The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer.

Over the past decade, colorectal cancer has reported a higher incidence in younger adults and a lower mortality rate. Recently, the influence of the intestinal flora in the initiation, progression, and treatment of colorectal cancer has been extensively studied, as well as their positive therapeutic impact on inflammation and the cancer microenvironment. Historically, traditional Chinese medicine (TCM) has been widely used in the treatment of colorectal cancer via promoted cancer cell apoptosis, inhibited cancer metastasis, and reduced drug resistance and side effects. The present research is more on the effect of either herbal medicine or intestinal flora on colorectal cancer. The interactions between TCM and intestinal flora are bidirectional and the combined impacts of TCM and gut microbiota in the treatment of colon cancer should not be neglected. Therefore, this review discusses the role of intestinal bacteria in the progression and treatment of colorectal cancer by inhibiting carcinogenesis, participating in therapy, and assisting in healing. Then the complex anticolon cancer effects of different kinds of TCM monomers, TCM drug pairs, and traditional Chinese prescriptions embodied in apoptosis, metastasis, immune suppression, and drug resistance are summarized separately. In addition, the interaction between TCM and intestinal flora and the combined effect on cancer treatment were analyzed. This review provides a mechanistic reference for the application of TCM and intestinal flora in the clinical treatment of colorectal cancer and paves the way for the combined development and application of microbiome and TCM.

Pinellia genus: A systematic review of active ingredients, pharmacological effects and action mechanism, toxicological evaluation, and multi-omics application.

The dried tuber of Pinellia ternata (Thunb.) Breit, Pinelliae Rhizoma (PR, also named 'Banxia' in Chinese), is widely used in traditional medicine. This review aims to provide detail summary of active ingredients, pharmacological effects, toxic ingredients, detoxification strategies, and omic researches, etc. Pharmacological ingredients from PR are mainly classified into six categories: alkaloids, amino acids, polysaccharides, phenylpropanoids, essential oils, and glucocerebrosides. Diversity of chemical composition determines the broad-spectrum efficacy and gives a foundation for the comprehensive utilization of P. ternata germplasm resources. The pharmacological compounds are involved in inhibition of cancer cells by targeting various pathways, including activation of immune system, inhibition of proliferation and cycle, induction of apoptosis, and inhibition of angiogenesis. The pharmacological components of PR act on nervous system by targeting neurotransmitters, activating immune system, decreasing apoptosis, and increasing redox system. Lectins, one major class of the toxic ingredients extracted from raw PR, possess significant toxic effects on human cells. Inflammatory factors, cytochrome P450 proteins (CYP) family enzymes, mammalian target of rapamycin (mTOR) signaling factors, transforming growth factor-ß (TGF-ß) signaling factors, and nervous system, are considered to be the target sites of lectins. Recently, omic analysis is widely applied in Pinellia genus studies. Plastome genome-based molecular markers are deeply used for identifying and resolving phylogeny of Pinellia genus plants. Various omic works revealed and functional identified a series of environmental stress responsive factors and active component biosynthesis-related genes. Our review summarizes the recent progress in active and toxic ingredient evaluation, pharmacological effects, detoxification strategies, and functional gene identification and accelerates efficient utilization of this traditional herb.

Repeated and multiple fecal microbiota transplantations plus partial enteral nutrition as the first-line treatment in active pediatric Crohn's disease.

Background: Most studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn's disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children. Methods: We retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy. Results: Twenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 ± 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029). Conclusion: This study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.

Application of natural antioxidants from traditional Chinese medicine in the treatment of spinal cord injury.

