0.30 × 40 mm disposable sterile acupuncture needle pro- duced by Suzhou Medical Products Factory Co. Ltd (Suzhou, China). The acupuncture depth is at the range of 5–10 mm after routine disinfection and acupoint selection is DU20 (Baihui), DU24 (Shenting), EX-HN3 (Yintang), HT7 (Shenmen), SP6 (Sanyinjiao). The angle and depth of needling will take the standard of each acupoint into con- sideration. After participants experience a needling sensa- tion (Deqi sensation), a low-frequency pulse electro- acupuncture therapeutic apparatus (XS-998B04; Nanjing Xiaosong Medical Instrument Research Institute Co. Ltd, Nanjing, China) will be connected to the needle handle of DU20 and EX -HN3 and set to a continuous wave at a fre- quency of 2 Hz. The intensity of the stimulus will depend on the participant’s tolerance and stimulation will be con- tinuous for 30 min. All acupuncture procedures will be performed by the same acupuncturist.
This study will use the following exclusion criteria: (1) the presence of the following conditions in the subject’s past history that might trigger chronic fatigue: (a) or- ganic causes, such as acute or chronic liver disease (for example, hepatitis, liver cirrhosis), anemia, tuberculosis, chronic lung disease, cardiovascular disease (for ex- ample, heart failure, hypertension), endocrine/metabolic disease (for example, diabetes, thyroid gland disease, severe obesity), autoimmune disease (for example, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis), malignant tumors, or infectious dis- ease; and (b) psycho-social causes, such as depression, anxiety neurosis, recent severe stress, schizophrenia, alcoholism, or an eating disorder (anorexia nervosa, bulimia nervosa); (2) subjects who have taken the follow- ing drugs within the past 2 weeks: antihypertensive drugs, antidepressants, anti-anxiety agents, hypnotics, or antihistamines; (3) pregnant or breast-feeding women; (4) subjects who are participating in other clinical trials; (5) subjects who are overworked; (6) subjects who have experienced a hypersensitive reaction after acupuncture treatment (in the case of participants with an experience of acupuncture treatment); (7) subjects who are inmates at group facilities, such as social welfare institutions; (8) subjects who do not provide informed consent; and (9) others whose clinical trial conductors are considered in- appropriate for participating in this trial [5,20].
Assessment of De Qi sensation induced by acupuncture In our study, the assessment of De Qi sensation perceived by the patients is based on the Chinese version of the ”modified” Massachusetts General Hospital Acu- puncture Sensation Scale (C-MMASS) (see Additional file 1). Before the trial, the concept of “De Qi and its correlated sensations” will be explained to all partici- pants by the recorder. At the end of each treatment ses- sion after the removal of the needles, patients will be asked to fill in the C-MMASS form to evaluate the intensities of 11 acupuncture sensations: soreness, aching, deep pressure, heaviness, fullness/distension, tingling, numbness, dull pain, warmth, cold, and throbbing. The intensities of these sensations are evaluated on a 0–10 cm VAS, where 0 represents “none” and 10 represents “intolerably strong sense.” There is also an additional blank row at the end of the form that the patient can use to assess any other sensations. The MASS index will then be calculated.
higher quality, have been conducted, but the results they report are uneven, and thus little light is shed upon the role of acupuncture in treating FMS. One well-designed study  randomised 100 FMS patients into among four groups (one given true acupuncture, and the other three, sham acupuncture), with two sessions per week being given for 12 weeks. No differences were found among any of the outcome measures, but this is not surprising, as the authors used a standard prescription of acupuncture points, which is not the correct proce- dure . Similar results have been found in another study, also well designed, which concluded that the level of analgesia attained is independent of the location of the acupuncture needles . On the contrary, another well-designed study  obtained positive results on comparing real acupuncture with a placebo in terms of relieving pain, asthenia and anxiety, with a reduction of 7 points on the scale of the Fibromyalgia Impact Ques- tionnaire. Another study, carried out in 2008, also reported a reduction in pain intensity and an improve- ment in quality of life, three months after acupuncture treatment was applied to a group of FMS patients, in comparison with tricyclic antidepressant treatment and exercise . Acupuncture appears to be both safe and effective in treating depression, and is comparable with antidepressant treatment .
Acupuncture, as a typical traditional Chinese medicine (TCM), has been applied for thousands of years . The rapid development of acupuncture both within and out- side China over the last few decades has itself led to great innovations in practice. Many studies, including clinical reports and systematic reviews, have investigated the benefits and success of acupuncture in relieving symptoms for various acute and chronic diseases, while a large history of clinical practice demonstrates that acu- puncture appears to have an irreplaceable effect in trea- ting depression and its symptoms, when compared with modern medicine and its antidepressive treatment. How- ever, methodological flaws in design undermine the validity of these studies [9-11]. For example, two system- atic reviews by Smith in the Cochrane Collaboration show that the clinical evidence for acupuncture treat- ment of depression is relatively limited before 2003 and that the quality of the clinical trials has improved between 2003 and 2008. The curative effects of acupunc- ture for depression are impossible to confirm [12,13].
