[Tiaoshen acupuncture for primary insomnia: a pilot randomized controlled trial].

OBJECTIVE: To observe the effects of Tiaoshen (regulating the spirit) acupuncture on cognitive function and sleep quality in patients with primary insomnia (PI). METHODS: Sixty patients with PI were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off, 1 case was excluded). The patients in the observation group were treated with acupuncture at Baihui (GV 20), Shenting (GV 24), Sishencong (EX-HN 1), and bilateral Benshen (GB 13), Shenmen (HT 7), Neiguan (PC 6), Sanyinjiao (SP 6). The patients in the control group were treated with shallow needling at non-effective points. Each treatment was provided for 30 min, once every other day, 3 treatments per week for 4 weeks. The Montreal cognitive assessment (MoCA), digit span test (DST), trail making test (TMT)-A, Pittsburgh sleep quality index (PSQI), and fatigue scale-14 (FS-14) were used to assess cognitive function and sleep quality before and after treatment, as well as in follow-up of 4-week after treatment completion. Correlation analysis was conducted between the differences in PSQI scores and differences in MoCA scores before and after treatment in the observation group. RESULTS: Compared with before treatment, the total score, visuospatial and executive function score and delayed memory score of MoCA as well as DST backward score were increased (P<0.01), while TMT-A time, PSQI and FS-14 scores were significantly reduced (P<0.01) after treatment and in follow-up in the observation group. Compared with before treatment, the PSQI score in the control group was reduced (P<0.01, P<0.05). After treatment and in follow-up, the observation group had significantly higher total score, visuospatial and executive function score, delayed memory score of MoCA, and DST backward score compared to the control group (P<0.05, P<0.01). In the observation group, the TMT-A time was significantly shorter than that in the control group (P<0.05, P<0.01), and the PSQI and FS-14 scores were significantly lower than those in the control group (P<0.01). In the observation group, there was a negative correlation between the difference in PSQI scores (post-treatment minus pre-treatment) and the difference in MoCA scores (post-treatment minus pre-treatment) (r=-0.481, P<0.01). A similar negative correlation was found between the difference in PSQI scores (follow-up minus pre-treatment) and the difference in MoCA scores (follow-up minus pre-treatment) (r=-0.282, P<0.05). CONCLUSION: Tiaoshen acupuncture could improve cognitive function, enhance sleep quality, and alleviate daytime fatigue in patients with PI. The improvement in cognitive function in patients with PI is correlated with the improvement in sleep quality.

Electroacupuncture Inhibits Ferroptosis Induced by Cerebral Ischemiareperfusion.

BACKGROUND: Electroacupuncture (EA) treatment has been recommended by World Health Organization (WHO) for years on cerebral ischemia treatment, but the specific mechanism is still elusive. Studies have shown that EA can relieve brain damage after ischemic stroke by inhibiting programmed cell death (PCD), such as apoptosis, necroptosis, and autophagy. Ferroptosis, a unique form of cell death, has been highlighted recently and found to occur in I/R injury. We, therefore, investigated whether EA plays an essential role in relieving cerebral I/R injury via ferroptosis. METHODS: The modified MCAO/R rats model was established and then divided into four groups with or without EA treatment. Neurological deficit score and TTC staining were used to evaluate the neurological deficit and infarct volume of each group. Transmission electron microscope (TEM) and immunofluorescence staining were applied for mitochondrial ultrastructure and ROS accumulation observation, respectively. The proteins and mRNA expression of ACSL4, TFR1, and GPX4 were assessed by western blot and qPCR to detect the progress of ferroptosis. RESULTS: EA treatment improved neurological deficits and reduced infarct volume. Moreover, EA significantly relieved the mitochondrial morphological changes and inhibited ROS Production in MCAO rats. In terms of its mechanism, EA obviously decreased the ACSL4 and TFR1 expressions and promoted GPX4 levels in MCAO/R model rats. CONCLUSION: These findings indicate that EA might play an essential role in relieving cerebral I/R injury via ferroptosis.

Effect of 'hand and foot acupuncture with twelve needles' on hemiplegia patients with 'qi deficiency and blood stasis' syndrome in the convalescent stage of Ischaemic stroke: study protocol for a randomised controlled trial.