Spinal cord injury (SCI) is a devastating central nervous system disease, caused by physical traumas. With the characteristic of high disability rate, catastrophic dysfunction, and enormous burden on the patient's family, SCI has become a tough neurological problem without efficient treatments. Contemporarily, the pathophysiology of SCI comprises complicated and underlying mechanisms, in which oxidative stress (OS) may play a critical role in contributing to a cascade of secondary injuries. OS substantively leads to ion imbalance, lipid peroxidation, inflammatory cell infiltration, mitochondrial disorder, and neuronal dysfunction. Hence, seeking the therapeutic intervention of alleviating OS and appropriate antioxidants is an essential clinical strategy. Previous studies have reported that traditional Chinese medicine (TCM) has antioxidant, anti-inflammatory, antiapoptotic and neuroprotective effects on alleviating SCI. Notably, the antioxidant effects of some metabolites and compounds of TCM have obtained numerous verifications, suggesting a potential therapeutic strategy for SCI. This review aims at investigating the mechanisms of OS in SCI and highlighting some TCM with antioxidant capacity used in the treatment of SCI.

Needle-Warming Moxibustion plus Multirehabilitation Training to Improve Quality of Life and Functional Mobility of Patients with Rheumatoid Arthritis after Medication.

Objective: Patients treated with medication for rheumatoid arthritis (RA) often improve but continue to have active diseases. The study aims to investigate whether needle-warming moxibustion (NWM) plus multirehabilitation training can improve quality of life (QoL) and functional mobility of RA patients after medication. Methods: Eighty-four RA patients were selected as study participants, including 42 patients receiving medication (medication group) and 42 patients receiving NWM plus multirehabilitation training (NWM + MRT group). The scores of disease symptoms, pain (visual analogue scale (VAS)), sleep quality (Pittsburgh Sleep Quality Index (PSQI)), functional mobility (Fugl-Meyer assessment scale (FMAS)), self-rating anxiety scale (SAS), self-rating depression scale (SDS), and QoL (SF-36) were compared before and after treatment. When patients were discharged from the hospital, they were given a questionnaire for treatment satisfaction. Results: After treatment, decreases in the scores of the VAS, PSQI, SAS, and SDS were observed in both cohorts, especially in the NWM + MRT group (P < 0.05). The FMAS scores of upper limbs and lower limbs were increased after treatment, which were higher in the NWM + MRT group in comparison with the medication group (P < 0.05). Of note, patients in the NWM + MRT group scored higher in various dimensions of the SF-36 scale (P < 0.05), showing better QoL. The satisfaction survey showed that the NWM + MRT group had a higher proportion of patients being satisfied and a lower proportion of patients being dissatisfied (P < 0.05). Conclusion: NWM plus multirehabilitation training could significantly attenuate disease symptoms, improve QoL, recover functional mobility, and reduce the risk of anxiety and depression in RA patients.

Ethanolic Extract from Pteris wallichiana Alleviates DSS-Induced Intestinal Inflammation and Intestinal Barrier Dysfunction by Inhibiting the TLR4/NF-κB Pathway and Regulating Tight Junction Proteins.

The aim of the research was to determine the protective effect and mechanism of Pteris wallichiana J. Agardh extract (PWE) on DSS-induced ulcerative colitis (UC) in mice. In this research, PWE is rich in flavonoids and diterpenoids by UPLC-MS/MS analysis. In LPS-induced RAW264.7 cells, PWE reduced the productions of inflammatory factors (i.e., NO, TNF-α, IL-6, and IL-1ß). In DSS-induced UC in mice, PWE improved disease activity index (DAI) score, attenuated oxidative stress by decreasing MPO and MDA activities and activating GSH and SOD levels, and inhibited TNF-α, IL-6, and IL-1ß expressions in the colonic tissues. PWE also improved the intestinal barrier by upregulating the expressions of tight junction proteins, including occludin and ZO-1. Moreover, PWE extract alleviated intestinal inflammation by suppressing the TLR4/MyD88/NF-κB signaling pathway. Conclusion: PWE can alleviate DSS-induced UC in mice by increasing the expressions of intestinal tight junction proteins and inhibiting the TLR4/NF-κB inflammatory pathway.