AR has become a global and intractable disease. Besides negative impacts on patients’ quality of life, it results in various kinds of diseases which may cause the loss of working ability and life. Although the symptoms can be relieved effectively by various topical or oral drugs, sus- ceptibility to the disease cannot be changed. Specific im- munotherapy can relieve the allergic symptoms, but long-term treatment always results in poor compliance . Acupuncture, on behalf of traditional treatments, reflects the emphasis of TCM on “mind-regulation”. In all kinds of diseases, especially physical and mental dis- orders, treatments which emphasize both a patient’s physiological and mental state, play an important role. Recent research proves that  AR is a physical and mental disorder, being closely related to social psycho- logical factors. AR patients, especially those with moder- ate and severe disease, are likely to have mental and behavior problems due to the chronic and unstable symptoms, continuous and unsuccessful treatments, ac- cumulated medical expenses, and effects on their social function. Furthermore, a patient’s mental and behavior problems may aggravate their illness . As a result, a vicious cycle is formed.
A recent systematic review concluded that acupunc- ture and EA has become a popular and complementary practice in the treatment of LBP . The availability and practicability of acupuncture are also important factors to consider; the advantages of acupuncture are that it is simple, convenient and has few contraindica- tions. However, it is still not possible to verify its effectiveness compared to EA in patients with LBP, but rather as an adjunct to other forms of therapy. Furthermore, most studies evaluate only aspects of short-term pain. Thus, it is suggested that more studies be conducted with the aim of verifying the effectiveness of acupuncture and EA in the medium term, in addition to investigating the effects of treat- ments on psychosocial aspects.
Neurocognitive deficits are common in patients with severe TBI. Patients who fail to fully recover conscious- ness may enter a disorder of consciousness (DOC) such as coma, a vegetative state, or a minimally conscious state . With the development of diagnostic tools such as functional magnetic resonance and electroen- cephalography, clinicians are able to detect DOC in patients with severe TBI and commence early inter- vention [6, 7]. Current therapeutic strategies for DOC include behavioral, pharmacological, and neurostimu- latory approaches, among which the latter two have been intensively studied. For example, amantadine and other dopaminergic agents have shown beneficial ef- fects in promoting recovery after TBI, but warrant fur- ther systemic investigation [8–10]. As a potential restorative treatment for DOC, neurostimulation has attracted increasing interest. A study of thalamic deep brain stimulation demonstrated a remarkable behavioral recovery in patients with TBI . Non-invasive forms of neurostimulation, such as transcranial magnetic stimula- tion and transcranial direct current stimulation, have shown some short-term effects on behavioral improve- ment, but need further study [12–14].
The word dizziness is used to mean various sensations of body orientation and position that are frequently diffi- cult for patients to describe. Dizziness is difficult to de- fine, impossible to measure, and a challenge to diagnose . Most patients with chronic symptoms are not re- lieved by medical treatment . Chronic dizziness is a major public health concern. There are millions of pa- tients with chronic dizziness. However, neither the mech- anism nor safe and effective treatment methods have been clarified. Any treatment method that reduces chronic diz- ziness would be an important intervention. Our study will indicate that, despite the difficulty of diagnosis, practi- tioners can identify patients who can safely benefit from acupuncture. A number of patients with dizziness would prefer acupuncture over pharmacotherapy when our study demonstrates the effectiveness and safety of acupuncture to treat chronic dizziness. This will be especially relevant for patients who do not respond to medical therapy or who experience adverse side effects to drug therapy.
As one of the most important complementary and alter- native therapies, acupuncture has been used to treat a var- iety of diseases for more than 2000 years . The WHO listed asthma and other 42 indications for acupuncture in 1979  and classified the diseases treated by acupunc- ture into 4 categories, 107 illnesses in 2002, including asthma . The National Institutes of Health (NIH) rec- ommended acupuncture as an adjunctive treatment in comprehensive management programs of addiction, stroke rehabilitation, asthma, etc. [12, 15]. The British Thoracic Society suggested that health care professionals should be aware of the common use of complementary and alterna- tive medicine in asthma treatment, including acupuncture . Previous studies suggested that acupuncture was ef- fective in alleviating asthmatic symptoms and could be used as an adjunct to the conventional medical manage- ment of asthma . Acupuncture also improved lung function and decreased medication dosages . Our pre- vious clinical study found that acupuncture reduced the degree and frequency of exacerbations in patients with asthma  and had regulatory effects on mucosal and cellular immunity in patients with allergic asthma .
