Acupoint application therapy alleviates pain by regulating immune function through inhibiting TLR4/MyD88/NF-κB p65 signaling in a primary dysmenorrhea rat model. / 穴位贴敷通过TLR4/MyD88/NF-κBé€šè·¯è°ƒèŠ‚åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„å ç–«åŠŸèƒ½.

OBJECTIVES: To investigate the effects of graphene-based warm uterus acupoint paste on uterine Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway and Th1/Th2 immune balance in primary dysmenorrhea ( PD ) model rats, so as to reveal its immunological mechanisms of relieving dysmenorrhea. METHODS: Thirty SD female rats were randomly divided into 3 groups：normal group, model group and acupoint paste group, with 10 rats in each group. PD rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days. At the same time of modeling, graphene-based warm uterus acupoint paste was applied to the acupoints of "Guanyuan" (CV4), bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6) of rats in the acupoint paste group. The application was continuously applied once daily for 10 d, 5 h each time. On the 11th day, oxytocin was injected intraperitoneally to observe the writhing latency, writhing times within 30 min and writhing score of rats in each group. The spleen and thymus indexes were calculated. The pathological changes of spleen and thymus tissue were observed after HE staining. The contents of serum immunoglobulin (Ig) A, IgG, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA . The protein and mRNA expression levels of TLR4, MyD88 and NF-κB p65 in rat uterine tissue were detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the writhing times and writhing scores within 30 min of rats in the model group were significantly increased(P<0.001), and the rats showed writhing reaction (P<0.01). The spleen index and thymus index were significantly decreased(P<0.01, P<0.05). The spleen and thymus had obvious pathological changes. The contents of IgA, IgG, TNF-α, IL-2 and IFN-γ in serum were significantly increased, while the contents of serum IL-4 and IL-10 were significantly decreased(P<0.001, P<0.01). The expression levels of TLR4, MyD88, NF-κB p65 protein and corresponding mRNA in uterine tissue were significantly increased(P<0.001). Following intervention, compared with the model group, the writhing latency time of rats in the acupoint paste group was prolonged, and the writhing times and writhing scores within 30 min were significantly decreased (P<0.001). The spleen index and thymus index were significantly increased(P<0.01, P<0.05). The pathological changes of spleen and thymus were improved. The contents of serum IgA, IgG, TNF-α, IL-2 and IFN-γ were significantly decreased, while the contents of IL-4 and IL-10 were significantly increased(P<0.001, P<0.05, P<0.01). The expression of TLR4, MyD88, NF-κB p65 protein and the corresponding mRNA levels in uterine tissue were decreased(P<0.001, P<0.01). CONCLUSIONS: Graphene-based warm uterus acupoint paste can regulate the immune balance of Th1/ Th2 by regulating TLR4/ MyD88/ NF-κB p65 signaling pathway, repair the pathological damage of immune tissue, improve immune function, and effectively relieve the pain symptoms of PD rats.

Acupoint compatibility effect: increasing "effect value" and expanding "effect domain". / è §ç©´é ä¼æ•ˆåº”.

By summarizing and exploring the theoretic connotation, key of functions and effect mechanism of acupoint compatibility, the effect of acupoint compatibility is concluded as the increase of "effect value" and the expansion of "effect domain". The increase of "effect value" is the concrete embodiment by the value of medical assessment scale, the value of objective index detection in clinical trial and the value of index detection in experiment research. The expansion of "effect domain" is the increase of effect target and the extension of effect scope. The paper interprets the scientific connotation of acupoint compatibility therapy from a new perspective, and emphasizes the innovative approaches to research while bringing forth new ideas on the research method. It is anticipated that a novel breakthrough can be achieved in the study of acupoint compatibility and the improvement of acupuncture-moxibustion efficacy.

[Clinical observation on cluster acupuncture at scalp points combined with exercise therapy in treatment of limb spasm after stroke].

OBJECTIVE: To observe the clinical effect of cluster acupuncture at scalp points in treating limb spasm after stroke on the basis of conventional exercise therapy. METHODS: A total of 72 patients with limb spasm after stroke were randomly divided into an observation group (36 cases, 5 cases dropped off) and a control group (36 cases, 6 cases dropped off). The control group was treated with exercise therapy. In the observation group, on the basis of the control group, penetrating technique of acupuncture was exerted at Qianding (GV 21) to Baihui (GV 20), Xinhui (GV 22) to Qianding (GV 21), etc. once a day, 5 days a week for 4 weeks. Before and after treatment, the changes of the modified Ashworth scale (MAS), simplified Fugl-Meyer motor assessment (FMA), and modified Barthel index (MBI) scores of the two groups were compared. RESULTS: After treatment, the MAS scores of upper and lower limbs in the two groups were lower than before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, the scores of FMA and BMI in the two groups were higher than before treatment (P<0.05), and the score of MBI in the observation group was higher than the control group (P<0.05). CONCLUSION: On the basis of conventional exercise therapy, cluster acupuncture at scalp points can reduce the spasm, improve motor function and activities of daily living in patients with limb spasm after stroke.

Neural circuit control of innate behaviors.

