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Major depressive disorder is the most common mental disorder with significant economic burden and limited treatments. Acupuncture has emerged as a promising non-pharmacological treatment for reducing depressive symptoms. However, the potential mechanisms and clinical effectiveness of acupuncture are not fully understood. This review aimed to: (1) summarize the available evidence on the mechanisms and clinical effectiveness of acupuncture for depression, and then (2) compare with pharmacological interventions, guiding future studies. Studies with animal models of depression and patients have shown that acupuncture could increase hippocampal and network neuroplasticity and decrease brain inflammation, potentially to alleviating depressive disorders. Overall clinical studies indicated that acupuncture could relieve primary depression, particularly milder cases, and was helpful in the management of post-stroke depression, pain-related depression, and postpartum depression both as an isolated and adjunct treatment. It was emphasized that acupuncture combined with antidepressant pharmacological treatment not only enhanced the improvement of primary and secondary depressive symptoms but also reduced the side effects of the medical treatment, which is the main cause for high dropout rates with drug treatment. In summary, substantial evidence from animal and human researches supported the beneficial effect of acupuncture in depression. However, most clinical trials of acupuncture were small, and it is unclear whether their findings can be generalized, so more studies are needed.

Acupuncture can regulate peripheral inflammatory response mainly through somatosensory-vagal/sympathetic nerve-splenic/adrenal/local reflex pathway. Besides, acupuncture may also play an anti-inflammatory role through gut microbiota and neuro-endocrine pathway. The effects of acupuncture have acupoint specificity and time window effect, and are influenced by voltage, current and frequency of electroacupuncture. Future research should focus on the connection and interaction of multiple targets, pathways and mechanisms in the brain, and clarify the multi-target advantages of acupuncture anti-inflammatory.针刺主要通过躯体感觉神经-迷走/交感神经-脾/肾上腺/局部反射通路发挥调节外周炎性反应效应，还能通过肠道菌群和神经-内分泌通路产生作用。针刺的作用具有穴位特异性和时间窗效应，且受电针的电压/电流/频率影响。未来研究应关注多靶点、多途径、多机制在脑中的联系与交互，明确针刺抗炎的多靶点优势。.

Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI. Methods: Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, α7 nicotinic acetylcholine receptor (α7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of α7nAChR antagonists (methyllycaconitine and α-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABAA) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABAA receptor) or muscimol (agonist of GABAA receptor) were assessed. Results: EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABAA receptor in DMV to ameliorate inflammation. Conclusions: The present study revealed that EA of hindlimb regions inhibited the expression of GABAA receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of α7nAChR-mediated JAK2/STAT3 signaling pathway.

OBJECTIVE To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA). METHODS In this multicenter, randomized, sham-controlled trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent-to-treat population, which included all randomized participants who had ≥1 post-baseline measurement. RESULTS Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between-group differences were 13.0% (97.5% confidence interval [97.5% CI] 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI -1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26. CONCLUSION Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow-up.

Background Research on the effect of acupuncture has been limited. Whether the effect of acupuncture is equivalent to placebo has been the focus of debate in this field. This study will explore the specific and non-specific effects of acupuncture for knee osteoarthritis (KOA) by functional magnetic resonance imaging (fMRI). Methods and design Ninety participants diagnosed with KOA will be randomly divided into the acupuncture group, sham acupuncture group, and waiting list group in a ratio of 1:1:1. Except for the waiting list group, the other participants will receive acupuncture or sham acupuncture three sessions per week for 4 weeks respectively. The primary outcome will be the response rate which is defined on an individual basis as at least a 2-point decrease in the numerical rating scale (NRS) of pain at the end of intervention period compared with the baseline. fMRI scans will be performed at baseline and the end of the intervention period to examine the response of various brain regions. The secondary outcomes will include the Western Ontario and McMaster Osteoarthritis Index (WOMAC), State-Trait Anxiety Scale-State Anxiety Subscale (STAI-S), and Stanford Expectations of Treatment Scale (SETS). Pearson’s correlation coefficient will be performed to investigate the changes in brain activity and clinical variables. Discussion The results of our study will help to evaluate the specific and nonspecific effects of acupuncture combined with clinical and brain function changes based on KOA. Trial registration Chinese Clinical Trial Registry ChiCTR1900025799. Registered on 9 September 2019.