Changes from baseline in the NIH-CPSI total score will be analyzed using linear mixed-effects models. The observed change from baseline score at each assessment point will be considered as the dependent variable. The model will include the baseline value, treatment group (acupuncture and sham acupuncture), visit and treat- ment × visit interaction. Treatment group comparisons at each visit will be estimated by differences between least squares means from the treatment × visit inter- action, with accompanying p values and 95% CIs. Log-transformation may be applied in the case of serious violations of the model assumptions (normality and con- stant variance of the residuals). If not appropriate, the Wilcoxon rank-sum test will be used. The effect of the treatment will be estimated by the difference (or ratio, in the case of log-transformation) between treatments and will be presented along with its associated 95% CI. The same approach as for the NIH-CPSI total score will be used in other longitudinal continuous outcomes such as NIH-CPSI subscales (pain, urinary symptoms, and QoL). Other categorical data or ordinal data will be com- pared between groups using the Wilcoxon rank-sum test, chi-square test or Fisher ’ s exact test, as appropriate. The James and Bang blinding indices will be used to assess the success of blinding. The James blinding index is a variation on the statistic in which 1 represents per- fect blinding. The Bang blinding index for each group represents the proportion of participants making a cor- rect treatment guess beyond chance; 0 represents perfect blinding, a positive index indicates a correct guess, and a negative index indicates a guess in the opposite direction . For all statistical analyses, SAS 9.4 software will be used. All hypothesis testing will be carried out at the 5% (two-sided) significance level.
clinical experience, more than 20 acupoints have been se- lected as the main acupoints in neck pain. An appropriate repeatable treatment has not been established. Secondly, although shallow needle insertion and non-acupoints have been widely used in acupuncture research in sham groups, it has been suggested that these methods have therapeutic effects and are adjusted to accommodate different patients according to traditional Chinese medicine (TCM) theory . The academic literature also indicates that the human body has more than 2200 singular points within formal naming beyond meridians . The notion of a non-acupoint is obscure and there may be a role for specific factors of non-acupoints lateral to the acupoints . Moreover, recent academic literature has shown that shallow puncture also produces analgesic effects in pain disorders. Thirdly, it has been reported that about 40% of subjects in these trials could distinguish non-penetrating sham acupuncture from real acu- puncture .
Methods/design: This is a prospective randomizedcontrolled pilot study with four balanced treatment arms (usual care, acupuncture, training, and training plus acupuncture). Each arm will have 24 patients. After the initial screening examination and randomization, a 6-week treatment period follows, with treatment frequencies decreasing at 2-week intervals. After completion of the intervention, two follow-up evaluations will be performed 3 and 6 months after the start of treatment. At predefined times, the various outcomes (pain intensity, health-related quality of life, pain duration, autonomic regulation, and heart rate variability) as well as the participants ’ acceptance of the complex treatment will be evaluated with valid assessment instruments (Migraine Disability Assessment, PHQ-D, GAD-7, and SF-12) and a headache diary. The acupuncture treatment will be based on the rules of TCM, comprising a standardized combination of acupuncture points and additional points selected according to individual pain localization. The training therapy comprises a combination of strength training, endurance training, and training to improve flexibility and coordination. Besides descriptive analyses of the samples, their comparability will be assessed using an analysis of variance (ANOVA) or chi-squared tests. Analyses will be performed on an intention-to-treat basis. Potential interaction effects will be calculated using a repeated-measures ANOVA to test the primary and secondary hypotheses. In supplementary analyses, the proportion of treatment responders (those with a 50% reduction in the frequency of pain episodes) will be determined for each treatment arm.
The effect of acupuncture on insomnia is consistently emerging as an alternative treatment for insomnia. In a systematic review by Yeung et al., 20 randomized con- trolled trials were analyzed to assess the effect of acu- puncture on insomniapatients by comparing them with control patients given a benzodiazepine, with results in- dicating that acupuncture was more effective. The study, however, has certain limitations including an undefined criterion for diagnosis, lack of randomization or blinded conditions, and small sample sizes . Several other studies investigate the effect on acupuncture as a treat- ment for insomnia by comparing different acupuncture therapies, the effects of using and not using moxa, and comparison with placebo sleeping pills [9-11]. One of these studies shows that auricular acupuncture therapy is more effective for insomnia than two other therapies, and another suggests that acupuncture therapy with moxa is more effective than without [9,10]. Cheuk et al., in a review of 33 clinical trials on the effects of acupunc- ture on insomnia, conclude that many trials indicate acupuncture treatment improves quality of sleep, but fu- ture trials need to be more methodologically rigorous, and that extant trials may be prone to the risk of bias coming from the definition of insomnia, participant characteristics, acupoints, and treatment regimen . Despite the number of studies related to acupuncture and insomnia in the literature however, it is necessary
One of the most common SD associated with stroke is insomnia . Insomnia is characterized by difficulty in falling asleep and staying asleep, early morning awakening, and nonrestorative sleep. The primary pharmacological treatments for insomnia are benzodiazepines, nonbenzo- diazepine sedatives, and melatonin agonists. Although ef- fective pharmacologic treatments for insomnia are available, these medications often cause side effects such as residual daytime sedation, drowsiness, dizziness, light- headedness, cognitive impairment, motor incoordination, and dependence . The mainstay of nonpharmacologic intervention for insomnia is cognitive behavioral therapy (CBT). However, CBT often causes an acute reduction in total sleep time (TST) during the first few weeks of treat- ment, which means that SD improvements with CBT require long-term implementation .
