An inorganic-organic-polymeric nanovehicle for targeting delivery of doxorubicin: Rational assembly, pH-stimulus release, and dual hyperthermia/chemotherapy of hepatocellular carcinoma.

Efficiently synergistic therapy of hepatocellular carcinoma (HCC) by chemotherapeutic drug and photothermal agent remains a considerable challenge. Here, we report a nanodrug that integrates specific hepatoma-targeted delivery, pH-triggered drug release, and cooperative photothermal-chemotherapy function. By grafting the easily self-assembled CuS@polydopamine (CuS@PDA) nanocapsulation with polyacrylic acid (PAA), an inorganic-organic-polymeric hybrid nanovehicle was developed as a dual photothermal agent and carrier for loading antitumor drug-doxorubicin (DOX) through electrostatic adsorption and chemical linking antibody against GPC3 commonly overexpressed in HCC, resulting in the nanodrug, CuS@PDA/PAA/DOX/GPC3. The multifunctional nanovehicle had excellent biocompatibility, stability, and high photothermal conversion efficiency, due to the rationally designed binary CuS@PDA photothermal agent. The 72-h accumulative drug release in pH 5.5 tumor microenvironment can reach up to 84%, far higher than 15% measured in pH 7.4 condition. Notably, in contrast to the merely 20% survival rate of H9c2 and HL-7702 cells exposed to free DOX, their viabilities in the nanodrug circumstance can maintain 54% and 66%, respectively, suggesting the abated toxicity to the normal cell lines. When exposed to the hepatoma-targeting nanodrug, the viability of HepG2 cells was found to be 36%, which further drastically declined to 10% plus 808-nm NIR irradiation. Moreover, the nanodrug is potent to cause tumor ablation in HCC-modeled mice, and the therapeutic efficacy can be greatly enhanced under NIR stimulus. Histology analyses reveal that the nanodrug can effectively alleviate the chemical damage to heart and liver, as compared to free DOX. This work thus offers a facile strategy for design of targeting anti-HCC nanodrug toward combined photothermal-chemotherapy.

Rational assembly of RGD/MoS2/Doxorubicin nanodrug for targeted drug delivery, GSH-stimulus release and chemo-photothermal synergistic antitumor activity.

Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity. MoS2 nanosheets were synthesized and modified by ανß3 integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier. Further, covalent coupling of antitumor drug, thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS2/DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment. The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.

Comparative efficacy of different types of acupuncture as adjuvant therapy on carotid atherosclerosis: a protocol for systematic review and network meta-analysis.

INTRODUCTION: Carotid atherosclerosis (CAS) is a disease of the aorta caused by lipid metabolism disorders and local inflammation. Acupuncture combined with traditional western medicine (such as aspirin or atorvastatin) for the treatment of CAS has been widely applied in clinical practice, but there is still a lack of supporting evidence for its efficacy and safety on CAS. Therefore, this systematic review and network meta-analysis (NMA) will summarise the effects of different types of acupuncture treatments on CAS, and a ranking of the therapeutic classes will also be presented, aiming to provide evidence-based medicine for its extensive clinical application. METHODS AND ANALYSIS: Systematic and NMA searches will be conducted in seven electronic databases: PubMed, EMBASE, Medline, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database and Chongqing VIP databases. The search time is from their inception to December 2020, regardless of language and publication type. Randomised controlled trials and controlled clinical trials that include patients with CAS receiving acupuncture therapy compared with a control group will be considered eligible. The primary outcomes include the carotid intima-media thickness and vessel plaque quantification; the secondary outcomes include the carotid plaque Crouse score, greyscale median, lipid levels, the incidence of cardiovascular events, safety and adverse events. The selection of studies, data extraction, quality assessment and risk of bias assessment will be conducted by two independent reviewers. The NMA will be analysed with Stata V.15.0, RevMan V.5.3 software and WinBUGS V.1.4.3. ETHICS AND DISSEMINATION: Ethical approval will not be required for this study as it will be based on de-identified, aggregated published data. We will publish the findings in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020207260.

Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial.

