Using Mobile Integrated Health and telehealth to support transitions of care among patients with heart failure (MIGHTy-Heart): protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Nearly one-quarter of patients discharged from the hospital with heart failure (HF) are readmitted within 30 days, placing a significant burden on patients, families and health systems. The objective of the 'Using Mobile Integrated Health and Telehealth to support transitions of care among patients with Heart failure' (MIGHTy-Heart) study is to compare the effectiveness of two postdischarge interventions on healthcare utilisation, patient-reported outcomes and healthcare quality among patients with HF. METHODS AND ANALYSIS: The MIGHTy-Heart study is a pragmatic comparative effectiveness trial comparing two interventions demonstrated to improve the hospital to home transition for patients with HF: mobile integrated health (MIH) and transitions of care coordinators (TOCC). The MIH intervention bundles home visits from a community paramedic (CP) with telehealth video visits by emergency medicine physicians to support the management of acute symptoms and postdischarge care coordination. The TOCC intervention consists of follow-up phone calls from a registered nurse within 48-72 hours of discharge to assess a patient's clinical status, identify unmet clinical and social needs and reinforce patient education (eg, medication adherence and lifestyle changes). MIGHTy-Heart is enrolling and randomising (1:1) 2100 patients with HF who are discharged to home following a hospitalisation in two New York City (NY, USA) academic health systems. The coprimary study outcomes are all-cause 30-day hospital readmissions and quality of life measured with the Kansas City Cardiomyopathy Questionnaire 30 days after hospital discharge. The secondary endpoints are days at home, preventable emergency department visits, unplanned hospital admissions and patient-reported symptoms. Data sources for the study outcomes include patient surveys, electronic health records and claims submitted to Medicare and Medicaid. ETHICS AND DISSEMINATION: All participants provide written or verbal informed consent prior to randomisation in English, Spanish, French, Mandarin or Russian. Study findings are being disseminated to scientific audiences through peer-reviewed publications and presentations at national and international conferences. This study has been approved by: Biomedical Research Alliance of New York (BRANY #20-08-329-380), Weill Cornell Medicine Institutional Review Board (20-08022605) and Mt. Sinai Institutional Review Board (20-01901). TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, NCT04662541.

[Effect of electroacupuncture serum on expression of myogenic differentiation antigen and autophagy-related protein Beclin 1 in cultured muscle satellite cells under starvation].

OBJECTIVE: To explore the effect of electroacupuncture (EA) serum on expression of myogenic differentiation antigen (Myod) and autophagy-related protein Beclin 1 in cultured muscle satellite cells of rats under starvation conditions. METHODS: The primary multifidus muscle satellite cells of one male SD rat were isolated and cultured to obtain the 3rd generation of cells. The EA serum was got from the rat received EA stimulation of bilateral "Weizhong" (BL40, 2 Hz/10 Hz, 1 mA, duration of 20 min, once daily for 7 days). The cell suspension (2×104/well) of the 3rd generation of cultured cells was transferred to each well of a 96-well plate in medium containing 10% fetal bovine serum (FBS). Twelve duplicate wells were set up for the blank control serum (without FBS), 10% FBS, 10% EA serum, 20% EA serum and 30% EA serum groups and incubated for 12 h and 24 h, respectively. Each well was supplemented with 10 µL CCK-8 reagent to be incubated for 1 h again for observing the state of cell proliferation. After culturing the primary muscle satellite cells in serum-free medium for 12 h, the cells were randomly divided into serum-free group, 10% fetal bovine serum group and optimal concentration electroacupuncture serum group, and serum of corresponding concentration was added respectively. The expression levels of Beclin 1 and cell-proliferation-related protein Myod were detected by Western blot. RESULTS: CCK-8 assay displayed that the proliferation levels were significantly higher at 12 h and 24 h after serum intervention in the 10% FBS, 10% EA serum, 20% EA serum and 30% EA serum groups than that in the blank control serum group (P<0.01), and at 24 h in the 3 EA serum groups than in the 10% FBS group (P<0.01), but without significant difference among the three EA serum groups (P>0.05). As a result, 10% EA serum was selected as the optimal concentration for Western blot tests. No significant difference was found in the expression levels of Myod and Beclin 1 proteins among the serum-free, 10% FBS and 10% EA serum groups before intervention (P>0.05), and there was a marked up-regulation of Myod expression and an obvious down-regulation of Beclin 1 expression at 12 h in both the 10% EA serum and 10% FBS groups in comparison with their own pre-intervention (P<0.05). There were a marked up-re-gulation of Myod expression at both 12 h and 24 h and Beclin 1 expression at 24 h in both the 10% EA serum group and 10% FBS group than that in the serum-free group (P<0.05), and an obvious down-regulation of Beclin 1 expression at 12 h in both 10% FBS and 10% EA serum groups than that in the serum-free group (P<0.05, P<0.01). After 24 h's serum intervention, there was an increase of Myod expression and a reduction of Beclin 1 expression in both 10% FBS and 10% EA serum groups compared with those after the 12 h intervention (P<0.05). No significant differences were found between the 10% FBS and 10% EA serum groups in the expression levels of Myod and Beclin 1 proteins (P>0.05). CONCLUSION: EA serum can promote proliferation of cultured muscle satellite cells under starvation conditions, which is related to its functions in regulating expression of Beclin 1 and cell-proliferation-related protein Myod.