A Cochrane systematic review of acupuncture for shoulder pain concluded that there is not enough pub- lished evidence of sufficient quality to support or refute its use . A trial of acupuncture for shoulder pain concluded that acupuncture is an effective long-term treatment for patients with shoulder pain (from soft- tissue lesions) in a primary care setting . Typically acupuncturists often use a combination of local and distal points to treat a condition such as CSP. According to ex- perience from our clinical practice, we consider that distal points could improve range of motion while local points could be effective in providing pain relief. Therefore we hypothesize that acupuncture at local acupoints in com- bination with distal acupoints may be more effective than needling points separately to treat CSP. This project will not only increase the knowledge about the effects of acu- puncture treatment for CSP, but also confirm the effect of a combination of local and distal acupoints.
There are several limitations of this study. First, sleep quality is not assessed by objective measurement such as polysomnography or actigraphy. There are some difficul- ties for us to perform these tests. Most hemodialysis patients refused to go through polysomnography in our pilot studies when they were required to stay a whole night in hospital. Actigraphy seems easily accepted but this equipment is unavailable in all centers. Due to limited financial support, we have to make the best of a well-acknowledged scale to assess the outcome. In a future study, actigraphy should be included. Second, anxiety and depression are commonly accompanied with sleep disorders but are not assessed in this study. Recent study has suggested that they have positive correla- tions with PSQI score . A more comprehensive assess- ment of the effect of auricular acupressure will include sleep quality, anxiety and depression, and quality of life in future study.
This is the first reported randomized, controlledtrial on the efficacy and tolerability of traditional Chinese acu- puncture compared with electro-acupuncture and sham acupuncture in patients with refractory RA using multiple local and distal points. Although the pain scores did not differ between the 3 groups, this study shows that both traditional acupuncture and electro-acupuncture may serve as an adjunct by reducing the number of tender joints in patients with refractory RA compared to sham acupuncture. Previous studies published about the effi- cacy of acupuncture are difficult to interpret due to meth- odological problems . The important point of our study is that it is a study in the methodology of acupunc- ture research as discussed in the following paragraphs. Previous studies used different definitions for sham acu- puncture, including insertion of needles adjacent to tradi- tional point without manipulation , points with no known effects , points far away from the painful area without stimulation , distant arbitrary points , Patients progress through the trial
In this study, we found that the addition of oral Amlodipine to the standard chelation therapy reduced the myocardial iron concentration in transfusion-depen- dent thalassemia major patients. This combination is more effective than iron chelators alone. After 6 months of treatment, the myocardial iron concentration decreased signi ﬁ cantly (p-value <0.001). This is explained by the mechanism of iron uptake in the heart tissues, which is mediated by the L-type calcium channels. The relative improvement of MIC in the amlo- dipine patients was consistent with a previous study by Fernandes et al (2016), also indicating a signi ﬁ cant reduction in the MIC and improvement in the heart T2* after treatment with amlodipine in 57 patients older than 6 years of age. 26,37
The primary outcome of this study is the cumulative UAS in each group. After a normality test, the total score will be compared using the independent t test (parametric) or the Mann-Whitney U test (non-paramet- ric) according to the normality of the data. In secondary outcome analysis, the VAS score for itching intensity and the DLQI will be used to analyze the difference, and differences between groups in mean change between baseline and measurements made at 1, 2, 3, and 4 weeks will be analyzed by repeated measures two-factor ana- lysis. The HAMA, HAMD, humoral immunity index, and serum total IgE measurement will be compared using the independent t test (parametric) or the Mann-Whitney U test (non-parametric) according to the normality of the data. The χ2 test or logistic regression will be used to analyze dichotomous outcomes. Adverse events will be compared between groups using the χ2 test or Fisher’s exact test. Missing values will be replaced using the method of last observation carried forward. If the partici- pant dropout rate is > 20%, sensitivity analysis will be con- ducted with the data included.