BACKGROUND: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce. OBJECTIVE: To assess the long-term efficacy of acupuncture for CP/CPPS. DESIGN: Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938). SETTING: Ten tertiary hospitals in China. PARTICIPANTS: Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture. INTERVENTION: Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment. MEASUREMENTS: The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. RESULTS: A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P < 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P < 0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported. LIMITATION: Sham acupuncture might have had certain physiologic effects. CONCLUSION: Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment. PRIMARY FUNDING SOURCE: China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine.

Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report.

After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient's condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.

The efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction: A protocol for systematic review and meta-analysis.

BACKGROUND: Many cancer patients experience gastrointestinal adverse reaction during chemotherapy. Pharmacological interventions are commonly used to treat chemotherapy-induced gastrointestinal side effects but have various limitations. Clinical trials have indicated that moxibustion may alleviate gastrointestinal dysfunction and improve quality of life (QoL) after chemotherapy. This study aims to assess the efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction through a systematic review and meta-analysis. METHODS: All randomized controlled trials (RCTs) related to moxibution targeting chemotherapy-induced gastrointestinal adverse reaction will be searched in online databases, such as PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP Database) and WanFang Database from their inception to May 1, 2020. The primary outcome is the incidence and severity of chemotherapy-related gastrointestinal toxicities (nausea and vomiting, diarrhea and constipation). The secondary outcomes include the quality of life, biological parameters' alteration, and adverse events. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 researchers. The Cochrane Collaboration's Review Manager (RevMan 5.3) software will be used to conduct the direct meta-analysis. RESULTS: This study will provide a comprehensive review of the available evidence for the treatment of chemotherapy-induced gastrointestinal adverse reaction with moxibustion. CONCLUSION: The conclusion of this study will provide evidence to judge whether moxibustion is an effective and safety therapeutic intervention for chemotherapy-induced gastrointestinal adverse reaction. PROSPERO REGISTRATION NUMBER: CRD42020182990.

Randomized controlled trial for the efficacy of electroacupuncture in the treatment of urge urinary incontinence: A clinical study protocol.

BACKGROUND: Despite that the urge urinary incontinence (UUI) is a nonfatal disease, it can lead to anxiety, embarrassment and depression to the patient. UUI is a common public health problem that can significantly affect the quality of life of the patient. Several conservative treatments have been recommended for the treatment of UUI; however, their efficiency remains unclear, leaving the disease without a real effective treatment. The clinical application of acupuncture to treat UUI is currently considered an effective approach despite the limited evidence that support its efficiency. The aim of this study is to assess the efficacy and safety of electroacupuncture therapy in the treatment of UUI. METHODS AND ANALYSIS: A randomized, parallel, controlled study will be performed. Patients with UUI treated with electroacupuncture group (EA) will compare with the sham-treated sham EA (SA) patients. A total of 100 participants with UUI will be randomly allocated to either the EA or the SA group with a 1:1 ratio. The treatment of UUI patients will performed 3 times per week, for 8 weeks in 30-minute sessions. At the end of the treatment the patients will be followed-up until week 32. The primary outcomes include scores of incontinence questionnaire-short form, the average 24-hour urgency incontinence episodes, and the average 24-hour urge episodes responses from baseline until the 4th, 8th , 24th, and 32nd week. The secondary outcomes included the average 24-hour urine volume and the average 24-hour micturition frequency responses from baseline until the 8th and 32nd week, as well as the change in incontinence quality of life scores from baseline at the 8th and 32nd week. In addition, the degree of satisfaction of the participants undergoing acupuncture treatment will be measured at the 4th and 8th week. The participants' clinical acupuncture expectations were evaluated at baseline, and the questionnaire for urinary incontinence diagnosis was used to identify stress incontinence, mixed urinary incontinence, and urge incontinence at baseline. DISCUSSION: This is a randomized, controlled, observer-blinded trial of electroacupuncture treatment for UUI. The results of this trial will provide more evidence on whether electroacupuncture is efficacious for treating UUI.

The duration of acupuncture effects and its associated factors in chronic severe functional constipation: secondary analysis of a randomized controlled trial.