Effect of auricular electroacupuncture combined with body acupuncture in improving the consciousness of patients after traumatic brain injury: Study protocol for a randomized controlled trial.

BACKGROUND: Traumatic brain injury (TBI) has become a major cause of morbidity and mortality both in China and abroad. Disorders of consciousness following severe TBI is a common refractory complication, resulting in difficult rehabilitation and poor life quality. However, effective therapeutic approaches remain limited. Although acupuncture has been widely applied in the treatment of neurological disorders in China, its efficacy and safety for consciousness recovery remain to be elucidated. METHODS: Here, we conduct a study design and protocol of a randomized, blinded, controlled study to evaluate the efficacy and safety of electroacupuncture at auricular acupoints "heart" and "brainstem" combined with body acupuncture in the consciousness recovery of patients with TBI. A total of 80 patients with initial Glasgow coma scale score between 3 and 8 points will be recruited in the trial and randomized into intervention (combined application of auricular electroacupuncture and body acupuncture) group or control (conventional treatment) group. Patients in the intervention group will receive electroacupuncture at bilateral auricular acupoints "heart" and "brainstem" (4 points in total) combined with body acupuncture in addition to conventional treatment while patients in the control group will receive conventional treatment alone for 8 weeks. The primary outcomes are changes of Glasgow coma scale score and mismatch negativity of event-related brain potentials at baseline after 4 weeks after the final treatment and 4 weeks after the final treatment. The secondary outcome measures will be changes of Barthel and FuglMeyer scores at baseline after 4 weeks after the final treatment and 4 weeks after the final treatment. The safety will also be assessed by monitoring the incidence of adverse events and changes in vital signs during the study. DISCUSSION: Results from this trial will significantly support the application of auricular acupuncture and body acupuncture in the consciousness recovery of patients with severe TBI. If found to be effective and safe, auricular acupuncture combined with body acupuncture will be a valuable complementary option for comatose patients with TBI. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800020245. Registered on 21 December 2018.

Therapeutic effect of Fu's subcutaneous needling for hemiplegic shoulder pain among stroke survivors: Study protocol for a randomized controlled trial.

