[Visual acupotomy intervention mitigates pain reaction by improving intervertebral disc degeneration and inhibiting apoptosis of nucleus pulposus cells in rabbits with cervical spondylosis].

OBJECTIVE: To investigate the effect of visual acupotomy intervention on intervertebral disc degeneration, nucleus pulposus cell apoptosis and expression of apoptosis related proteins in rabbits with cervical spondylosis (CS), so as to explore its mechanism underlying improvement of CS. METHODS: A total of 48 male New Zealand rabbits were randomly divided into blank control, model, acupotomy and medication (meloxicam) groups, with 12 rabbits in each group. The neck type CS model was established by forcing the rabbit to make a neck flexion for 5 hours in a restrained chamber, once daily for 12 weeks. Rabbits of the medication group received an intramuscular injection of meloxicam (0.35 mg/kg), once daily for 4 consecutive weeks, and those of the acupotomy group received ultrasound-guided acupotomy intervention, once a week for 4 weeks. The pain threshold (PT) was measured by using a VonFrey electronic pain detector. The levels of prostaglandin E2 (PGE2), 5-hydroxytryptamine (5-HT) and substance P (SP) in serum were detected by ELISA. The severity of intervertebral disc degeneration was observed by using magnetic resonance imaging (MRI) and given scores in accordance with Suzuki's and colleague's "new classification system of cervical disk degeneration". The apoptosis of nucleus pulposus cells was analyzed by TUNEL staining. The protein expression levels of apoptosis-related protein Fas, cysteinyl aspartate-specific protease-3 (Caspase-3), B-cell lymphoma-2 asso-ciated X protein (Bax) and B-cell lymphoma-2 protein (Bcl-2) were measured by Western blot. RESULTS: Compared with the blank control group, the PT and Bcl-2 expression and MRI score were significantly down-regulated (P<0.01, P<0.001), whereas the contents of serum PGE2, 5-HT and SP, ratios of TUNEL-positive cells, and expression of Fas, Caspase-3 and Bax were considerably up-regulated (P<0.001, P<0.05, P<0.01) in the model group. In contrast to the model group, both the medication and acupotomy groups had an obvious increase in the levels of PT and Bcl-2 expression and MRI score (P<0.05, P<0.01), and a significant decrease in the contents of serum PGE2, 5-HT, SP, ratios of TUNEL-positive cells, and expression of Fas, Caspase-3 and Bax proteins (P<0.05). No significant differences were found between the medication and acupotomy groups in all the indexes mentioned above (P>0.05). CONCLUSION: Visual acupotomy intervention can mitigate the pain state of CS rabbits, which may be related to its functions in improving the intervertebral disc degeneration, reducing inflammatory reactions and apoptosis of nucleus pulposus cells.

Changes in brain connectivity linked to multisensory processing of pain modulation in migraine with acupuncture treatment.

Migraine without aura (MWoA) is a major neurological disorder with unsatisfactory adherence to current medications. Acupuncture has emerged as a promising method for treating MWoA. However, the brain mechanism underlying acupuncture is yet unclear. The present study aimed to examine the effects of acupuncture in regulating brain connectivity of the key regions in pain modulation. In this study, MWoA patients were recruited and randomly assigned to 4 weeks of real or sham acupuncture. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. A modern neuroimaging literature meta-analysis of 515 fMRI studies was conducted to identify pain modulation-related key regions as regions of interest (ROIs). Seed-to-voxel resting state-functional connectivity (rsFC) method and repeated-measures two-way analysis of variance were conducted to determine the interaction effects between the two groups and time (baseline and post-treatment). The changes in rsFC were evaluated between baseline and post-treatment in real and sham acupuncture groups, respectively. Clinical data at baseline and post-treatment were also recorded in order to determine between-group differences in clinical outcomes as well as correlations between rsFC changes and clinical effects. 40 subjects were involved in the final analysis. The current study demonstrated significant improvement in real acupuncture vs sham acupuncture on headache severity (monthly migraine days), headache impact (6-item Headache Impact Test), and health-related quality of life (Migraine-Specific Quality of Life Questionnaire). Five pain modulation-related key regions, including the right amygdala (AMYG), left insula (INS), left medial orbital superior frontal gyrus (PFCventmed), left middle occipital gyrus (MOG), and right middle cingulate cortex (MCC), were selected based on the meta-analysis on brain imaging studies. This study found that 1) after acupuncture treatment, migraine patients of the real acupuncture group showed significantly enhanced connectivity in the right AMYG/MCC-left MTG and the right MCC-right superior temporal gyrus (STG) compared to that of the sham acupuncture group; 2) negative correlations were established between clinical effects and increased rsFC in the right AMYG/MCC-left MTG; 3) baseline right AMYG-left MTG rsFC predicts monthly migraine days reduction after treatment. The current results suggested that acupuncture may concurrently regulate the rsFC of two pain modulation regions in the AMYG and MCC. MTG and STG may be the key nodes linked to multisensory processing of pain modulation in migraine with acupuncture treatment. These findings highlighted the potential of acupuncture for migraine management and the mechanisms underlying the modulation effects.

