Effect of Acupuncture for Methadone Reduction : A Randomized Clinical Trial.

BACKGROUND: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. OBJECTIVE: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. DESIGN: Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123). SETTING: 6 MMT clinics in China. PARTICIPANTS: Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. INTERVENTION: Acupuncture or sham acupuncture 3 times a week for 8 weeks. MEASUREMENTS: The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). RESULTS: Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of -11.7 mm VAS (CI, -18.7 to -4.8 mm; P < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. LIMITATION: Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. CONCLUSION: Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

TNEA therapy promotes the autophagic degradation of NLRP3 inflammasome in a transgenic mouse model of Alzheimer's disease via TFEB/TFE3 activation.

BACKGROUND: The impairment in the autophagy-lysosomal pathway (ALP) and the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome represent two molecular events leading to neurodegeneration and neuroinflammation in Alzheimer's disease (AD), a devastating neurodegenerative disorder without a cure. Previously we demonstrated the cognitive-enhancing effect of a combined electroacupuncture (EA) therapy termed TNEA in a transgenic mouse model of AD, involving activation of transcription factor EB (TFEB), a master regulator of ALP. However, whether and how TNEA inhibits NLRP3 inflammasome via TFEB-mediated ALP in AD remains to be investigated. METHODS: 5xFAD mice overexpressing amyloid-ß (Aß) were treated with TNEA or EA on its composing acupoints (GB13 and GV24). The changes in the signaling pathways regulating NLRP3 inflammasome, the association of NLRP3 inflammasome with ALP, and the roles of TFEB/TFE3 in mice brains were determined by immunoblots, immunohistochemistry and AAV-mediated knockdown assays. RESULTS: TNEA inhibits the activation of NLRP3 inflammasome and the release of active interleukin 1ß (IL1B) in the hippocampi of 5xFAD mice. Mechanistically, TNEA promoted the autophagic degradation of inflammasome components via activating both TFEB and TFE3 by modulating kinases including AMPK and AKT. The composing acupoints in TNEA showed synergistic effects on regulating these molecular events and memory improvement. CONCLUSION: Our findings suggest that TNEA attenuates AD-associated memory impairment via promoting TFEB/TFE3-mediated autophagic clearance of Aß and NLRP3 inflammasome, and partially reveal the molecular basis of combined acupoints therapy originated from ancient wisdom.

Transauricular Vagal Nerve Stimulation at 40 Hz Inhibits Hippocampal P2X7R/NLRP3/Caspase-1 Signaling and Improves Spatial Learning and Memory in 6-Month-Old APP/PS1 Mice.

OBJECTIVES: Transauricular vagal nerve stimulation (taVNS) at 40 Hz attenuates hippocampal amyloid load in 6-month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, but it is unclear whether 40-Hz taVNS can improve cognition in these mice. Moreover, the underlying mechanisms are still unclear. MATERIALS AND METHODS: 6-month-old C57BL/6 (wild type [WT]) and APP/PS1 mice were subjected to 40-Hz taVNS. Novel Object Recognition and the Morris Water Maze were used to evaluate cognition. Hippocampal amyloid-ß (Aß)1-40, Aß1-42, pro-interleukin (IL)-1ß, and pro-IL-18 were measured using enzyme-linked immunosorbent assays. Hippocampal Aß42, purinergic 2X7 receptor (P2X7R), nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), Caspase-1, IL-1ß, and IL-18 expression were evaluated by western blotting. Histologic assessments including immunofluorescence, immunohistochemistry, Nissl staining, and Congo red staining were used to assess microglial phagocytosis, neuroprotective effects, and Aß plaque load. RESULTS: 40-Hz taVNS improved spatial memory and learning in 6-month-old APP/PS1 mice but did not affect recognition memory. There were no effects on the cognitive behaviors of 6-month-old WT mice. taVNS at 40 Hz modulated microglia; significantly decreased levels of Aß1-40, Aß1-42, pro-IL-1ß, and pro-IL-18; inhibited Aß42, P2X7R, NLRP3, Caspase-1, IL-1ß, and IL-18 expression; reduced Aß deposits; and had neuroprotective effects in the hippocampus of 6-month-old APP/PS1 mice. These changes were not observed in 6-month-old WT mice. CONCLUSION: Our results show that 40-Hz taVNS inhibits the hippocampal P2X7R/NLRP3/Caspase-1 signaling and improves spatial learning and memory in 6-month-old APP/PS1 mice.

