Study of Differential Serum Metabolites in Patients with Adenomatous Polyps of Colon and Yang-Deficiency Constitution Based on Ultra-performance Liquid Chromatography-Mass Spectrometry 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 constitution 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. Conclusion 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)

Combination of Geniposide and Eleutheroside B Exerts Antidepressant-like Effect on Lipopolysaccharide-Induced Depression Mice Model Abstract Objective To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide (LPS)-induced depression mice model. Methods Depression mice model was established by lipopolysaccharide (LPS) injection. Totally 48 mice were randomly divided into 6 groups (8 rats per group) according to a random number table, including normal, model, fluoxetine (20 mg/kg), geniposide (100 mg/kg) + eleutheroside B (100 mg/kg), geniposide + eleutheroside B + WAY 100635 (0.03 mg/kg), geniposide + eleutheroside B+ N-methyl-D-aspartic acid receptor (NMDA, 75 mg/kg) groups, respectively. After continuous administration for 10 days, autonomic activity tests after 30 min of administration were performed on the 10th day. On the 11th day, except for the normal group, the mice in the other groups were intraperitoneally injected with LPS (1 mg/kg), and the behavioral tests were performed 4 h later. Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha (TNF- α) and interleukin-1 β (IL-1 β) levels in mice serum. The mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear transcription factor (NF- κB) were detected by real-time quantitative polymerase chain reaction. Western-blot analysis was used to detect IDO and NF- κB protein expressions in hippocampus tissue. Results Compared with the normal group, a single administration of LPS increased the immobility time in the forced swimming test (FST) and tail suspension test (TST, P<0.01), without affecting autonomous activity. Compared with the model group, fluoxetine and geniposide + eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST, decreased serum IL-1 β content, inhibited the expression levels of NF- κ B gene and protein in hippocampus tissues (P<0.05 or P<0.01). Compared with the model group, geniposide + eleutheroside B treatment significantly reduced serum TNF-α content and inhibited IDO mRNA and protein expressions in hippocampus (P<0.05 or P<0.01). In addition, NMDA partly prevented the inhibition of IDO mRNA expression by geniposide + eleutheroside B; NMDA and WAY-100635 also partly prevented the reduction of IL-1 ß content induced by geniposide + eleutheroside B treatment (P<0.05 or P<0.01). Conclusions The combination of geniposide and eleutheroside B showed a certain antidepression-like effect. Its main mechanism of action may be contributed to inhibiting the activation of NF- κB, decreasing the proinflammatory cytokines such as TNF-α, IL-1 β, and inhibiting in the neuroinflammatory reaction. Additionally, it also affects tryptophan metabolism, reduces the expression of a key enzyme of tryptophan metabolism, IDO. And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.

Comments on “Traditional Chinese Medicine Use in the Treatment of Acute Heart Failure in Western Medicine Hospitals in China: Analysis from the China PEACE Retrospective Heart Failure Study”