BACKGROUND: Electroacupuncture (EA) has been shown to improve complete spontaneous bowel movements (CSBMs), but the duration of its effects remains unknown. The objective of this study was to explore the duration of acupuncture effects after treatment and its associated factors for chronic severe functional constipation (CSFC). METHODS: This was a secondary analysis of a multicenter, randomized, sham-acupuncture (SA) controlled trial that included 1075 participants with CSFC. The primary outcome, the duration of acupuncture effects after treatment, was the number of weeks during the 12-week follow-up period that participants were to meet the weekly CSBM responder criteria. A weekly CSBM responder was defined as a participant who had at least three CSBMs for a given week and an increase from baseline of at least one CSBM for that same week. We performed a retrospective multivariate analysis to explore potential factors associated with sustained acupuncture effects. RESULTS: The duration of acupuncture effects in the EA group (5.5 weeks) was significantly higher than the duration of SA effects in the SA group (2.2 weeks) with a between-group difference of 3.2 weeks (95% CI, 2.77-3.78; p < 0.001). A younger age and higher baseline CSBMs per week [regression coefficient (RC) -0.06, 95% confidence interval (CI) (-0.06 to -0.04); RC 2.43, 95% CI 1.78-3.60; respectively] were associated with longer durations of acupuncture effects. CONCLUSIONS: EA had sustained post-treatment effects for CFSC. A significant association among a younger age, higher baseline CSBMs and sustained acupuncture effects was observed. Further research is needed to confirm the association. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01726504). Registered on 26 August 2012.

Acupoint catgut embedding for the treatment of obesity in adults: A systematic review protocol.

BACKGROUND: Obesity is the biggest chronic health problems among adults worldwide and the main predisposing factor in many types of systemic diseases such as hypertension, diabetes, and so on. In clinical reports on Traditional Chinese Medicine, acupoint catgut embedding has been shown to improve various clinical indicators for diseases including obesity and body mass index (BMI), but the safety of this and method has not been assessed. METHODS: This systematic review searched the following 8 databases between from January 2015 to December 2018: the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wan-fang Database, the China Doctoral Dissertations Full-text Database and the China Master's Theses Full-text Database, and will manually searched the list of medical journals as a supplement. RCTs containing acupoint catgut embedding method for the treatment of obesity will be included. By reading the titles, abstracts and full texts, the 2 reviewers will independently complete the studies selection, data extraction, and quality assessment. The bias risk assessment, data synthesis, and subgroup analysis were performed using Revman 5.1 software. RESULTS: The primary outcome measures include weight, improvement rate, secondary outcome measures include BMI, waist circumference, hip circumference, waist-to-hip ratio, fat percentage, and so on. The safety assessment includes the incidence of adverse events. The results will be displayed as the risk ratio of the dichotomous data, the standardized mean difference or weighted mean difference for the continuous data. CONCLUSION: This systematic review will retrieve clinical randomized controlled trials (RCT) on acupoint catgut embedding for obesity in 8 databases, aiming to describe and update existing evidence on the efficacy and safety of acupoint catgut embedding for obesity in adults. PROSPERO REGISTRATION NUMBER: CRD42018098793.

Acupuncture for adults with overactive bladder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Overactive bladder is stated as the occurrence of urinary urgency which will cause negative impacts and decrease patients' health-related quality of life. The aim of this systematic review is to assess the efficiency and safety of acupuncture for adults with overactive bladder (OAB) comparing with sham-acupuncture, drugs, and acupuncture plus drugs. METHODS: We independently searched 9 databases from beginning to August 15, 2017. Two writers extracted data at the same time independently. Study outcomes were calculated by standardized mean differences (SMD) with 95% confidence intervals (CIs) and mean difference (MD) with 95% CIs. RESULTS: Ten randomized controlled trials (RCTs) with 794 patients were included in this systematic review. The combined results showed that electroacupuncture (EA) may be more effective than sham electroacupuncture (sham EA) in improving the 24-hour nocturia episodes and EA may enhance tolterodine for relieving voiding symptoms and enhancing patients' quality of life. However, more trials with high quality and larger sample sizes will be needed in the future to provide sufficient evidence. Only 15 of 794 OAB patients from the included studies reported mild adverse reactions related to EA, therefore, acupuncture is safe for treating OAB. CONCLUSION: Acupuncture might have effect in decreasing the number of micturition episodes, incontinence episodes, and nocturia episodes. However, the evidence is insufficient to show the effect using acupuncture alone or the additional effect to drugs in treating OAB.