In Situ Imaging of Formaldehyde in Live Mice with High Spatiotemporal Resolution Reveals Aldehyde Dehydrogenase-2 as a Potential Target for Alzheimer's Disease Treatment.

Alterations in formaldehyde (FA) homeostasis are associated with the pathology of Alzheimer's disease (AD). In vivo tracking of FA flux is important for understanding the underlying molecular mechanisms, but is challenging due to the lack of sensitive probes favoring a selective, rapid, and reversible response toward FA. In this study, we re-engineered the promiscuous and irreversible phenylhydrazines to make them selective and reversible toward FA by tuning their nucleophilicity. This effort resulted in PFM309, a selective (selectivity coefficient KFA,methylglyoxal = 0.06), rapid (t1/2 = 32 s at [FA] = 200 µM), and reversible fluorogenic probe (K = 6.24 mM-1) that tracks the FA flux in both live cells and live mice. In vivo tracking of the FA flux was realized by PFM309 imaging, which revealed the gradual accumulation of FA in the live mice brain during normal aging and its further increase in AD mice. We further identified the age-dependent loss of catabolism enzymes ALDH2 and ADH5 as the primary mechanism responsible for formaldehyde excess. Activating ALDH2 with the small molecular activator Alda1 significantly protected neurovascular cells from formaldehyde overload and consequently from impairment during AD progress both in vitro and in vivo. These findings revealed PFM309 as a robust tool to study AD pathology and highlight ALDH2 as a potential target for AD drug development.

[Prostatitis studies in China from 2000 to 2020: A Knowledge Atlas-based study on the development trend of contemporary disciplines].

OBJECTIVE: To review and analyze the trend of researches on prostatitis in China in the past two decades. METHODS: We searched the core collection of China National Knowledge Infrastructure (CNKI) for studies on prostatitis, and analyzed the data obtained using Excel, Citespace and VOSviewer. RESULTS: Totally, 1 216 original articles were identified, with 3 271 keywords, ≥3-time high-frequency keywords accounting for 12.9%, with "", "", "chronic prostatitis", "prostatitis", and "" as the top 5 ones, each with a centrality higher than 300. Major prostatitis-related studies focused on the 8 keywords, namely, prostatitis, prostatic fluid, rats, prostate, syndromes, efficacy observation, compound (in traditional Chinese medicine, TCM), and therapeutic application. The included literature involved 2 808 authors, with 402 involved more than twice and most of them in a scattered manner. The major topics of prostatitis studies varied in the past two decades, focusing on TCM therapies, promotion of blood circulation and stasis and comprehensive nursing in 2000－2001, on animal models, CD4+ lymphocytes and other experimental molecules in 2007－2010, on urodynamics, risk factors and specific antigens in 2013－2016, and on literature information resources in 2016. CONCLUSIONS: The immune mechanism remains a hot topic in the future researches on prostatitis. In terms of treatment of the disease, TCM has a potential value, and more practice and studies are required for an optimal combination of TCM and Western medicine. Strengthened collaborative efforts are needed to establish an authoritative source channel for the keywords, and incorporate it into the national standard system, and above all, to integrate the prostatitis study into multi-disciplinary researches, eliminate academic barriers, encourage collaborative innovation with multiple parties, and promote the exchanges and development in this field.

An evidence mapping and analysis of registered COVID-19 clinical trials in China.