BACKGROUND: Hemiplegia is a common sequela after stroke, and acupuncture is one of the most common physical therapies used to treat hemiplegia during the recovery stage after ischaemic stroke. 'Hand and foot acupuncture with twelve needles' is an acupuncture treatment performed after stroke. The principal objective of this study is to assess the efficacy and safety of 'hand and foot acupuncture with twelve needles' for hemiplegia in the convalescent stage of ischaemic stroke. METHODS: This is the protocol for a randomised, controlled clinical trial with two groups: a 'hand and foot acupuncture with twelve needles' group and a routine acupuncture group. A total of 208 participants will be randomly assigned to two different groups in a 1:1 ratio and will undergo conventional rehabilitation. Limb function will be evaluated by the simplified Fugl-Meyer assessment scale, Barthel Index, modified Ashworth scale and National Institute of Health stroke scale. The participants will be evaluated at baseline (on the day of enrolment) and followed up at 2 weeks, 1 month, 2 months and 3 months after enrolment. DISCUSSION: The results of this study will provide evidence on the effectiveness of 'hand and foot acupuncture with twelve needles' in the treatment of limb dysfunction that can be used for future evaluations. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1900021774 . Registered on 8 March 2019.

Effect of fire needle therapy on mild-moderate benign prostatic hyperplasia: Protocol for a randomized controlled pilot trial.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common non-cancerous disease of the prostate and leads to lower urinary tract symptoms in middle-aged and elderly males. Fire needle therapy could improve the lower urinary tract symptoms associated with mild-moderate BPH in clinical practice. The aim of the present pilot study is to assess the preliminary effects of fire needle therapy on mild-moderate BPH. METHODS: The present study is a prospective parallel randomized controlled pilot trial. A total of 60 eligible participants will be randomly assigned to a treatment or control group at a 1:1 ratio. The treatment group will receive fire needle therapy and the control group will receive watchful waiting with lifestyle advice and education regarding BPH. Participants will receive intervention for 4 weeks, with a follow-up period of 4 additional weeks. Adverse events will be recorded to assess the safety and tolerability of fire needle therapy for mild-moderate BPH. The primary outcome will be the change in the International Prostate Symptom Score. The secondary outcomes will include the change in the mean number of nightly urinations, the maximum urinary flow rate, the average flow rate, and the prostate volume as measured by a B-mode ultrasound device. All outcome measures will be observed at baseline and at 4 and 8 weeks following the beginning of treatment. DISCUSSION: The present study will provide evidence of the preliminary effects of fire needle therapy on mild-moderate BPH and indicate an optimal sample size for future studies.

Effects of moxibustion on symptoms of mild cognitive impairment: protocol of a systematic review and meta-analysis.

INTRODUCTION: Mild cognitive impairment (MCI) is considered the intermediate phase between normal age-related cognitive decline and dementia. Moxibustion has gained increased popularity for the management of MCI in China.This study aimed to evaluate the effects and safety of moxibustion on symptoms of MCI. METHODS AND ANALYSIS: Four English databases and six Chinese databases will be searched from their inception to October 2019: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, China National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, SinoMed, China Doctoral Dissertations Full-text Database and the China Master's Theses Full-text Database. Only clinical randomised controlled trials and the first period in randomised cross-over trial related to moxibustion for MCI will be included. The primary outcomes include the improvement of cognitive function, as measured by validated assessment tools. The secondary outcomes include changes in the activity of daily living scale, effective rate and the incidences of adverse events. The selection of studies, data extraction and risk of bias assessment will be carried out by two independent reviewers. Review Manager V.5.3 software will be used for statistical analyses. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The risk of bias of included studies will be assessed by the Cochrane Handbook risk of bias tool. Evidence quality will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: Ethics approval is not required as no private information from individuals are collected. The results will be published in a peer-reviewed journal or disseminated in relevant conferences. TRIAL REGISTRATION NUMBER: CRD42018112657.

Caudatin potentiates the anti-tumor effects of TRAIL against human breast cancer by upregulating DR5.

BACKGROUND: The ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to preferentially induce apoptosis in transformed cells while sparing most normal cells is well established. However, the intrinsic and acquired resistance of tumors to TRAIL-induced apoptosis limits its therapeutic applicability. PURPOSE: We investigated the effect of caudatin, a species of C-21 steroidal glycosides isolated from the roots of Cynanchum auriculatum, on TRAIL-induced apoptosis in human breast cancer cells. METHODS: Cell growth inhibition was evaluated by the CCK-8 assay. The cell cycle distribution was assessed by propidium iodide flow cytometry. Apoptosis was determined by TUNEL staining. Protein expression was detected by western blotting analysis. RESULTS: Caudatin enhanced TRAIL-induced apoptosis in human breast cancer cells. This sensitization was achieved by upregulating death receptor 5 (DR5). Knockdown of DR5 abolished the enhancing effect of caudatin on TRAIL responses. The caudatin-induced upregulation of DR5 was accompanied by increased expression of CHOP and phosphorylation of p38 MAPK and JNK. CHOP knockdown blocked caudatin-upregulated DR5 expression. Moreover, cotreatment of breast cancer cells with p38 MAPK and JNK inhibitors significantly counteracted the caudatin-induced expression of DR5. CONCLUSION: Our results showed that caudatin sensitized breast cancer cells to TRAIL-induced apoptosis through activation of CHOP, p38 MAPK and JNK-mediated upregulation of DR5 expression. The combination of TRAIL and caudatin may be a promising therapeutic approach for the treatment of breast cancer.