Genistein-3'-sodium sulfonate ameliorates cerebral ischemia injuries by blocking neuroinflammation through the α7nAChR-JAK2/STAT3 signaling pathway in rats.

BACKGROUND: Neuroinflammation plays a pivotal role in the acute progression of cerebral ischemia/reperfusion injury (I/RI). We previously reported that genistein-3'-sodium sulfonate (GSS), a derivative from the extract of the phytoestrogen genistein (Gen), protects cortical neurons against focal cerebral ischemia. However, the molecular mechanism underlying the neuroprotective effects exerted by GSS remains unclear. PURPOSE: The present study focused on the anti-inflammatory effects of GSS following I/RI in rats. STUDY DESIGN: Randomized controlled trial. METHODS: The tMCAO rat model and LPS-stimulated BV2 in vitro model were used. Longa's scare was used to observe neurological function. TTC staining and Nissl staining were used to evaluate brain injury. ELISA, qRT-PCR, Western blotting and immunofluorescent staining methods were used to detect cytokine concentration, mRNA level, protein expression and location. RESULTS: GSS treatment improves neurological function, reduces the volume of cerebral infarction, attenuates proinflammatory cytokines and inactivates the phosphorylation of JAK2 and STAT3 in I/RI rats. Furthermore, GSS increased the expression of α7nAChR. More importantly, the neuroprotective, anti-inflammatory and inhibiting JAK2/STAT3 signaling pathway effects of GSS were counteracted in the presence of alpha-bungarotoxin (α-BTX), an α7nAChR inhibitor, suggesting that α7nAChR is a potential target associated with the anti-inflammatory effects of GSS in the I/RI rats. GSS also inhibited BV2 cells from releasing IL-1ß via the α7nAChR pathway after LPS stimulation. CONCLUSION: GSS protects against cerebral I/RI through the expression of α7nAChR and inhibition of the JAK2/STAT3 pathway. Our findings provide evidence for the role of the cholinergic anti-inflammatory pathway in neuroinflammation and uncover a potential novel mechanism for GSS treatment in ischemic stroke. The downstream signals of GSS, α7nAChR- JAK2/STAT3 could also be potential targets for the treatment of I/RI.

Genistein-3'-sodium sulfonate Attenuates Neuroinflammation in Stroke Rats by Down-Regulating Microglial M1 Polarization through α7nAChR-NF-κB Signaling Pathway.

Microglial M1 depolarization mediated prolonged inflammation contributing to brain injury in ischemic stroke. Our previous study revealed that Genistein-3'-sodium sulfonate (GSS) exerted neuroprotective effects in ischemic stroke. This study aimed to explore whether GSS protected against brain injury in ischemic stroke by regulating microglial M1 depolarization and its underlying mechanisms. We established transient middle cerebral artery occlusion and reperfusion (tMCAO) model in rats and used lipopolysaccharide (LPS)-stimulated BV2 microglial cells as in vitro model. Our results showed that GSS treatment significantly reduced the brain infarcted volume and improved the neurological function in tMCAO rats. Meanwhile, GSS treatment also dramatically reduced microglia M1 depolarization and IL-1ß level, reversed α7nAChR expression, and inhibited the activation of NF-κB signaling in the ischemic penumbra brain regions. These effects of GSS were further verified in LPS-induced M1 depolarization of BV2 cells. Furthermore, pretreatment of α7nAChR inhibitor (α-BTX) significantly restrained the neuroprotective effect of GSS treatment in tMCAO rats. α-BTX also blunted the regulating effects of GSS on neuroinflammation, M1 depolarization and NF-κB signaling activation. This study demonstrates that GSS protects against brain injury in ischemic stroke by reducing microglia M1 depolarization to suppress neuroinflammation in peri-infarcted brain regions through upregulating α7nAChR and thereby inhibition of NF-κB signaling. Our findings uncover a potential molecular mechanism for GSS treatment in ischemic stroke.