Objective: We aimed to explore the feasibility of evaluating the comparative effectiveness and safety of electroacupuncture (EA) relative to manual acupuncture (MA) for the treatment of knee osteoarthritis (KOA). Methods: A multicenter randomized controlled clinical trial was conducted in Beijing from September 2017 to January 2018. A total of 60 participants with KOA were randomly allocated to either EA ( n = 30) or MA ( n = 30) groups. Participants in the EA group were treated with EA at six to seven local traditional acupuncture points or ah shi points, and two to three distal points. Participants in the MA group had the same schedule as the EA group except that the electrical apparatus featured a working power indicator without actual current output, constituting a sham EA procedure, in order to blind participants. Both groups received 24 sessions over 8 weeks. The primary outcome was response rate, defined as a change of ⩾50% from baseline in the total scores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) after 8 weeks. Secondary outcomes included pain, stiffness, function, quality of life, and acupuncture-related adverse events (AEs) at 4 and 8 weeks. Results: Of 60 participants randomized, 53 (88%) completed the study. Response rates were 43% for the EA group and 30% for the MA group by the intention-to-treat analysis. Although significant differences were observed in WOMAC pain, stiffness, and function scores within both groups, between-group differences at 8 weeks did not reach statistical significance (odds ratio = 1.75 (95% confidence interval = 0.593–5.162)). Rates of AEs were low and similarly distributed between groups. Conclusion: Both EA and MA interventions in KOA were feasible and appeared safe. Whether or not EA may have a stronger impact on pain and function requires further evaluation through larger, adequately powered, randomized controlled trials. Trial registration number: NCT03274713.

Although, acupoint specificity is regarded as the core of scientific issues in electroacupuncture (EA), the difference of EA on treating functional dyspepsia (FD) at different acupoints is unclear. Therefore, this study aims to investigate the different therapeutic effects of EA at lower extremity or abdominal acupoints on the mucosal integrity and lower-inflammatory response in FD. The intragastric administration of iodoacetamide (IA) was performed in 48 rats to establish the FD model. These rats were randomly divided into the control group, the model group and the six EA groups receiving stimulation at the lower extremity (ST36, ST37, and ST39) or abdominal acupoints (ST25, CV4, and CV12) separately. The open-field test (OFT) was measured after 8 weeks of IA, and gastric emptying was evaluated after 10 days of the EA treatment. The local inflammation markers of CD45, eosinophil major basic protein (EMBP), and the tight junction proteins ZO1 and Claudin3 were assessed by immunofluorescence in all groups. Western blot analysis showed that the EMBP and Occludin1 levels in the duodenal. EA at lower extremity acupoint ST36 could improve the gastric emptying. EA at lower extremity acupoints reduced the immunoreactivity of EMBP, but the CD45 was reregulated by the ST37 and ST39 acupoints. The lower extremity acupoints also ameliorated FD-tight junction protein in the expression of Claudin3 and ZO1. However, only the ST36 suppressed the expression of EMBP and recovered the expression of Occludin1. Similarly, the effect of EA at abdominal acupoints was not obvious either in facilitating gastric motility or in improving inflammatory and mucosal injury. EA at lower extremity and abdominal acupoints with the same stimulation parameters had different therapeutic effects in gastric emptying, intestinal mucosal integrity, and inflammation response, thus proving the specificity of acupoints.

Taking the clinical trial of acupuncture in treatment of postprandial distress syndrome as an example, this paper proposes that the acupuncture clinical trial protocol should be optimized in view of acupuncture prescription, acupuncture frequency and outcomes. Besides, the data quality of acupuncture clinical trial should be improved in consideration of data sharing and electronic data capture so as to provide a reference for the majority of researchers to optimize and implement acupuncture clinical trial.结合针刺治疗餐后不适综合征案例，提出从针刺治疗处方、针刺治疗频次、结局指标方面完善针刺临床研究方案，从数据共享和电子数据采集角度提升针刺临床研究数据质量，为广大科研工作者优化和实施针刺临床研究提供参考。.

To comprehensively shed light on whether viewing football games is associated with a higher risk of cardiovascular disease (CVD). Electronic databases were searched through 17 May 2018. All studies focusing on the association between viewing football matches and the fatal or non-fatal CVD were identified. Viewing football matches was associated with a higher risk of fatal overall CVD (RR: 1.06, 95%CI: 1.01-1.12) in both men (RR: 1.13, 95%CI: 1.004-1.28) and women (RR: 1.08, 95%CI: 1.01-1.15). Subgroup analysis showed that failure of the team has a higher risk of fatal overall CVD (RR: 1.29, 95%CI: 1.15-1.45). However, lower risk of fatal overall CVD from spectators was observed when team obtained a victory (RR: 0.80, 95%CI: 0.66-0.96). For non-fatal CVD, viewing football matches was associated with a higher risk of non-fatal overall CVD (RR: 1.24, 95%CI: 1.09-1.41) in both men (RR: 1.73, 95%CI: 1.12-2.69) and women (RR: 1.25, 95%CI: 1.08-1.45). Subgroup analysis showed that viewing football matches was associated with a higher risk of non-fatal myocardial infarction (RR: 1.20, 95%CI: 1.04-1.38) in both men and women (RR: 1.51, 95%CI: 0.99-2.28; RR: 1.21, 95%CI: 1.08-1.36, respectively). No significant increase was found in fatal or non-fatal stroke. Viewing football matches was associated with a higher risk of the fatal and non-fatal CVD, especially in male spectators. The victory of team could have a lower risk of fatal CVD. Therefore, precautionary measures should be required for the reduction of healthcare burden in football matches.