BACKGROUND: This article aims to summarize the key characteristics of registered trials of 2019 novel coronavirus (COVID-19), in terms of their spatial and temporal distributions, types of design and interventions, and patient characteristics among others. METHODS: A comprehensive search of the registered COVID-19 trials has been performed on platforms including ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (WHO ICTRP), Chinese Clinical Trials Registry (CHiCTR), Australian Clinical Trials Registry, Britain's National Research Register (BNRR), Current Control Trials (CCT), and Glaxo Smith Kline Register. Trials registered at the first 8 weeks of the COVID-19 outbreak are included, without language restrictions. For each study, the registration information, study design, and administrator information are collected and summarized. RESULTS: A total of 220 registered trials were evaluated as of February 27, 2020. Hospital-initiated trials were the majority and account for 80% of the sample. Among the trials, pilot studies and phase 4 trials are more common and represent 35% and 19.1% of the sample, respectively. The median sample size of the registered trials is 100, with interquartile range 60-240. Further, 45.9% of the trials mentioned information on a data monitoring committee. 54.5% of the trials did not specify the disease severity among patients they intend to recruit. Four types of interventions are most common in the experimental groups across the registered studies: antiviral drugs, Traditional Chinese Medicine (TCM), biological agents, and hormone drugs. Among them, the TCM and biological agents are frequently used in pilot study and correspond to a variety of primary endpoints. In contrast, trials with antiviral drugs have more targeted primary outcomes such as "COVID-19 nucleic acid test" and "28-day mortality." CONCLUSIONS: We provide an evidence mapping and analysis of registered COVID-19 clinical trials in China. In particular, it is critical for ongoing and future studies to refine their research hypothesis and better identify their intervention therapies and the corresponding primary outcomes. It is also imperative for multiple public health divisions and research institutions to work together for integrative clinical data capture and sharing, with a common objective of improving future studies that evaluate COVID-19 interventions.

Anti-Aß agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of Aß-targeting agents for mild to moderate Alzheimer's disease. METHODS: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses. RESULTS: Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-Cog) between anti-Aß drugs and placebo (mean difference (MD): 0.20, 95% CI -0.40 to 0.81; I 2=99.8%; minimal important difference 3.1-3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aß clearance may differ in effect (MD: -0.96, 95% CI -0.99 to -0.92) from drugs that reduce Aß production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aß drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit. DISCUSSION: From current evidence, anti-Aß interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aß clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small. TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42019126272.

Electroacupuncture Involved in Motor Cortex and Hypoglossal Neural Control to Improve Voluntary Swallowing of Poststroke Dysphagia Mice.

The descending motor nerve conduction of voluntary swallowing is mainly launched by primary motor cortex (M1). M1 can activate and regulate peripheral nerves (hypoglossal) to control the swallowing. Acupuncture at "Lianquan" acupoint (CV23) has a positive effect against poststroke dysphagia (PSD). In previous work, we have demonstrated that electroacupuncture (EA) could regulate swallowing-related motor neurons and promote swallowing activity in the essential part of central pattern generator (CPG), containing nucleus ambiguus (NA), nucleus of the solitary tract (NTS), and ventrolateral medulla (VLM) under the physiological condition. In the present work, we have investigated the effects of EA on the PSD mice in vivo and sought evidence for PSD improvement by electrophysiology recording and laser speckle contrast imaging (LSCI). Four main conclusions can be drawn from our study: (i) EA may enhance the local field potential in noninfarction area of M1, activate the swallowing-related neurons (pyramidal cells), and increase the motor conduction of noninfarction area in voluntary swallowing; (ii) EA may improve the blood flow in both M1 on the healthy side and deglutition muscles and relieve PSD symptoms; (iii) EA could increase the motor conduction velocity (MCV) in hypoglossal nerve, enhance the EMG of mylohyoid muscle, alleviate the paralysis of swallowing muscles, release the substance P, and restore the ability to drink water; and (iv) EA can boost the functional compensation of M1 in the noninfarction side, strengthen the excitatory of hypoglossal nerve, and be involved in the voluntary swallowing neural control to improve PSD. This research provides a timely and necessary experimental evidence of the motor neural regulation in dysphagia after stroke by acupuncture in clinic.

Botulinum toxin type A for hand tremor: a meta-analysis of randomised controlled trials.

