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As part of traditional Chinese medicine, acupoints are considered a dynamic functional area, which can reflect the internal condition of the body. When the body is suffering from disease or injury, corresponding acupoints are believed to be activated and manifest in several sensitized forms, including expansion of the receptive field, pain sensitization, and heat sensitization. Such phenomena are believed to gradually disappear concomitantly with recovery from the disease. Acupoint states are therefore changeable according to health status, a phenomenon known as acupoint sensitization. This review aims to provide an overview of acupoint sensitization based on existing research results and determine priorities for future research. Systematic literature retrieval was conducted in Medline, Embase, Cochrane Library, CINAHL, and AMED from inception to 18 July 2018. Current evidence from research findings to date indicate that acupoint sensitization is based on neurogenic inflammation and that stimulation of sensitized acupoints presents a potential trend of generating a better clinical effect when compared with stimulation of unsensitized points.

Objective. The aim of this study was to investigate the difference of efficacy between conventional moxibustion (CM) and smoke-free moxibustion (SM) for patients with osteoarthritis of the knee (KOA). Methods. This is a multicentre, randomized, single blinded, parallel-group clinical trial. Patients with KOA were randomly allocated to CM group (69) and SM group (69) in 7 hospitals of China. Moxibustion treatment in 12 sessions over 4 weeks was administrated at 3 acupuncture points (EX-LE4, ST35, and ST36). Patients completed standard questionnaires at baseline and after 2 weeks, 4 weeks, 8 weeks, and 12 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from the baseline to 4 weeks. The secondary outcomes include Visual Analogue Scale (VAS) and Patient Global Assessment score (PGA). Results. Analyses showed that the WOMAC score improved in pain (95% CI,-0.1[-1.2 to 0.9], p=0.76), stiffness (95% CI,-0.1 [-0.5 to 0.3], p=0.71), and function (95% CI, 2.2 [-1.3 to 5.8], p=0.22) compared between the two groups at 4 weeks, as well as the VAS score (95% CI,0.1 [-0.3 to 0.6], p=0.60). Similar results presented at 8 and 12 weeks. No statistically significant difference was observed between CM and SM groups for outcome measurements. Conclusions. It suggested that smoke generated during moxibustion treatment does not affect the efficacy of moxibustion in the treatment of KOA, which should be taken into account to be removed for the sake of reducing environmental pollution or moxa smoke exposure of acupuncturists or patients. This trial is registered with Clinical Trials.gov, NCT02772055.

Purinergic P2X7 receptor, a nonselective cation channel, is highly expressed in immune cells as well as cardiac smooth muscle cells and endothelial cells. Its activation exhibits to mediate nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome activation, resulting in the release of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), and pyroptosis, thus triggering inflammatory response. These pathological mechanisms lead to the deterioration of various cardiovascular diseases, including atherosclerosis, arrhythmia, myocardial infarction, pulmonary vascular remodeling, and cardiac fibrosis. All these worsening cardiac phenotypes are proven to be attenuated after the P2X7 receptor inhibition in experimental studies. The present review aimed to summarize key aspects of P2X7 receptor–mediated inflammation and pyroptosis in cardiovascular diseases. The main focus is on the evidence addressing the involvement of the P2X7 receptor in the inflammatory responses to the occurrence and development of cardiovascular disease and therapeutic interventions.

Background: The prognostic factors for efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer remain unknown. The purpose of this study is to evaluate the efficacy of PARP inhibitors and to explore their prognostic factors in ovarian cancer.Methods: PubMed, Embase, and conference databases were searched for relevant prospective clinical trials. The primary outcomes included overall survival (OS), progression-free survival (PFS), and their prognostic factors. Secondary outcomes included PFS2, time to first subsequent therapy (TFST), time to second subsequent therapy (TSST), chemotherapy-free interval (CFI), and their prognostic factors. Hazard ratio (HR) with a 95% confidence interval (CI) was used as an effect measure.Results: PARP inhibitors significantly prolonged PFS in patients with ovarian cancer regardless of their BRCA and HRD status (HR = 0.44, 95% CI = 0.36–0.55). BRCA mutation, HRD-positive status, and sensitivity to platinum represented effective prognostic factors for PFS (Pinteraction < 0.01 and within-trial interaction HR < 1). Other clinicopathological factors did not predict the benefit of PFS (Pinteraction > 0.10). Moreover, PARP inhibitors significantly increased PFS2, TFST, TSST, and CFI, with significant BRCA-related differences. However, HRD-related differences could not be evaluated due to the lack of eligible studies. Furthermore, PARP inhibitors did not translate into prolonged OS, although there was a benefit associated with OS (HR = 0.84, 95% CI = 0.70–1.02). PARP inhibitors used as maintenance therapy after first or subsequent line therapy improved OS (HR = 0.77, 95% CI = 0.63–0.93).Conclusions: PARP inhibitors can significantly prolong PFS, PFS2, TFST, TSST, and CFI in ovarian cancer patients. BRCA mutation, HRD-positive status, and sensitivity to platinum are effective prognostic factors for the efficacy of PARP inhibitors. However, despite the PFS improvement, this does not translate into prolonged OS for patients.