The Chinese Herbal Formula Huoxiang Zhengqi Dropping Pills Prevents Acute Intestinal Injury Induced by Heatstroke by Increasing the Expression of Claudin-3 in Rats.

Intestinal injury has been regarded as an important causative factor for systemic inflammation during heatstroke, and maintaining intestinal integrity has been a potential target for the prevention of HS. Huoxiang Zhengqi Dropping Pills (HZPD) is a modern preparation of Huoxiang Zhengqi and widely used to prevent HS. The present study aims to explore the protective effect of HZDP on intestinal injury during heatstroke and analyze its potential pharmacodynamic basis. Male rats in the control and HS groups were given normal saline, and those in the HZDP groups were given HZDP (0.23, 0.46, and 0.92 g/kg) before induction of HS. Serum contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intestinal fatty acid-binding protein (iFABP), and diamine oxidase (DAO) were determined using ELISA. Histopathology of intestinal injury was observed following H&E staining. The expression of claudin-3 was determined using western blot, immunohistochemistry, and immunofluorescence techniques. Moreover, network pharmacological tools were used to analyze the potential pharmacodynamic basis and the mechanism of HZDP. Treatment with HZDP significantly prolonged the time to reach Tc. Compared with the control group, the contents of TNF-α, IL-6, iFABP, and DAO in HS rats increased markedly. HZDP treatments reduced these levels significantly, and the effects in the middle dose group (0.46 g/kg) were most obvious. HZDP also attenuated intestinal injury and significantly reversed the decrease in claudin-3 expression. Bioinformatics analysis suggested that 35 active ingredients and 128 target genes of HZDP were screened from TCMSP and 93 target genes intersected with heatstroke target genes, which were considered potential therapeutic targets. TNF-α and IL-6 were the main inflammatory target genes of HZDP correlated with HS. These results indicated that HZDP effectively protected intestinal barrier function and prevented acute intestinal injury by increasing the expression of claudin-3 in rats, eventually improving heat resistance.

Upper Extremity Contralaterally Controlled Functional Electrical Stimulation Versus Neuromuscular Electrical Stimulation in Post-Stroke Individuals: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Electrical stimulation has been employed as a safe and effective therapy for improving arm function after stroke. Contralaterally controlled functional electrical stimulation (CCFES) is a unique method that has progressed from application in small feasibility studies to implementation in several randomized controlled trials. However, no meta-analysis has been conducted to summarize its efficacy. OBJECTIVE: To summarize the effect size of CCFES through measures of upper extremity motor recovery compared with that of neuromuscular electrical stimulation (NMES). METHODS: The PubMed, Cochrane Library, EMBASE, Scopus, and Google Scholar databases were searched. Randomized controlled trials (RCTs) were selected and subjected to meta-analysis and risk of bias assessment. RESULTS: 6 RCTs were selected and 267 participants were included. The Upper Extremity Fugl-Meyer assessment (UEFMA) was included in all studies, the Box and Blocks test (BBT) and active range of motion (AROM) were included in 3 and 4 studies, respectively. The modified Barthel Index (mBI) and Arm Motor Abilities Test (AMAT) were included in 2 and 3 studies, respectively. The CCFES group demonstrated greater improvement than the NMES did in UEFMA (SMD = .42, 95% CI = .07-.76), BBT (SMD = .48, 95% CI = .10-.86), AROM (SMD = .54, 95% CI = .23-.86), and mBI (SMD = .54, 95% CI = .12-.97). However, the results for AMAT did not differ significantly (SMD = .34, 95% CI = -.03-.72). CONCLUSION: Contralaterally controlled functional electrical stimulation produced greater improvements in upper extremity hemiplegia in people with stroke than NMES did. PROSPERO registration number: CRD42021245831.

