Abstract:Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance. New devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness, skin thickness, size of the sensing electrode, pressure applied on the electrode, interelectrode distance, room temperature, and humidity. Morphological studies have identified that blood vessels, hair follicles, and nervous components are enhanced in the meridians/acupoints, which represent areas of potentially high neuronal activity. Recent evidence shows that nitric oxide (NO) concentrations are enhanced in skin acupoints/meridians. L-arginine-derived NO synthesis modifies skin norepinephrine (NE) synthesis/release in acupoints/meridians, and NO-NE activations play an important role in mediating the skin conductance responses to electrical stimulation. NOergic signaling molecules interact with gap junction and transient receptor potential vanilloid type-1. Other studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain area. Pathological body conditions caused considerable changes in skin conductance or impedance at acupoints. Although systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field, the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components, and NOergic signaling molecules and neuropeptides involved in the skin low resistance at acupoints. The increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system, which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.
Keywords:acupuncture points;skin electric resistance;nitric oxide;norepinephrine;transient receptor potential vanilloid type-1;neuropeptides
Abstract:Objective:To assess the effect and safety of bloodletting puncture at hand twelve Jing-Well points (HTWPs) in acute stroke patients with conscious disturbance.Methods:In this multi-center and randomized controlled trial, 360 patients suffered from ischemic or hemorrhagic stroke with conscious disturbance within 48 h from the onset of symptom were divided into bloodletting (180 cases) and control (180 cases) groups using a block randomization. Patients in both groups received routine Western medicine, and patients in the bloodletting group received additional bloodletting puncture at HTWPs on admission immediately before conventional treatment. The primary outcome measure was Glasgow Coma Scale (GCS) score and the secondary outcomes included blood pressure, respiratory rate and pulse rate. All variables were evaluated at baseline (before bloodletting), 0 (after bloodletting immediately), 15, 30, 50 and 80 min post bloodletting.Results:At 80 min post bloodletting, the proportion of patients with improved consciousness in the bloodletting group was greater than the control group (P<0.05). In the separate analysis of moderate consciousness disturbance subgroup, bloodletting therapy benefited ischemic patients, and improved the eye and language response of GCS score at 15, 30, 50, 80 min post bloodletting (P<0.05 or P<0.01). No significant differences were observed regarding the secondary outcomes between two groups (P>0.05).Conclusion:The bloodletting puncture at HTWPs was safe and could improve conscious levels of ischemic stroke patients, highlighting a first-aid intervention for acute stroke. (Registration No. ChiCTR-INR-16009530)
Keywords:acute stroke;bloodletting;Jing-Well point;conscious disturbance;randomized controlled trial;Glasgow Coma Scale
Abstract:Objective:To conduct a pilot trial to explore the effectiveness and safety of moxibustion robots in treating primary dysmenorrhea (PD) and evaluate its feasibility in clinic.Methods:A total of 70 participants with PD were allocated to either moxibustion robot (MR) group (35 cases) or manual moxibustion (MM) group (35 cases) using computer-generated randomization. One acupoint Guanyuan (CV 4) was selected to receive moxa heat stimulation. Two groups of participants were given 3 menstrual cycles of MM and MR treatment respectively (once a day, 5 days a session) and received another 3 menstrual cycles follow-up. The degree of pain was evaluated by short-form McGill pain questionnaire (SF-MPQ) and the symptoms of dysmenorrhea were evaluated by Cox Menstrual Symptom Scale (CMSS). The safety was measured by the occurrence rate of adverse events (AEs), including burns (blisters, red and swollen), itching, bowel changes, menstrual cycle disorder, menorrhagia and fatigue, etc.Results:A total of 62 patients completed the trial, 32 in MR group and 30 in MM group. Compared with baseline, scores of SF-MPQ and CMSS significantly decreased in both groups (P<0.05), and no significant difference was observed between the two groups in the 3rd and 6th menstrual cycles (P>0.05). The total occurrence rate of AEs in MR group was 2.1%, which was significantly lower than MM group (7.2%, P<0.05).Conclusion:MR has the same effect as MM at SF-MPQ and CMSS in patients with PD. However, MR is safer than MM (Trial registration No. ChiCTR1800018236).
Keywords:primary dysmenorrhea;moxibustion robot;randomized controlled pilot trial
Abstract:Objective:To explore the effect of low-frequency magnetic stimulation at Shenmen (HT 7) acupoint on blood oxygen levels in the prefrontal cortex of healthy subjects.Methods:Functional near-infrared spectroscopy (fNIRS) technology was used to collect real-time data of oxygenated hemoglobin (oxy-Hb) in the prefrontal cortex of 16 healthy subjects at resting state and low-frequency magnetic stimulation of Shenmen. The mean and integral values of blood oxygen concentration were analyzed.Results:Compared with the resting state, the mean and integral values of blood oxygen concentration decreased during the task period, recovery period, and the whole process in the magnetic stimulation of Shenmen acupoint (P<0.05). In particular, the difference was statistically significant in the recovery period (P<0.01).Conclusions:The prefrontal cortex was widely activated and produced an immediate effect by reducing the local blood oxygen concentration at lowfrequency magnetic stimulation of Shenmen acupoint, which verifies the sedative effect of Shenmen acupoint.