Effects of electroacupuncture at BL33 on detrusor smooth muscle activity in a rat model of urinary retention.

BACKGROUND: Detrusor smooth muscle (DSM) underactivity may lead to urinary retention (UR). Electroacupuncture (EA) at BL33 may be effective in improving DSM contractions. OBJECTIVES: This study aimed to investigate: (1) the effect of EA at BL33; and (2) the effect of different manipulation methods at BL33 on the modulation of DSM contractions in UR rats. METHODS: 30 male Sprague-Dawley rats were anaesthetised with urethane and modelled by urethral outlet obstruction. First, 2 Hz EA at BL33, SP6 and LI4 wasrandomly applied to the UR rats for 5 min to observe the immediate effects (n=10); second, manual acupuncture (MA) (n=10) and 100 Hz EA (n=10) were applied with the same programme. DSM electromyography (EMG) and cystometrogram data were evaluated. RESULTS: (1) 2 Hz EA at BL33 and SP6 significantly increased DSM discharging frequency (0.80±0.10 Hz, P<0.001, and 0.22±0.14 Hz, P=0.038), shortened micturation intervals (65.67±20.65 s, P=0.008, and 35.62±15.84 s, P=0.042), prolonged the duration of voiding (2.13±0.61 s, P=0.005, and 0.47±0.16 s, P=0.015), and reduced residual pressure (-0.91±0.31 mmHg, P=0.019, and -0.66±0.27 mmHg, P=0.046). EA at LI4 was not associated with any functional effects (P>0.05). Compared with SP6, EA at BL33 had greater positive effects on DSM discharging frequency, duration of discharging, and duration of voiding (all P<0.05). (2) No statistically significant differences were shown between MA, 2 Hz EA and 100 Hz EA interventions when stimulating at BL33, SP6 or LI4. CONCLUSIONS: EA at BL33 improved DSM contractions to a greater degree than EA at SP6 or LI4. There were no differences in effect when stimulating using 2 Hz EA, 100 Hz EA and MA.

A comparative study of electroacupuncture at Zhongliao (BL33) and other acupoints for overactive bladder symptoms.

Electroacupuncture (EA) at Zhongliao (BL33) can improve the symptoms of overactive bladder (OAB), such as urinary frequency, urgency, and incontinence. However, its performance compared with other acupoints remains unclear. This study investigated the effects of EA at BL33 with deep needling on rats with OAB by detecting urodynamics in eight groups: no intervention group, D-BL33 group (deep needling at BL33), S-BL33 group (shallow needling at BL33), non-acupoint group (needling at the non-acupoint next to BL33), Weizhong (BL40) group, Sanyinjiao (SP6) group, Tongtian (BL7) group, and Hegu (LI4) group. Results revealed that EA at BL33 with deep needling, BL40, and SP6 prolonged the intercontraction interval (ICI) of rats with OAB (P = 0.001, P = 0.005, P = 0.046, respectively, post-treatment vs. post-modeling). Furthermore, the change in ICI from post-modeling in the D-BL33 group was significantly greater than those of the no intervention and other EA groups (all P < 0.01). Significantly shortened vesical micturition time (VMT) and elevated maximum detrusor pressure (MDP) were also observed in the D-BL33 group (P = 0.017 and P = 0.024, respectively, post-treatment vs. post-modeling). However, no statistically significant differences in the changes of VMT and MDP from post-modeling were observed between D-BL33 and the other EA groups. In conclusion, EA at BL33 with deep needling may inhibit acetic-acid-induced OAB more effectively.

Acupuncture at homotopic acupoints exerts dual effects on bladder motility in anesthetized rats.