Anti-nociceptive effects of Sedum Lineare Thunb. on spared nerve injury-induced neuropathic pain by inhibiting TLR4/NF-κB signaling in the spinal cord in rats.

Neuropathic pain is still a critical public health problem worldwide. Thereby, the search for novel and more effective strategies against neuropathic pain is urgently considered. It is known that neuroinflammation plays a crucial role in the pathogenesis of neuropathic pain. SedumLineare Thunb. (SLT), a kind of Chinese herb originated from the whole grass of Crassulaceae plant, was reported to possess anti-inflammatory activity. However, whether SLT has anti-nociceptive effect on neuropathic pain and its possible underlying mechanisms remains poorly elucidated. In this study, a rat model of neuropathic pain induced by spared nerve injury (SNI)was applied. SLT (p.o.) was administered to SNI rats once every day lasting for 14 days. Pain-related behaviors were assessed by using paw withdrawal threshold (PWT) and CatWalk gait parameters. Expression levels of inflammatory mediators and pain-related signaling molecules in the spinal cord were detected using western blotting assay. The results revealed that SLT (30, 100, and 300 mg/kg, p.o.) treatment for SNI rats ameliorated mechanical hypersensitivity in a dose-dependent manner. Application of SLT at the most effective dose of 100 mg/kg to SNI rats not only significantly blocked microglial activation, but also markedly reduced the protein levels of spinal HMGB1, TLR4, MyD88, TRAF6, IL-1ß, IL-6, and TNF-α, along with an enhancement in gait parameters. Furthermore, SLT treatment dramatically inhibited the phosphorylation levels of both IKK and NF-κB p65 but obviously improved both IκB and IL-10 protein expression in the spinal cord of SNI rats. Altogether, these data suggested that SLT could suppress spinal TLR4/NF-κB signaling pathway in SNI rats, which might at least partly contribute to its anti-nociceptive action, indicating that SLT may serveas a potential therapeutic agent for neuropathic pain.

Electroacupuncture ameliorates mechanical hypersensitivity by down-regulating spinal Janus kinase 2/signal transducer and activation of transcription 3 and interleukin 6 in rats with spared nerve injury.

BACKGROUND: Evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway participates in the pathogenesis of neuropathic pain. Our previous study revealed that electroacupuncture (EA) attenuated neuropathic pain via activation of alpha-7 nicotinic acetylcholine receptor (α7nAChR) in the spinal cord. However, whether 2 Hz EA alleviates neuropathic pain by regulating the downstream molecules JAK2/STAT3 has not been fully clarified. METHODS: Paw withdrawal threshold (PWT) was used as a marker of mechanical allodynia in rats with spared nerve injury (SNI). After applying 2 Hz EA on day 3, 7, 14 and 21 post-surgery, spinal expression of JAK2, STAT3 and pro-inflammatory cytokine interleukin (IL)-6 was examined using quantitative reverse transcription and real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Intrathecal injection of the α7nAChR antagonist alpha-bungarotoxin (α-Bgtx) was used to further explore the mechanism underlying the effects of 2 Hz EA on expression of JAK2/STAT3 in SNI rats. RESULTS: It was found that levels of spinal STAT3 and IL-6 mRNA, as well as levels of phosphorylated (p)-JAK2, p-STAT3 and IL-6 protein, were markedly increased in SNI rats. 2 Hz EA attenuated the SNI-induced up-regulation of p-JAK2, p-STAT3 and IL-6 expression in the spinal cord. Furthermore, intrathecal injection of α-Bgtx (1.0 µg/kg) not only inhibited the effect of 2 Hz EA on mechanical hypersensitivity but also ameliorated the down-regulation of p-JAK2, p-STAT3 and IL-6 expression induced by 2 Hz EA. CONCLUSION: This study revealed that 2 Hz EA attenuated SNI-induced mechanical hypersensitivity and the concomitant up-regulation of spinal JAK2, STAT3 and IL-6 in SNI rats, suggesting that suppression of the JAK2/STAT3 signaling pathway might be the mechanism underlying the therapeutic effect of 2 Hz EA on neuropathic pain.