The aim of this study was to investigate whether contralateral moxibustion would generate a similar analgesic effect with ipsilateral moxibustion. Contra- and ipsilateral moxibustion were separately applied to Zusanli (ST36) acupoints of inflammatory pain mice. The analgesic effect was evaluated, respectively, by licking/biting time (LBT) of formalin-induced inflammatory pain and thermal withdrawal latency (TWL) of complete Freund’s adjuvant- (CFA-) induced inflammatory pain. For formalin-induced pain, compared with formalin group, the total LBT of ipsi- and contralateral moxibustion reduced in both phase I and phase II, but there was no significant difference between ipsi- and contralateral moxibustion. For CFA-induced inflammatory pain, compared with CFA group, TWL of ipsi- and contra-Moxi groups increased immediately after moxibustion intervention; however there was no obvious difference between ipsi- and contralateral moxibustion at any timepoint. It indicated that contralateral moxibustion had a similar analgesic effect with ipsilateral moxibustion in both formalin- and CFA-induced pain. These results suggest that both ipsi- and contralateral moxibustion could be applied for pain relief.

Background: Tai Chi Chuan(TCC), as a mind-body exercise, may have a positive impact on physical function and psychological well-being in breast cancer patients. The latest systematic review and meta-analysis of TCC for breast cancer was made 4 years ago and some new clinical trials about it were published. We remade a systematic review and meta-analysis to evaluate the effect of TCC in breast cancer patients. Methods: In this systematic review and meta-analysis, we searched MEDLINE (via PubMed), EMBASE (via embase.com), CENTRAL, CNKI, COVIP, Wanfang, Chaoxing, CiNii, J-SSTAGE, DBpia, and ThaiJO with no language restrictions from inception to December 31, 2018 (updated on February 16, 2020), for randomized clinical trials comparing TCC with non-exercised therapy in breast cancer patients. The primary outcome was quality of life in patients with breast cancer and data pooled by a random-effects model. Subgroup analyses were conducted to estimate the effect of different durations of TCC for breast cancer patients. This study was registered in PROSPERO, number CRD 4201810326. Results: Fifteen articles involving a total of 885 breast cancer participants were included in this review. Compared with non-exercised therapy, TCC had a significant effect on quality of life in breast cancer patients (SMD = 0.37, 95% CI 0.15-0.59, p = 0.001), and subgroup analysis found that TCC showed beneficial effect in 12 weeks and 25 weeks (12 weeks: SMD = 0.40, 95% CI 0.19-0.62, p = 0.0003; 25 weeks: SMD = 0.38, 95% CI 0.15-0.62, p = 0.002). Meta-analyses of secondary outcomes showed that 3 weeks TCC increased shoulder function (SMD = 1.08, 95% CI 0.28-1.87, p = 0.008), 12 weeks TCC improved pain (SMD = 0.30, 95% CI 0.08-0.51, p = 0.007), shoulder function (SMD = 1.34, 95% CI 0.43-2.25, p = 0.004), strength of arm (SMD = 0.44, 95% CI 0.20-0.68, p = 0.0004), and anxiety (MD = -4.90, 95% CI -7.83 to -1.98, p = 0.001) in breast cancer patients compared with the control group. Conclusions: TCC appears to be effective on some physical and psychological symptoms and improves the quality of life in patients with breast cancer. Additional randomized controlled trials with a rigorous methodology and low risk of bias are needed to provide more reliable evidence.