Effect of acupuncture on sleep quality and hyperarousal state in patients with primary insomnia: study protocol for a randomised controlled trial.

INTRODUCTION: Primary insomnia (PI) is commonly defined as a state of having disturbed daytime activities due to poor night-time sleep quality. Studies have demonstrated that it is a disorder of 24 h hyperarousal, expressed in terms of physiological, cognitive and cortical activation. Acupuncture is considered to be beneficial to restore the normal sleep-wake cycle. The aim of the trial is to assess the therapeutic effects of acupuncture on sleep quality and hyperarousal state in patients with PI. METHODS AND ANALYSIS: This study is a randomised, patient-assessor-blinded, sham controlled trial. -88 eligible patients with PI will be randomised in a ratio of 1:1 to the intervention group (real acupuncture) and control group (sham acupuncture, superficial insertion at irrelevant acupuncture points). Acupuncture intervention will be given to all participants three times a week for 4 weeks, followed up for 8 weeks.The primary outcome measures are the Pittsburgh Sleep Quality Index (PSQI) and Hyperarousal scale (HAS). The secondary outcomes are Fatigue scale-14 (FS-14), polysomnography (PSG), heart rate variability (HRV) and Morning Salivary Cortisol Level (MSCL). Outcomes will be evaluated at baseline, post-treatment period and 8 weeks follow-up. All main analyses will be carried out on the basis of the intention-to-treat principle. ETHICS/DISSEMINATION: This protocol has been approved by the Medical Ethical Committee of Beijing Traditional Chinese Medicine Hospital (Beijing TCM Hospital) on 5 January 2015. The permission number is 2014BL-056-02. The study will present data concerning the clinical effects of treating primary insomnia with acupuncture. The results will help to demonstrate if acupuncture is an effective therapy for improving sleep quality in association with a decreased hyperarousal level as a possible underlying mechanism. The findings from this study will be shared with the healthcare professionals, general public and relevant organisations through publication of manuscripts and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN16079489; Pre-results.

Efficacy of acupuncture for primary insomnia: a randomized controlled clinical trial.

Objectives. To investigate the six-week influence of acupuncture on sleep quality and daytime functioning in primary insomnia. Methods. The study was a double-dummy, single-blinded, randomized, placebo-controlled clinical trial. A total of 180 patients with primary insomnia were randomly assigned to 3 groups: verum group underwent verum acupuncture plus placebo; estazolam group underwent estazolam plus sham acupuncture; sham group underwent sham acupuncture plus placebo. The outcome was measured by Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the 36-item short-form health survey (SF-36). Results. The three groups showed significant improvement compared with the pretreatment baseline. Compared with the other two groups, the verum group reported improved sleep quality (SQ) and vitality (VT), decreased daytime dysfunction (DD) and sleepiness (ESS score). The differences were kept from the treatment period to the end of the trial. Discussion. Verum acupuncture appeared to be more effective in increasing sleep quality and daytime functioning than sham acupuncture and estazolam. Trial Registration. The trial is registeded with ClinicalTrials.gov ISRCTN12585433.

[Randomized controlled study on proximal needling for sciatica].