Effect of Compound Laser Acupuncture-Moxibustion on Blood Glucose, Fasting Insulin and Blood Lipids Levels in Type 2 Diabetic Rats Abstract Objective To investigate the effect of compound laser acupuncture-moxibustion on blood glucose, fasting insulin and blood lipids levels in type 2 diabetes mellitus (T2DM) rats. Methods Forty male Wistar rats were randomly divided into 4 groups, including the normal group, model control group, laser group and sham laser group (n=10 per group). The rats in the normal group were fed with a standard diet. Rats in other groups were fed with a high-sugar and high-fat diet for 4 weeks, then intraperitoneally injected with 1% streptozotocin to induce T2DM model. The laser group was irradiated by 10.6 µm and 650 nm compound laser on bilateral Pishu (BL 20), Shenshu (BL 23) and Sanyinjiao (SP 6) for 5 min, 6 times a week for 5 weeks. The sham laser group received the same treatment as the laser group, but without laser output. The model control group and normal group were not treated. Blood glucose levels were measured before and after 1, 2, 3, 4 and 5 weeks of treatment. The serum levels of fasting insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were analyzed after the last treatment. Results The blood glucose levels in the model control group increased during the 5 weeks of treatment compared with the normal group (P<0.05), while those in the laser group were significantly lower than the model control group after weekly treatment (P<0.01 or P<0.05). After 1, 2 and 3 weeks of treatment, the blood glucose levels in the laser group decreased obviously compared with the sham laser group (P<0.01 or P<0.05). Compared with the normal group, the levels of fasting insulin, TC and LDL in the model control group notably increased (P<0.01 or P<0.05), while their levels in the laser group were significantly lower than the model control group after 5 weeks of treatment (P<0.05 or P<0.01). However, no statistically significant differences were observed in TG or HDL levels among the 4 groups (P>0.05). Conclusion The compound laser acupuncture-moxibustion of 10.6 µm and 650 nm had positive effects on the regulation of hyperglycemia and insulin resistance in T2DM rats, which may be a potential treatment for T2DM, and also provide an alternative to the traditional acupuncture and moxibustion therapy.

Moxibustion Promotes Formation of Granulation in Wound Healing Process through Induction of Transforming Growth Factor-β in Rats Abstract Objective To examine the effect of moxibustion on the wound healing process and its mechanism using a rat wound model. Methods Sixty male Sprague-Dawley rats were randomly divided into a sham-treated group (n=30, wound surgery only) and a moxibustion group (n=30, wound treated with moxibustion). Circular full-thickness skin wounds were produced in rats. Moxibustion was applied to the edge of wound and was continued on alternating days till 14 days after surgery, followed by measurement of wound size. Expression of collagens, prolyl-4-hydroxylase (P4H) and transforming growth factor-β (TGF-β) were evaluated by histochemical study and real-time polymerase chain reaction. Results The size of the wound lesion was significantly reduced in rats treated with moxibustion as compared to that in sham-treated rats at 4–10 days after wounding (P<0.01). Moxibustion stimulated mRNA expression of collagens at 4 days (P<0.01), but not at 7 days, accompanied by enhanced proliferation of P4H-positive fibroblasts. Of importance, expression of TGF-β in tissue from the wound lesion treated with moxibustion was significantly increased as compared to that in sham-treated rats at 4 days (P<0.01 or P<0.05), but not at 7 days. Conclusions The treatment with moxibustion promoted the wound healing process in the early phase through proliferation of fibroblasts and rapid formation of granulation, possibly mediated by induction of TGF-β which is a key molecule in the physiological process of wound healing. Moxibustion can be expected to be effective as complementary treatment for intractable ulcers.

Is Chinese Medicine Injection Applicable for Treating Acute Lung Injury and Acute Respiratory Distress Syndrome? A Systematic Review and Meta-analysis of Randomized Controlled Trials Abstract Objective To assess the efficacy and safety of Chinese medicine injection (CMI) for treating acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Methods Randomized controlled trials (RCTs) were identified by searching 3 English databases and 4 Chinese databases from their inceptions until February 2019. The Cochrane Handbook was used to evaluate risk of bias in the included studies. Data analysis was conducted using RevMan 5.3.3 software. Results A total of 19 eligible RCTs involving 1,334 participants was included in this systematic review and meta-analysis. The main meta-analysis showed that CMI combined with conventional therapy (CT) was more effective than CT alone in reducing the acute physiology and chronic health evaluation (APACHE) H score [mean difference (MD): −1.74 points, 95% confidence interval (CI): −2.77 to −0.71, I2=0] and increasing the total effective rate [relative risk (RR): 1.35, 95% CI: 1.17 to 1.56, I2=37%]. Compared with CT, CMI combined with CT showed improvements in the arterial partial pressure of oxygen (PaO2, MD: 9.25 mm Hg, 95% CI: 0.87 to 17.63, I2=98%) and oxygenation index [arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2), MD: 50.75 mm Hg, 95% CI: 35.18 to 66.31, I2=94%]. CMI plus CT was superior to CT in reducing the systemic inflammatory response syndrome (SIRS) score (MD: −0.84 points, 95% CI: −1.26 to −0.42, I2=65%), length of hospital stay (MD: −4.22 days, 95% CI: −6.49 to −1.95, I2=92%), and duration of mechanical ventilation (MD: −2.94 days, 95% CI: −4.68 to −1.21, I2=89%). Only 1 study reported adverse events. Conclusions CMI as an adjuvant therapy showed great potential benefits for the treatment of ALI/ARDS. However, we could not make a definite conclusion due to low quality of included studies and uncertain security. Future studies should focus on improving research design, especially in blindness and placebo. The reporting of adverse events was also needed.