All animals possess a plethora of innate behaviors that do not require extensive learning and are fundamental for their survival and propagation. With the advent of newly-developed techniques such as viral tracing and optogenetic and chemogenetic tools, recent studies are gradually unraveling neural circuits underlying different innate behaviors. Here, we summarize current development in our understanding of the neural circuits controlling predation, feeding, male-typical mating, and urination, highlighting the role of genetically defined neurons and their connections in sensory triggering, sensory to motor/motivation transformation, motor/motivation encoding during these different behaviors. Along the way, we discuss possible mechanisms underlying binge-eating disorder and the pro-social effects of the neuropeptide oxytocin, elucidating the clinical relevance of studying neural circuits underlying essential innate functions. Finally, we discuss some exciting brain structures recurrently appearing in the regulation of different behaviors, which suggests both divergence and convergence in the neural encoding of specific innate behaviors. Going forward, we emphasize the importance of multi-angle and cross-species dissections in delineating neural circuits that control innate behaviors.

Discovery of novel antagonists targeting the DNA binding domain of androgen receptor by integrated docking-based virtual screening and bioassays.

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa.

[Report on the disciplinary development of acupuncture-moxibustion and tuina in 24 colleges and universities of TCM in China from 2013 to 2017].

The questionnaire of Acupuncture-Moxibustion and Tuina Applying for First-Level Discipline was issued to 24 colleges and universities of TCM in China. The questionnaire systematically investigated the recent disciplinary development of acupuncture-moxibustion and tuina from the aspects of specialty construction, student enrollment, faculty construction, personnel training quality, teaching quality and scientific research results. As a result, from 2013 to October of 2017, the above aspects in 24 colleges and universities of TCM in China showed an increasing trend year by year. Based on this survey, this report aimed to fully reflect the disciplinary development of acupuncture-moxibustion and tuina in China, which could analyze the current situation for education departments and training units, and provide data reference and support for acupuncture and tuina discipline to become a first-class discipline.

Inhibition of the RhoA/Rho-associated, coiled-coil-containing protein kinase-1 pathway is involved in the therapeutic effects of simvastatin on pulmonary arterial hypertension.

BACKGROUND: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. METHODS: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i.p.) on the first day of the study. The MCT + simvastatin group received simvastatin (2 mg/kg) daily for 4 weeks, after which pulmonary arterial pressure was measured by right heart catheterization. The protein and mRNA levels of Rho and ROCK1 were measured by immunohistochemistry, Western blot, and PCR. For in vitro experiments, human pulmonary endothelial cells were divided into seven groups: control, simvastatin, monocrotaline pyrrole (MCTP), MCTP + simvastatin, MCTP + simvastatin + mevalonate, MCTP + simvastatin + farnesyl pyrophosphate (FPP), and MCTP + simvastatin + FPP + geranylgeranyl pyrophosphate (GGPP). After 72 h exposed to the drugs, the protein and mRNA levels of RhoA and ROCK1 were measured by Western blot and PCR. RESULTS: The MCT group showed increased mean pulmonary arterial pressure, marked vascular remodeling, and increased protein and mRNA levels of RhoA and ROCK1 compared to the other groups (P < 0.05). In vitro, the MCTP group showed a marked proliferation of vascular endothelial cells, as well as increased protein and mRNA levels of RhoA and ROCK1 compared to the MCTP + simvastatin group. The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. CONCLUSIONS: Simvastatin improved vascular remodeling and inhibited the development of PAH. The effects of simvastatin were mediated by inhibition of RhoA/ROCK1. Simvastatin decreased RhoA/ROCK1 overexpression by inhibition of mevalonate, FPP, and GGPP synthesis.

[Application exploration of comparative effectiveness research in clinical efficacy optimization of abdominal acupuncture].

The concepts and characteristics of comparative effectiveness research (CER) are analyzed to explore its scientific research methodology in clinical efficacy optimization of abdominal acupuncture. The designs of CER focus on patients, which emphasize assessment of comprehensive efficacy in real medical environment instead of simple efficacy in randomized controlled trial (RCT). Its research strategy involves four categories and three subject, covering acquiring, saving and management, comparison and application of clinical evidence, which has practical application value in comprehensive comparison of advantages and efficacy rules of different acupuncture therapies and acupoint prescriptions. By establishing clinical registration system, oversized-sample data could be acquired from different centers to effectively overcome insufficient sample-induced sampling error. It has important value in system summary and optimization of clinical efficacy of abdominal acupuncture. The CER fully illustrates clinical reality of acupuncture-moxibustion and provides strong support of scientific data for optimization of curative effect. It embodies prescription standardization, manipulation normalization and methodization of syndrome differentiation in clinic of abdominal acupuncture, which is expected to achieve evidence-based optimization of treatment prescription and technique in abdominal acupuncture.

[Effects of puerarin on fatty superoxide in aged mice induced by D-galactose].

OBJECTIVE: To study the effect of puerarin on fatty superoxide of aged mice induced by D-galactose. METHOD: The aged mice were induced by s.c. 0.12 g.kg-1 D-galactose for 6 weeks. Meanwhile, they were treated with three doses of puerarin once a day for 6 weeks. Then the spontaneous behavior was tested in the aged mice using open field at the next day after the last treatment. And the activity of SOD, the contents of MDA and lipofuscin in brain, liver, and serum were measured with Ultravioletray spectrometer and Fluorospectrophometer analysis system. RESULT: Compared with the D-galactose control group, puerarin of 50 mg.kg-1 and 100 mg.kg-1 puerarin significantly increased the spontaneous behavior, remarkably promoted the activity of SOD of brain, liver, and serum in the aged mice, and significantly decreased the contents of MDA and lipofuscin. CONCLUSION: Puerarin can improve the activity of antioxidase of the modelling aged-mice induced by D-galactose.