Association of ZNF331 and WIF1 methylation in peripheral blood leukocytes with the risk and prognosis of gastric cancer.

BACKGROUND: Peripheral blood leukocyte (PBL) DNA methylation may serve as a surrogate marker to evaluate the susceptibility to and prognosis of gastric cancer (GC). In this study, blood-derived DNA methylation levels of two tumour-related genes, namely, ZNF331 and WIF1, and their impacts on the risk and prognosis of GC were evaluated. METHODS: In total, 398 GC cases and 397 controls were recruited for the study. Then, all cases were followed up for 5 years. ZNF331 and WIF1 promoter methylation status in PBLs was measured using a methylation-sensitive high-resolution melting method. Logistic and Cox regression models were used to analyse the correlation between gene methylation and the risk and prognosis of GC. Confounders were balanced through propensity score (PS) matching. RESULTS: High ZNF331 methylation significantly decreased GC risk after PS adjustment (OR = 0.580, 95% CI: 0.375-0.898, P = 0.015), which also presented in males (OR = 0.577, 95% CI: 0.343-0.970, P = 0.038). However, WIF1 methylation was not associated with GC risk. Additionally, significant combined effects between ZNF331 methylation and the intake of green vegetables and garlic were observed (OR = 0.073, 95% CI: 0.027-0.196, P < 0.001 and OR = 0.138, 95% CI: 0.080-0.238, P < 0.001, respectively). Furthermore, ZNF331 and WIF1 methylation had no impact on the prognosis of GC. CONCLUSION: ZNF331 methylation in PBLs may affect GC risk in combination with the consumption of green vegetables and garlic and may act as a potential biomarker of GC.

Reference gene selection for expression studies in the reproductive axis tissues of Magang geese at different reproductive stages under light treatment.

In quantitative PCR research, appropriate reference genes are key to determining accurate mRNA expression levels. In order to screen the reference genes suitable for detecting gene expression in tissues of the reproductive axis, a total of 420 (males and females = 1:5) 3-year-old Magang geese were selected and subjected to light treatment. The hypothalamus, pituitary and testicular tissues were subsequently collected at different stages. Ten genes including HPRT1, GAPDH, ACTB, LDHA, SDHA, B2M, TUBB4, TFRC, RPS2 and RPL4 were selected as candidate reference genes. The expression of these genes in goose reproductive axis tissues was detected by real-time fluorescent quantitative PCR. The ΔCT, geNorm, NormFinder and BestKeeper algorithms were applied to sort gene expression according to stability. The results showed that ACTB and TUBB4 were the most suitable reference genes for the hypothalamic tissue of Magang goose in the three breeding stages; HPRT1 and RPL4 for pituitary tissue; and HPRT1 and LDHA for testicular tissue. For all three reproductive axis tissues, ACTB was the most suitable reference gene, whereas the least stable reference gene was GAPDH. Altogether, these results can provide references for tissue expression studies in geese under light treatment.

Electroacupuncture Attenuates Ischemic Brain Injury and Cellular Apoptosis via Mitochondrial Translocation of Cofilin.

