Abstract:Objective:To assess the effectiveness of Jiuwei Zhuhuang Powder (JWZH), a Tibetan patent medicine in treating upper respiratory tract infection (URTI) associated cough in children.Methods:The study was a multicenter, randomized, open-label, controlled trial. A total of 142 children aged 2 to 14 years old, with URTIassociated cough within 48 h of onset, were randomly assigned to two groups at a 1:1 ratio by computer-generated randomization sequence. Children were treated with JWZH (1 to 1.5 g, twice to thrice daily) in the treatment group or conventional treatment (Pediatric Paracetamol, Artificial Cow-bezoar and Chlorphenamine Maleate Granules, 0.25 to 1 g, thrice daily) in the control group for 5 days. The primary endpoints were the time to cough resolution and 4-day cough resolution rate. The secondary endpoints were the daily improvement in symptom scores and cough resolution rate during the study period.Results:A total of 138 children were included in the intention-to-treat analysis, with 71 cases in the treatment group and 67 cases in the control group. Compared with the conventional treatment, the children receiving JWZH had a shorter time to cough resolution [hazard ratio, 2.10; 95% confidence interval (CI), 1.29–3.40; P=0.003]. The median time to cough resolution for children receiving JWZH was shorter than that of the conventional treatment (2 days vs. 3 days; P<0.001). The 4-day cough resolution rate in the JWZH group was higher than that of the control group (94.4% vs. 74.6%; risk difference: 19.8%, 95% CI: 8.1%–31.5%; relative risk: 1.265, 95% CI: 1.088–1.470; P=0.001). There were no statistically significant differences in the improvement of other symptoms caused by URTI (P>0.05). Adverse events was reported in 5.6% (4/71) and 4.5% (3/67) in participants of JWZH and PPACCM groups (P>0.05), respectively, which were all mild and resolved without treatment.Conclusion:JWZH seemed to be a safe and effective therapy for URTI-associated cough in children. (Trial registration No. ChiCTR2000039421)
Keywords:child cough;upper respiratory tract infection;Jiuwei Zhuhuang Powder;randomized controlled trial;Tibetan medicine
Abstract:Objective:To test the hypothesis that β-glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against "external pernicious influences".Methods:A total of 138 participants with PQi deficiency (PQD) were randomized to receive β-glucan (200 mg daily) or placebo for 12 weeks. Participants' PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants' immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS).Results:PQi status was not significantly different between the β-glucan and placebo treatment groups at baseline but improved significantly in the β-glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1–5), risk score (scale: 0-1), and proportion of PQD participants (%) at finish line was 0.49 (0.35–0.62), 0.48 (0.35–0.61), and 0.36 (0.25–0.47), respectively. Additionally, β-glucan improved URTI symptom (scale: 1–9) and PROMIS physical (scale: 16.2–67.7) and mental (scale: 21.2–67.6) scores by a magnitude (95% CI) of 1.0 (0.21–1.86), 5.7 (2.33–9.07), and 3.0 (–0.37–6.37), respectively, over placebo.Conclusions:β-Glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as β-glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974)
Abstract:Objective:To study the differences between the serum metabolites in patients with adenomatous polyps of the colon and yang-deficiency constitution and those without colon polyps and with balanced constitution, and look for biomarkers that can be used to distinguish between the two groups.Methods:General patient information was gathered, and Chinese medicine constitutions were collected in 940 patients who underwent electronic colonoscopy. A total of 119 patients with adenomatous polyps of the colon and yang-deficiency constitution were included in the experimental group, and 150 patients without colon polyps and with balanced constitution were included in the control group. Metabolomics analysis was performed on the fasting venous blood obtained from each patient in both groups. Principal component analysis and orthogonal partial least squares discriminant analysis were performed on the detection results, potential biomarkers were screened, metabolic pathway changes were determined, and the metabolic processes involved were discussed.Results:A total of 59 differential biomarkers between the experimental group and the control group were identified. The differential metabolites were found mainly in the glycerophospholipid metabolism pathway, and the bile acid 3-oxo-4,6-choladienoic acid was the biomarker that distinguished the experimental group from the control group.Conclusions:With the help of metabolomics analysis, the differential metabolites in patients with adenomatous polyps of the colon and yang-deficiency constitution and those in patients without colon polyps and with balanced constitution could be identified. The biomarker 3-oxo-4,6-choladienoic acid may have potential diagnostic value in patients with adenomatous polyp of the colon and yang-deficiency constitution. (Trial Registration No. NCT02986308)
Abstract:Objective:To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygenglucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons.Methods:The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway.Results:MTT showed that TSPN (50, 25 and 12.5 μg/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 μg/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 μg/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 μg/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-Ⅱ/LC3B-Ⅰ, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 μg/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 μg/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01).Conclusions:TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.