BACKGROUND: Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin and clonazepam) due to side effects and frequent dose limitations. Botulinum toxin type A (BoNT-A) has been widely used to treat tremor, but its efficacy and safety are uncertain. AIMS: To evaluate the efficacy and safety of BoNT-A in the treatment of hand tremor. METHODS: We searched the MEDLINE, EMBASE, PsycINFO and Cochrane Library databases for relevant randomised controlled trials of the effects of BoNT-A injections on tremors, up to 20 February 2020. A meta-analysis of comparative effects was performed using R studio software, and publication bias was examined using Egger's test. RESULTS: Six studies examining a total of 245 participants with tremor were included in the meta-analysis. The primary outcome of meta-analysis showed no difference in clinical tremor scale scores between the BoNT-A group versus the placebo group (standardised mean difference (SMD): -0.42, 95% confidence interval (CI): -1.94 to 1.10; I2 = 96%). For clinical tremor scale scores, subgroup analyses suggested that the BoNT-A group may differ in terms of multiple sclerosis (MS) related tremor (SMD: -1.10; 95% CI: -2.17 to -0.04; I2 = 79%) compared to a placebo, but the difference did not exist in the outcome of essential tremor (ET) or hand tremor (MD: -1.31; 95% CI: -3.39; 1.31; I2 = 97%). Grip strength (MD: -1.25, 95% CI: -5.99 to 3.50, I2 = 97%) was slightly lower in the BoNT-A group, but the difference was not significant. The incidence of adverse events (AEs), including hand weakness (RR: 2.96, 95% CI: 1.40 to 6.24, I2 = 37%), was significantly greater in the BoNT-A group than in the placebo group. Two studies were assessed as having an overall low risk of bias. CONCLUSIONS: Our study confirms that BoNT-A injections are unlikely to have an impact on patients with hand tremors. However, subgroup analysis suggested that BoNT-A injections could have possible benefits in MS-related tremor. While moderate to severe hand weakness AEs often limits their use in clinical practice, additional well-designed double-blind, placebo-controlled trials are needed to provide more robust conclusions.

Transcatheter arterial chemoembolisation followed by three-dimensional conformal radiotherapy versus transcatheter arterial chemoembolisation alone for primary hepatocellular carcinoma in adults.

BACKGROUND: Hepatocellular carcinoma, also called malignant hepatoma, is a primary malignancy of the liver. Despite regular surveillance conducted in high-risk populations, most people with hepatocellular carcinoma are diagnosed at an advanced stage. Consequently, only a minority of people with the disease are suitable for surgical resection when diagnosed. OBJECTIVES: To compare the beneficial and harmful effects of transcatheter arterial chemoembolisation (TACE) followed by three-dimensional conformal radiotherapy (3-DCRT) versus TACE alone in adults with primary hepatocellular carcinoma, considered unsuitable for surgical resection. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science up to 31 May 2018. We checked reference lists for all included studies and related reviews for further relevant articles. SELECTION CRITERIA: We included all randomised clinical trials comparing TACE followed by 3-DCRT versus TACE alone in people with primary hepatocellular carcinoma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as suggested by Cochrane. We presented the results of the fixed-effect model in the absence of statistical heterogeneity. Otherwise, we reported the results from the random-effects model meta-analysis. We assessed risk of bias of the included trials using bias risk domains and presented the review results incorporating the methodological quality of the trials using GRADE. Our main conclusions were based on the analysis up to three years' follow-up. MAIN RESULTS: We identified eight randomised clinical trials (632 participants) that fulfilled our inclusion criteria. All eight trials were at high risk of bias, and we rated the evidence as low to very low certainty. The mean age ranged from 16 years to 78 years. The proportion of men ranged from 60% to 75% and the proportion of people with stage III primary hepatocellular carcinoma ranged from 22% to 85%. The median follow-up duration was 12 months (2 months to 38 months).TACE followed by 3-DCRT compared with TACE alone may have reduced all-cause mortality at three years' follow-up (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.73 to 0.88; 552 participants; 7 trials; low-certainty evidence). TACE followed by 3-DCRT compared with TACE alone may reduce the proportion of participants without tumour response (complete response plus partial response) (RR 0.49, 95% CI 0.39 to 0.61; 632 participants; 8 trials; low-certainty evidence). Data, from one trial on health-related quality of life, favoured the TACE followed by 3-DCRT group, but the provided data were ill-defined (very low-certainty evidence). None of the trials reported serious adverse events. The results on non-serious adverse events were as follows: TACE followed by 3-DCRT compared with TACE alone showed no difference in the results for proportion of participants with leukopenia (RR 1.12, 95% CI 0.92 to 1.34; 438 participants; 5 trials; very low-certainty evidence) and serum transaminases elevation (RR 1.67, 95% CI 0.66 to 4.27; 280 participants; 4 trials; very low-certainty evidence). However, the proportion of participants with total bilirubin elevation was larger in the TACE followed by 3-DCRT group than in the TACE alone group (RR 2.69, 95% CI 1.34 to 5.40; 172 participants; 2 trials; very low-certainty evidence). The rate of participants with serum alpha-fetoprotein (AFP) without decline or normalisation was significantly lower in the TACE followed by 3-DCRT group than in the TACE group, but these data were from one trial only (Chi² = 7.24, P = 0.007; very low-certainty evidence). AUTHORS' CONCLUSIONS: TACE followed by 3-DCRT may be associated with lower all-cause mortality and increased tumour response, despite the increased toxicity expressed by a higher rise of total bilirubin. Our review findings should be considered with caution because of the methodological weaknesses in the included trials, resulting in low- to very low-certainty evidence. Data on serious adverse events and health-related quality of life are lacking. We are also very much uncertain in the results of the reported non-serious adverse events. High-quality trials are needed to assess further the role of TACE followed by 3-DCRT for unresectable hepatocellular carcinoma.