Altered Brain Regional Homogeneity Following Contralateral Acupuncture at Quchi (LI 11) and Zusanli (ST 36) in Ischemic Stroke Patients with Left Hemiplegia: An fMRI Study Abstract Objective To study the effect of contralateral acupuncture (CAT) at acupoints of Quchi (LI 11) and Zusanli (ST 36) on the unaffected limbs of ischemic stroke patients with left hemiplegia based on regional homogeneity (ReHo) indices. Methods Ten ischemic stroke patients with left hemiplegia received CAT on right side at LI 11 and ST 36. Functional magnetic resonance imaging (fMRI) was performed before and after acupuncture. A ReHo analytical method was used to compare brain responses of patients before and after CAT operated by REST software. Results The stimulation at both LI 11 and ST 36 on the unaffected limbs produced significantly different neural activities. CAT elicited increased ReHo values at the right precentral gyrus and superior frontal gyrus, decreased ReHo value at right superior parietal lobule, left fusiform gyrus and left supplementary motor area. Conclusions Acupuncture at one side could stimulate bilateral regions. CAT could evoke the gyrus which was possibly related to motor recovery from stroke. A promising indicator of neurobiological deficiencies could be represented by ReHo values in post-stroke patients.

Tiaobu Xinshen Recipe (调补心肾方) Improved Mild Cognitive Impairment of Alzheimer’s Disease Patients with Xin (Heart) and Shen (Kidney) Deficiency Abstract Objective To observe the intervention effects of Tiaobu Xinshen Recipe (调补心肾方, TXR) on patients with mild cognitive impairment caused by Alzheimer’s disease (MCI-AD). Methods Totally 88 MCI-AD patients with syndrome of Xin (Heart) and Shen (Kidney) deficiency were assigned to the experimental group (47 cases, treated with TXR) and the control group (41 cases, treated with donepezil hydrochloride) using a random number table. Final recruited qualified patients were 44 cases in the experimental group and 39 cases in the control group. The therapeutic course was 12 weeks. Neuropsychological scales [mini mental state examination (MMSE) and Montreal cognitive assessment (MoCA)], and Chinese medicine (CM) dementia syndromes scales were performed in all patients, and results were compared between groups or intra-group before and after treatment. Results MMSE and MoCA scores of the two groups were increased after treatment compared with those before treatment (P<0.05). But there was no statistical difference in MMSE or MOCA scores after treatment between the two groups (P>0.05). CM dementia syndrome score was significantly decreased after treatment in the experimental group compared with the control group (P<0.01). Visual spatial and executive function scores and delayed recall scores of the two groups were increased compared with those before treatment (P<0.01). Conclusion TXR could effectively improve cognitive impairment of MCI-AD patients with syndrome of Xin and Shen deficiency.