Keywords:total saponins of Panax notoginseng;oxygen-glucose deprivation and reoxygenation;neuroprotection;ischemia-reperfusion;Akt/mTOR pathway;Chinese medicine
Abstract:Objective:To investigate the effect of curcumin on viability of clear cell renal cell carcinoma (ccRCC) and analyze its possible mechanism.Methods:In cell lines of A498 and 786-O, the effects of curcumin (1.25, 2.5, 5 and 10 μmol/L) on the viability of ccRCC were analyzed at 24, 48 and 72 h by MTT assay. The protein expression levels of ADAMTS18 gene, p65, phosphorylation p65 (pp65), AKT, phosphorylation AKT (pAKT) and matrix metallopeptidase 2 (MMP-2) before and after curcumin (10 μmol/L) treatment were examined by Western blotting. Real-time PCR and methylation specific PCR (MSP) were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment (10 μmol/L).Results:Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose- and time-dependent manner (P<0.01). Up-regulation of ADAMTS18 gene expression with down-regulation of ADAMTS18 gene methylation was reflected after curcumin treatment, accompanied by down-regulation of nuclear factor κB (NF-κkB) related protein (p65 and pp65), AKT related protein (AKT and pAKT), and NF-κB/AKT common related protein MMP-2. With ADAMTS18 gene overexpressed, the expression levels of p65, AKT and MMP2 were downregulated, of which were conversely up-regulated in silenced ADAMTS18 (sh-ADAMTS18). The expression of pp65, pAKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC (NF-κB inhibitor) and LY294002 (AKT inhibitor).Conclusion:Curcumin could inhibit the viability of ccRCC by down-regulating ADAMTS18 gene methylation though NF-κB and AKT signaling pathway.
Abstract:Objective:To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula (FZKA) on tumor microenvironment (TME).Methods:CIBERSORTx was used for analysis of TME. Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas (TCGA) was employed to identify the differential expression genes (DEGs) between tumor and paracancerous tissues in lung adenocarcinoma (LUAD) from TCGA-LUAD. Additionally, DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression. The core targets of FZKA were analyzed in lung adenocarcinoma TME. Protein-protein interaction database was employed to predict down-stream of target. Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549, H1299 and PC9 cell lines.Results:The active and resting mast cells were significantly associated with prognosis of LUAD (P<0.05). Of the targets, CCNA2 as an important target of FZKA (hazard ratio=1.41, 95% confidential interval: 1.01–2.01, P<0.05) was a prognostic target and significantly associated with mast cells. CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state. BCL1L2, ACTL6A and ITGAV were down-stream of CCNA2, which were validated by qRT-PCR in A549 cell.Conclusion:FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.
