[Mechanism of electroacupuncture penetration needling for relieving synovial inflammation of knee osteoarthritis through TLR4/MyD88/NF-κB signal pathway].

OBJECTIVE: To observe the effects of electroacupuncture (EA) penetration needling on Toll-like receptors 4/myeloid differentiation factor 88/nuclear factor-kappa B (TLR4/MyD88/NF-κB) signaling pathway in rat synovium and the serum-related inflammatory factors, so as to explore the mechanism of EA penetration needling on synovial inflammation in rats with knee osteoarthritis (KOA). METHODS: SD male rats were randomly divided into sham-operation group, model group, EA+penetration needling group, and conventional EA group, with 16 rats in each group. The rats model was prepared by anterior cruciate ligment transection and these rats were forced to exercise for 8 weeks after operation. After successful modeling, in the EA+penetration needling group, the needles were inserted at "Dubi" (ST35) "Neixiyan" (EX-LE4), and at "Xuehai"(SP10) "Liangqiu"(ST34) on the right hind limb, towards each other, 5-8 mm in depth, respectively. In the conventional EA group, the needles were inserted at ST35 and EX-LE4 on the right hind limb, obliquely, at 30° angle to the skin, 3-5 mm in depth; and were inserted at SP10 and ST34 on the right hind limb perpendicularly, 3-5 mm in depth. In these two groups, electric stimulation was operated with dense-disperse wave, 2 Hz/10 Hz in frequency and 0.5-1.5 mA in intensity, retained for 20 min in each treatment. The treatment was given once daily, 10 days as 1 course of treatment, and 2 courses were required at the interval of 2 days. After the intervention, the knee joint effusion was observed by musculoskeletal ultrasound; the contents of IL-1ß, IL-6 and TNF-α in serum were determined by ELISA; the morphological changes in the synovium were observed after H.E. staining; the positive expression of NF-κB p65 in the synovial membrane was detected by immunohistochemical method; the expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 proteins in the synovial membrane were determined by Western blot. RESULTS: Compared with the sham-operation group, in the model group, the knee joint effusion was obviously increased, the synovial lining cells were distributed irregularly, the cells were disarranged, the pannus was formed largely, and a great number of the inflammatory cells were infiltrated; the contents of serum IL-1ß, IL-6 and TNF-α, the positive expression of NF-κB p65, the protein expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 in the synovial tissue were increased (P<0.05). Compared with the model group, the knee joint effusion was reduced, the synovial lining cells were proliferated, a small number of the inflammatory cells were infiltrated, and the pannus was formed lightly; the contents of serum IL-1ß, IL-6 and TNF-α, the positive expression of NF-κB p65, the protein expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 in the synovial tissue were lower (P<0.05) in the EA+penetration needling group and the conventional EA group. In the conventional EA group, the knee joint effusion was increased, the synovial lining cells were proliferated, the inflammatory cells were infiltrated largely, and the pannus was formed increasingly; the contents of serum IL-1ß, IL-6 and TNF-α, and the protein expression levels of TLR4, MyD88 and NF-κB p65 in the synovial tissue were increased when compared with the EA+penetration needling group (P<0.05). CONCLUSION: The EA+penetration needling can significantly relieve the synovial inflammatory reaction and the knee joint effusion in KOA rats. The mechanism is probably related to down-regulating the downstream inflammatory cascade through inhibiting the transduction of TLR4/MyD88/NF-κB signaling pathway.

[Adjunctive therapy of xuezhikang capsule for coronary heart disease: a systematic review and meta-analysis of randomized controlled trials].

OBJECTIVE: To systematically evaluate the effect and safety of Xuezhikang Capsule (XZKC) for adjuvant treatment for coronary heart disease (CHD) patients accompanied with or without dyslipidemia. METHODS: China National Knowledge Infrastructure (CNKI) Database, Chongqing VIP Database (VIP), Wanfang Data base, Cochrane Library, and Medline (PubMed) were retrieved with the deadline of August 30, 2013. Randomized controlled trials (RCT) of XZKC in treating CHD patients with or without dyslipidemia were all included. Assessment of bias risk for included studies was conducted according to the Cochrane Handbook for Systematic Reviews of Intervention (Version 5.0.2): Criteria for judging risk of bias in the "risk of bias" assessment tool. Review Management (5.1.0) was employed for data statistics. If there was no significant heterogeneity, results from the random-effect model were presented. If the heterogeneity was not substantial, a meta-analysis was not performed and a narrative and qualitative summary was performed instead. RESULTS: A total of 28 RCTs (6,949 patients) were included after screening results. The methodological quality of included trial was generally lower. Results of Metaanalysis showed that XZKC was beneficial for CHD patients in decreasing cardiovascular events: when compared with the basic treatment group, the relative risk (RR) was 0.53 and 95% confidence interval (CI) was [0.35, 0.81]; when compared with the placebo + basic treatment group, RR was 0.52 and 95% CI was [0.42, 0.65]; when compared with the basic treatment group, RR for improving symptoms of angina was 1.20 and 95% CI was [1. 12, 1.30]; when compared with the basic treatment group, RR for improving abnormal ECG was 1.38 and 95% CI was [1.21, 1.57]. Thirteen studies showed that XZKC + basic treatment was obviously superior in lowering total cholesterol (TC) to that of the basic treatment group. Three studies showed that XZKC + basic treatment was obviously superior in lowering total cholesterol (TC) to that of the placebo + basic treatment group. Thirteen studies showed that XZKC + basic treatment was obviously superior in lowering low density lipoprotein cholesterol (LDL-C) to that of the basic treatment group. Three studies showed that XZKC + basic treatment was obviously superior in lowering LDL-C to that of the placebo + basic treatment group. A total of 18 studies describing adverse reactions (ADs) involved 61 ADs in the XZKC + basic treatment group. All suffered from mild symptoms or were improved after treatment. No severe ADs occurred. CONCLUSION: Treatment of CHD by XZKC might lower the occurrence of cardiovascular events in CHD patients accompanied with or without dyslipidemia, relieve clinical symptoms, improve ECG, lower blood lipid levels, and with less adverse reactions.