BACKGROUND: Hemiplegic shoulder pain (HSP) is a frequent complication after stroke and limits patients' physical functioning of the affected arm, thus compromising their quality of life. Fu's subcutaneous needling (FSN) has been widely applied in the treatment of pain diseases in China; however, its efficacy and safety for HSP remain to be elucidated. We therefore conducted a randomized, controlled trial to summarize the current evidence on the effects of FSN on the recovery outcomes of stroke survivors with HSP. METHODS: Here, we conduct a study design and protocol of a randomized, blinded, controlled study to evaluate the efficacy and safety of FSN in patients with HSP. A total of 60 patients with numerical rating scale (NRS) score above 1 will be recruited in the trial and randomized into FSN group or usual care (UC) group. Patients in the FSN group will receive FSN treatment combined with UC treatment while patients in the UC group will receive UC treatment alone for 4 weeks. The primary outcomes are changes of NRS at baseline, after the 1st treatment, after the final treatment and 4 weeks after the final treatment. Secondary measurements will be changes of Fugl-Meyer score, constant score, MPQ-SF score, quality of life score, and range of motion at baseline, after the final treatment, and 4 weeks after the final treatment. The safety will also be assessed by monitoring the incidence of adverse events and changes in vital signs during the study. DISCUSSION: Results from this trial will significantly support the application of FSN in the recovery of patients with HSP. If found to be effective and safe, FSN will be a valuable complementary option for patients with HSP. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900021644 (registered on March 2, 2019).

Acupuncture for uterine fibroids: Protocol for a systematic review of randomized controlled trials.

BACKGROUND: Uterine fibroids represent the most common gynecological benign tumors in reproductive females. Acupuncture has been applied as a therapeutic modality in China to treat uterine fibroids. However, currently, few critical systematic reviews regarding the effect of acupuncture on uterine fibroids have been published. Our proposed review aims to evaluate the current evidence on the efficacy of acupuncture for uterine fibroids. METHODS: A total of 7 databases were searched from their inception to December 2018, including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure database, the Chinese Biomedical database, and the Wanfang database. The primary outcomes will be reduction in uterine volume and number of fibroids. Secondary outcomes are pelvic or low-back pain, assessed by Visual Analog Scale (VAS); Irregular menstrual periods; Low-abdominal pressure symptoms such as frequent or urgent urination, or constipation and adverse events. Data synthesis will be computed by RevManV.5.3.5 software when a data-analysis is allowed. Methodological quality will be evaluated with the risk of bias according to Cochrane Handbook. RESULTS: This study will provide high-quality evidence of acupuncture for uterine fibroids. CONCLUSION: The conclusion of this systematic review will provide evidence to judge whether acupuncture is an effective therapeutic intervention for patients with uterine fibroids. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019120484.

[Phosphorylated Focal Adhesion Kinase, Phosphinositides 3 Kinase and Aggrecan Genes and Proteins in Cartilage Cells Are Probably Involved in Needle Knife Intervention Induced Improvement of Knee Osteoarthritis in Rabbits].

