminal HVDC transmission systems using SISO open-loop gains

The ports of a three-phase voltage source converter have multiple frequency electrical parameters, which makes HVDC systems with these converters present multiple input multiple output (MIMO) characteristics. The generalized Nyquist criterion of the MIMO model is often used to analyze the system stability. However, this model is more difficult to obtain than the single-input single-output (SISO) model, and the stability margin and the oscillation frequency band are difficult to capture. To solve these problems, this paper took the two-terminal HVDC transmission system as the research object to derive a SISO model that can be measured by a port. Moreover, this study also proposed a method for analyzing the system stability through envelope SISO open-loop gains. Finally, the key port and parameters affecting the system stability were analyzed according to the stability margin, which provided theoretical support for the design of the system parameters. The established model and the proposed analysis method were verified in a MATLAB/Simulink simulation model

Rapid Estimation of Binding Activity of Influenza Virus Hemagglutinin to Human and Avian Receptors

A critical step for avian influenza viruses to infect human hosts and cause epidemics or pandemics is acquisition of the ability of the viral hemagglutinin (HA) to bind to human receptors. However, current global influenza surveillance does not monitor HA binding specificity due to a lack of rapid and reliable assays. Here we report a computational method that uses an effective scoring function to quantify HA-receptor binding activities with high accuracy and speed. Application of this method reveals receptor specificity changes and its temporal relationship with antigenicity changes during the evolution of human H3N2 viruses. The method predicts that two amino acid differences at 222 and 225 between HAs of A/Fujian/411/02 and A/Panama/2007/99 viruses account for their differences in binding to both avian and human receptors; this prediction was verified experimentally. The new computational method could provide an urgently needed tool for rapid and large-scale analysis of HA receptor specificities for global influenza surveillance.National Key Project (2008ZX10004-013)National Institutes of Health (U.S.) (grant AI07443)Singapore-MIT Alliance for Research and TechnologyMassachusetts Institute of Technology. International Science and Technology Initiatives Global Seed FundNational Basic Research Program (973 Program) (2009CB918503)National Basic Research Program (973 Program) (2006CB911002

Traditional Chinese Herbal Patch for Short-Term Management of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective. To assess the short-term efficacy and safety of two kinds of Traditional Chinese herbal patches, Fufang Nanxing Zhitong Gao (FNZG) and Shangshi Jietong Gao (SJG), for painful knee osteoarthritis (OA). Methods. Patients were randomly enrolled in a double-blind, placebo-controlled study to receive FNZG (n=60), SJG (n=60), or placebo patch (n=30) for 7 days. Outcome measures included visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Traditional Chinese Medicine Syndrome Questionnaire (TCMSQ) subscale. Results. Although there was no significant difference among, three groups in short-term pain management, patients receiving FNZG got significant improvement in symptom of fear of coldness as compared with placebo patch (P=0.029). The most common local adverse events of rash, itching, erythema, and slightly damaged skin were observed in 7% of participants. Conclusions. FNZG may be a useful treatment for symptom of knee OA and merits long-term study in broader populations

Molecular mechanisms of the Guizhi decoction on osteoarthritis based on an integrated network pharmacology and RNA sequencing approach with experimental validation