OBJECTIVE: To investigate the potential mechanisms of electroacupuncture (EA) to prevent ischemic stroke. METHODS: The method of middle cerebral artery occlusion (MCAO) was employed to establish a rat model of ischemic stroke. Seventy-eight Sprague-Dawley rats were divided into the sham group, MCAO + EA control (EC) group, and MCAO + EA (EA) group according to a random number table (n=26 per group). EA was applied to the acupoints of Baihui (DU 20) and Shenting (DU 24) 5 min and 6 h, respectively after the onset of MCAO. Rats in the sham and EC groups received only light isoflurane anesthesia for 30 min after MCAO. The neuroprotective effects of EA were evaluated by rota-rod test, neurological deficit scores and infarct volumes. Additionally, Nissl staining and immunostaining were performed to examine brain damage, rod formation, cellular apoptosis, and neuronal loss induced by ischemia. The activities of caspase-3, and expression levels of cofilin and p-cofilin in mitochondria and cytoplasm after ischemic injury were determined by Western blot. RESULTS: Compared with the EC group, EA significantly improved neuromotor function and cognitive ability after ischemic stroke (P<0.05 or P<0.01). Therapeutic use of EA also resulted in a significant decrease of cofilin rod formation and microtubule-associated protein-2 (MAP2) degradation in the cortical penumbra area compared with the EC rats (P<0.01). Furthermore, Western blot analysis showed that EA stimulation significantly inhibited mitochondrial translocation of cofilin and caspase-3 cleavage (P<0.05 or P<0.01). Additionally, brain damage (infarct volume and neuropathy), cellular apoptosis and neuronal loss induced by ischemia were remarkably suppressed by EA in the cortical penumbra of rats (P<0.05 or P<0.01). CONCLUSION: EA treatment after ischemic stroke may attenuate ischemic brain injury and cellular apoptosis through the regulation of mitochondrial translocation of cofilin, a novel mechanism of EA therapy.

Evaluation of eight-style Tai chi on cognitive function in patients with cognitive impairment of cerebral small vessel disease: study protocol for a randomised controlled trial.

INTRODUCTION: Cerebral small vessel disease (CSVD) is a critical factor that causes cognitive decline and progresses to vascular dementia and acute cerebrovascular events. Tai chi has been proven to improve nerve plasticity formation and directly improve cognitive function compared with other sports therapy, which has shown its unique advantages. However, more medical evidence needs to be collected in order to verify that Tai chi exercises can improve cognitive impairment due to CSVD. The main purposes of this study are to investigate the effect of Tai chi exercise on neuropsychological outcomes of patients with cognitive impairment related to CSVD and to explore its mechanism of action with neuroimaging, including functional MRI (fMRI) and event-related potential (P300). METHODS AND ANALYSIS: The design of this study is a randomised controlled trial with two parallel groups in a 1:1 allocation ratio with allocation concealment and assessor blinding. A total of 106 participants will be enrolled and randomised to the 24-week Tai chi exercise intervention group and 24-week health education control group. Global cognitive function and the specific domains of cognition (memory, processing speed, executive function, attention and verbal learning and memory) will be assessed at baseline and 12 and 24 weeks after randomisation. At the same time, fMRI and P300 will be measured the structure and function of brain regions related to cognitive function at baseline and 24 weeks after randomisation. Recruitment is currently ongoing (recruitment began on 9 November 2020). The approximate completion date for recruitment is in April 2021, and we anticipate to complete the study by December 2021. ETHICS AND DISSEMINATION: Ethics approval was given by the Medical Ethics Committee of the Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine (approval number: 2019-058-04). The findings will be disseminated through peer-reviewed publications and at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000033176; Pre-results.

Electroacupuncture Attenuates Ischemic Brain Injury and Cellular Apoptosis via Mitochondrial Translocation of Cofilin / 中国结合医学杂志

OBJECTIVE@#To investigate the potential mechanisms of electroacupuncture (EA) to prevent ischemic stroke.@*METHODS@#The method of middle cerebral artery occlusion (MCAO) was employed to establish a rat model of ischemic stroke. Seventy-eight Sprague-Dawley rats were divided into the sham group, MCAO + EA control (EC) group, and MCAO + EA (EA) group according to a random number table (n=26 per group). EA was applied to the acupoints of Baihui (DU 20) and Shenting (DU 24) 5 min and 6 h, respectively after the onset of MCAO. Rats in the sham and EC groups received only light isoflurane anesthesia for 30 min after MCAO. The neuroprotective effects of EA were evaluated by rota-rod test, neurological deficit scores and infarct volumes. Additionally, Nissl staining and immunostaining were performed to examine brain damage, rod formation, cellular apoptosis, and neuronal loss induced by ischemia. The activities of caspase-3, and expression levels of cofilin and p-cofilin in mitochondria and cytoplasm after ischemic injury were determined by Western blot.@*RESULTS@#Compared with the EC group, EA significantly improved neuromotor function and cognitive ability after ischemic stroke (P<0.05 or P<0.01). Therapeutic use of EA also resulted in a significant decrease of cofilin rod formation and microtubule-associated protein-2 (MAP2) degradation in the cortical penumbra area compared with the EC rats (P<0.01). Furthermore, Western blot analysis showed that EA stimulation significantly inhibited mitochondrial translocation of cofilin and caspase-3 cleavage (P<0.05 or P<0.01). Additionally, brain damage (infarct volume and neuropathy), cellular apoptosis and neuronal loss induced by ischemia were remarkably suppressed by EA in the cortical penumbra of rats (P<0.05 or P<0.01).@*CONCLUSION@#EA treatment after ischemic stroke may attenuate ischemic brain injury and cellular apoptosis through the regulation of mitochondrial translocation of cofilin, a novel mechanism of EA therapy.