OBJECTIVE To investigate the effects of long-term exposure to moxa smoke on acupuncturists and to consider the association between physical symptoms and gender, age, secondhand smoke (SHS) exposure, and the duration of exposure. METHODS A self-report, web-based questionnaire was used to evaluate the effects of moxa smoke on acupuncturists. Logistic regression was used to analyze the relationship between physical symptoms and possible correlative factors. RESULTS A total of 858 questionnaires were analyzed. The data showed that 42.42% of acupuncturists had been exposed to moxa smoke for 5-10 years. The most frequent symptom was tearing (32.98%) and the least frequent symptom was asthma (5.24%). Logistic regression analysis showed that female acupuncturists were slightly more susceptible to cough and tearing than males (cough: OR: 1.583, 95% CI: 1.079, 2.321, P = 0.019; tearing: OR: 1.519, 95% CI: 1.094,2.108, P = 0.013). Acupuncturists aged over 25 years reported a slightly lower incidence of eye itchiness than those aged under 25 years (26-40 years: OR: 0.604, 95% CI: 0.379, 0.965, P = 0.035; over 40 years: OR: 0.330, 95% CI: 0.114, 0.958, P = 0.042). Ophthalmodynia occurred less in acupuncturists aged 26-40 years (OR: 0.591, 95% CI: 0.359,0.970, P = 0.038) than in those younger than 25 years. The only association between prevalence of symptoms and tobacco use and SHS exposure was that smokers had a lower occurrence of phlegm in the throat (OR: 0.579, 95% CI: 0.392, 0.856, P = 0.006). Shortness of breath was less frequent in participants exposed to moxa smoke for more than 5 years (5-10 years: OR: 0.400, 95% CI: 0.204, 0.785, P = 0.008; 11-20 years: OR: 0.392, 95% CI: 0.178, 0.864, P = 0.02), but a slightly higher incidence of eye itchiness was found in those with over 20 years of moxa exposure (OR: 4.200, 95% CI: 1.344, 3.128, P = 0.014). CONCLUSION The most frequent symptom of moxa smoke exposure in acupuncturists was tearing. The association of symptoms with age and duration of exposure to moxa smoke were rather complicated; hence, care should be taken in drawing conclusions about the safety of moxa smoke based solely on its potentially harmful ingredients.

Background Conventional moxibustion is a representative non-drug intervention in traditional Chinese medicine, and it has been reported to produce encouraging results and benefits in relieving symptoms and improving the quality of life for patients with knee osteoarthritis (KOA) in previous clinical trials and systematic reviews. Given that increasing concerns on the safety of generated smoke from conventional moxibustion have received much attention, smoke-free moxibustion is regarded as a potential alternative. However, whether smoke-free moxibustion would display a similar efficacy to that of conventional moxibustion still remains unclear. Therefore, this randomized controlled trial attempts to investigate the difference of efficacy between conventional moxibustion and smoke-free moxibustion in patients with KOA. Methods/design This is a multicenter, randomized, single-blinded, parallel-group clinical trial. A total of 138 eligible participants with KOA will be randomly allocated to two groups (conventional moxibustion group and smoke-free moxibustion group) in seven hospitals in China. Participants will receive 12 sessions of moxibustion treatment at three acupoints (EX-LE4, ST35, and ST36) over a period of 4 weeks (3 sessions per week). A smoke-removing device is placed at the top of the moxibustion device for the smoke-free moxibustion group (n = 69), while the conventional moxibustion group (n = 69) is treated with traditional moxibustion. The primary outcome measure will be the change of the global scale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from the baseline to 4 weeks. Secondary outcomes include the visual analog scale VASand Patient Global Assessment scores. Follow-up measurements will be performed on the 8th and 12th weeks after random allocation. Discussion This study will contribute to providing a solid foundation for the selection of moxibustion in clinical application as well as future research in moxibustion therapy. Trial registration ClinicalTrials.gov, NCT02772055. Registered on 12 May 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1846-2) contains supplementary material, which is available to authorized users.

Hydrogen sulfide (H2S) is an important mediator participating in both physiological and pathological systems and related to the inflammatory process. Acupuncture has a therapeutic effect on inflammatory pain. However, whether H2S generated in the central nervous system (CNS) is a mediator of electroacupuncture (EA) treatment for inflammatory pain is unknown. We injected complete Freund’s adjuvant (CFA) to induce inflammatory pain and applied EA treatment as an interventional strategy for pain relief. The results presented here show that S-adenosyl-l-methionine (SAM), an allosteric activator of cystathionine-β-synthetase (CBS), may reverse the therapeutic effect of EA. CBS-induced H2S generation might get involved in the mechanism of EA-induced analgesia in the hippocampus on chronic inflammatory pain.