Background: Acupuncture is a widely used treatment for knee osteoarthritis, but evidence of its effectiveness from randomised controlled trials (RCTs) is contradictory. Objective: To systematically review RCTs to determine whether the effect of acupuncture is dose dependent for symptom management in knee osteoarthritis. Methods: Seven English/Chinese databases were searched through January 2017. Study quality was assessed using the Cochrane Collaboration tool. Slavin’s qualitative best-evidence synthesis approach was used to provide methodological rigour. Included RCTs were separated into three categories according to the dose of acupuncture treatment: high dosage (HD), medium dosage (MD) and low dosage (LD). Correlation between dose and effect of treatment was analysed. Results: Eight RCTs with a total of 2106 subjects met the eligibility criteria. Numbers of studies using the various doses of acupuncture were 1 for LD, 1 for MD and 6 for HD, respectively. Compared with LD and MD acupuncture treatments, strong evidence showed that there was a positive correlation between HD acupuncture treatment and positive outcomes. Conclusion: The effect of acupuncture may be associated with dose of acupuncture, with a higher dosage related to better treatment outcomes in terms of relief of pain and dysfunction in patients with knee osteoarthritis.

OBJECTIVES: This study aimed to assess the clinical benefit of device therapy on controlling the symptoms of Meniere’s disease (MD). MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Internet, and Wanfang Data before January 13, 2018. We selected randomized controlled clinical trials, case-controlled studies, and cohort studies that dealt with outcomes of device therapy for the treatment of MD. RESULTS: Sixteen trials met our inclusion criteria. The use of device therapy resulted in improved vertigo control, which was described as a reduction in the number of vertigo days by month (weighted mean difference [WMD]: 3.15, 95% confidence interval [CI]: 2.00–4.31), in the number of vertigo episodes by month (WMD: 7.37, 95% CI: 2.40–12.35), and in the vertigo visual analog score (WMD: 41.51, 95% CI: 34.68–48.34). In addition, the overall complete vertigo control (class A) rate was 50% (95% CI: 37%–64%). The device therapy also reduced the number of sick days by month (WMD: 4.56, 95% CI: 2.15–6.97), and the functional level improved (WMD: 2.66, 95% CI: 2.15–3.17). The electrocochleographic parameters decreased. The device therapy proved beneficial for hearing changes (WMD: 3.19, 95% CI: 0.66–5.71). No publication bias was found in the funnel plot and the results of Egger’s test. CONCLUSION: This study showed that the device therapy might reduce vertigo attacks and sick days in patients with MD. Additionally, the function level and hearing level may improve after the device therapy. In addition, the decrease in electrocochleographic parameters showed that inner ear electrophysiology improved after device therapy.

Objective: To evaluate the effectiveness of acupuncture in patients with vascular cognitive impairment no dementia (VCIND) in comparison with citicoline, an agent for cognitive disturbances associated with chronic cerebral disorders. Design: A randomized controlled multicenter trial. Setting: In three hospitals in Beijing, China. Subjects: A total of 216 patients with VCIND were recruited. Interventions: Patients with VCIND (mean age of 65.4 years) were randomized to receive acupuncture (two sessions per week) or oral citicoline (100 mg three times daily) over three months. Main measures: The primary outcome was the change from baseline to three months in cognitive symptom, measured by Alzheimer’s disease Assessment Scale, cognitive subscale (ADAS-cog). Secondary outcomes included changes from baseline to six months in ADAS-cog, executive function measured by the Clock Drawing Test (CDT), and functional disability measured by the Ability of Daily Living (ADL) scale at three and six months. Results: At three months, the acupuncture group had a greater decrease in mean ADAS-cog score (−2.33 ± 0.31) than the citicoline group (−1.38 ± 0.34) with a mean difference of −0.95 (95% CI, −1.84 to −0.07, P = 0.035). The mean change from baseline to six months in ADAS-cog also significantly favored acupuncture treatments (acupuncture change −2.61 vs citicoline −1.25, difference: −1.36 points; 95% CI, −2.20 to −0.51; P = 0.002). There was no difference between the two groups on CDT and ADL scores at either time point. Conclusion: Compared with citicoline, acupuncture has comparable and even superior efficacy with improved cognitive and daily living performance as a complementary and alternative medicine treatment for VCIND.