Antioxidant and Antiapoptotic Polyphenols from Green Tea Extract Ameliorate CCl 4 -Induced Acute Liver Injury in Mice Abstract Objective To investigate the phenolic composition, antioxidant properties, and hepatoprotective mechanisms of polyphenols from green tea extract (GTP) in carbon tetrachloride (CCl4)-induced acute liver injury mouse model. Methods High-performance liquid chromatography was used to analyze the chemical composition of the extract. Antioxidant activity of GTP was assessed by O2∙-, OH∙, DPPH∙, and ferric-reducing antioxidant power (FRAP) assay in vitro. Sixty Kunming mice were divided into 6 groups including control, model, low-, medium-, and high-doses GTP (200, 400, 800 mg/kg) and vitamin E (250 mg/kg) groups, 10 in each group. GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl4. Hepatoprotective effects of GTP were evaluated in a CCl4-induced mouse model of acute liver injury, using commercial enzyme linked immunosorbent assay kits, histopathological observation, terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling (TUNEL) assay and Western blot. Results GTP contained 98.56 µg gallic acid equivalents per milligram extract total polyphenols, including epicatechingallate, epigallocatechin gallate, epicatechin, and epigallocatechin. Compared with the model group, low-, medium-, or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase (P<0.01). Histopathological observation confirmed that pretreatment of GTP prevented swelling and necrosis in CCl4-exposed hepatocytes. Hepatoprotective effects of low-, medium-, and high-dose GTP were associated with eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Additionally, low-, medium-, and high-dose GTP decreased cell apoptosis in the CCl4-exposed liver (P<0.01). Phosphorylated nuclear factor kappa-B (NF-κB), p53, Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene, cytochrome C, and cleaved caspase-3 levels were downregulated compared with the model group (P<0.01). Conclusion GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways.

Chang’an II Decoction (肠安 II 号方)-Containing Serum Ameliorates Tumor Necrosis Factor-α-Induced Intestinal Epithelial Barrier Dysfunction via MLCK-MLC Signaling Pathway in Rats Abstract Objective To investigate the effect of Chang’an II Decoction (肠安 II 号方))-containing serum on intestinal epithelial barrier dysfunction in rats. Methods Tumor necrosis factor (TNF)-α-induced injury of Caco-2 monolayers were established as an inflammatory model of human intestinal epithelium. Caco-2 monolayers were treated with blank serum and Chang’an II Decoction-containing serum that obtained from the rats which were treated with distilled water and Chang’an II Decoction intragastrically at doses of 0.49, 0.98, 1.96 g/(kg·d) for 1 week, respectively. After preparation of containing serum, cells were divided into the normal group, the model group, the Chang’an II-H, M, and L groups (treated with 30 ng/mL TNF-α and medium plus 10% high, middle-, and low-doses Chang’an II serum, respectively). Epithelial barrier function was assessed by transepithelial electrical resistance (TER) and permeability of fluorescein isothiocyanate (FITC)-labeled dextran. Transmission electron microscopy was used to observe the ultrastructure of tight junctions (TJs). Immunofluorescence of zonula occludens-1 (ZO-1), claudin-1 and nuclear transcription factor-kappa p65 (NF-κ Bp65) were measured to determine the protein distribution. The mRNA expression of myosin light chain kinase (MLCK) was measured by real-time polymerase chain reaction. The expression levels of MLCK, myosin light chain (MLC) and p-MLC were determined by Western blot. Results Chang’an II Decoction-containing serum significantly attenuated the TER and paracellular permeability induced by TNF-α. It alleviated TNF-α-induced morphological alterations in TJ proteins. The increases in MLCK mRNA and MLCK, MLC and p-MLC protein expressions induced by TNF-α were significantly inhibited in the Chang’an II-H group. Additionally, Chang’an II Decoction significantly attenuated translocation of NF-κ Bp65 into the nucleus. Conclusion High-dose Chang’an II-containing serum attenuates TNF-α-induced intestinal barrier dysfunction. The underlying mechanism may be involved in inhibiting the MLCK-MLC phosphorylation signaling pathway mediated by NF-κ Bp65.