Associations of serum 25(OH) vitamin D levels with clinical and radiological outcomes in multiple sclerosis, a systematic review and meta-analysis.

BACKGROUND: Vitamin D supplementation is recommended for patients with multiple sclerosis (MS). However, a recent meta-analysis based on low-quality trials suggested no evidence of supplementation benefit. A systematic review and meta-analysis of high-quality observational cohort studies should provide us further evidences. METHODS: MEDLINE, EMBASE, and WEB-of-SCIENCE databases were systematically searched to identify eligible studies published before October 2018. Prospective cohort studies assessing the associations of serum 25(OH)D levels with MS relapses, radiological inflammatory lesions, or changes in expanded disability status scale in adults (≥18 years) with MS were included. Pooled RRs were calculated using fixed-effect or random-effects model depending on heterogeneity. RESULTS: Thirteen studies and 3498 patients were included. Each 25 nmol/L increase in serum 25(OH)D levels was associated with a reduction in (1) clinical relapse rate [RR = 0.90; 95% confidence interval (CI) = 0.83-0.99], (2) gadolinium-enhancing lesions (RR = 0.69; 95% CI = 0.60-0.79), (3) new/enlarging T2 lesions (RR = 0.86; 95% CI = 0.77-0.95), and (4) new active lesions (RR = 0.81; 95% CI = 0.74-0.89) in the magnetic resonance imaging(MRI). CONCLUSIONS: Serum 25(OH)D levels are associated with a modest decrease in relapse rate and radiological inflammatory activities in patients with MS. The association with disability worsening remains inconclusive.

Acupotomy versus acupuncture for cervical spondylotic radiculopathy: protocol of a systematic review and meta-analysis.

INTRODUCTION: Cervical spondylotic radiculopathy (CSR) is the most common pattern of cervical spondylosis, which is a serious and common degenerative disease. Both acupotomy and acupuncture have been widely used clinically to treat CSR in China with satisfied efficacy. However, there is no systematic review comparing the effectiveness of these two therapies. The aim of this study is to compare the therapeutic efficacy and safety between acupotomy and acupuncture for patients with CSR to provide evidence for clinical practice. METHODS AND ANALYSIS: The following electronic databases will be searched: Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure , China Biology Medicine disc, Wanfang Database and Chinese Scientific Journal Database (VIP). The randomised controlled trials of acupotomy versus acupuncture with/without additional treatment for CSR will be searched in the databases from their inception to December 2018 by two researchers independently. Visual analogue scale, symptom score and neck disability index will be assessed as the primary outcomes. The total effective rate, curative rate, adverse events and amount of rescue medication used will be assessed as the secondary outcomes. The Review Manager 5.3 will be used for meta-analysis and the evidence level will be assessed by using the method for Grading of Recommendations Assessment, Development and Evaluation. Continuous outcomes will be presented as the weighted mean difference or standardised mean difference with 95% CI, whereas dichotomous data will be expressed as relative risk with 95% CI. If the included studies have existing heterogeneity (p<0.05), then a random-effects model will be used. Otherwise, we will calculate using a fixed-effects model. ETHICS AND DISSEMINATION: Ethical approval is not required because no primary data are collected. This review will be published in a peer-reviewed journal and will be presented at an international academic conference for dissemination. PROSPERO REGISTRATION NUMBER: CRD42019117348.

Preparation of a novel Grifola frondosa polysaccharide-chromium (III) complex and its hypoglycemic and hypolipidemic activities in high fat diet and streptozotocin-induced diabetic mice.