RNA-binding proteins (RBPs) have been shown to be dysregulated in cancer transcription and translation, but few studies have investigated their mechanism of action in soft tissue sarcoma (STS). Here, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to identify differentially expressed RBPs in STS and normal tissues. Through a series of biological information analyses, 329 differentially expressed RBPs were identified. Functional enrichment analysis showed that differentially expressed RBPs were mainly involved in RNA transport, RNA splicing, mRNA monitoring pathways, ribosome biogenesis and translation regulation. Through Cox regression analyses, 9 RBPs (BYSL, IGF2BP3, DNMT3B, TERT, CD3EAP, SRSF12, TLR7, TRIM21 and MEX3A) were all up-regulated in STS as prognosis-related genes, and a prognostic model was established. The model calculated a risk score based on the expression of 9 hub RBPs. The risk score could be used for risk stratification of patients and had a high prognostic value based on the receiver operating characteristic (ROC) curve. We also established a nomogram containing risk scores and 9 key RBPs to predict the 1-year, 3-year, and 5-year survival rates of patients in STS. Afterwards, methylation analysis showed significant changes in the methylation degree of BYSL, CD3EAP and MEX2A. Furthermore, the expression of 9 hub RBPs was closely related to immune infiltration rather than tumor purity. Based on the above studies, these findings may provide new insights into the pathogenesis of STS and will provide candidate biomarkers for the prognosis of STS.

IntroductionPostoperative ileus (POI) is an inevitable complication of almost all abdominal surgeries, which results in prolonged hospitalisation and increased healthcare costs. Various treatment strategies have been developed for POI but with limited success. Electroacupuncture (EA) might be a potential therapy for POI. However, evidence from rigorous trials that evaluated the effectiveness of EA for POI is limited. Thus, the aim of this study was to examine whether EA can safely reduce the time to the first defecation after laparoscopic surgery in patients with POI.Methods and analysisThis multicentre randomised sham-controlled trial will be conducted in four hospitals in China. A total of 248 eligible participants with colorectal cancer who will undergo laparoscopic surgery will be randomly allocated to an EA group and a sham EA group in a 1:1 ratio. Treatment will be performed starting on postoperative day 1 and continued for four consecutive days, once per day. If the participant is discharged within 4 days after surgery, the treatment will cease on the day of discharge. The primary outcome will be the time to first defecation. The secondary outcome measures will include time to first flatus, tolerability of semiliquid and solid food, length of postoperative hospital stay, postoperative nausea and vomiting, abdominal distension, postoperative pain, postoperative analgesic, time to first ambulation, blinding assessment, credibility and expectancy and readmission rate.Ethics and disseminationEthics approval was obtained from the Ethics Committee of Beijing University of Chinese Medicine (number 2020BZHYLL0116) and the institutional review board of each hospital. The results will be disseminated through peer-reviewed publications. This study protocol (V.3.0, 6 March 2020) involves human participants and was approved by the ethics committees of Beijing University of Chinese Medicine (number 2020BZHYLL0116), Beijing Friendship Hospital Affiliated to Capital Medical University (number 2020-P2-069-01), Beijing Chao-Yang Hospital Affiliated to Capital Medical University (number 2020-3-11-2), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (number 20/163-2359), and the Affiliated Hospital of Qingdao University (number QYFYKYLL711311920). The participants gave informed consent to participate in the study before taking part.Trial registration numberChiCTR2000038444.

White matter lesions induced by chronic cerebral hypoperfusion are associated with cognitive impairment in vascular dementia (VaD). Previous studies have shown that acupuncture can ameliorate the cognitive deficits of individuals with VaD. However, the neuroimaging mechanisms of acupuncture on white matter perfusion and integrity remain elusive. In this study, the VaD model was induced by bilateral common carotid arteries occlusion (BCCAO) in rats. Novel object recognition task and Morris water maze were performed to evaluate short-term memory and spatial learning and memory. Arterial spin labeling and diffusion tensor imaging (DTI) were used to measure the cerebral blood flow (CBF) and the white matter integrity. Pathological examinations detected the myelin loss and concomitant neuroinflammation. The results demonstrate that BCCAO rats with reduced CBF exhibited worse performance and altered DTI parameters, including decreased fractional anisotropy, increased radial diffusivity, and axial diffusivity in white matter regions. Acupuncture ameliorated cognitive impairment, increased CBF, and protected the myelin sheath integrity but not the axons of BCCAO rats. These protective effects of acupuncture on white matter were significantly correlated with improved CBF. Pathological examination confirmed that the loss of myelin basic protein and microglial accumulation associated IL-1β and IL-6 production were attenuated by acupuncture treatment. Our findings suggest that acupuncture protects cognitive function of BCCAO rats by improving white matter perfusion and integrity.