Background: Our aim was to determine the potential pharmacological mechanisms of the Guizhi decoction (GZD) in the treatment of osteoarthritis (OA) through an integrated approach of network pharmacological analyses, RNA sequencing (RNA-seq), and experimental validation.Methods: The quality control and identification of bioactive compounds of the GZD were carried out by using ultra-performance liquid chromatography (UPLC), and their OA-related genes were identified through overlapping traditional Chinese medicine systems pharmacology database (TCMSP), DrugBank and SEA Search Server databases, and GeneCards. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were implemented after constructing the component–target network. RNA-seq was used to screen differentially expressed genes (DEGs) under intervention conditions with and without the GZD in vitro. The crossover signaling pathways between RNA-seq and network pharmacology were then analyzed. Accordingly, protein–protein interaction (PPI) networks, GO, and KEGG analysis were performed using the Cytoscape, STRING, or DAVID database. The OA rat model was established to further verify the pharmacological effects in vivo. Hematoxylin–eosin (H&E) and safranin O/fast green (S-O) staining were used to grade the histopathological features of the cartilage. We verified the mRNA and protein expressions of the key targets related to the TNF signaling pathways in vivo and in vitro by qPCR, Western blotting (WB), and immunofluorescence assay. In addition, we also detected inflammatory cytokines in the rat serum by Luminex liquid suspension chip, which included tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β).Results: Eighteen compounds and 373 targets of the GZD were identified. A total of 2,356 OA-related genes were obtained from the GeneCards database. A total of three hub active ingredients of quercetin, kaempferol, and beta-sitosterol were determined, while 166 target genes associated with OA were finally overlapped. The RNA-seq analysis revealed 1,426 DEGs. In the KEGG intersection between network pharmacology and RNA-seq analysis, the closest screening relevant to GZD treatment was the TNF signaling pathway, of which TNF, IL-6, and IL-1β were classified as hub genes. In consistent, H&E and S-O staining of the rat model showed that GZD could attenuate cartilage degradation. When compared with the OA group in vivo and in vitro, the mRNA levels of TNF-α, IL-1β, IL-6, matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 9 (MMP9) were all downregulated in the GZD group (all p < 0.05). The expression levels of anabolic proteins (Col2α1 and SOX9) were all higher in the GZD group than in the OA group (p < 0.05), while the expression levels of the catabolic proteins (MMP9 and COX-2) and TNF-α in the GZD group were significantly lower than those in the OA group (p < 0.05). In addition, the expression levels of TNF, IL-6, and IL-1β were upregulated in the OA group, while the GZD group prevented such aberrations (p < 0.01).Conclusion: The present study reveals that the mechanism of the GZD against OA may be related to the regulation of the TNF signaling pathway and inhibition of inflammatory response

Effectiveness, Medication Patterns, and Adverse Events of Traditional Chinese Herbal Patches for Osteoarthritis: A Systematic Review

Objective. The aim of this study is to systematically evaluate the evidence whether traditional Chinese herbal patches (TCHPs) for osteoarthritis (OA) are effective and safe and analyze their medication patterns. Methods. A systematic literature search was performed using all the possible Medical Subject Headings (MeSH) and keywords from January 1979 to July 2013. Both randomized controlled trials (RCTs) and observational studies were included. Estimated effects were analyzed using mean difference (MD) or relative risk (RR) with 95% confidence intervals (CI) and meta-analysis. Results. 86 kinds of TCHPs were identified. RCTs and controlled clinical trials (CCTs) which were mostly of low quality favored TCHPs for local pain and dysfunction relief. TCHPs, compared with diclofenac ointment, had significant effects on global effectiveness rate (RR = 0.50; 95% CI (0.29, 0.87)). Components of formulae were mainly based on the compounds “Xiao Huo Luo Dan” (Minor collateral-freeing pill) and “Du Huo Ji Sheng Tang” (Angelicae Pubescentis and Loranthi decoction). Ten kinds of adverse events (AEs), mainly consisting of itching and/or local skin rashes, were identified after 3-4 weeks of follow-up. Conclusions. TCHPs have certain evidence in improving global effectiveness rate for OA; however, more rigorous studies are warranted to support their use

Clinical and Epidemiologic Characteristics of 3 Early Cases of Influenza A Pandemic (H1N1) 2009 Virus Infection, People’s Republic of China, 2009

A national network is essential for controlling this infection

Genomic Polymorphism of the Pandemic A (H1N1) Influenza Viruses Correlates with Viral Replication, Virulence, and Pathogenicity In Vitro and In Vivo

The novel pandemic A (H1N1) virus was first identified in Mexico in April 2009 and quickly spread worldwide. Like all influenzas, the H1N1 strain-specific properties of replication, virulence, and pathogenicity are a result of the particular genomic sequence and concerted expression of multiple genes. Thus, specific mutations may support increased virulence and may be useful as biomarkers of potential threat to human health. We performed comparative genomic analysis of ten strains of the 2009 pandemic A (H1N1) influenza viruses to determine whether genotypes associated with clinical phenotypes, which ranged from mild to severe illness and up to lethal. Virus replication capacity was tested for each strain in vitro using cultured epithelial cells, while virulence and pathogenicity were investigated in vivo using the BALB/c mouse model. The results indicated that A/Sichuan/1/2009 strain had significantly higher replication ability and virulence than the other strains, and five unique non-synonymous mutations were identified in important gene-encoding sequences. These mutations led to amino acid substitutions in HA (L32I), PA (A343T), PB1 (K353R and T566A), and PB2 (T471M), and may be critical molecular determinants for replication, virulence, and pathogenicity. Our results suggested that the replication capacity in vitro and virulence in vivo of the 2009 pandemic A (H1N1) viruses were not associated with the clinical phenotypes. This study offers new insights into the transmission and evolution of the 2009 pandemic A (H1N1) virus