[Clinical efficacy of different waves of electroacupuncture on knee osteoarthritis and its effect on TGF-ß1 in joint fluid].

OBJECTIVE: To observe the therapeutic effects of different waves of electroacupuncture (EA) on knee osteoarthritis (KOA), and to explore the mechanism of different waves of EA on promoting cartilage repair. METHODS: Ninety- seven patients with KOA were randomly divided into a dilatational wave group (32 cases, 2 cases dropped off), a continuous wave group (32 cases, 2 cases dropped off) and a discontinuous wave group (33 cases, 3 cases dropped off). The same acupoints of Xuehai (SP 10), Liangqiu (ST 34), Dubi (ST 35) and Neixiyan (EX-LE 4) were selected in the three groups. The dilatational wave (frequency of 2 Hz/10 Hz) was used in the dilatational wave group, the continuous wave (frequency of 10 Hz) was used in the continuous wave group, and the discontinuous wave (frequency of 10 Hz) was used in the discontinuous wave group. All the needles were retained for 30 min. All the treatment was given 3 times a week (on Monday, Wednesday and Friday) for 4 weeks. Lysholm knees scoring scale (LKSS) was used to evaluate the knee joint function before and after treatment, and the content of transforming growth factor-ß1 (TGF-ß1) in the joint effusion before and after treatment was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared before treatment, the total score and each score of LKSS were increased after treatment in the three groups (all P<0.05). The improvements of total score, pain score, instability score, swelling score of LKSS in the continuous wave group and the dilatational wave group were superior to those in the discontinuous wave group (all P<0.05). The content of TGF-ß1 in the joint effusion in each group was increased after treatment (P<0.05), and the improvement in dilatational wave group was superior to thoes in the continuous wave group and the discontinuous wave group (all P<0.05). CONCLUSION: The three different waves of EA could all improve the clinical symptoms of KOA, which may promote cartilage repair by increasing TGF-ß1 content. The dilatational wave had the best overall effect, which can be used as a clinical optimal treatment.

Clinical efficacy of different waves of electroacupuncture on knee osteoarthritis and its effect on TGF-β1 in joint fluid / 中国针灸

OBJECTIVE@#To observe the therapeutic effects of different waves of electroacupuncture (EA) on knee osteoarthritis (KOA), and to explore the mechanism of different waves of EA on promoting cartilage repair.@*METHODS@#Ninety- seven patients with KOA were randomly divided into a dilatational wave group (32 cases, 2 cases dropped off), a continuous wave group (32 cases, 2 cases dropped off) and a discontinuous wave group (33 cases, 3 cases dropped off). The same acupoints of Xuehai (SP 10), Liangqiu (ST 34), Dubi (ST 35) and Neixiyan (EX-LE 4) were selected in the three groups. The dilatational wave (frequency of 2 Hz/10 Hz) was used in the dilatational wave group, the continuous wave (frequency of 10 Hz) was used in the continuous wave group, and the discontinuous wave (frequency of 10 Hz) was used in the discontinuous wave group. All the needles were retained for 30 min. All the treatment was given 3 times a week (on Monday, Wednesday and Friday) for 4 weeks. Lysholm knees scoring scale (LKSS) was used to evaluate the knee joint function before and after treatment, and the content of transforming growth factor-β1 (TGF-β1) in the joint effusion before and after treatment was determined by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#Compared before treatment, the total score and each score of LKSS were increased after treatment in the three groups (all <0.05). The improvements of total score, pain score, instability score, swelling score of LKSS in the continuous wave group and the dilatational wave group were superior to those in the discontinuous wave group (all <0.05). The content of TGF-β1 in the joint effusion in each group was increased after treatment (<0.05), and the improvement in dilatational wave group was superior to thoes in the continuous wave group and the discontinuous wave group (all <0.05).@*CONCLUSION@#The three different waves of EA could all improve the clinical symptoms of KOA, which may promote cartilage repair by increasing TGF-β1 content. The dilatational wave had the best overall effect, which can be used as a clinical optimal treatment.