BACKGROUND: In Chinese medicine, dual effects on target organs are considered a primary characteristic of acupoint. Acupoints may be classified as heterotopic or homotopic in terms of spinal segmental innervation: homotopic acupoints contain afferent innervation in the same segment from which efferent fibers innervate target visceral organs, and heterotopic acupoints utilize different spinal segments to innervate target visceral organs than the segment receiving the afferent signal. It is well-known that dual effects of acupuncture on the bladder can be generated based on different states of the bladder, however, the dual effects of single acupoint stimulation and acupoint site-specificity (homotopic acupoints and heterotopic acupoints) on the bladder have yet to be investigated. METHODS: Twenty Sprague-Dawley rats were anesthetized and the intravesical pressure was measured via a manometric balloon inserted into the bladder. The acupuncture needle was separately inserted to a depth of 4 mm at the acupoints RN1 (Huiyin), RN3 (Zhongji), BL28 (Pangguangshu), BL32 (Ciliao), RN2 (Qugu) or BL23 (Shenshu), and manually rotated right then left with a frequency of 2 Hz for 1 min. Following acupuncture stimulation, bladder pressure was recorded and compared against the pre-stimulation measurements. RESULTS: During the bladder's active state, manual acupuncture (MA) at RN1, RN3, BL28, BL32 or RN2 inhibited bladder motility (P < 0.01). In the static bladder, MA at RN1, RN3, BL28, BL32, RN2 or BL23 increased bladder motility (P < 0.01). CONCLUSIONS: MA at homotopic acupoints may produce dual effects on bladder motility: inhibiting bladder motility when in an active state and enhancing bladder motility when in a static state.

Acupuncture for adults with overactive bladder: a systematic review protocol.

INTRODUCTION: Overactive bladder (OAB) is a symptom syndrome defined by the International Continence Society (ICS) as 'the presence of urinary urgency (both daytime and nighttime), usually accompanied by increased frequency and nocturia with or without urge urinary incontinence in the absence of a urinary tract infection or other obvious pathology'. Clinical studies indicate that acupuncture could reduce micturition over 24 h, urgency episodes over 24 h, and improve quality of life among people with OAB. This systematic review protocol details the proposed methods for evaluating the effectiveness and safety of acupuncture for OAB. METHODS AND ANALYSIS: The following databases will be searched for relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Incontinence Group Trials Register, MEDLINE, EMBASE, Chinese Biomedical Literature Database (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP database), Wan-Fang Data, and China National Knowledge Infrastructure (CNKI) and will hand search a list of medical journals as a supplement. Any randomised controlled trials in English or Chinese without restriction of publication status will be included with treatment of OAB. Outcomes will mainly include number of micturition episodes over 24 h, number of urgency episodes over 24 h and number of incontinence episodes over 24 h. Two reviewers will independently screen the titles, abstracts or even full texts, and extract data. Two other reviewers will assess study quality. Revman 5.1 software will be used to conduct meta-analysis and calculate the risk ratio for dichotomous data. Weighted mean difference or standard mean difference will be calculated for continuous data. The Cochrane collaboration's tool will be used to assess the risk of bias. DISSEMINATION: This systematic review protocol will provide information on acupuncture therapy for OAB. The results will be disseminated through peer-reviewed publication or conference presentations. PROTOCOL REGISTRATION: PROSPERO CRD42014010181.

Effect of blinding with a new pragmatic placebo needle: a randomized controlled crossover study.