Effects of Exercise During or Postchemotherapy in Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Exercise may effectively reduce side effects caused by chemotherapy. However, no meta-analyses of exercise during or postchemotherapy for cancer patients have been definitely performed to guide clinical practice. AIMS: To evaluate and summarize available scientific evidence to provide recommendations of an exercise intervention for cancer patients undergo chemotherapy. METHODS: A systematic review and meta-analysis were performed with databases searching of MEDLINE, Cochrane Library, and Embase from their inception to October 15, 2017. Literature was selected to identify randomized controlled trials of exercise during or postchemotherapy for cancer patients. Risk-of-bias assessment was performed by two reviewers independently. Data were analyzed using the Cochrane Collaboration's RevMan 5.3 (Review Man, Copenhagen, Denmark). RESULTS: A total of 10 trials with 838 participants were included in our study. Exercise could have a beneficial effect in cancer patients undergo chemotherapy in the outcome of physical fitness (MD: 0.16, 95% CI: 0.08-0.25, p < .01 and MD: 2.46, 95% CI: 1.44-3.47, p < .01) and depression (MD: -1.36, 95% CI: -2.68 to -0.04, p = .04), but not in FACT-G, FACT-B, anxiety, weight, and BMI (all p > .05). Exercise sequence (during or postchemotherapy) did not influence the effect of exercise for cancer patients undergo chemotherapy. In total, six studies were assessed as an overall low risk of bias. Subgroup analyses and sensitivity analyses reached results similar to those of the meta-analyses, which reflected our results were reliable and robust. LINKING EVIDENCE TO ACTION: Exercise seems to have a beneficial effect on physical fitness and depression, but not on quality of life, anxiety, weight, and BMI. More specific and detailed description of the implementation of exercise programs should be proposed in the future.

Nonpharmacological Interventions for Cancer-Related Fatigue: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Nonpharmacological interventions are the first recommendation for cancer-related fatigue, according to current guidelines. There are many forms of nonpharmacological interventions for addressing cancer-related fatigue, but the preferred means remain controversial and are not stated in the guidelines. Therefore, we evaluated the comparative effects and ranks of all major nonpharmacological interventions, according to different assessment methods, in cancer patients with fatigue. METHODS: Medline, Embase, Cochrane Library, and Allied and Complementary Medicine Database were searched for randomized controlled trials on nonpharmacological treatments for cancer-related fatigue. We assessed the trials' methodological quality using the Cochrane Risk of Bias tool. A Bayesian network meta-analysis and a comparative effects ranking were performed with Aggregate Data Drug Information System software. RESULTS: A total of 16,675 items were obtained from the databases, and 182 studies comprising 18,491 participants were included in the analysis. Based on the ranking probabilities, multimodal therapy and qigong ranked best with a Brief Fatigue Inventory; for a Functional Assessment of Cancer Therapy-fatigue scale, combined psychosocial therapies and bright white light therapy ranked best; for the Piper Fatigue Scale, resistance exercise and mindfulness-based stress reduction ranked best; for a multidimensional fatigue inventory, multimodal therapy and cognitive behavioral therapy (CBT) ranked best; for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), acupuncture and CBT ranked best; and for the Profile of Mood States Fatigue Subscale, multimodal therapy, qigong, aerobic exercise, and CBT ranked best. Comprehensive analysis of the results indicated that multimodal therapy, CBT, and qigong might be the optimum selections for reducing cancer-related fatigue. Most of the included studies had low risk of methodological quality problems; however, 59 studies had low methodological quality. LINKING EVIDENCE TO ACTION: Different interventions have their own sets of advantages for addressing cancer-related fatigue. These results can be utilized as evidence-based interventions for healthcare workers and patients to manage cancer-related fatigue.