MiR-7-5p suppresses stemness and enhances temozolomide sensitivity of drug-resistant glioblastoma cells by targeting Yin Yang 1.

Glioblastoma multiforme (GBM) is the most malignant tumor of the central nervous system, and chemoresistance blunts the effect of temozolomide (TMZ) in the treatment of GBM. Clarifying the underlying mechanism of chemoresistance might yield novel strategies to improve the patients' response to chemotherapeutics. Mounting evidence indicates that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. At present, miR-7-5p has been recognized as a tumor suppressor involved in multiple cancers. However, the biological effects of miR-7-5p in TMZ resistance have not been illuminated. In this study, we used RNA sequencing and high-throughput screening techniques, which revealed that miR-7-5p is significantly downregulated in TMZ resistant LN229 cells (LN229/TMZ-R) compared to control cells (LN229), and low miR-7-5p expression was correlated with recurrence in GBM patients. Ectopic overexpression of miR-7-5p sensitized LN229/TMZ-R cells to TMZ and suppressed the stemness of glioblastoma stem cells (GSCs). Further experiments demonstrated that miR-7-5p exerts its role by directly targeting the 3'-untranslated region of Yin Yang 1 (YY1). Our findings suggest that combinational use of miR-7-5p and TMZ might be a promising therapeutic strategy to increase the long-term drug response in GBM patients.

Melatonin attenuates chronic pain related myocardial ischemic susceptibility through inhibiting RIP3-MLKL/CaMKII dependent necroptosis.

Chronic pain aggravates cardiovascular injury via incompletely understood mechanisms. While melatonin may participate in the pathophysiological process of chronic pain, its cardiovascular effects under chronic pain states remains unknown. In this study, chronic pain was induced by spared nerve injury model (SNI) for 4 weeks. We showed decreased the ipsilateral hind paw withdrawal mechanical threshold (PWMT) in SNI mice. High dose melatonin treatment (60 mg/kg, i.p.) could reversed nociceptive threshold in SNI mice. To verify the effect of chronic pain on the cardiac tolerance to ischemic stress, mice were subjected to myocardial ischemia-reperfusion (MI/R) in vivo. SNI mice showed exaggerated MI/R-induced detrimental effects and myocardial necroptosis compared with control group (P < .05). Mechanically, an increased level of tumor necrosis factor-α (TNF-α) was found in SNI group following by a robust interaction of RIP1/RIP3. RIP3-induced phosphor-MLKL and CaMKII more significantly in SNI mice (P < .05). We found that RIP3 deficiency provided a comparable protection against MI/R-induced necroptosis under chronic pain conditions. More importantly, low dose melatonin (20 mg/kg, i.p.) treatment 10 min before reperfusion decreased the level of TNF-α following with a negatively regulating the RIP3 induced phosphor-MLKL/CaMKII signaling, thus significantly reduced ROS production and cardiomyocyte necroptosis and ameliorated cardiac function. In summarize, our results demonstrated that chronic pain sensitizes heart to MI/R injury and myocardial necrosis plays an important role in this pathophysiological process. We also define melatonin acted as triple cardioprotective effects: ameliorating TNF-α level, suppressing RIP3-MLKL/CaMKII signaling induced necroptosis and exerting analgesia effect.

DDR2-CYR61-MMP1 Signaling Pathway Promotes Bone Erosion in Rheumatoid Arthritis Through Regulating Migration and Invasion of Fibroblast-Like Synoviocytes.

