Abstract:Background:Knee osteoarthritis (OA) is a major cause of disability among the older adults. Few treatments are safe and effective. Moxibustion is commonly used in treating knee OA in Chinese medicine (CM). CO2 Laser moxibustion device is a substitute for traditional moxibustion, which mimics the effects of traditional moxibustion. More data are needed to support its application in knee OA.Objective:The trial aims to assess the effect and safety of CO2 laser moxibustion in patients with knee osteoarthritis compared with a sham control.Methods:This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO2 laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.Discussion:CO2 laser moxibustion device, designed as a substitute for CM moxibustion, is easy to use and control with no choking smoke and smell, and is a plausible method for double-blind research. This study would provide rigorous evidence for the effect and safety of CO2 laser moxibustion in treating knee OA (Trial registration No.: ISRCTN15030019).
Abstract:Background:The incidence of cognitive impairment (CI) is gradually increasing, which has attracted more attention from medical researchers worldwide. Definitive mechanisms of pathogenesis remain elusive, and there are few medications that have been proven effective for CI. The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases, including CI.Objective:The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules (GLJC,龟龄集胶囊) in treating mild-to-moderate CI with Shen (Kidney) and marrow deficiency syndrome.Methods:This is a randomized, double-blind, positive-controlled, multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm. Individuals in the experimental arm (174 cases) took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day. Individuals in the active comparator arm (174 cases) took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day. The intervention period included two sessions over 24 weeks. The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment, which was defined as an increase in the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) Scale. The secondary outcomes were improvement in independence, daily living ability, and Chinese medicine (CM) syndrome, which were measured with the Alzheimer's disease Rating Scale-Cognitive Project (ADAS-Cog), Clinical Dementia Rating (CDR) Total Score, Activities of Daily Living (ADL) Total Score and the Chinese Medicine Symptom Scale (CM-SS), respectively. Serum acetylcholine, acetylcholinesterase, bax and bcl-2 were monitored to explore the mechanism of GLJC on CI. In addition, safety measures, including vital signs, electrocardiography, laboratory indicators (full blood count, kidney and liver function tests, routine urine test and routine stool test) and adverse events, were also recorded.Discussion:The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome. If successful, the results would provide a viable treatment for patients with mild-to-moderate CI. (Clinical Trials.gov. ID: NCT03647384. Registered on 23 August 2018)
Abstract:Objective:To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills (速效救心丸, SXJ) on myocardial ischemia and reperfusion (I/R) injury.Methods:Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion, the mice were then divided into the sham group (n=7), the I/R group (n=13), the tirofiban group (TIR, positive drug treatment, n=9), and the SXJ group (n=11). Infarct size (IS), risk region (RR), and left ventricle (LV) were analyzed with double staining methods. In addition, H9C2 rat cardiomyocytes were cultured with Na2S2O4 to simulate I/R in vitro. The phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2), protein kinase B (AKT), glycogen synthase kinase-3β (GSK3β), and protein expression of GATA4 in nucleus were detected with Western blot assay.Results:The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group (SXJ, 22.4%±6.6%; TIR, 20.8%±3.3%; vs. I/R, 35.4%±3.7%, P<0.05, respectively). In vitro experiments showed that SXJ increased the Na2S2O4-enhanced phosphorylation of AKT/GSK3β and nuclear expression of GATA4.Conclusion:SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3β and GATA4 signaling pathways.