Electroacupuncture Modulates Spinal BDNF/TrκB Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats.

Neuropathic pain is more complex and severely affects the quality of patients' life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/TrκB cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and TrκB mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and TrκB expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.

Electroacupuncture Treatment Suppresses Transcription Factor IRF8 in Spinal Cord of Rats with Spared Nerve Injury.

Objective: Neuropathic pain with complex mechanisms has become a major public health problem that greatly impacts patients' quality of life. Therefore, novel and more effective strategies against neuropathic pain need further investigation. Electroacupuncture (EA) has an ameliorating effect on neuropathic pain following spared nerve injury (SNI), but the underlying mechanism remains to be fully clarified. Interferon regulatory factor 8 (IRF8), a critical transcription factor, was reported to be involved in the modulation of neuropathic pain. Here, we focused on exploring whether 2 Hz EA stimulation exerts an inhibitory action on spinal IRF8 in SNI rats. Methods: In this study, SNI rats were treated with 2 Hz EA once every other day for 21 days. Paw withdrawal threshold (PWT) was applied to determine the analgesic effect of 2 Hz EA on SNI rats. The spinal IRF8 and CX3CRl expressions were detected with qRT-PCR and western blot, and immunofluorescence staining was used to evaluate colocation of IRF8 or CX3CRl with microglial activation marker CD11b in the spinal cord. Results: It was found that SNI induced significant elevation of spinal IRF8 and CX3CRl mRNA and protein expression. Additionally, immunofluorescence results showed that SNI elicited the coexpression of IRF8 with CD11b, as well as CX3CRl with CD11b in the spinal cord. Meanwhile, 2 Hz EA treatment of SNI rats not only reduced IRF8 and CX3CRl mRNA and protein expression, but also reversed the coexpression of IRF8 or CX3CRl with CD11b in the spinal cord, along with an attenuation of SNI-evoked mechanical hypersensitivity. Conclusion: This experiment highlighted that 2 Hz EA can inhibit IRF8 expression and microglial activation in the spinal cord of SNI rats. Hence, targeting IRF8 may be a promising therapeutic strategy for 2 Hz EA treatment of neuropathic pain.

Electroacupuncture Alleviates Spared Nerve Injury-Induced Neuropathic Pain And Modulates HMGB1/NF-κB Signaling Pathway In The Spinal Cord.

BACKGROUND: Neuropathic pain with complications greatly affects patients worldwide. High mobility group box 1 (HMGB1) has been shown to contribute to the pathogenesis of neuropathic pain; thus, suppression of HMGB1 may provide a novel therapeutic option for neuropathic pain. Electroacupuncture (EA) has been indicated to be effective in attenuating neuropathic pain, but the underlying mechanism remains to be fully clarified. We aim to explore whether 2Hz EA stimulation regulates the spinal HMGB1/NF-κB signaling in neuropathic pain induced by spared nerve injury (SNI). MATERIALS AND METHODS: Paw withdrawal threshold and CatWalk gait analysis were used to assess the effect of 2Hz EA on pain-related behaviors in SNI rats. Administration of 2Hz EA to SNI rats once every other day lasting for 21 days. Expression of spinal protein molecules were detected using Western blot and immunofluorescence staining. RESULTS: It was found that SNI significantly induced mechanical hypersensitivity and decrease of gait parameters, and subsequently increased the levels of HMGB1, TLR4, MyD88, and NF-κB p65 protein expression. 2Hz EA stimulation led to remarkable attenuation of mechanical hypersensitivity, upregulation of spinal HMGB1, TLR4, MyD88, and NF-κB p65 protein expressions induced by SNI, and significant improvement in gait parameters. Furthermore, immunofluorescence staining also confirmed that 2Hz EA obviously suppressed the co-expression of microglia activation marker CD11b and TLR4 or MyD88, as well as the activation of NF-κB p65 in SNI rats. CONCLUSION: This study suggested that blockade of HMGB1/NF-κB signaling in the spinal cord may be a promising therapeutic approach for 2Hz EA management of SNI-induced neuropathic pain.