Regulation of matrix metalloproteinases (MMPs) by collagen in the fibroblast-like synoviocytes (FLSs) plays a critical role in joint destruction in rheumatoid arthritis (RA). Our previous study indicated that discoidin receptor 2 (DDR2) mediated collagen upregulation of MMPs. However, the precise underlying mechanism remains unclear. We report here that CYR61, a secreted, extracellular matrix-associated signaling protein which is capable of regulating a broad range of cellular activities, including cell adhesion, migration, proliferation, and apoptosis, is significantly upregulated in collagen II-stimulated RA FLS. Further studies found that collagen II-activated phosphorylated-DDR2 induces CYR61 through activation of transcription factor activator protein 1 (AP-1). The elevated CYR61, in turn, accelerates MMP1 production via ETS1 (ETS proto-oncogene 1). In addition, CYR61 significantly promotes FLS invasion and migration. Blockade of CYR61 by an adenovirus expressing CYR61 shRNA (Ad-shCYR61) in vivo remarkably ameliorated the severity of arthritis, reduced inflammatory cytokine secretion, and attenuated bone erosion as detected by micro-computed tomography (µCT), in collagen-induced arthritis (CIA) rats. Taken together, we uncovered the Collagen II-DDR2-AP-1-CYR61-ETS1-MMP1 loop in RA FLS. In which, CYR61 acts as a hinge to promote cartilage damage through regulating FLS invasion, migration, and MMP1 production and the inflammatory cascade in RA. Thus, CYR61 may be a promising diagnostic and therapeutic target for RA treatment. © 2016 American Society for Bone and Mineral Research.

A novel NF-κB/YY1/microRNA-10a regulatory circuit in fibroblast-like synoviocytes regulates inflammation in rheumatoid arthritis.

The main etiopathogenesis of rheumatoid arthritis (RA) is overexpressed inflammatory cytokines and tissue injury mediated by persistent NF-κB activation. MicroRNAs widely participate in the regulation of target gene expression and play important roles in various diseases. Here, we explored the mechanisms of microRNAs in RA. We found that microRNA (miR)-10a was downregulated in the fibroblast-like synoviocytes (FLSs) of RA patients compared with osteoarthritis (OA) controls, and this downregulation could be triggered by TNF-α and IL-1ß in an NF-κB-dependent manner through promoting the expression of the YingYang 1 (YY1) transcription factor. Downregulated miR-10a could accelerate IκB degradation and NF-κB activation by targeting IRAK4, TAK1 and BTRC. This miR-10a-mediated NF-κB activation then significantly promoted the production of various inflammatory cytokines, including TNF-α, IL-1ß, IL-6, IL-8, and MCP-1, and matrix metalloproteinase (MMP)-1 and MMP-13. In addition, transfection of a miR-10a inhibitor accelerated the proliferation and migration of FLSs. Collectively, our data demonstrates the existence of a novel NF-κB/YY1/miR-10a/NF-κB regulatory circuit that promotes the excessive secretion of NF-κB-mediated inflammatory cytokines and the proliferation and migration of RA FLSs. Thus, miR-10a acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment.

Clinical study on the treatment of knee osteoarthritis of Shen-Sui insufficiency syndrome type by electroacupuncture.

OBJECTIVE: To study the clinical effificacy of electroacupuncture (EA) on treating knee osteoarthritis (KOA) of Shen ()-Sui () insuffificiency (SSI) syndrome type. METHODS: A total of 245 patients (279 knees) of KOA-SSI were randomly assigned to two groups by lottery: 141 knees in the treatment group and 138 knees in the control group. The treatment group was managed with EA at the dominant points of Neixiyan (Ex-LE4) and Waixiyan (Ex-LE5) as well as the conjugate points of Xuanzhong (GB39) and Taixi (KI3) for 30 min, once a day, with 15 days as one course; 2 courses were applied with a 5-day interval in between. The control group was treated with intra-articular injection of 2 mL hyaluronic acid into the affected joint every 7 days for 5 times in total. The clinical effects on the patients in different stages were observed, and their symptom scores of knee and contents of cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2alpha) (PGE(2alpha)) and matrix metalloproteinases-3 (MMP-3), in the knee joint fluid were measured before and after treatment. RESULTS: The study was completed in 235 patients (263 knees); four patients (7 knees) in the treatment group and six patients (9 knees) in the control group dropped out. Comparison of therapeutic effects (excellent and effective rates) between the two groups showed insignificant differences (P>0.05). Symptom scores of knee and contents of cytokines in the knee flfluid after treatment were lowered signifificantly in the patients of stage I-III in both groups (P<0.05 or P<0.01). However, the lowering of the total symptom score of knee in the patients of stage III in the treatment group was more signifificant (P<0.05). CONCLUSIONS: EA could effectively alleviate the clinical symptoms in KOA patients of stage III, showing an effect superior to that of hyaluronic acid. EA also shows action in suppressing the secretion of IL-1, IL-6, TNF-alpha, PGE(2alpha) and MMP-3 in the knee flfluid.