Keywords:Shenmen acupoint;transcranial magnetic stimulation;functional near-infrared spectroscopy;prefrontal lobe;healthy subjects
Abstract:Objective:To assess whether adjuvant Chinese patent medicines (CPMs) to standard treatment could reduce recurrent bleeding after variceal bleeding in cirrhotic patients.Methods:This study retrospectively collected 555 consecutive patients who recovered from variceal bleeding. A population-based cohort study was established depending on if adjuvant CPMs were administered to prevent rebleeding. A total of 139 patients who had taken ≥28 cumulative defined daily doses (cDDDs) of CPMs were included in the CPMs cohort, and 416 patients who used <28 cDDDs of CPMs were enrolled in the non-CPMs cohort. On evaluation of rebleeding incidence, 1: 2 propensity score matched was used to estimate for reducing bias. Patients were followed for at least 12 months. The end-point of this study was clinically significant esophagogastric variceal rebleeding.Results:Following multivariate analysis, CPMs therapy was an independent factor for variceal rebleeding [adjusted hazard ratio (AHR)=0.657; 95% confidence interval=0.497–0.868; P=0.003]. After the 1:2 propensity score matching, a significant reduction (23.5%) in the incidence of variceal rebleeding in patients was observed, from 58.3% in the non-CPMs cohort to 44.6% in the CPMs cohort (modified log-rank test, P=0.002) within a year. The AHRs for rebleeding were 0.928, 0.553, and 0.105, for 28–90 cDDDs, 91–180 cDDDs, and >180 cDDDs of CPMs, respectively. The median rebleeding interval in the CPMs cohort was significantly larger compared with the non-CPMs cohort (113.5 vs. 93.0 days; P=0.008).Conclusion:Adjuvant CPMs to standard therapy can significantly reduce the incidence of variceal rebleeding and delay the time to rebleeding.
Abstract:Objective:To investigate the cardioprotective effect of Danqi Tablet (DQT, 丹七片) on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).Methods:Rat ischemic heart model was induced by ligation of left anterior descending coronary artery. Totally 40 Sprague-Dawley rats were randomly divided into sham group, model group, DQT group (1.5 mg/kg daily) and trimetazidine (TMZ) group (6.3 mg/kg daily) according to a random number table, 10 rats in each group. Twenty-eight days after continuous administration, cardiac function was assessed by echocardiography and the structures of myocardial cells were observed by hematoxylineosin staining. The level of adenosine triphosphate (ATP) in myocardial cells was measured by ATP assay kit. Expressions level of key transcriptional regulators, including PGC-1α, Sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK), and downstream targets of PGC-1α, such as mitofusin 1 (MFN1), mitofusin 2 (MFN2) and superoxide dismutase 2 (SOD2) were measured by Western blot. Expression level of PGC-1α was examined by immunohistochemical staining.Results:The rat ischemic heart model was successfully induced and the heart function in model group was compromised. Compared with the model group, DQT exerted cardioprotective effects, up-regulated the ATP production in myocardial cells and inhibited the infiltration of inflammatory cells in the margin area of infarction of the myocardial tissues (P<0.01). The expressions of PGC-1α, SIRT1 and AMPK were increased in the DQT group (all P<0.05). Furthermore, the downstream targets, including MFN1, MFN2 and SOD2 were up-regulated (P<0.05 or P<0.01). Compared with the TMZ group, the expression levels of PGC-1α, MFN1 and SOD2 were increased by DQT treatment (P<0.05 or P<0.01).Conclusions:DQT regulated energy metabolism in rats with ischemic heart model through AMPK/SIRT1-PGC-1α pathway. PGC-1α might serve as a promising target in the treatment of ischemic heart disease.
Abstract:Objective:To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE).Methods:Ten out of 85 SD rats were randomly selected as the sham group (n=10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and highdose of Tojapride as well as omeprazole groups (n=10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered with 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κBp65), κB kinase beta (IKKβ), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively.Results:The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKβ levels were significantly higher in the model group (P<0.05). However, the IKKβ levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (P<0.01 or P<0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05).Conclusions:Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKβ expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.
Abstract:Objective:To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes.Methods:The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C.C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase α (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters.Results:PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05).Conclusion:PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.