Assessment of Passive Stiffness of Medial and Lateral Heads of Gastrocnemius Muscle, Achilles Tendon, and Plantar Fascia at Different Ankle and Knee Positions Using the MyotonPRO.

BACKGROUND The aim of this study was to assess the passive stiffness of the medial and lateral gastrocnemius (MG and LG), Achilles tendon (AT), and plantar fascia (PF) at different ankle and knee positions. MATERIAL AND METHODS Stiffness was assessed using a portable hand-held device (MyotonPRO). In 30 healthy participants (15 males, 15 females) with the knee fully extended or flexed 90°, stiffness of the MG, LG, AT, and PF was measured at 50° plantar flexion, 0° (neutral position), and 25° dorsiflexion (not for AT) of the ankle joint by passive joint rotation. RESULTS With the knee fully extended, passive dorsiflexion caused significant increase in muscle stiffness (P<0.001), whereas AT and PF stiffness increased with passive ankle dorsiflexion regardless of knee position (P<0.001). Increased stiffness was observed in MG compared to LG (P<0.001) and at the 3-cm site of AT compared to the 6-cm site (P<0.05). Stiffness was greater in LG compared to MG at -50° plantar flexion (P<0.001) and was greater in MG compared to LG at 25° dorsiflexion (P<0.05). Stiffness of AT increased in a distal-to-proximal pattern: 0 cm >3 cm >6 cm (P<0.001). CONCLUSIONS Stiffness assessed by use of the MyotonPRO was similar assessments using other techniques, suggesting that the MyotonPRO is capable of detecting the variations in stiffness of MG, LG, AT, and PF at different ankle and knee positions.

Psychosocial interventions for Alzheimer's disease cognitive symptoms: a Bayesian network meta-analysis.

BACKGROUND: Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. METHODS: We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini-Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. RESULTS: We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. CONCLUSION: Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice.

Effects of Fluoxetine on Poststroke Dysphagia: A Clinical Retrospective Study.

BACKGROUND: To investigate whether fluoxetine improves poststroke dysphagia and to detect the potential relationship between serum brain-derived neurotrophic factor (BDNF) levels and fluoxetine effects. METHODS: In this retrospective study, 159 stroke patients who met our study criteria were included. In total, 110 patients were placed in the control group, and 49 patients were placed in the fluoxetine group. Demographic and clinical characteristics of the patients were collected for the baseline assessment. Functional independence measure scores and American speech-language-hearing association/functional communication measures scores for swallowing were collected to evaluate the patients' swallowing function. Patients' serums were collected at weeks 1 and 3 after admission, and serum BDNF levels were measured by enzyme-linked immunosorbent assay. T test, chi-squared test, and general linear model analysis were performed to determine the differences between the two groups. RESULTS: A significantly higher improvement of swallowing function was observed in the fluoxetine group compared with that of the control group (P = .023). In addition, a general linear model analysis showed that the treatment of fluoxetine has a statistically significant effect on swallowing improvement after adjustment of swallowing score on admission, stroke types, and interval between the onset of stroke and admission (P = .022, R2 = .46, adjusted R2 = .446). There is no significant difference in the change of serum BDNF levels in the two groups (P = .269). CONCLUSIONS: This study suggests that treatment with fluoxetine in stroke patients with dysphagia may improve swallowing function. A placebo-controlled, randomized clinical trial is warranted to confirm this finding.

Acupuncture at KI3 in healthy volunteers induces specific cortical functional activity: an fMRI study.