Background: Rhein is considered to have beneficial influence on diabetic nephropathy. Animal experiments suggested that the mechanisms of rhein against diabetic nephropathy may involve many processes, but the credibility of the evidence is unclear. Therefore, we conducted systematic review and meta-analysis of pre-clinical animal data to assess the current evidence for rhein effects and mechanisms in treating diabetic nephropathy.Methods: The databases of PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP information database, Wanfang Data Information Site, and Chinese Biomedical Literature were searched for this review. SYRCLE’s risk of bias tool for animal studies was applied to assess the methodological quality of studies. A meta-analysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions by using RevMan 5.3 and STATA/SE 12.0 software. This study was registered with PROSPERO, number CRD42018105220.Results: Twenty-five studies involving 537 animals were included. There was significant association of rhein with levels of blood glucose (P < 0.05), serum creatinine (Scr) (P < 0.05), urine protein (P < 0.05), kidney tubules injury index (P < 0.05), relative area of kidney collagen (P < 0.05), transforming growth factor-β1 (P < 0.05), malondialdehyde (P < 0.05), and superoxide dismutase (P < 0.05) compared with that in the control group. No significant association between rhein and endothelin (P > 0.05) was found. Subgroup analysis showed that the hypoglycemic effect of rhein on type 2 diabetic nephropathy was better than on type 1 diabetic nephropathy (P < 0.05).Conclusions: These findings suggested that rhein has beneficial effects on animal models of diabetic nephropathy, and that the mechanisms are mostly involved with ameliorating levels of TGF-β1, renal fibrosis, metabolism, and oxidative stress status. However, some factors such as possible publication bias, methodological quality, and sample size may affect the accuracy of positive findings. These limitations suggested that a cautious interpretation of the positive results of this systematic review and meta-analysis is necessary. Therefore, high methodological quality and well-reported animal experiments are needed in future research.

Chronic pain is a debilitating and rather common health problem. The present shortage in analgesic drugs with a favorable spectrum but without remarkable side effects furthered the search for alternative therapeutic manipulations. Increasing evidence from both basic and clinical research on acupuncture, a main alternative therapy of traditional Chinese medicine, suggests that chronic pain is sensitive to acupuncture procedures. Clarification of the underlying mechanisms is a challenge of great theoretical and practical significance. The seminal hypothesis of Geoffrey Burnstock and the astounding findings of Maiken Nedergaard on the involvement of purinergic signaling in the beneficial effects of acupuncture fertilized the field and led to an intensification of research on acupurines. In this review, we will summarize the state-of-the-art situation and try to forecast how the field is likely to develop in the future.

Purinergic signaling has recently been suggested to constitute the cellular mechanism underlying acupuncture-induced analgesia (AA). By extending the original hypothesis on endogenous opioids being released during AA, Geoffrey Burnstock and Maiken Nedergaard supplied evidence for the involvement of purinoceptors (P2 and P1/A1 receptors) in the beneficial effects of AA. In view of certain pain states (e.g. neuropathic pain) which respond only poorly to therapy with standard analgesics, as well as with respect to the numerous unwanted effects of opioids and non-steroidal anti-inflammatory drugs, it is of great significance to search for alternative therapeutic options. Because clinical studies on AA yielded sometimes heterogeneous results, it is of eminent importance to relay on experiments carried out on laboratory animals, by evaluating the data with stringent statistical methods including comparison with a sufficient number of control groups. In this review, we summarize the state of the art situation with respect to the participation of P2 receptors in AA and try to forecast how the field is likely to move forward in the future.

Introduction Knee osteoarthritis is a common form of arthritis in elderly patients that is characterised by pain and functional limitation. Moxibustion has been employed to relieve chronic pain as an alternative therapy for knee osteoarthritis. However, the evidence of its efficacy is equivocal due to the low methodological quality in most clinical studies. Therefore, we are performing a double-blinded, double-placebo, randomised controlled trial to evaluate the efficacy of moxibustion in participants with knee osteoarthritis. Methods and analysis This is a multicentre, double-blinded, double-placebo, randomised controlled clinical trial. 144 eligible participants with knee osteoarthritis will be randomly assigned to two different groups in a 1:1 ratio. Participants in the moxibustion group will undergo active moxibustion plus placebo gel, whereas participants in the control group will receive diclofenac sodium gel plus placebo moxibustion. Each participant will receive 12 sessions of active/placebo moxibustion at three acupoints (ST35, ST36 and EX-LE4) as well as 2 months of follow-up. Diclofenac sodium gel or placebo gel at a dose of 4 g per knee will be applied three times per day for 4 weeks. The primary outcome measure will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score change at the end of the intervention period from baseline. The secondary outcome measures include changes of other subscales (pain, stiffness and function) of WOMAC, visual analogue scale and patient globalassessment. The safety of moxibustion and diclofenac sodium gel will be assessed at every visit. Ethics and dissemination This trial has been approved by the Sichuan Regional Ethics Review Committee (permission number: 2015KL-014). The results of this study are expected to provide clinical evidence on the efficacy of moxibustion for pain relief and physical function improvement in patients with knee osteoarthritis. The findings will be submitted for publication in peer-reviewed medical journals and presented at relevant academic conferences. Trial registration number NCT02769572.