OBJECTIVE: We have demonstrated that needle knife (acupotomy) treatment can improve knee osteoarthritis (KOA) in rabbits. The present study was designed to examine its effect on expression of phosphorylated focal adhesion kinase (p-FAK), phosphinositides 3 kinase (p-PI 3 K) and Aggrecan genes and proteins in the knee-joint cartilage tissues of KOA rabbits, so as to explore its partial molecular mechanism underlying improvement of KOA. METHODS: Forty-nine New Zealand male rabbits were randomly divided into normal control, model, model +inhibitor, needle knife, needle knife+ inhibitor, electroacupuncture (EA), EA +inhibitor groups (n=7 in each). The KOA model was established by modified Videman method (left hindlimb extension immobilization and ankle dorsal flexion 60°). Acupotomy relaxing manipulation was applied to the lateral collateral ligament and patellar ligament of the left knee-joint, two times a week for 4 weeks, and EA (2 Hz/100 Hz, 3 mA) was applied to the left "Liangmen" (ST 21), "Xuehai" (SP 10), "Neixiyan " (EX-LE 4) and "Dubi" (ST 35) for 20 min, three times a week, for 4 weeks. About 2 h before every needle-knife or EA treatment or at the corresponding time-point, intra-articular cavity injection of PF-562271(a specific antagonist of FAK, 200 µmol/L, 0.5 mL)was performed in the three inhibitor groups. The expression levels of p-FAK, p-PI 3 K, Aggrecan genes and proteins in the cartilage tissues were measured with quantitative Real-time PCR and Western blot, separately. RESULTS: After modeling, the expression levels of p-FAK and p-PI 3 K genes and proteins were significantly up-regulated (P<0.05, P<0.01), while those of Aggrecan protein and mRNA considerably down-regulated in the model group in comparison with the normal group (P<0.01). Following 4 weeks' needle-knife or EA treatment, the expression levels of p-FAK and p-PI 3 K and Aggrecan proteins in both EA and needle-knife groups, and Aggrecan mRNA in the needle knife group were significantly up-regulated (P<0.05, P<0.01). After administration of p-FAK antagonist, modeling-induced upregulation of expression of p-FAK mRNA and protein and p-PI 3 K protein, as well as modeling-induced down-regulation of Aggrecan mRNA and protein were significantly suppressed in the model+inhibitor group (P<0.05, P<0.01), and needle knife-induced and EA-induced up-regulation of expression of p-FAK, p-PI 3 K and Aggrecan mRNAs and proteins was notably suppressed respectively in comparison with the needle knife and EA groups (P<0.05, P<0.01). The effect of needle knife was significantly superior to that of EA in up-regulating p-PI 3 K and Aggrecan mRNAs as well as p-FAK, p-PI 3 K and Aggrecan proteins (P<0.05, P<0.01). CONCLUSION: Needle knife intervention can up-regulate the expression levels of p-FAK, p-PI 3 K and Aggrecan proteins and mRNAs in the cartilage tissue of the knee-joint in KOA rabbits, suggesting an involvement of FAK-PI 3 K signaling in the needle knife-induced improvement of KOA.

Effect of Acupotomy on FAK-PI3K Signaling Pathways in KOA Rabbit Articular Cartilages.

OBJECTIVE: By observing the needle-knife of KOA rabbit morphology, knee joint cartilage p-FAK, p-PI3K, Aggrecan gene, and protein expression, to study the effect of needle-knife to promote cartilage cell synthesis metabolism mechanism. METHOD: 49 male New Zealand rabbits, randomly divided into normal group (Z), model group (M), model-inhibitors (MP), needle-knife group (D), needle-knife inhibitors group (DP), electroacupuncture group (E), and electroacupuncture inhibitors (EP). RT-PCR and Western Blot were used to test each animal cartilage p-FAK, p-PI3K, and Aggrecan gene and protein expression level. RESULTS: Compared with N group, p-FAK and p-PI3K protein and mRNA expression of M group, D group, and E group increased (P < 0.05), while the protein and mRNA expression of Aggrecan reduced (P < 0.05). Compared with M group, p-FAK, p-PI3K, Aggrecan protein, and mRNA of E and D group increased (P < 0.05). Compared with E group, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression of D group increased (P < 0.05); after adding inhibitors, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression reduced (P < 0.05). CONCLUSION: Needle-knife therapy can promote the repairment of cartilage cells by activating FAK-PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism.

Acupuncture for Primary Dysmenorrhea: A Meta-analysis of Randomized Controlled Trials.