BACKGROUND: Using functional magnetic resonance imaging (fMRI), we determined brain regions that were activated/deactivated more by acupuncture at Taixi (KI3) than by non-acupoint or sham acupuncture. METHODS: A total of 30 healthy volunteers were randomly divided into a KI3 group (15 subjects) and non-acupoint group (15 subjects). Subjects in KI3 group received a sham acupuncture and then a real acupuncture, fMRI was performed before and after sham acupuncture as well as after ture acupuncture. Subjects in non-acupoint group received a ture acupuncture and the fMRI was performed before and after ture acupuncture. The fMRI data obtained were successively analyzed using DPARSF2.3 and REST1.8 software, yielding regional homogeneity (ReHo) and amplitude of low frequency fluctuations (ALFF) values. RESULTS: Compared with sham acupuncture, ALFF values were higher in Brodmann area (BA) 10 and lower in BA7 and BA18. ReHo values after real acupuncture at KI3 were higher in the right sub-lobar region and BA10 and were lower in BA31. Compared with the changes before and after real acupuncture at non-acupoint, the changes at KI3 showed higher ALFF valued in the left cerebellum posterior lobe, BA10, BA39, BA31 and decreased ALFF was observed in the BA18, BA19 and BA40; and higher ReHo values were shown in left cerebellum posterior lobe pyramis, left cerebellum anterior lobe. BA37, BA10, BA39, BA31 and lower ReHo values were shown in BA18 and BA31. CONCLUSION: Acupuncture at KI3 has a specific effect on certain brain regions associated with perception, body movement, spirit, and association. Additionally, visual and auditory cortices were affected, which may be related to the clinical applications of KI3 acupuncture in auditory and cognitive disorders, hypomnesis, loss of concentration, and the loss of ability to work and learn. TRIAL REGISTRATION: The research ethics committee was achieved at 01/08/2012, the NO. was ChiECRCT-2012011. Website for Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=7123 . This study was registered at www.chictr.org, the Clinical Trial Registration Number was ChiCTR-TRC-12002427, and the registration number was achieved at 18/08/2012. The name of IRB that provided approval for the study and clearly state is Chinese Clinical Trail Registry.

Brain areas involved in the acupuncture treatment of AD model rats: a PET study.

BACKGROUND: Acupuncture may effectively treat certain symptoms of Alzheimer's disease (AD). Although several studies have used functional brain imaging to investigate the mechanisms of acupuncture treatment on AD, these mechanisms are still poorly understood. We therefore further explored the mechanism by which needling at ST36 may have a therapeutic effect in a rat AD model. METHODS: A total of 80 healthy Wistar rats were divided into healthy control (n = 15) and pre-model (n = 65) groups. After inducing AD-like disease, a total of 45 AD model rats were randomly divided into three groups: the model group (n = 15), the sham-point group (n = 15), and the ST36 group (n = 15). The above three groups underwent PET scanning. PET images were processed with SPM2. RESULTS: The brain areas that were activated in the sham-point group relative to the model group were primarily centred on the bilateral limbic system, the right frontal lobe, and the striatum, whereas the activated areas in the ST36 group were primarily centred on the bilateral limbic system (pyriform cortex), the bilateral temporal lobe (olfactory cortex), the right amygdala and the right hippocampus. Compared with the sham-point group, the ST36 group showed greater activation in the bilateral amygdalae and the left temporal lobe. CONCLUSION: We concluded that needling at a sham point or ST36 can increase blood perfusion and glycol metabolism in certain brain areas, and thus may have a positive influence on the cognition of AD patients.

Conservative medical intervention as a complement to CDT for BCRL therapy: a systematic review and meta-analysis of randomized controlled trials.

Background: The effect of first-line complex decongestive therapy (CDT) for breast cancer-related lymphedema (BCRL) depending on various factors forces patients to seek additional treatment. Therefore, this meta-analysis was conducted to evaluate the effect of different conservative medical interventions as a complement to CDT. This is the first meta-analysis that includes various kinds of conservative treatments as adjunctive therapy to get broader knowledge and improve practical application value, which can provide recommendations to further improve BCRL patients' health status. Methods: RCTs published before 18 December 2023 from PubMed, Embase, Cochrane Library, and Web of Science databases were searched. RCTs that compared the effects of conservative medical intervention were included. A random-effects or fixed-effects model was used based on the heterogeneity findings. Study quality was evaluated using the Cochrane risk of bias tool. Results: Sixteen RCTs with 690 participants were included, comparing laser therapy, intermittent pneumatic compression (IPC), extracorporeal shock wave therapy (ESWT), electrotherapy, ultrasound, diet or diet in combination with synbiotic supplement, traditional Chinese medicine (TCM), continuous passive motion (CPM), and negative pressure massage treatment (NMPT). The results revealed that conservative medical intervention as complement to CDT had benefits in improving lymphedema in volume/circumference of the upper extremity [SMD = -0.30, 95% CI = (-0.45, -0.15), P < 0.05, I 2 = 51%], visual analog score (VAS) for pain [SMD = -3.35, 95% CI (-5.37, -1.33), P < 0.05, I 2 = 96%], quality of life [SMD = 0.44, 95% CI (0.19, 0.69), P < 0.05, I 2 = 0], and DASH/QuickDASH [SMD = -0.42, 95% CI (-0.70, -0.14), P < 0.05, I 2 = 10%] compared with the control group. Subgroup analysis revealed that laser therapy and electrotherapy are especially effective (P < 0.05). Conclusion: Combining conservative medical interventions with CDT appears to have a positive effect on certain BCRL symptoms, especially laser therapy and electrotherapy. It showed a better effect on patients under 60 years old, and laser therapy of low to moderate intensity (5-24 mW, 1.5-2 J/cm2) and of moderate- to long-term duration (≥36-72 sessions) showed better effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354824, identifier CRD42022354824.