Keywords:myocardial ischemia and reperfusion injury;Suxiao Jiuxin Pills;GATA4;Chinese medicine;mouse
Abstract:Objective:To investigate the therapeutic and synergistic effects of QHC (combination of quercetin (Q), hirudin (H) and cinnamaldehyd (C)) on Schwann cell differentiation and myelination against high glucose (HG) induced injury.Methods:Primary-culture Schwann cells exposed to HG (50 mmol/L) for 72 h and Schwann cell–dorsal root ganglion (DRG) neuron cocultures exposed to HG (50 mmol/L) for 7 days were employed as in vitro model of diabetic neuropathy. The cells were randomly divided into 10 groups: control (CON, 25 mmol/L glucose), HG (50 mmol/L glucose), HG plus 10 μmol/L quercetin (Q), HG plus 0.04 IU/mL hirudin (H), HG plus 100 nmol/L cinnamaldehyd (C), HG plus 10 μmol/L quercetin and 0.04 IU/mL hirudin (QH), HG plus 10 μmol/L quercetin and 50 nmol/L cinnamaldehyd (QC), HG plus 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd (HC), HG plus 10 μmol/L quercetin, 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd (QHC) or 10 μmol/L U0126. Cell differentiation was evaluated by periaxin immunofluorescence staining. The protein expression levels of myelin protein zero (P0), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), extracellular signal-regulated kinase (ERK), p-ERK, p-c-Jun, c-Jun, notch intracellular domain (NICD) and the mRNA expression levels of P0, MBP, MAG, Krox-20, Notch1 and Jagged1 were detected by Western blotting and real-time quantitative PCR analysis. The secretion of ciliary neurotrophic factor (CNTF) was determined by enzyme-linked immunosorbent assay (ELISA). The number and length of the myelin segments were evaluated by MBP immunofluorescence staining. The expression and the location of p-ERK in cocultures were detected by MAG and p-ERK immunofluorescence double staining.Results:Co-treatment with Q, C, H and their combination promoted Schwann cell differentiation, increased CNTF secretion, up-regulated the protein and mRNA expressions of myelin, and increased the number and length of the myelin segments (P<0.01 or P<0.05). In particular, the combination therapy of Q, H and C was superior to the respective monotherapy (P<0.01). Combination therapy of QHC exhibited higher inhibitory activities for ERK signaling related molecules than each monomer or the combination of the two monomers (P<0.01).Conclusions:QHC combination yielded synergy in promoting Schwann cell differentiation and myelination and the protective effect may involve in the inhibition of ERK signaling pathway, providing scientific evidence for better understanding of combination of Q, H and C in clinical applications.
Abstract:Objective:To investigate the effect of Modified Xiaochaihu Decoction (MXD, 加味小柴胡汤) on collagen degradation in rats with chronic pancreatitis (CP).Methods:Rats were injected dibutyltin dichloride (DBTC, 7 mg/kg of body weight) into the right caudal vein to induce CP model. Thirty heallhy male Wistar rats were randomly divided into three groups by a random number table: the control, the model and the treatment groups. Rats of treatment group were administered MXD (10 g/kg of body weight) orally once daily starting from the day post-model establishment. Pancreatic tissues were harvested after 28-day feeding and fibrosis was evaluated by picro-sirius red staining. The contents of collagen type Ⅰ and Ⅲ were detected using enzymelinked immunosorbent assay (ELISA), the expression of matrix metalloproteinase 13 (MMP13) and tissue inhibitor of metalloproteinase 1 (TIMP1) was analyzed by Western blot and real-time polymerase chain reaction (PCR).Results:The fibrosis scoring of pancreatic tissues, the concentrations of collagen type Ⅰ and Ⅲ, the expression levels of MMP13 and TIMP1 proteins and mRNA in the model group were all increased compared with the control group (P<0.05). After treatment with MXD, the fibrosis scoring of pancreatic tissues, the concentrations of collagen type Ⅰ and Ⅲ, the expression levels of MMP13 proteins and mRNA in the teatment group were all decreased compared with the model group (P<0.05), but there were no significant differences in the expression levels of TIMP1 proteins and mRNA (P>0.05).Conclusion:MXD could promote collagen degradation and reverse pancreatic fibrosis in CP rats via a mechanism involve up-regulation of MMP13 expression.