Objectives: The objectives of this study were to identify the mean safe needling depth and angle at BL40 between subjects, taking into account variables including sex and body mass index (BMI). Methods: One hundred and twenty-four participants who had undergone magnetic resonance imaging (MRI) examination of the knee region for clinical indications were included in this study. BL40 needling sites were localized by World Health Organization (WHO) standards and were measured by MRI. As much as 70% of the value of AN (from the needle insertion point to the popliteal artery) was considered to represent the safe depth, and angle alpha between the BL40 straight line and the AN line was regarded as the safe angle. Results: Overall, mean safe depth regardless of BMI and sex was 18.51 ± 3.56 mm (95% confidence interval (CI), 17.88%–19.14%). Mean safe depth was 17.24 ± 3.14 mm in the low and normal BMI group, 18.76 ± 2.90 mm in the overweight group, and 22.01 ± 3.71 mm in the obese group. Thirteen patients (10.5%) had internal deviation of angle alpha (95% CI, 5.6%–15.3%), while 111 patients (89.5%) had external deviation (95% CI, 84.7%–94.4%). The mean internal and external deviations of angle alpha were 8.78° ± 2.92° (95% CI, 7.01°–10.55°) and 9.75° ± 3.46° (95% CI, 9.10°–10.41°), respectively. Conclusion: We would suggest that, when using a straight needle insertion at BL40, it is safe to advance a 25-mm needle approximately 12.5 mm, and 17.5 mm should be safe for patients with BMI greater than 28 kg/m2. Practitioners should decrease the depth of penetration when treating patients of low body weight or height.

Ischemic stroke is the major type of cerebrovascular disease usually resulting in death or disability among the aging population globally. Oxidative stress has been closely linked with ischemic stroke. Disequilibrium between excessive production of reactive oxygen species (ROS) and inherent antioxidant capacity leads to subsequent oxidative damage in the pathological progression of ischemic brain injury. Acupuncture has been applied widely in treating cerebrovascular diseases from time immemorial in China. This review mainly lays stress on the evidence to illuminate the possible mechanisms of acupuncture therapy in treating ischemic stroke through regulating oxidative stress. We found that by regulating a battery of molecular signaling pathways involved in redox modulation, acupuncture not only activates the inherent antioxidant enzyme system but also inhibits the excessive generation of ROS. Acupuncture therapy possesses the potential in alleviating oxidative stress caused by cerebral ischemia, which may be linked with the neuroprotective effect of acupuncture.

To systematically review the effect of acupuncture on emotional disorder in the patients with migraine and knee osteoarthritis and its effect time limit.The randomized controlled trials of acupuncture for migraine or knee osteoarthritis were retrieved from the databases, starting from the time of establishment through to December, 2018, i.e. the Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP and Wanfang. The bias risk assessment tool of Cochrane Review Manual 5.1.0 was adopted to evaluate the quality of trials in methodology. RevMan 5.3 software was used for the Meta-analysis.A total of 12 articles were included, with 2450 cases. Regarding the immediate effect, the score of the emotional function subscale of migraine-specific quality-of-life questionnaire (MSQ) in the acupuncture group was higher than the control group (6.38[2.78,9.98],Acupuncture effectively maintains the healthy emotion in the patients with migraine and the effect is sustainable for 3 months after treatment. But the improvement of acupuncture is not remarkable in emotional disorder induced by knee osteoarthritis.

This 16-week randomised controlled trial (8-week treatment followed by 8-week follow-up) evaluated the symptomatic improvement in patients with knee osteoarthritis on 3 sessions per week of acupuncture (TSWA) compared to 1 session per week of acupuncture (OSWA). Sixty participants were randomised to either the TSWA or the OSWA group in a 1:1 ratio. The primary outcome was response rate, defined as the percentage of participants achieving ≥2 points decrease on the numerical rating scale (NRS) and ≥6 points decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Additional outcomes included response rates at weeks 4 and 16, NRS, WOMAC, Patient Global Assessment, 12-item Short Form Health Survey (SF-12), and treatment credibility and expectancy. No significant difference was seen in response rate between TSWA and OSWA groups at week 8 (64.7% vs 50.0%; difference, 14.7 percentage points [95% CI, -10.1 to 39.4 percentage points], P = 0.435). At weeks 4 and 16, the TSWA group had higher response rates than the OSWA group (week-4: difference, 44.7 percentage points [95% CI, 23.2-66.1 percentage points], P = 0.001; week-16: difference, 46.0 percentage points [95% CI, 24.4-67.6 percentage points], P < 0.001). Participants in the TSWA group experienced significantly greater improvements in NRS, WOMAC function, and Patient Global Assessment than those in the OSWA group. There were no significant between-group differences in WOMAC stiffness and SF-12. In summary, TSWA immediately improved knee pain and dysfunction compared with OSWA. In addition, the benefit of TSWA persists throughout follow-up.