Context • Primary dysmenorrhea (PD) is one of the most common complaints among young women. Acupuncture has been widely applied as a therapeutic modality in China and abroad for PD; however, the evidence for its benefits is still not convincing. Objective • The study intended to conduct a systematic review of randomized, controlled trials (RCTs) to evaluate the evidence regarding the use of acupuncture in treating PD. Design • The research team retrieved reports for RCTs published in 7 databases from their inception to March 2016, with no language restrictions: PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure database, the Chinese Biomedical database, and the Wanfang database. Setting • The study was conducted at the Beijing University of Traditional Chinese Medicine (Beijing, China). Participants • Participants in the reviewed studies were women aged 14 to 49 y who had received a diagnosis of PD in the absence of any visible pelvic pathology. Interventions • The types of acupuncture included traditional acupuncture, electroacupuncture, ear acupuncture, scalp acupuncture, superficial acupuncture, electrosuperficial acupuncture, wrist-ankle acupuncture, and abdominal acupuncture. Outcome Measures • The primary outcome was pain relief measured using a visual analogue scale (VAS), a verbal rating scale (VRS), or a numerical rating scale (NRS). The secondary outcomes included (1) overall improvement as measured by the short-form McGill pain questionnaire or symptom scale based on the Clinical Study Guideline for New Developed Chinese Medicine, (2) menstrual distress as measured by the Menstrual Distress Questionnaire, (3) quality of life as measured by a validated scale (eg, the short-form 36), and (4) adverse effects. Results • Twenty-three trials enrolling a total of 2770 patients were included in the review. Overall, most trials were of poor quality. Among the trials, only 6 were evaluated as having a low risk of bias, 3 of which indicated that acupuncture was statistically more effective than sham acupuncture-mean difference (MD), -3.51; 95% confidence interval (CI), -5.27 to -1.75; P < .0001; I², 0%-or no treatment-MD, -21.95; 95% CI, -25.45 to -18.45; P < .00001; I², 0%-on the VAS (0 to 100 mm). Acupuncture also showed superiority to the control arms on the VRS, the NRS, and the McGill pain questionnaire, but those findings had been influenced by methodological flaws. Conclusions • The available evidence suggests that acupuncture may be effective for PD and justifies future high-quality studies.

[Effect of Electroacupuncture Serum on Proliferation of Cultured Multifidus Muscle Satellite Cells and Expression of Pax-7, MyoD and p-Akt].

OBJECTIVE: To observe the effect of electroacupuncture (EA) serum on proliferation of multifidus muscle sa-tellite cells (SCs) and expression of paired box transcription factor Pax-7, MyoD and protein kinase B (PKB or Akt) proteins of SCs, so as to explore its underlying mechanism in promoting repair of multifidus muscles. METHODS: Thirty-two SD rats were randomly assigned to control, model, EA-Weizhong (BL 40) and EA-Shenshu (BL 23) groups. The multifidus muscle injury (MFMI) model was established by injection of 0.5% bupivacaine hydrochloride (400 µL) into the bilateral L4-L5 paravertebral muscles (4 points, 100 µL for each point). EA stimulation was separately applied to bilateral BL 40 and BL 23 for 20 min, once daily, 4 days altogether. Blood samples of the abdominal artery of rats in the above mentioned 4 groups were separately collected for extracting serum, followed by deactivation and filtration, and then were respectively applied to the Dulbecco's Modified Eagle Media (DMEM) culturing each multifidus muscle SCs of the normal serum, model serum, EA-BL 40 serum and EA-BL 40 serum+LY 294002 (an inhibitor of phosphotidylinsitol-3-kinase, PI 3 K), EA-BL 23 serum and EA-BL 23 serum+LY 294002 groups for ana-lyzing the impact of EA serum on the proliferation state of SCs by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) methods, respectively. The expression of Pax-7, MyoD and phosphorylated (p)-Akt proteins of the cultured SCs was detected for characterization of SCs by Western blot. RESULTS: Compared with the normal serum group, the proliferation levels (detected by both CCK-8- and EdU) and the expression levels of MyoD and p-Akt proteins of SCs in the model serum group were significantly increased (P<0.05, P<0.01), while in comparison with the model serum group, the proliferation and expression levels of MyoD and p-Akt proteins of SCs were further significantly increased in both EA-BL 23 and EA-BL 40 serum groups (P<0.01, P<0.05), but not in the EA-BL 40 serum+LY 294002 and EA-BL 23 serum+LY 294002 groups (P>0.05), suggesting an involvement of PI 3 K in the proliferation of SCs. No marked differences were found in the proliferation levels between the EA-BL 23 and EA-BL 40 serum groups and in the expression levels of Pax-7 proteins among the 6 serum groups (P>0.05). CONCLUSIONS: Both EA-BL 40 and EA-BL 23 serum can promote proliferation of multifidus muscle SCs, which may contribute to the effect of EA intervention in promoting repair of the injured muscle, partially by way of Akt/PI 3 K signaling.