Abstract:Objective:To investigate the effect of hydro-ethanolic extract of Zataria multiflora (Z. multiflora) on endothelin level, total and differential white blood cells (WBC) count of sensitized guinea pigs.Methods:Five groups of guinea pigs sensitized to ovalbumin (OA) were given drinking water alone (group S), drinking water containing three concentrations of Z. multiflora (0.2, 0.4 and 0.8 mg/mL as groups S+Z1, S+Z2 and S+Z3) and dexamethasone (group S+D), n=6 for each group. The endothelin levels as well as total and differential WBC count in blood of sensitized and control guinea pigs were evaluated using enzyme linked immunosorbent assay method, and hemocytometer and Wright-Giemsa's staining of blood sample smear respectively.Results:Blood endothelin levels, total and most differential WBC count were increased but lymphocytes decreased in sensitized animals compared to controls (all P<0.01). In groups S+D, S+Z2 and S+Z3 endothelin level, total and differential WBC counts were significantly improved compared with group S (P<0.01). Although, all measured parameters in group S+Z1 was lower than group S+D (P<0.01), some parameters in group S+Z3 were greater than in group S+D (P<0.05 to P<0.01).Conclusion:The results showed an anti-inflammatory effect of Z. multiflora extract in sensitized guinea pigs, which may suggest a therapeutic potential for the plant on asthma.
Abstract:Objective:To evaluate the efficacy of electro-acupuncture (EA) or transcutaneous electrical acupoint stimulation (TEAS) on perioperative cerebral blood flow (CBF) and neurological function in ischemic stroke (IS) patients undergoing carotid artery stenting (CAS).Methods:In total, 124 consecutive IS patients were randomly allocated to the EA, TEAS, and sham groups (groups A, T, and S; 41, 42, and 41 cases, respectively) by softwarederived random-number sequence. Groups A and T received EA and TEAS, respectively, at the Shuigou (GV 26) and Baihui (GV 20), Hegu (LI4) and Waiguan (TE 5) acupoints. Group S received sham EA. The stimulation was started from 30 min before surgery until the end of the operation. The primary outcome was the CBF at 30 min after surgery, which was measured by transcranial Doppler sonography. The secondary outcomes included hyperperfusion incidence and neurological function. National Institutes of Health Stroke Scale (NIHSS) and General Evaluation Scale (GES) scores were recorded at 1 week, 1 month, and 3 months postoperatively.Results:Mean CBF velocity at 30 min after surgery in groups A and T was much lower than that in Group S (P<0.05); the incidence of hyperperfusion in Groups A and T was also lower than that in group S (P<0.05). Acupuncture was an independent factor associated with reduced incidence of hyperperfusion (OR=0.042; 95% CI: 0.002–0.785; P=0.034). NIHSS and GES scores improved significantly at 1 week postoperatively in Groups A and T than in Group S (P<0.05). Relative to Group S, groups A and T exhibited significantly lower incidences of moderate pain, as well as higher incidences of satisfaction with anesthesia, at 1 day postoperatively (P<0.05).Conclusion:EA or TEAS administered in combination with local anesthesia during CAS can inhibit transient increases in CBF, reduce the incidence of postoperative hyperperfusion, and improve neurological function. (Registration No. ChiCTR-IOR-15007447)
Keywords:electro-acupuncture;transcutaneous electrical acupoint stimulation;carotid artery stenting;cerebral blood flow;neurological function
Abstract:Objective:To evaluate the effectiveness and safety of oral Chinese herbal medicines (CHMs) on post-percutaneous coronary intervention (PCI) patients with depressive disorder in coronary heart disease (CHD).Methods:A literature search was conducted through databases including PubMed, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Chinese Biomedical Literature Database (SinoMed), Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and Wanfang Database up to August 2018. Randomized controlled trials (RCTs) comparing CHMs with placebo or no additional treatments on the basis of standard conventional pharmacological therapies were included. Data extraction, analyses and quality assessment were performed according to the Cochrane standards. RevMan 5.3 software was used to synthesize the results.Results:A total of 16 RCTs enrolling 1,443 participants were included in this systematic review. When compared with antidepressants alone, CHMs showed similar benefits with less side effects [risk ratio=0.54, 95% confidence interval (CI) 0.43 to 0.69, 582 patients]; meanwhile, the combination therapy may have more advantages than antidepressants alone [mean difference (MD)=–1.03, 95%CI –1.81 to –0.25, 267 patients). When identified with placebo, CHMs seem to have more advantages in relieving depressive symptoms (MD=–19.00, 95%CI –20.02 to –17.98, 189 patients). However, when compared with basic treatment of post-PCI, CHMs showed different results in two trials. In terms of post-PCI related clinical symptoms, CHMs seem to have more advantages in relieving chest pain and other general clinical symptoms. However, the heterogeneity in this review was generally high, it may be caused by different interventions used in each trial and the low quality of the trials.Conclusions:In total, CHMs showed potentially beneficial effects on depressive symptoms and post-PCI related clinical symptoms. However, because of small sample size and potential bias of most trials, this result should be interpreted with caution. More rigorous trials with larger sample size and higher quality are warranted to give high quality of evidence to support the use of CHMs for CHD complicated with depression.