BACKGROUND: The survival of early placement (within 72h after admission) of transjugular intrahepatic portosystemic shunts (early-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) is controversial. OBJECTIVES: We performed a systemic review and meta-analysis to assess whether early-TIPS could improve survival in patients with cirrhosis and acute variceal bleeding. METHODS: Systematic search of the literature was conducted from PubMed, EMBASE, and Cochrane Library published before June 25, 2019 for eligible studies that compared early-TIPS with a combination of endoscopic variceal ligation (EVL) or endoscopic injection sclerotherapy (EIS) plus pharmacotherapy in the therapeutic effect in AVB patients. RESULTS: A total of 5 studies with 1,754 participants were enrolled. The early-TIPS demonstrated a significant improvement in prevention of treatment failure (OR=0.11,95%CI=0.05-0.23), 6-weeks mortality (OR=0.24,95%CI=0.13-0.46), rebleeding within 6 weeks (OR=0.21,95%CI=0.12-0.36), rebleeding within 1 year (OR=0.16,95%CI=0.07-0.36), new or worsening ascites (OR=0.33,95%CI=0.21-0.53), except in encephalopathy (OR=1.29,95%CI=0.996-1.67). For 1-year mortality, significant prior effect was also observed in early-TIPS (OR=0.64,95%CI=0.46-0.90), and the beneficial effect in Child-Pugh C patients (OR=0.35,95%CI=0.18-0.68) was equal to Child-Pugh B patients (OR=0.34,95%CI=0.25-0.58). No difference in liver transplantation and mortality caused by liver failure was observed. CONCLUSSIONS: Early covered-TIPS could be recommended for the management of AVB patients in cirrhosis with demonstrating a significant improvement in treatment failure, both short- and long-term mortality, rebleeding risk, and new or worsening ascites compared to standard therapy, especially for the high-risk AVB patients. It will also apply to patients in Child-Pugh A until the solutions to prevent hepatic encephalopathy in future researches were found.

Background: The current clinical guidelines on post-traumatic stress disorder (PTSD) recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) of drugs. However, there is uncertainty about the efficacy of other drugs and selecting which treatments work best for which patients. Therefore, we aimed to estimate efficacy and acceptability of pharmaceutical management for adults with PTSD. Methods: We searched the Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and ISIWeb of Science for randomized controlled trials (RCTs) until June 21, 2019. We included placebo-controlled and active-comparators trials of pharmaceutical management for adults with PTSD diagnosed according to standard operationalized criteria. The outcomes were defined as efficacy (improvement in symptoms of PTSD, based on evaluation results of clinician rating scales or interview instruments; core symptoms, including re-experiencing, avoidance, and hyperarousal; other symptoms, including depression and anxiety) and acceptability (all-cause discontinuation, and discontinuation due to adverse effects). Findings: 66 studies with 78 trials comprising of 8,083 patients diagnosed with PTSD were identified. There were two kind of comparisons in included studies, one of them was the comparison between 31 active drugs and placebo, another comparison was active-comparator between 12 active drugs aiming at exploring the differences among different drugs. In terms of efficacy, all active drugs demonstrated superior effect than placebo (SMD = -0.33, 95%CI: -0.43 to -0.23). The medications were superior to placebo in reducing the symptom of re-experiencing, avoidance, hyperarousal, depression, and anxiety. For acceptability, medicine interventions for PTSD showed no increase in all-cause discontinuation compared with placebo (RR = 0.95, 95%CI: 0.88 to 1.03). Nevertheless, in terms of safety, medicine interventions indicated a higher risk of adverse effect compared with placebo (RR = 1.47, 95%CI: 1.24 to 1.75). Compared with placebo, the SSRIs and atypical antipsychotics drugs had significant efficacy whether in patients with severe or extremely severe PTSD status. However, only atypical antipsychotics (SMD = -0.29, 95%CI: -0.48 to -0.10) showed superior efficacy than placebo in veterans. Interpretation: Medication management could be effective in intervention of PTSD, which demonstrated a sufficient improvement in the core symptoms. This meta-analysis supports the status of SSRIs and SNRIs as recommended pharmacotherapy for PTSD. However, patients with different clinical characteristics of PTSD should consider individualized drug management. Furthermore, more high-quality researches are required to confirm these findings. Funding Statement: The authors stated that no funding was received for this research. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The authors used the guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement.