Electroacupuncture treatment upregulates α7nAChR and inhibits JAK2/STAT3 in dorsal root ganglion of rat with spared nerve injury.

BACKGROUND: Neuropathic pain with complicated mechanism severely disrupts patient quality of life. The novel approaches and more effective management should be further investigated. It was reported that alpha-7 nicotinic acetylcholine receptor (α7nAChR) and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling in dorsal root ganglion (DRG) contributed to the pathogenesis of neuropathic pain. Our previous study has shown that electroacupuncture (EA) alleviated neuropathic pain via activating α7nAChR in the spinal cord. However, whether the effect of 2 Hz EA on spared nerve injury (SNI)-induced neuropathic pain is mediated through modulation of α7nAChR and JAK2/STAT3 pathway in the DRG remains unclear. MATERIALS AND METHODS: The SNI-induced neuropathic pain rat model was used in this study. After application of 2 Hz EA treatment to SNI rats on day 3, 7, 14 and 21 post-surgery, the expression levels of α7nAChR, JAK2/STAT3 and some cytokines in DRG were determined by qRT-PCR and Western blot analysis. RESULTS: We found that SNI induced significant down-regulation of α7nAChR mRNA and protein expression. SNI also obviously elicited the decrease in anti-inflammatory cytokine IL-10 protein expression. The enhancement of p-JAK2, p-STAT3, pro-inflammatory cytokines IL-1ß and IL-6 protein levels induced by SNI were also observed. However, 2 Hz EA treatment to SNI rats distinctly improved α7nAChR and IL-10 levels and reduced p-JAK2, p-STAT3, IL-1ß and IL-6 expression in the DRG. CONCLUSION: Our present study suggested that 2 Hz EA treatment indeed activated α7nAChR, suppressed JAK2/STAT3 signaling and re-balanced the relationship between pro-inflammatory and anti-inflammatory cytokines in DRG of SNI rat, which provided insight into our understanding of the mechanism for 2 Hz EA to attenuate neuropathic pain.

Electroacupuncture regulates the DREAM/NF-κB signalling pathway and ameliorates cyclophosphamide-induced immunosuppression in mice.

BACKGROUND: Immune responses inhibit invasion by pathogens and antigens. Thus, it is important to promote the immune response in immunosuppressed patients. OBJECTIVE: To examine whether electroacupuncture (EA) promotes the immune response by regulating the downstream regulatory element antagonist modulator / nuclear factor kappa B (DREAM/NF-κB) signalling pathway in a mouse model of cyclophosphamide (CP)-induced immunosuppression, and determine the most effective frequency. METHODS: Twenty-four Kunming mice were intraperitoneally injected with CP to establish an immunosuppression model and six mice were injected with the same volume of normal saline as a control. The 24 mice were randomly divided into four groups: manual acupuncture, 2 Hz EA treatment, 100 Hz EA treatment and alternating 2/100 Hz EA treatment. After EA treatment for 3 days, immune response, natural killer (NK) cell toxicity and the expression of cytokines and DREAM/NF-κB were assessed. RESULTS: EA treatment, especially at alternating 2/100 Hz frequency, improved spleen and thymus indices, increased lactate dehydrogenase and acid phosphatase levels, promoted concanavalin A- and lipopolysaccharide-induced splenocyte proliferation, increased NK cell toxicity and ameliorated CP-induced immunosuppression in mice. Additionally, 2/100 Hz EA treatment increased interleukin (IL)-2, IL-6, IL-12, tumour necrosis factor-α and interferon-γ levels and decreased IL-10 levels in CP-induced immunosuppressed mice. Finally, it was found that 2/100 Hz EA treatment increased p-IκBα and NF-κB expression and decreased DREAM and IκBα expression, suggesting that this treatment activates the NF-κB signalling pathway. CONCLUSION: 2/100 Hz EA treatment might be an effective way to enhance immune responses in CP-induced immunosuppressed mice.