[Effects of time factors on acupoint sticking therapy for preventing and treating bronchial asthma].

OBJECTIVE: To observe the influence of time factors on acupoint sticking therapy for preventing and treating bronchial asthma. METHODS: Seventy-one cases were randomly divided into a dog days group (n= 30), a Sanjiu days group (n=21) and a daily days group (n=20). They were all treated with ginger moxibustion plus acupoint sticking of Chinese medicine at Dazhui (GV 14) and Feishu (BL 13) etc. This treatment was applied once at the beginning of the first dog days, the middle dog days and the last dog days respectively in the dog days group, and once at the beginning of the first nine days, the middle nine days and the last nine days in coldest days of winter respectively in the Sanjiu days group, and once every other 10 days during 30 days except the dog days or the Sanjiu days in the daily days group. Their therapeutic effects and quality of life and changes of serum level of interleukin 13 (IL-13) were observed. RESULTS: The total effective rate of the dog days group was 83.3% (25/30), the Sanjiu days group and the daily days group were 61.9% (13/21) and 65.0% (15/20) respectively, with no significant differences among three groups (all P>0.05). After treatment, there were no significant differences in quality of life and changes of serum level of IL-13 among three groups, but there were significant differences between before and after treatment (P<0.01, P<0.001). CONCLUSION: Acupoint sticking is an effective therapy for bronchial asthma. It can be practiced in the whole year for the result of this study that medicines and acupoints are the leading factors of this therapy and the time factors have no influence on therapeutic effect.

Effects of time factors on acupoint sticking therapy for preventing and treating bronchial asthma / 中国针灸

<p><b>OBJECTIVE</b>To observe the influence of time factors on acupoint sticking therapy for preventing and treating bronchial asthma.</p><p><b>METHODS</b>Seventy-one cases were randomly divided into a dog days group (n= 30), a Sanjiu days group (n=21) and a daily days group (n=20). They were all treated with ginger moxibustion plus acupoint sticking of Chinese medicine at Dazhui (GV 14) and Feishu (BL 13) etc. This treatment was applied once at the beginning of the first dog days, the middle dog days and the last dog days respectively in the dog days group, and once at the beginning of the first nine days, the middle nine days and the last nine days in coldest days of winter respectively in the Sanjiu days group, and once every other 10 days during 30 days except the dog days or the Sanjiu days in the daily days group. Their therapeutic effects and quality of life and changes of serum level of interleukin 13 (IL-13) were observed.</p><p><b>RESULTS</b>The total effective rate of the dog days group was 83.3% (25/30), the Sanjiu days group and the daily days group were 61.9% (13/21) and 65.0% (15/20) respectively, with no significant differences among three groups (all P>0.05). After treatment, there were no significant differences in quality of life and changes of serum level of IL-13 among three groups, but there were significant differences between before and after treatment (P<0.01, P<0.001).</p><p><b>CONCLUSION</b>Acupoint sticking is an effective therapy for bronchial asthma. It can be practiced in the whole year for the result of this study that medicines and acupoints are the leading factors of this therapy and the time factors have no influence on therapeutic effect.</p>