As a component of traditional Chinese medicine (TCM), acupuncture has the potential to lower blood pressure (BP) in patients with hypertension. Emerging evidence indicates that the acupuncture-induced inhibition of high BP occurs through the activation of the pathway in the afferent, central, and efferent pathways. An increasing number of studies have demonstrated that acupuncture not only activates distinct brain regions under conditions of hypertension caused by an imbalance between the sympathetic and parasympathetic systems but also modulates neurotransmitters in related brain regions to alleviate the autonomic response. The activity of these pathways can be assessed by injecting agonists or inhibitors or by performing neurotomy. This review focuses on the clinical and mechanistic studies of acupuncture in modulating BP, which might provide a neurobiological foundation for the effects of acupuncture. Although many mechanisms underlying the effects of acupuncture on cardiovascular function have been identified, further investigation is warranted.

Background: White matter lesions induced by chronic cerebral hypoperfusion (CCH) are common pathological changes, and are associated with cognitive impairment in vascular dementia (VaD). It has been reported that acupuncture can improve cognitive deficits of VaD rats through increasing cortical cerebral blood flow and attenuating neuroinflammation. However, the effects of acupuncture on white matter perfusion and white matter structural integrity have been not investigated. Methods: VaD was induced by bilateral common carotid arteries occlusion (BCCAO) in Wistar rats. Morris water maze (MWM) was used to evaluated the spatial learning and memory of rats. Arterial spin labeling imaging (ASL) and diffusion tensor imaging (DTI) were performed to measure the cerebral blood flow and white matter integrity in corpus callosum, external capsule, internal capsule, optic nerve and optic tract. Pathological staining was also applied to detect the myelin loss and neuroinflammation. Results: BCCAO rats with declined cerebral blood flow exhibited significant worse MWM performance, and altered DTI parameters including decreased fractional anisotropy, elevated radial diffusivity and axial diffusivity in white matter regions. After acupuncture treatment at GV20 and ST36, cognitive dysfunction, disruption of white matter perfusion and integrity were reversed. Pathological results supported that acupuncture could attenuate the loss of myelin sheath and microglia activation. Conclusions: Our findings suggest that acupuncture treatment protects cognitive impairment of BCCAO rats through increasing subcortical white matter perfusion and improving white matter lesions. Keywords: Acupuncture; ASL; DTI; cerebral blood flow; white matter; microglia activation

IntroductionKnee osteoarthritis (KOA) is one of the leading causes of disability. The effectiveness of acupuncture for treating KOA remains controversial. This protocol describes the method of a systematic review and meta-analysis evaluating the effectiveness and safety of acupuncture for treating KOA.Methods and analysisFour English databases (PubMed, Embase, Cochrane Library databases and Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, and Wanfang) will be searched from the database inception to 1 September 2021. All randomised controlled trials related to acupuncture for KOA will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be pain intensity. Risk of bias will be assessed using the Cochrane Collaboration’s tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The strength of recommendations and quality of evidence will be assessed using the Grading of Recommendations Assessment Development and Evaluation working group methodology.Ethics and disseminationEthics approval is not required because individual patient data are not included. This protocol was registered in the international Prospective Register of Systematic Reviews on 25 February 2021. The systematic review and meta-analysis will be submitted for publication in a peer-reviewed journal. The findings will also be disseminated through conference presentations.Trial registration numberCRD42021232177.

Emerging evidence suggests that acupuncture treatment has anti-oxidative effects that affect cognitive impairment in vascular dementia (VD) rats. In the present study, we aimed to investigate whether thioredoxin-1 (Trx-1)/thioredoxin reductase-1 (TrxR-1) was involved in the beneficial effects of acupuncture. After 2-weeks of acupuncture treatment, Morris water maze (MWM), dihydroethidium (DHE) staining, Nissl staining and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to assess the effects of acupuncture on cognitive function and hippocampal neuronal injury in two-vessel occlusion (2VO) model. The protein and mRNA levels of Trx-1 and TrxR-1, the activity of TrxR-1 as well as the phosphorylation of the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway were measured by Western blot, real-time PCR analysis, TrxR-1 activity analysis and immunofluorescence (IF) staining respectively. We found that there were oxidative and apoptotic injury in the CA1 area, accompanied with the decreased expressions of Trx-1 and TrxR-1 in the hippocampus. Acupuncture ameliorated cognitive deficits caused by cerebral ischemic injury and inhibited oxidative stress and neuronal apoptotic injury in the hippocampus. Acupuncture also up-regulated the expressions of Trx-1 and TrxR-1, increased the activity of TrxR-1, accompanied with inhibiting the activation of the ASK1-JNK/p38 pathway. However, the effects of acupuncture on improving cognitive function, inhibiting oxidative stress and neuron apoptotic damage were blocked by Trx-1siRNA. In conclusion, these findings indicated that acupuncture treatment improved VD though anti-oxidative and anti-apoptotic mechanisms which involved the up-regulations of Trx-1/TrxR-1 and inhibitions of ASK1-JNK/p38 pathway.