Placebo control is a useful method for determining the efficacy of a therapy. In acupuncture researches, the preferred method for placebo control is acupuncture using a placebo needle that has a blunt tip and achieves no skin penetration. We performed a crossover study to validate the blinding effect of a new type of placebo needle. Sixty volunteers were randomized to receive acupuncture using 2 types of needles with different sequences: sequence AB, involving first the pragmatic placebo needle and then the real needle, and sequence BA, in a reverse order. Placebo acupuncture was performed by administering the placebo needle through an adhesive pad without skin penetration on the acupoints LI4, RN12, BL25, and BL36. Real acupuncture was performed by needling through the pad and penetrating the skin to 15 mm using a real needle on the same acupoints. The acupuncture was administered every other day with 3 sessions for 1 type of needle. The primary outcome was the perception of needle penetration. Besides degree of acupuncture pain, type, and degree of needle sensation, needle acceptability and factors influencing the subject blinding effect were assessed. Needle penetration was felt by 100%, 90% (54/60), 88.3% (53/60), and 95% (57/60) of volunteers receiving placebo acupuncture and 98.3% (59/60), 96.7% (58/60), 95% (57/60), and 95% (57/60) of volunteers receiving real acupuncture on LI4, RN12, BL25, and BL36, respectively. Differences of the volunteers' perception of needle penetration between the placebo needle and real needle were not significant for the 4 acupoints (all P > 0.05). Volunteers experienced fewer distension sensations (P = 0.01), a lower degree of needle sensation (P = 0.007), and less pain (P = 0.006) during placebo acupuncture than during real acupuncture. The placebo needle was more easily accepted than the real needle (OR = 1.63, 95% CI, 1.01-2.64). The influences of age, sex, educational level, acupuncture experience, needle sensation, acupuncture pain, and needle acceptability on volunteers' perception of needle penetration were not significant. The pragmatic placebo needle is a valid control for acupuncture research. It produces a good subject blinding effect with a similar appearance to conventional acupuncture needles and no skin penetration when applied.

Effect of electroacupuncture versus pelvic floor muscle training plus solifenacin for moderate and severe mixed urinary incontinence in women: a study protocol.

BACKGROUND: In women with mixed urinary incontinence, pelvic floor muscle training and solifenacin is the recommended conservative treatment, while electroacupuncture is a safe, economical and effective option. METHODS/DESIGN: In this prospective, multi-center, randomized controlled trial, five hundred women with mixed urinary incontinence, from 10 centers will be randomized to receive either electroacupuncture or pelvic floor muscle training plus solifenacin. Women in the acupuncture group will receive electroacupuncture for 3 sessions per week, over 12 weeks, while women in the control group will receive pelvic floor muscle training plus solifenacin (5 mg once daily) for 36 weeks. The primary outcome measure is the proportion of change in 72-hour incontinence episode frequency from baseline to week 12. The secondary outcome measures include eleven items, including proportion of participants with ≥50% decrease in average 72-h incontinence episode frequency, change from baseline in the amount of urine leakage and proportion of change from baseline in 72-h incontinence episode frequency in week 25-36, and so forth. Statistical analysis will include covariance analysis, nonparametric tests and t tests. DISCUSSION: The objective of this trial is to compare the efficacy and safety of electroacupuncture versus pelvic floor muscle training plus solifenacin in women with moderate and severe mixed urinary incontinence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02047032.

Effect of electroacupuncture versus prucalopride for severe chronic constipation: protocol of a multi-centre, non-inferiority, randomised controlled trial.

BACKGROUND: Acupuncture is safe and may be effective for severe chronic constipation. The World Gastroenterology Organisation recommends prucalopride for patients for whom previous laxative use failed to provide satisfactory relief. METHODS/DESIGN: In this prospective, multi-centre, randomised controlled trial, five hundred sixty patients with severe chronic constipation (two or less spontaneous complete bowel movements per week) from 14 centres will be randomised to receive either electroacupuncture or prucalopride. Participants in the electroacupuncture group will receive electroacupuncture for eight weeks, while participants in the control group will take prucalopride (2 mg once daily) for 32 weeks. The primary outcome measure is the proportion of patients having ≥ 3 spontaneous, complete bowel movements per week, averaged over week three to eight. The secondary outcome measures include eight items, including the proportion of patients having ≥ 3 spontaneous, complete bowel movements per week averaged over week 9-32, the proportion of patients with one or more increases in spontaneous, complete bowel movements per week from baseline, mean Bristol Stool Scale, etc. Statistical analysis will include the CMH test, nonparametric tests and t tests. DISCUSSION: We aimed to compare the effect of electroacupuncture versus prucalopride for severe chronic constipation. The limitation of this study is that participants and acupuncturists will not be blinded. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 02047045.