Abstract:Objective:To evaluate the influence of different transcutaneous electrical acupoint stimulation (TEAS) modes on ovarian responses and pregnancy outcomes in patients with infertility undergoing in vitro fertilization and embryo transfer (IVF-ET).Methods:Two hundred infertility patients undergoing IVF-ET were divided randomly into experimental groups (TEAS groups: E-Ⅰ, E-Ⅱ, E-Ⅲ, and E-Ⅳ, 40 cases each group) and a control group (mock TEAS group, 40 patients) using the random number method. The patients in the experimental groups received TEAS treatment of 20, 30, 40 and 50 mA for the E-Ⅰ, E-Ⅱ, E-Ⅲ and E-Ⅳ groups, respectively. The control group received a treatment of 5 mA. TEAS was applied at acupoints of Guanyuan (RN 4), Zhongji (RN 3), Sanyinjiao (SP 6), Zigong (EX-CA 1), and Taixi (KI 13), once a day for 30 min each time for a treatment period of 10–13 d. Treatment effect was assessed using the following indicators: endometrial thickness on the 6th day of gonadotropin treatment (GN6 day), endometrial thickness on the day on chorionic gonadotropin administration (HCG day), number of ovarian follicles on HCG day, number of ova captured, amount of estrogen required for each harvested ova, number of mature ova divided by the total number of ova, percentage of high-quality embryos, and clinical pregnancy.Results:Endometrial thickness in the experimental groups on the HCG day was significantly better than that of the control group after TEAS stimulation (P=0.01). TEAS exhibited a greater impact on the number of ova captured (P=0.003). However, the effect of TEAS stimulation on the high-quality embryo rate and clinical pregnancy in patients was not statistically significant (P>0.05).Conclusions:TEAS is an effective method in improving the ovarian state. When the stimulus intensity was at 40 mA and above, it could be helpful to improve the patient's endometrial condition and endometrial receptivity and to retrieve more oocytes. (Trial registration No. ChiCTR-TRC-11001780)
Abstract:Objectives:To investigate the effect of auriculotherapy on reducing labor anxiety.Methods:In this randomized clinical trial, 166 nulliparous pregnant women admitted to the Labor Ward of Izadi Hospital in Qom, Iran were included and assigned to two groups by randomized block design. In the intervention group (83 cases), auriculotherapy in "Shenmen, Thalamic, Zero, Brain, and Brain stem" was performed in dilatations of 4, 6 and 8 cm, between the contractions for 30 s in both ears at interval 1 h. While the control group received routine care. The Spielberger Inventory were completed pre- and post-interventions.Results:The auriculotherapy was effective to reduce anxiety state in the intervention group compared to the control group (P=0.001). The score of state anxiety in the intervention group reduced for 7.0, 8.0 and 11.0 U in 4, 6, and 8 cm dilatations after the intervention. The score of trait anxiety in the intervention group reduced for 3.8, 4.0 and 8.3 U in 4, 6, and 8 cm dilatations after the intervention. There was no significant difference of delivery mode and newborns' weight and Apgar score between groups (P>0.05). No adverse postpartum outcome such as hemorrhage has been observed in both groups.Conclusion:Since most women are anxious during labor, it seems that auriculotherapy can be an easy and safe method to reduce labor anxiety. (Trial registration No. irct20121230011944n4)
Abstract:Background:To illustrate the research framework, overall knowledge structure, and development trends of Chinese medicine (CM) treatment for osteosarcoma (OS) by using a bibliometric analysis and newly developed visualization tools.Methods:Research datasets were acquired from the Web of Science (WOS) database from January 1, 1980 to September 30, 2019. VOS viewer and Citespace software was used to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution of institutes, distribution of journals, citation and H-index status, co-authorship status, research hotspots and co-citation status were analyzed.Results:A total of 223 publications in the WOS database met the requirement. The number of published articles showed a rise but the citation frequency and the H-index of China were relatively low. The cooperation between the countries, institutes and authors were relatively weak. Most publications were basic researches. Most of the previous researches focused on basic mechanisms of CM in treating OS, and therapy and improvement of dosage form may become a frontier in this research field.Conclusions:Compared with other fields, the field of CM treatment for osteosarcome is still in infancy. The distribution of researches is imbalanced and cooperation between countries, institutions and authors remains to be strengthened. Furthermore, basic research occupies an absolute dominant position, and the exploration of the molecular mechanism of CM in preventing and treating OS may become a key point in the future.