Polysaccharide from Grifola frondosa is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel Grifola frondosa polysaccharide-chromium (III) [GFP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GFP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 6.97 mg/mL, pH 7.75 and temperature 71.73 °C, respectively. The pH was the most significant factor, followed by reaction temperature and concentration of CrCl3. Under the deduced optimal conditions (CrCl3 7.0 mg/mL, pH 7.7 and temperature 70.0 °C), the experimental chelation rate was 28.01% ±â€¯0.18% for GFP-Cr(III) complex, which agreed closely with the predicted value (27.61%). Fourier transform infrared (FTIR) spectroscopy revealed that the primary sites of chromium (III)-binding in polysaccharides were OH and CN groups, leading to the structure of GFP-Cr(III) complex was loose than the original polysaccharide. Nevertheless, Cr(III) did not make a fundamental change in the structure of GFP when comparing the FTIR spectra of GFP and GFP-Cr(III) complex. Additionally, the effects of GFP-Cr(III) complex on hyperglycemia and hyperlipidemia in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in diabetic mice fed a high-fat diet (HFD) supplemented with GFP-Cr(III) complex (900 mg/kg day) were significantly lower than the diabetic group (P < 0.01). These results suggest that GFP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Comparative analysis of the compatibility effects of Danggui-Sini Decoction on a blood stasis syndrome rat model using untargeted metabolomics.

Danggui-Sini Decoction (DSD) is one of the most widely used traditional Chinese medicine formulae (TCMF) for treating various diseases caused by cold coagulation and blood stasis due to its effect of nourishing blood to warm meridians in clinical use. However, studies of the mechanism of how it dispels blood stasis and its compatible regularity are challenging because of the complex pathophysiology of blood stasis syndrome (BSS) and the complexity of DSD, with multiple active ingredients acting on different targets. Observing variations of endogenous metabolites in rats with BSS after administering DSD may further our understanding of the mechanism of BSS and the compatible regularity of DSD. In this study, to understand the pathogenesis of BSS and assess the compatibility effects of DSD, an ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry-based untargeted metabolomics approach was used. Serum metabolic profiles in rats with BSS that was induced by an ice water bath associated with subcutaneous injection of epinephrine hydrochloride were compared with the intervention groups which were administered with DSD or its compatibility. Using pattern recognition analysis, a clear separation between the BSS model and control group was observed; DSD and its compatibility intervention groups were clustered closer toward the control than the model group, which corroborates results of hemorheology studies. In addition, 20 metabolites were considered as potential biomarkers associated with the development of BSS. Nine metabolites were regulated by DSD in intervening blood stasis, they were considered to be correlated with the effect of nourishing blood to warm meridians. Additionally, the results suggested that the intervention effect of DSD on BSS may involve regulating four pathways, namely, arachidonic acid metabolism, glycerophospholipid metabolism, bile acid biosynthesis, and pyruvate metabolism. Moreover, each functional unit (monarch, minister, and assistant) in DSD regulates different metabolites and metabolic pathways to achieve different effects on dispelling blood stasis; however, their intervention efficacies are inferior to the holistic formula, which may be due to the synergism of the bioactive ingredients in seven herbs of DSD. This study demonstrated that metabolomics is a powerful tool for evaluating the efficacy and compatibility effects of traditional Chinese medicine (TCM).

Investigation of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced liver fibrosis in rats by 1H-NMR-based metabonomics and network pharmacology approaches.