Abstract:Objective:To help selecting appropriate meridians and acupoints in clinical practice and experimental study for Parkinson's disease (PD), the rules of meridians and acupoints selection of acupuncture and moxibustion were analyzed in domestic and foreign clinical treatment for PD based on data mining techniques.Methods:Literature about PD treated by acupuncture and moxibustion in China and abroad was searched and selected from China National Knowledge Infrastructure and MEDLINE. Then the data from all eligible articles were extracted to establish the database of acupuncture-moxibustion for PD. The association rules of data mining techniques were used to analyze the rules of meridians and acupoints selection.Results:Totally, 168 eligible articles were included and 184 acupoints were applied. The total frequency of acupoints application was 1,090 times. Those acupoints were mainly distributed in head and neck and extremities. Among all, Taichong (LR 3), Baihui (DU 20), Fengchi (GB 20), Hegu (LI 4) and Chorea-tremor Controlled Zone were the top five acupoints that had been used. Superior-inferior acupoints matching was utilized the most. As to involved meridians, Du Meridian, Dan (Gallbladder) Meridian, Dachang (Large Intestine) Meridian, and Gan (Liver) Meridian were the most popular meridians.Conclusions:The application of meridians and acupoints for PD treatment lay emphasis on the acupoints on the head, attach importance to extinguishing Gan wind, tonifying qi and blood, and nourishing sinews, and make good use of superior-inferior acupoints matching.
Keywords:Parkinson's disease;acupuncture and moxibustion;meridians and acupoints;data mining;association rules
Abstract:Chinese medical classics are important carriers for the inheritance, innovation and development of academic thoughts of Chinese medicine (CM), containing rich thoughts on diagnosis and treatment as well as therapeutic principles of CM. The international exchange of CM has a very long history. With the development of society, Western scholars in modern times are deepening their researches on Chinese medical classics. This would provide a new way for promoting CM in Western countries to investigate researches made by famed American scholars and their academic viewpoints.
Abstract:Acupuncture has been widely used for treating diseases since the ancient days in China, but the mechanism by which acupuncture exerts such powerful roles is unclear. Epigenetics, including DNA methylation, histone modification, and post-transcriptional regulation of miRNAs, is the study of heritable changes in gene expression that do not include DNA sequence alterations. Epigenetics has become a new strategy for the basic and clinical research of acupuncture in the last decade. Some investigators have been trying to illustrate the mechanism of acupuncture from an epigenetics perspective, which has shed new lights on the mechanisms and applications of acupuncture. Moreover, the introduction of epigenetics into the regulatory mechanism in acupuncture treatment has provided more objective and scientific support for acupuncture theories and brought new opportunities for the improvement of acupuncture studies. In this paper, we reviewed the literatures that has demonstrated that acupuncture could directly or indirectly affect epigenetics, in order to highlight the progress of acupuncture studies correlated to epigenetic regulations. We do have to disclose that the current evidence in this review is not enough to cover all the complex interactions between multiple epigenetic modifications and their regulations. However, the up-to-date results can help us to better understand acupuncture's clinical applications and laboratory research.