Background This study aims to determine whether 3 sessions per week of acupuncture treatment is superior to 1 session per week of acupuncture treatment for symptomatic outcomes in knee osteoarthritis. Methods/design This is a two parallel-group, assessor-blinded, randomized controlled trial. Sixty patients with knee osteoarthritis (Kellgren–Lawrence grade II or III) will be recruited and randomly allocated to receive 24 or 8 sessions (group M or group L) of acupuncture treatment in a 1:1 ratio. Patients in group M will receive 3 sessions per week of acupuncture for 8 weeks. Patients in group L will receive acupuncture once per week for 8 weeks. The primary outcome is the response rate—the percentage of patients achieving a decrease ≥ 2 points on a numerical rating pain scale and a decrease ≥ 6 points in the Western Ontario and McMaster Universities Osteoarthritis Index function score at 8 weeks compared with baseline. Secondary outcomes include pain, function, overall effect, quality of life, and treatment credibility and expectancy. Discussion Three sessions per week of acupuncture treatment may be superior to 1 session per week of acupuncture treatment for symptomatic outcomes in knee osteoarthritis. Results of the study will be of great importance for the guidelines of clinical therapy. Trial registration Clinicaltrials.gov, NCT03359603. Registered on 1 December 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3528-8) contains supplementary material, which is available to authorized users.

To summarize the research status and influencing factors of the time-effect of acupuncture and to explain and analyze the optimal effect timing of acupuncture, and provide reference for obtaining the best clinical therapeutic effect.Literature regarding the studies of the time-effect of acupuncture published from January 2000 to August 2018 was searched, concluded and analyzed in CNKI, WANFANG, VIP and PubMed databases.A total of 43 papers were included. The time-effect relationship of acupuncture was studied from various aspects: immediate effect, post-effect and total time-effect. The influencing factors of time-effect of acupuncture included needle retention time, acupoint types, number of acupoints and frequency of acupuncture treatment.Even though preliminary achievements have been made in the study of the time-effect of acupuncture, there are many limitations and deficiency. These studies are mostly isolated and unsystematic, and the observation time of needle retention time and post-effect is not long enough to observe the exact best induction period, half-life period and residual effect period of acupuncture.In the future, we should combine the existing research experience and achievements to formulate a more reasonable research plan and observe the entire period of acupuncture in a longitudinal direction.

Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA.This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation.This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals.ClinicalTrials.gov, NCT03274713 . Registered on 20 November 2017.

Background Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA. Methods/design This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation. Discussion This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals. Trial registration ClinicalTrials.gov, NCT03274713. Registered on 20 November 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3138-x) contains supplementary material, which is available to authorized users.

Osteoarthritis (OA) is a joint disease resulting in high rates of disability and low quality of life. The initial site of OA (bone or cartilage) is uncertain. The aim of the current study was to explore biomarkers and pathological processes in subchondral bone samples. The gene expression profile GSE51588 was downloaded from the Gene Expression Omnibus database. Fifty subchondral bone [knee lateral tibial (LT) and medial tibial (MT)] samples from 40 OA and 10 non-OA subjects were analyzed. After data preprocessing, 5439 genes were obtained for weighted gene co-expression network analysis. Highly correlated genes were divided into 19 modules. The yellow module was found to be highly correlated with OA (r = 0.71, p = 1e-08) and the brown module was most associated with the differences between the LT and MT regions (r = 0.77, p = 1e-10). Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment indicated that the yellow module was enriched in a variety of components including proteinaceous extracellular matrix and collagen trimers, involved in protein digestion and absorption, axon guidance, ECM-receptor interaction, and the PI3K-Akt signaling pathway. In addition, the brown module suggests that the differences between the early (LT) and end (MT) stage of OA are associated with extracellular processes and lipid metabolism. Finally, 45 hub genes in the yellow module (COL24A1, COL5A2, COL3A1, MMP2, COL6A1, etc.) and 72 hub genes in the brown module (LIPE, LPL, LEP, SLC2A4, FABP4, ADH1B, ALDH4A1, ADIPOQ, etc.) were identified. Hub genes were validated using samples from cartilage (GSE57218). In summary, 45 hub genes and 72 hub genes in two modules are associated with OA. These hub genes could provide new biomarkers and drug targets in OA. Further studies focusing on subchondral bone are required to validate these hub genes and better understand the pathological process of OA.