Liver fibrosis is a common consequence of chronic liver diseases resulting from multiple etiologies. Furthermore, prolonged unresolved liver fibrosis may gradually progress to cirrhosis, and eventually evolve into hepatocellular carcinoma (HCC). Corydalis saxicola Bunting (CS), a type of traditional Chinese folk medicine, has been reported to have hepatoprotective effects on the liver. However, the exact mechanism of how it cures liver fibrosis requires further elucidation. In this work, an integrated approach combining proton nuclear magnetic resonance (1H-NMR)-based metabonomics and network pharmacology was adopted to elucidate the anti-fibrosis mechanism of CS. Metabonomic study of serum biochemical changes by carbon tetrachloride (CCl4)-induced liver fibrosis in rats after CS treatment were performed using 1H-NMR analysis. Metabolic profiling by means of partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl4 was reduced after CS treatment. As a result, lipids, leucine, alanine, acetate, O-acetyl-glycoprotein and creatine were significantly restored after CS treatment, which regulated valine, leucine and isoleucine metabolism; arginine and proline metabolism; lipid metabolism and pyruvate metabolism. Additionally, 157 potential targets of CS and 265 targets of liver fibrosis were identified by means of network pharmacology. Subsequently, 5 target proteins, which are the intersection of potential CS targets and liver fibrosis targets, indicated that CS has potential anti-fibrosis effects through regulating alanine aminotransferase (ALT) activity, the farnesoid X receptor (FXR), cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1) and angiotensinogen. Chelerythrine and sanguinarine were the potential active compounds in CS for treating liver fibrosis through regulating ALT activity. This study is the first report to study the anti-fibrosis effects of CS on the basis of combining a metabonomics and network pharmacology approaches, and it may be a potentially powerful tool to study the efficacy and mechanisms of traditional Chinese folk medicines.

Right- and left-sided colorectal cancers respond differently to traditional Chinese medicine.

AIM: To explore the differences in the responses of left-sided colorectal cancer (LSCRC) and right-sided colon cancer (RSCC) to traditional Chinese medicine (TCM). METHODS: Patients with postoperative stage I-III colorectal cancer (CRC) were enrolled and divided into the LSCRC with or without TCM and RSCC with or without TCM groups depending on the primary tumor side and TCM administration. Patients in the TCM group were given TCM for at least 6 mo. Our research adopted disease-free survival (DFS) as the primary endpoint. We applied a Cox proportional hazards regression model for the multivariate factor analysis using Stata 12.0 and SPSS 22.0 software for data analysis. RESULTS: Of the 817 patients included in our study, 617 had LSCRC (TCM group, n = 404; Non-TCM group, n = 213), and 200 had RSCC (TCM group, n = 132; Non-TCM group, n = 68). The 6-year DFS for patients with LSCRC was 56.95% in the TCM group and 41.50% in the Non-TCM group (P = 0.000). For patients with RSCC, the 6-year DFS was 52.92% in the TCM group and 37.19% in the Non-TCM group (P = 0.003). Differences between LSCRC and RSCC were not statistically significant regardless of TCM ingestion. CONCLUSION: Patients with either LSCRC or RSCC and who took TCM experienced longer DFS; furthermore, patients with RSCC benefited more from TCM in DFS.

NMR-based metabolomics to determine acute inhalation effects of nano- and fine-sized ZnO particles in the rat lung.

Zinc oxide (ZnO) particles induce acute occupational inhalation illness in humans and rats. However, the possible molecular mechanisms of ZnO particles on the respiratory system remain unclear. In this study, metabolic responses of the respiratory system of rats inhaled ZnO particles were investigated by a nuclear magnetic resonance (NMR)-based metabolomic approach. Male Sprague-Dawley rats were treated with a series of doses of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles. The corresponding control groups inhaled filtered air. After 24 h, bronchoalveolar lavage fluid (BALF) and lung tissues were collected, extracted and prepared for (1)H and J-resolved NMR analysis, followed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). PCA and PLSDA models from analysis of BALF and hydrophilic lung NMR spectra demonstrated that dose response trends were restricted to the 250 nm ZnO particle exposure group and were not observed in the 35 nm ZnO particle exposure group. Increased isoleucine and valine, as well as decreased acetate, trimethylamine n-oxide, taurine, glycine, formate, ascorbate and glycerophosphocholine, were recorded in the BALF of rats treated with moderate and high dose 250 nm ZnO exposures. Decreases in taurine and glucose, as well as an increase of phosphorylcholine-containing lipids and fatty acyl chains, were detected in the lung tissues from 250 nm ZnO-treated rats. These metabolic changes may be associated with cell anti-oxidation, energy metabolism, DNA damage and membrane stability. We also concluded that a metabolic approach provides more complete measurements and suggests potential molecular mechanisms of adverse effects.