Abstract:Computational medicine is an emerging discipline that uses computer models and complex software to simulate the development and treatment of diseases. Advances in computer hardware and software technology, especially the development of algorithms and graphics processing units (GPUs), have led to the broader application of computers in the medical field. Computer vision based on mathematical biological modelling will revolutionize clinical research and diagnosis, and promote the innovative development of Chinese medicine, some biological models have begun to play a practical role in various types of research. This paper introduces the concepts and characteristics of computational medicine and then reviews the developmental history of the field, including Digital Human in Chinese medicine. Additionally, this study introduces research progress in computational medicine around the world, lists some specific clinical applications of computational medicine, discusses the key problems and limitations of the research and the development and application of computational medicine, and ultimately looks forward to the developmental prospects, especially in the field of computational Chinese medicine.
Keywords:computational medicine;model;computational Chinese medicine;artificial intelligence;big data
Abstract:Objective:To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus (T2DM).Methods:PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception up to July 2020, to identify randomised controlled trials (RCTs) that enrolled patients with T2DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs alone. The primary outcomes were haemoglobin A1c (HbA1c) and fasting blood glucose (FBG). The secondary outcomes included 2-h blood glucose (2hBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), and acupuncture-related adverse events. Mean difference (MD) and 95% confidence interval (CI) were used as the effect measure in the meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.Results:Twenty-one RCTs (n=1,188) were included. The meta-analytic results showed that the acupuncture group had greater reductions in FBG (MD –6.46 mg/dL, 95% CI –11.95 to –0.98; moderate-quality evidence) and HOMA-IR (MD –1.23, 95% CI –2.16 to –0.31; low-quality evidence), but comparable changes in HbA1c (MD –0.39%, 95% CI –0.84 to 1.61; very-low-quality evidence), 2hBG (MD –4.99 mg/dL, 95% CI –20.74 to 10.76; low-quality evidence), and FINS (MD –1.32 μIU/mL, 95% CI –3.76 to 1.12; low-quality evidence). No data on the incidence of diabetic complications were found. All acupuncture-related adverse events reported were mild.Conclusions:The current evidence suggests that acupuncture, as a complementary therapy to antidiabetic drugs, has a small but statistically significant effect on decreasing FBG and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and FINS remain uncertain. Acupuncture is generally safe in patients with mild diabetes. More evidence for the long-term effects of acupuncture on T2DM is needed. (Registration No. CRD42018115639)
Abstract:Objectives:To identify, examine and summarize the available evidence on the effectiveness and safety of acupuncture for in vitro fertilisation (IVF) outcomes.Methods:Eight electronic databases, including PubMed, EMBASE, Cochrane Database of Systematic Review, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database and VIP Database, were searched, supplemented by manual searches. Two researchers independently conducted the literature screening, data extraction, and methodological quality assessments. A narrative description was provided to show the general information and specific characteristics of the included studies. A bubble plot was used to visually display the overall effects of acupuncture on IVF outcomes.Results:Eighty-two studies were identified, including 64 primary studies and 18 systematic reviews. Transcutaneous electrical acupoint stimulation, electric acupuncture and manual acupuncture were applied in most studies and compared with no acupuncture, sham acupuncture and placebo acupuncture control groups. Sixty-three (98.4%) primary studies reported clinical pregnancy rate, and positive effects of acupuncture were found in 34 studies (54.0%). Live birth rate was reported in only 18 (28.1%) primary studies, of which 10 (55.6%) showed positive results. In addition, only 8 and 2 systematic reviews showed that acupuncture could increase clinical pregnancy events and live birth events, respectively. However, none of these reviews was of high methodological quality.Conclusions:Available evidence suggests that acupuncture therapy could improve clinical pregnancy rates. However, whether acupuncture could increase live birth events was difficult to determine based on the few studies that have reported this outcome indicator. Furthermore, the methodological quality of most systematic reviews was assessed as critically low or low. Studies with a rigorous design and standardized implementation should be performed to refine the available evidence.