The short-term effects of Jin's three needles in conjunction with mirror therapy on brain function in patients with upper limb disability following an ischemic stroke were evaluated using ReHo analysis.

BACKGROUND: Jin's three needle (JTN) is a commonly utilized treatment for ischemic stroke in China. Mirror therapy (MT) is also gradually transitioning from treating limb discomfort to restoring motor function in the damaged limb. Investigations into the 2 treatments' mechanisms of action are still ongoing. We used functional magnetic resonance imaging (fMRI) technique in this study to examine the effects of JTN combined with mirror therapy MT on brain function in patients with upper limb dysfunction in ischemic stroke, as well as potential central mechanisms. The goal was to provide a solid evidence-based medical basis to support the continued use of JTN combination MT. METHODS: This study will be a single-blind, randomized, and controlled experiment. Randomization was used to assign 20 patients who met the study's eligibility requirements to the JTN + MT treatment group or the JTN control group. Each intervention will last for 4 weeks, with 6 days of treatment per week. The JTN acupuncture points are 3 temporal acupuncture points on the opposite side of the wounded limb, 3 hand acupuncture points on the injured upper limb, 3 shoulder acupuncture points, Renzhong and Baihui, The (JTN + MT) group simultaneously takes MT for 30 minutes. fMRI of the brain using BOLD and T1-weighted images was done both before and after therapy. Brain areas exhibiting changes in regional homogeneity during the pre and posttreatment periods were analyzed. RESULTS: By the end of the treatment course, Jin three-needle therapy plus MT activated more relevant brain functional regions and increased cerebral blood oxygen perfusion than Jin three-needle therapy alone (P <.05). CONCLUSION: In patients with upper limb impairment following an ischemic stroke, JTN with MT may improve brain function reconstruction in the relevant areas.

Role of TRPV1 in electroacupuncture-mediated signal to the primary sensory cortex during regulation of the swallowing function.

AIMS: Electroacupuncture (EA) at the Lianquan (CV23) could alleviate swallowing dysfunction. However, current knowledge of its neural modulation focused on the brain, with little evidence from the periphery. Transient receptor potential channel vanilloid subfamily 1 (TRPV1) is an ion channel predominantly expressed in sensory neurons, and acupuncture can trigger calcium ion (Ca2+ ) wave propagation through active TRPV1 to deliver signals. The present study aimed to investigate whether TRPV1 mediated the signal of EA to the primary sensory cortex (S1) during regulation of swallowing function. METHODS: Blood perfusion was evaluated by laser speckle contrast imaging (LSCI), and neuronal activity was evaluated by fiber calcium recording and c-Fos staining. The expression of TRPV1 was detected by RNA-seq analysis, immunofluorescence, and ELISA. In addition, the swallowing function was assessed by in vivo EMG recording and water consumption test. RESULTS: EA treatment potentiated blood perfusion and neuronal activity in the S1, and this potentiation was absent after injecting lidocaine near CV23. TRPV1 near CV23 was upregulated by EA-CV23. The blood perfusion at CV23 was decreased in the TRPV1 hypofunction mice, while the blood perfusion and the neuronal activity of the S1 showed no obvious change. These findings were also present in post-stroke dysphagia (PSD) mice. CONCLUSION: The TRPV1 at CV23 after EA treatment might play a key role in mediating local blood perfusion but was not involved in transferring EA signals to the central nervous system (CNS). These findings collectively suggested that TRPV1 may be one of the important regulators involved in the mechanism of EA treatment for improving swallowing function in PSD.