OBJECTIVE: To compare the effect of proximal needling and routine acupuncture for sciatica. METHODS: Sixty patients with sciatica were randomly divided into a proximal needling group and a routine acupuncture group, 30 cases in each group. The proximal needling group was treated by proximal needling at Huantiao (GB 30). The routine acupuncture group was treated by acupuncture at Huantiao (GB 30), Yinmen (BL 37), Weizhong (BL 40), Yanglingquan (GB 34) etc. with routine acupuncture method. The Numerical Pain Rating Scales (NPRS) the Japanese Orthopaedic Association Scores (JOA) were all observed before, after treatment and in following up. RESULTS: The total effective rates were 100.0% (30/30) in both groups, with no significant difference between the two groups (P > 0.05) in 3 month follow up. After 5 treatments, the total improvement rate of 100.0% (30/30) in the proximal needling group was super to that of 80.0% (24/30) in the routine acupuncture group. The NPRS and JOA scores were all improved significantly after 5 treatment and in following up compared with those before treatment in two groups (all P < 0.01). After treatments, the improvement of the NPRS and JOA scores in the proximal needling group was greater than those in the routine acupuncture group (both P < 0.05). CONCLUSION: The proximal needling treatment has rapid and obvious therapeutic effect and analgesia on sciatica.

[Professor He Pu-ren: the founder of Santong method of acupuncture and moxibustion].

Professor He Pu-ren, the founder of Santong method of acupuncture and moxibustion, is a well known acupuncturist at home and abroad. His main contributions include combined martial arts and Chinese medicine, showing obvious therapeutic effect; taking part in establishment of The Department of Acupuncture, Beijing Chinese Medicine Hospital; creating Santong method of acupuncture and moxibustion; advocating fire needle therapy; writing medical books and teaching students; advocating the culture of acupuncture; making the metal model of acupuncture and moxibustion, and others. His achievements have become an important part of acupuncture and moxibustion science.

A potential target associated with both cancer and cancer stem cells: a combination therapy for eradication of breast cancer using vinorelbine stealthy liposomes plus parthenolide stealthy liposomes.

The cancer stem cells play a critical role in both initiation and relapse of the cancers as they are resistant to the most of cytotoxic agents and able to proliferate indefinitely. Vinorelbine stealthy liposomes and parthenolide stealthy liposomes were developed for providing beneficial pharmacological properties and to eradicate cancer stem cells and non-stem cancer cells together by a combination therapy. Cytotoxicity and cancer stem-like cells (side population, SP) identification were performed on human breast cancer cell lines MCF-7 and MDA-MB-231. SP cells were further sorted from MCF-7 cells and characterized. Inhibitory effect was evaluated on the sorted SP and non-SP cells. Antitumor activity was evaluated on MCF-7 xenografts in nude mice. SP cells were identified with a higher percentage in MCF-7 cells (3.8%) and lower in MDA-MB-231 cells (0.6%). Both vinorelbine and parthenolide inhibited the proliferation in MCF-7 and MDA-MB-231 cells. As compared to non-SP cells, inhibitory effect of vinorelbine in the SP cells was lower while a robust inhibitory effect was observed when applying vinorelbine in combination with parthenolide. In the MCF-7 xenografts, stealthy liposomal vinorelbine plus stealthy liposomal parthenolide produced a full inhibitory effect. This combination therapy may provide a potential strategy for eradication of breast cancer by targeting cancer together with cancer stem cells.

[Summarization of professor He Pu-ren's channel syndrome differentiation for treatment of complicated and difficult diseases].

Channel syndrome differentiation is a more commonly-used syndrome differentiation method of Professor HE Pu-ren clinically, which includes the 3 aspects: differentiation of diseases and syndromes on the channel parts along the body surface; differentiation of diseases and syndromes of the internal organs connected with the channels; differentiation of qi and blood of the channels. According to results of the channel syndrome differentiation, with flexible application of the HE's Santong methods and selection of corresponding treatment program, many complicated and difficult diseases are cured.

[He's Santong needling method for neurological functional deficit in the patient of ischemic apoplexy: randomized controlled multi-central study].

OBJECTIVE: To observe the therapeutic effect of He's Santong needling method on neurological functional deficit in the patient of ischemic apoplexy, and search for an effective method for treatment of ischemic apoplexy. METHODS: According to the randomized and multi-central trial principle, 319 cases enrolled were randomly assigned to an observation group of 161 cases and a control group of 158 cases. The observation group were treated with He's Santong needling method, i. e. blood letting, puncturing with a red-hot needle and filiform needle therapy by stages, and the control group were treated with acupuncture at 12 points of the hand and foot routinely selected in the department, once daily. After treatment of 30 days, changes of neurological functional deficit score were investigated in the two groups. RESULTS: The total effective rate was 91.93% in the observation group and 70. 25% in the control group with a significant difference between the two groups (P<0.05); there was no significant difference in changes of the neurological functional deficit score between the patients at the acute stage and the convalescence (P > 0.05). CONCLUSION: The therapeutic effect of He's Santong needling method on ischemic apoplexy at acute stage or convalescence is better than that of the routine point selection.