Background and purpose Tai chi has been suggested as a potential effective intervention for improving function and wellbeing in breast cancer patients. This systematic review evaluated the current evidence for the effectiveness of tai chi in patients with breast cancer. Methods Randomized Controlled Trials (RCTs) evaluating the effects of tai chi in breast cancer patients were identified through searches in OVID MEDLINE, AMED, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, CNKI, VIP, and Wanfang Data, up to June 2019. Meta-analyses were performed for results syntheses. Results Sixteen RCTs involving 1268 participants were included in this review. It was demonstrated that tai chi is no different from conventional supportive care interventions in improving fatigue, sleeping quality, depression or body mass index at either 3 months or 6 months; however it significantly improves overall quality of life (QoL) at 3 months. Moreover, tai chi, when offered as an adjunct to conventional therapy, is more effective in improving fatigue at 3 months, and QoL at 3 months and 6 months compared to conventional therapy alone. Conclusion Tai chi shows no improvement in fatigue compared with conventional supportive interventions, but it significantly relieves fatigue symptom for breast cancer patients when used with conventional supportive care interventions. Tai chi versus conventional supportive care interventions, and as an adjunct to conventional therapy is effective in improving QoL for breast cancer patients.

Background: Acupuncture therapy is frequently used to treat Knee Osteoarthritis (KOA) in clinic, and usually used local acupoints near the diseased knees as therapeutic targets. Some local acupoints appeared sensitization phenomenon which was called sensitized acupoints, which were regarded as important therapeutic targets to get better therapeutic effect on clinic. Therefore, it is necessary to explore the biological basis of acupoint sensitization. Meanwhile, there is a lack of an analysis of the metabolism for sensitized acupoints in KOA patients. Considering that acupuncture effect could be multi-targeted, omics (such as metabolomics) may be a useful method to reveal the relationship between sensitized acupoints and clinical efficacy of acupuncture. Methods and analysis: This study is a parallel design trial. Thirty KOA patients and 30 healthy volunteers will be recruited in this study. Mechanical pain threshold will be measured by Electron Von frey in order to confirm the highest sensitized acupoints. Then collect tissue fluid from the highest sensitized acupoints by micro dialysis technical, then apply electro-acupuncture method on the highest sensitized acupoints to treat KOA patients, after 20 sessions treatments, measure and collect again. Liquid chromatography-tandem mass spectrometry method will be used to analyze the metabonomics of dialysate. Results: This study will provide a high-quality evidence to reveal the local molecular mechanism of acupuncture sensitized acupoints for patient with KOA. Conclusion: This study will provide up-date evidence of whether acupuncture sensitized acupoints have local molecular mechanism for KOA. Trial registration number: NCT03599180 (24 Jul. 2018)

The aim of this study was to determine whether variation of temperature during moxibustion would generate division of analgesic effect. The moxibustion with different temperatures (37°C, 42°C, 47°C, and 52°C) was applied to ST36 acupoint for 30 minutes in chronic inflammatory or neuropathic pain mice. The analgesic effect was evaluated by thermal hyperalgesia test in chronic inflammatory pain and by mechanical allodynia in neuropathic pain, respectively. The results indicated that interventions of moxibustion with different temperature caused different analgesic effect on either chronic inflammatory induced by injection of complete Freund’s adjuvant (CFA) or neuropathic pain induced by spared nerve injury (SNI). In chronic inflammatory pain, different moxibustion temperature generated different intensity of analgesic effect: the higher the better. In chronic neuropathic pain, stronger analgesic effect was found in moxibustion with temperature 47°C or 52°C other than 37°C and 42°C. However, there is no significant difference displayed between moxibustion temperatures 47°C and 52°C or 37°C and 42°C. It implies that the temperature should be taken into account for moxibustion treatment to chronic inflammatory or neuropathic pain.