Keywords:Panax quinquefolium saponin;Chinese medicine;neonatal rat ventricular myocytes;hypoxiareperfusion;energy metabolism;adenosine monophosphate-activated protein kinase αpathways
Abstract:Objective:To investigate the effects of Weikang Capsule (胃康胶囊, WKC) on aspirin-related gastric and small intestinal mucosal injury by magnetically controlled capsule endoscopy (MCCE).Methods:Patients taking enteric-coated aspirin aged 40–75 years were enrolled in Beijing Anzhen Hospital, Capital Medical University from January 2019 to December 2019. The patients continued taking aspirin Tablet (100 mg per day) and underwent MCCE before and after 1-month combined treatment with WKC (0.9 g per time orally, 3 times per day). The gastrointestinal symptom score, gastric Lanza score, the duodenal, jejunal and ileal mucosal injury scores were used to evaluate the gastrointestinal injury before and after treatment. Adverse events including nausea, vomiting, abdominal pain, abdominal distension, abdominal discomfort, dizziness, or headache during MCCE and combined treatment were observed and recorded.Results:Twenty-two patients (male/female, 13/9) taking enteric-coated aspirin aged 59.5±11.3 years with a duration of aspirin use of 28.0 (1.0, 48.0) months were recruited. Compared with pre-treatment, the gastrointestinal symptom rating scale scores, gastric Lanza scores, and duodenal mucosal injury scores were significantly reduced after 1-month WKC treatment (P<0.05), and jejunal and ileal mucosal injury scores showed no obvious change. No adverse events occurred during the trial.Conclusions:WKC can alleviate gastrointestinal symptoms, as well as gastric and duodenal mucosal injuries, in patients taking enteric-coated aspirin; it does not aggravate jejunal or ileal mucosal injury, which may be an effective alternative for these patients (Clinical trial registry No. ChiCTR1900025451).
Abstract:Objective:To assess the efficacy and safety of Taohong Siwu Decoction (桃红四物汤, TSD), a Chinese herbal compound prescription, in patients with angina pectoris (AP).Methods:Randomized clinical trials (RCTs) comparing TSD plus conventional treatment (CT) with CT plus placebo or CT only in the patients with AP were searched in PubMed, Cochrane Library, Excerpta Medica Database, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific Journal Database, Chinese Clinical Trial Registry and International Clinical Trial Registry from their inception to March 2017. The primary outcomes include a composite event of death, acute myocardial infarction (AMI), and target vessel revascularization. The secondary outcomes include angina symptom, electrocardiogram (ECG) improvement and serum high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. The methodological quality of included studies and extracted available data were assessed. RevMan 5.3 software was used to conduct statistical analysis. The relative risk (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated. A funnel plot was used to evaluate the publication bias.Results:Among 204 studies identified in the literature search, 12 trials including 959 patients with AP met the inclusion criteria. No studies reported the primary outcome including death, AMI and target vessel revascularization. TSD combined with CT showed significant improvement in relieving angina symptom [RR=3.70, 95% CI (2.42, 5.67)] and ECG [RR=3.20, 95% CI (2.20, 4.65)] compared with CT alone. TSD combined with CT reduced the serum hs-CRP, TG, TC and LDL-C levels compared with CT alone. No serious adverse events were reported in TSD combined with CT.Conclusions:TSD combined with CT has a potential benefit on relieving AP without significant adverse events. However, the efficacy on the cardiovascular events needs to be assessed by more rigorously-designed, largescale, and multi-center RCTs in future.
Keywords:Taohong Siwu Decoction;systematic review;meta-analysis;angina pectoris;randomized controlled trial;Chinese medicine
Abstract:Warburgia ugandensis (W. ugandensis) is known by various names, including the East African greenheart, pepper bark tree, and Ugandan greenheart, and has a rich history of extensive use in the treatment of a host of human diseases in many African countries. This review is based on the botany and ethnopharmacological potentials of W. ugandensis for the treatment of pneumonia, asthma, malaria, candidiasis, skin infections, human immunodeficiency virus opportunistic infections, diarrhea, and measles given the common use in the management of these diseases. Extracts from W. ugandensis have strong antimicrobial activities against a broad spectrum of pathogens mainly because of the presence of abundant terpenoids, drimane, and coloratane type sesquditerpenoids amongst which are ugandensial, warburganal, mukaadial, and other secondary metabolites, such as tannins, flavonoids, saponins, steroids, and mannitol. This group of compounds gives the plant a high therapeutic value. Based on the review, there is a need for identification and isolation of the highly therapeutic phytochemical constituents and a drive for more preclinical and clinical trials to validate the safety and efficacy of the extracts. This gives basis for the potential development of new therapeutic drugs from the plant.