Sublingual delivery of insulin: effects of enhancers on the mucosal lipid fluidity and protein conformation, transport, and in vivo hypoglycemic activity.

The purposes of this study were to evaluate effects of enhancers for sublingual delivering insulin on the mucosal lipid fluidity and protein conformation, transport, and in vivo hypoglycemic activity in normal rats. The effects on sublingual mucosa, and aggregation states of insulin were estimated using fluorescence polarization, and circular dichroism method, respectively. The human immortalized oral epithelial cell monolayer was used for evaluating transport of insulin. Hydroxylpropyl-beta-cyclodextrin (HP-beta-CD), chitosan, polyethylene-polypropylene glycol, polyoxyethylene lauryl ether, polysorbate 80, egg lecithin, or oleic acid, was used as a penetration enhancer, respectively. The fluidity of sublingual mucosal lipid was markedly reduced by these enhancers excluding polysorbate 80, and the secondary structure of the mucosal proteins was also influenced by these enhancers. The hexamers of insulin were dissociated to monomers only by chitosan, polyoxyethylene lauryl ether, and egg lecithin. Nonetheless, plasma glucose levels in normal rats were significantly lowered after sublingual administration of insulin with an enhancer compared with those without an enhancer at the same time-point. The enhancing effects may be due to one or multiple factors: increasing the mucosal lipid fluidity, directly loosing the tight junction of epithelia, and dissociating the hexamers of insulin to monomers. Among these, the opened tight junction may correlate most with the enhancing effect in the mucosal permeability. Because the aggregates of insulin exist, the dissociation of the aggregates by an enhancer would benefit the permeability.

CDNA cloning of a short isoform of human liver NADP (H) -dependent retinol dehydrogenase/reductase and analysis of its characteristics.

In this report we found a new short PCR product when we amplified a 635 bp of NRDR fragment by RT-PCR. With 3'-Race and 5'-Race,we obtained two full-length cDNA sequences from human liver tissue,one 1 261 bp NRDR cDNA,another 1 003 bp NRDR isoform (NRDRiso,GenBank accession number:AY071856). The NRDR gene comprises eight exons and seven introns. The NRDRiso cDNA is produced by alternative splicing of NRDR cDNA, with the removal of 4, 5, 6 exons composed of consecutive 258 bp. The open reading frames of the NRDRiso cDNA predict a single polypeptide of 174 amino acids with the calculated minimum molecular mass of 18.6 kDa.

[Cloning and analysis of NADP(H) -dependent retinol dehydrogenase/reductase gene: a novel member of short-chain dehydrogenase/reductase].

The total RNA was purified from bovine liver. According to the cDNA sequences of human, mouse and rabbit NADP(H)-dependent retinol dehydrogenase/reductase (NRDR) gene, the gene-specific primers were designed and synthesized. In this study, we cloned the full-length cDNA of bovine liver NRDR by rapid amplification of cDNA ends (RACE) and RT-PCR methods. The bovine NRDR cDNA is 1 266 bp and the ORF, like other NRDR cDNAs, is 783 bp, encoding 260 amino acid residues. The bovine NRDR exhibited the identity in amino acid sequence to those of human, mouse and rabbit NRDR. It contains short-chain dehydrogenase/reductase (SDR) conservative motif and the peroxisomal targeting singal (PTS1) sequence at their C-terminal. In conclusion, the bovine NRDR cDNA was successfully cloned with RACE methods and submitted to GenBank(AF487454), whose nucleotide sequence and the deduced amino acid sequence were analyzed with Bioinformatics, that belongs to a novel peroxisomal SDR superfamily and plays an important role in the rate-limiting step of synthesizing retinoic acid. This is the first report suggesting the SDR participation of mammalian peroxisomers in retinoid metabolism and it provides a reliable foundation to further investigate the biological function of this protein and retinoic acid biosynthesis.

[Sequencing and bioinformatic analysis of NRDRiso cDNA].

This study describes the cDNA sequencing and the bioinformatic analysis of a novel NADP(H)-dependent retinol dehydrogenase/reductases isoform (NRDRiso). Based upon the concensus sequences of human and mouse NRDR coding region, we have identified a short 377 bp RT-PCR product from human liver tissue. The cDNA sequence of a NRDR isoform was then isolated using RACE approach and its sequence was analysed. The full-length cDNA is 1,003bp in length and was submitted to GenBank as NADP-dependent retinol dehydrogenase/reductase short isoform (NRDRiso). The open reading frames of NRDRiso cDNA is 525 bp.