A semimicroquality evaluation method on Panax notoginseng and its application in analysis of continuous cropping obstacles research samples / 中国中药杂志

Panax notoginseng is a commonly used traditional Chinese medicine with blood activating effect while has continuous cropping obstacle problem in planting process. In present study, a semimicroextraction method with water-saturated n-butanol on 0.1 g notoginseng sample was established with good repeatability (RSD<2.5%) and 9.6%-20.6% higher extraction efficiency of seven saponins than the conventional method. A total of 16 characteristic peaks were identified by LC-MS-IT-TOF, including eight 20(S)-protopanaxatriol (PPT) type saponins and eight 20(S)-protopanaxadiol (PPD) type saponins. The established method was utilized to evaluate the quality of notoginseng samples cultivated by manual intervened methods to overcome continuous cropping obstacles.As a result, HPLC fingerprint similarity, content of Fa and ratio of notoginsenoside K and notoginsenoside Fa (N-K/Fa) were found out to be as valuatable markers of the quality of samples in continuous cropping obstacle research, of which N-K/Fa could also be applied to the analysis of notoginseng samples with different growth years.Notoginseng samples with continuous cropping obstacle had HPLC fingerprint similarity lower than 0.87, in consistent with normal sample, and had significant lower content of notoginsenoside Fa and significant higher N-K/Fa (2.35-4.74) than normal group (0.45-1.33). All samples in the first group with manual intervention showed high similarity with normal group (>0.87), similar content of common peaks and N-K/Fa (0.42-2.06). The content of notoginsenoside K in the second group with manual intervention was higher than normal group. All samples except two displayed similarity higher than 0.87 and possessed content of 16 saponins close to normal group. The result showed that notoginseng samples with continuous cropping obstacle had lower quality than normal sample. And manual intervened methods could improve their quality in different levels.The method established in this study was simple, fast and accurate, and the markers may provide new guides for quality control in continuous cropping obstacle research of notoginseng.

Electroacupuncture ameliorates cognitive impairment and regulates the expression of apoptosis-related genes Bcl-2 and Bax in rats with cerebral ischaemia-reperfusion injury.

BACKGROUND: Post-stroke cognitive impairment seriously affects the quality of life and functional rehabilitation of patients with stroke. OBJECTIVE: To examine the effects of electroacupuncture (EA) at GV20 and GV24 on cognitive impairment and apoptosis including expression of apoptosis-related genes Bcl-2 and Bax in a rat model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO). METHODS: Thirty-five Sprague-Dawley rats were allocated to a sham operation control group (SC group, n=10) or underwent surgery and MCAO (n=25). Postoperatively the latter group was randomly subdivided into EA or untreated (IR) groups. Cognitive impairment was assessed using the Morris water maze (MWM). Apoptosis was examined by detection of Bcl-2 and Bax expression in the cerebral cortex. RESULTS: The EA group had significantly decreased neurological deficit scores compared to the IR group (p<0.05). In the MWM test, significant differences in escape latency and route were observed between the EA and IR groups (p<0.05). Rats in the EA group performed better in the probe trial than those in the IR group (p<0.05). EA treatment markedly reduced the number of TUNEL-positive cells compared to the IR group (20.13±4.30% vs 38.40±3.38%; p<0.001). Reverse transcription-polymerase chain reaction (RT-PCR) results showed the Bcl-2/Bax ratio was significantly increased in the EA group compared to the IR group (1.61±0.19 vs 0.50±0.05, p<0.01). CONCLUSIONS: These findings suggest that EA ameliorates cognitive impairment of rats with IR injury by modulating Bcl-2 and Bax expression.

Auricular therapy for chronic pain management in adults: A synthesis of evidence.

OBJECTIVE: To evaluate the efficacy and safety of auricular therapy (AT) on chronic pain. METHODS: A systematic review. Randomized controlled trials investigating AT for chronic pain were retrieved and RevMan 5.3 was used for meta-analysis. RESULTS: Fifteen trials were included. The overall assessment indicated that AT could be a promising intervention for chronic pain relief. Meta-analyses showed that AT decreased pain intensity, especially for chronic low back pain and chronic tension headache. The lasting effect of AT was not obvious, and it began to diminish 3 months after the completion of treatment. CONCLUSIONS: AT may positively control pain intensity for patients with chronic pain. However, due to the significant heterogeneity and methodological flaws identified in the analyzed trials, the current evidence on AT for chronic pain management is still uncertain. More rigorously designed large-scale randomized controlled trials are required to evaluate the efficacy of AT for patients with chronic pain.