Chinese clinical practice guidelines for acute infectious diarrhea in children.

BACKGROUND: The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. DATA SOURCES: The experts group of evidence development put forward clinical problems, collects evidence, forms preliminary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic "acute diarrhea" or "enteritis" and "adolescent" or "child" or "Pediatric patient" or "Baby" or "Infant". RESULTS: For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recommended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Saccharomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racecadotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease; otherwise, antibiotics are not recommended. CONCLUSION: The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

Semen Brassicae ameliorates hepatic fibrosis by regulating transforming growth factor-ß1/Smad, nuclear factor-κB, and AKT signaling pathways in rats.

PURPOSE: There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. METHODS: Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL·kg-1) at a dose of 200 mg·kg-1 twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract. After Semen Brassicae treatment, the morphology of the liver tissue was analyzed using hematoxylin and eosin and Masson's trichrome staining, and liver index and liver fibrosis grade were calculated. Thereafter, the levels of collagen-I, collagen-III, α-SMA, transforming growth factor (TGF)-ß1, p-Smad 2/3, Smad 2/3, Smad4, NF-κB-p65, p-NF-κB-p65, IL-1ß, IL-6, AKT, and p-AKT were determined using Western blotting. RESULTS: Compared with the untreated model group, the Semen Brassicae-treated group showed significantly decreased liver function indices; expression levels of collagen-I, collagen-III, and α-SMA; and hepatic fibrosis. Further studies also showed that the expression of TGF-ß1, Smad4, p-Smad 2/3/Smad 2/3, p-NF-κB-p65/NF-κB-p65, IL-1ß, IL-6, and p-AKT/AKT significantly decreased after the treatment. CONCLUSION: These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-ß1/Smad, NF-κB, and AKT signaling pathways and the reduction of extracellular matrix deposition.

Continuous Production of Isomalto-oligosaccharides by Thermo-inactivated Cells of Aspergillus niger J2 with Coarse Perlite as an Immobilizing Material.

The coarse perlite 40-80 mesh was selected as an immobilizing material and put into a packed bed reactor (PBR) to continuously convert maltose to isomalto-oligosaccharides (IMOs). The PBR was prepared by mixing the thermo-inactivated cells (TIC) from Aspergillus niger J2 strain with the coarse perlite, then the mixture was put into an overpressure-resistant column. Compared with diatomite 40-80 mesh and thin perlite 80-120 mesh in PBR, coarse perlite was chosen as the best filtration aid, when the ratio of coarse perlite versus TIC was 1:1. The thermal and pH stability of the free and immobilized TIC and the optimum conditions for the transglycosylation reactions were determined. The results show that approximately 75 and 82% and 87 and 91% of α-glucosidase activity were reserved for free and immobilized TIC at temperatures from 30 to 60 °C and pH from 3.00 to 7.00 for 12 h, respectively. With 30% malt syrup under the conditions of 50 °C and pH 4.00, a mini-scale packed bed reactor (Mi-PBR) and medium-scale packed bed reactor (Me-PBR) could continuously produce IMO over 25 and 34 days with the yield of effective IMO (eIMO) ≥ 35% and total IMO (tIMO) ≥ 50%, respectively. The strategy of mixing the coarse perlite with TIC in PBR is a novel approach to continuously produce IMO and has great application potential in industry.

Involvement of α7nAChR in electroacupuncture relieving neuropathic pain in the spinal cord of rat with spared nerve injury.