Clinical study on the treatment of knee osteoarthritis of Shen-Sui insufficiency syndrome type by electroacupuncture / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the clinical effificacy of electroacupuncture (EA) on treating knee osteoarthritis (KOA) of Shen ()-Sui () insuffificiency (SSI) syndrome type.</p><p><b>METHODS</b>A total of 245 patients (279 knees) of KOA-SSI were randomly assigned to two groups by lottery: 141 knees in the treatment group and 138 knees in the control group. The treatment group was managed with EA at the dominant points of Neixiyan (Ex-LE4) and Waixiyan (Ex-LE5) as well as the conjugate points of Xuanzhong (GB39) and Taixi (KI3) for 30 min, once a day, with 15 days as one course; 2 courses were applied with a 5-day interval in between. The control group was treated with intra-articular injection of 2 mL hyaluronic acid into the affected joint every 7 days for 5 times in total. The clinical effects on the patients in different stages were observed, and their symptom scores of knee and contents of cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2alpha) (PGE(2alpha)) and matrix metalloproteinases-3 (MMP-3), in the knee joint fluid were measured before and after treatment.</p><p><b>RESULTS</b>The study was completed in 235 patients (263 knees); four patients (7 knees) in the treatment group and six patients (9 knees) in the control group dropped out. Comparison of therapeutic effects (excellent and effective rates) between the two groups showed insignificant differences (P>0.05). Symptom scores of knee and contents of cytokines in the knee flfluid after treatment were lowered signifificantly in the patients of stage I-III in both groups (P<0.05 or P<0.01). However, the lowering of the total symptom score of knee in the patients of stage III in the treatment group was more signifificant (P<0.05).</p><p><b>CONCLUSIONS</b>EA could effectively alleviate the clinical symptoms in KOA patients of stage III, showing an effect superior to that of hyaluronic acid. EA also shows action in suppressing the secretion of IL-1, IL-6, TNF-alpha, PGE(2alpha) and MMP-3 in the knee flfluid.</p>

[Effects of shouwu-huanjing recipe on human sperm motility and fertility in vitro].

OBJECTIVE: To observe the effect of Shouwu-Huanjing Recipe(SWHJR) medicated serum on human sperm motility and fertility in vitro. METHODS: Human sperm was co-cultured with SWHJR medicated serum in vitro. Human sperm motility was evaluated by computer-assisted semen analysis(CASA). The acrosome reaction and the capability of penetrating zona-free hamster eggs were also observed. RESULTS: The co-cultured SWHJR medicated serum significantly increased the sperm motion velocity(VAP, VCL, VSL) (P < 0.01), the amplitude of lateral head movement (ALH) and the beat frequency of flagellum(BCF), the density of progressive motility sperms (P < 0.05), the acrosome reaction rate(P < 0.001), the fertilization rate(FR) and the fertilization index (FI) in sperm penetration assay(SPA) test (P < 0.01). The stimulation of SWHJR medicated serum occurred in dose-dependent manner. CONCLUSION: SWHJR can improve human sperm motility and fertility.

Effects of shouwu-huanjing recipe on human sperm motility and fertility in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the effect of Shouwu-Huanjing Recipe(SWHJR) medicated serum on human sperm motility and fertility in vitro.</p><p><b>METHODS</b>Human sperm was co-cultured with SWHJR medicated serum in vitro. Human sperm motility was evaluated by computer-assisted semen analysis(CASA). The acrosome reaction and the capability of penetrating zona-free hamster eggs were also observed.</p><p><b>RESULTS</b>The co-cultured SWHJR medicated serum significantly increased the sperm motion velocity(VAP, VCL, VSL) (P < 0.01), the amplitude of lateral head movement (ALH) and the beat frequency of flagellum(BCF), the density of progressive motility sperms (P < 0.05), the acrosome reaction rate(P < 0.001), the fertilization rate(FR) and the fertilization index (FI) in sperm penetration assay(SPA) test (P < 0.01). The stimulation of SWHJR medicated serum occurred in dose-dependent manner.</p><p><b>CONCLUSION</b>SWHJR can improve human sperm motility and fertility.</p>