Alpha-7 nicotinic acetylcholine receptor (α7nAChR) was reported to be involved in the modulation of neuropathic pain. Electroacupuncture (EA) has therapeutic effects on neuropathic pain induced by nerve injury, but the underlying mechanisms remain unclear. The present study was designed to investigate whether α7nAChR participates in the relieving effects of 2 Hz EA on neuropathic pain. Paw withdrawal threshold (PWT) was measured to study the EA-mediated analgesic effect in a rat model of spared nerve injury (SNI). The spinal α7nAChR and IL-1ß expression levels were determined by RT-PCR, Western blot analysis, and immunofluorescence staining. Additionally, immunofluorescence targeting the expression of CD11b, which is a molecular indicator of microglial activation. The results showed that 2 Hz EA stimulation significantly improved the expression of α7nAChR and reduced the production of IL-1ß and CD11b in the spinal cord of rats with SNI-induced neuropathic pain, along with the relief of mechanical hypersensitivity after EA treatment. Moreover, intrathecal injection of alpha-bungarotoxin (α-Bgtx), a selective antagonist for α7nAChR, at the dosage of 1.0 µg/kg, not only suppressed the analgesic effect of EA in SNI rats, but also inhibited the enhancement of α7nAChR expression and the reduction of IL-1ß expression induced by EA. In conclusion, our study indicated that 2 Hz EA reduces SNI-induced mechanical hypersensitivity via upregulating α7nAChR and downregulating IL-1ß and CD11b in the spinal cord of SNI rats, which might be one of the mechanisms underlying its effectiveness in the neuropathic pain.

[Clinical efficacy observation of acupuncture at suliao (GV 25) on improving regain of consciousness from coma in severe craniocerebral injury].

OBJECTIVE: To compare the clinical therapeutic effects differences between acupuncture at Suliao (GV 25) and Shuigou (GV 26) on promoting regain of consciousness from coma in severe craniocerebral injury. METHODS: Based on regular emergency treatments of neurosurgery, eighty-two cases of craniocerebral injury who were under stable condition were randomly divided into an observation group (42 cases) and a control group (40 cases). Suliao (GV 25) was selected as main aupoint, while Laogong (PC 8) and Yongquan (KI 1), etc. were selected as adjuvant acupoints and Neiguan (PC 6), Sanyinjiao (SP 6), Yifeng (TE 17) and Wangu (GB 12), etc. were selected as matching acupoints in the observation group where a strong needle manipulation was applied to improve the regain of consciousness. The main acupoint of Shuigou (GV 26) along with identical adjuvant acupoints and matching acupoints in the observation group were selected in the control group with identical strong needle manipulation. The treatment was given once a day in both groups, five times per week and ten times were considered as one session. The immediate clinical symptoms after acupuncture at Suliao (GV 25) and Shuigou (GV 26) were observed as well as Glasgow coma scale (GCS) before the treatment, after 45 days and 90 days of treatment to assess the resuscitation time and rate. Also the clinical efficacy was compared between both groups. RESULTS: The occurrence rate of sneezing reflex was 85.7% (36/42) in the observation group, which was higher than 25.0% (10/40) in the control group (P < 0.01). The average resuscitation time was (64.6 +/- 19.4) days in the observation group, which was obviously shorter than (73.8 +/- 14. 6) days in the control group (P < 0.05). The resuscitation rate was 88.1% (37/42) in the observation group, which was similar to 75.0% (30/40) in the control group (P > 0.05). Compared before the treatment, GCS were both improved after the treatment in two groups (both P < 0.01). The 90-day GCS was 9.52 +/- 2.32 in the observation group, which was superior to 8.47 +/-2.14 in the control group (P < 0.05). The curative and markedly effective rate was 45.2% (19/42) in the observation group, which was superior to 22.5% (9/40) in the control group (P < 0.05). CONCLUSION: The effect of acupuncture at Suliao (GV 25) on improving regain of consciousness from coma in severe craniocerebral injury is positive. It could specifically improve sneezing reflex and stimulate respiratory center, which has more obvious effect than acupuncture at Shuigou (GV 26).