Inhibitory effect of acupoint electrostimulation with different layers and intensities on muscular inflammatory pain and spinal WDR neuron activity. / ç©´ä½ä¸åŒå±‚æ¬¡å’Œå¼ºåº¦ç”µåˆºæ¿€ç¼“è§£è‚Œè‚‰ç‚Žæ€§ç—›åŠå¯¹è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.

Preparation of capsaicin-loaded ultrafine fiber film and its application in the treatment of oral ulcers in rats.

A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-L-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-L-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.

The Effect of Pre-Electroacupuncture on Nociceptive Discharges of Spinal Wide Dynamic Range Neurons in Rat.

Purpose: Spinal wide dynamic range (WDR) neurons are well studied in pain models and they play critical roles in regulating nociception. Evidence has started to accumulate that acupuncture produces a good analgesic effect via activating different primary fibers with distinct intensities. The purpose of the present study was to compare the distinct intensities of pre-electroacupuncture (pre-EA) at local muscular receptive fields (RFs), adjacent or contralateral non-RFs regulating the nociceptive discharges of spinal WDR neurons evoked by hypertonic saline (HS). Materials and Methods: Spinal segments of electrophysiological recording were identified by neural tracers applied at the left gastrocnemius muscle. The thresholds of Aß (TAß), Aδ (TAδ) and C (TC) components of WDR neurons were measured to determine the intensity of pre-EA by extracellular recording. The discharges of WDR neurons induced by distinct intensities of pre-EA and 200 µL HS (6%) injection in left gastrocnemius muscle of rats were observed by extracellular recording. Results: The spinal segments of WDR neurons were confirmed in lumbar (L)5-6 area according to the projective segments of dorsal root ganglion. TAß, TAδ and TC of WDR neurons was determined to be 0.5, 1, and 2 mA, respectively. The pre-EA with intensities of TAß (P < 0.05), TAδ (P < 0.05), TC (P < 0.05) or 2TC (P < 0.01) at ipsilateral adjacent non-RFs significantly reduced the discharges of WDR neurons, while at local RFs only pre-EA of TAδ (P < 0.05), TC (P < 0.05) and 2TC (P < 0.01) could inhibit the nociceptive discharges. In addition, intensity of pre-EA at contralateral non-RFs should reach at least TC to effectively inhibit the firing rates of WDR neurons (P < 0.01). Conclusion: Pre-EA could suppress nociceptive discharges of WDR neurons and the inhibitory effects were dependent on the distinct intensities and locations of stimulation.

Mechanism of tonifying-kidney Chinese herbal medicine in the treatment of chronic heart failure.

According to traditional Chinese medicine (TCM), chronic heart failure has the basic pathological characteristics of "heart-kidney yang deficiency." Chronic heart failure with heart- and kidney-Yang deficiency has good overlap with New York Heart Association (NYHA) classes III and IV. Traditional Chinese medicine classical prescriptions for the treatment of chronic heart failure often take "warming and tonifying kidney-Yang" as the core, supplemented by herbal compositions with functions of "promoting blood circulation and dispersing blood stasis." Nowadays, there are still many classical and folk prescriptions for chronic heart failure treatment, such as Zhenwu decoction, Bushen Huoxue decoction, Shenfu decoction, Sini decoction, as well as Qili Qiangxin capsule. This review focuses on classical formulations and their active constituents that play a key role in preventing chronic heart failure by suppressing inflammation and modulating immune and neurohumoral factors. In addition, given that mitochondrial metabolic reprogramming has intimate relation with inflammation, cardiac hypertrophy, and fibrosis, the regulatory role of classical prescriptions and their active components in metabolic reprogramming, including glycolysis and lipid ß-oxidation, is also presented. Although the exact mechanism is unknown, the classical TCM prescriptions still have good clinical effects in treating chronic heart failure. This review will provide a modern pharmacological explanation for its mechanism and offer evidence for clinical medication by combining TCM syndrome differentiation with chronic heart failure clinical stages.

[Sensory and sympathetic nerves are involved in the changes of skin temperature, blood infusion and inflammatory cytokines of cutaneous tissue in the sensitized area of colitis rats].

OBJECTIVE: To investigate the changes of skin temperature, blood infusion and inflammatory cytokines of cutaneous tissue in the sensitized area of colitis model rats, as well as the relationship between sensory and sympathetic nerves and the formation of sensitized area, and to initially reveal the partial physical-chemical characteristics of the sensitized area in the colitis model rats. METHODS: Thirty-five male SD rats were randomly divided into a control group (n=10), a model group (n=18) and a guanethidine group (n=7). 5% dextran sulfate sodium (DSS) was adopted for 6-day free drinking to establish colitis model in the model group and the guanethidine group. On day 6 and 7, in the guanethidine group, guanethidine solution (30 mg/kg) was injected intraperitoneally for sympathetic block. On day 7, after injection of evans blue (EB) solution, the EB extravasation areas on the body surface were observed to investigate the distribution and physical-chemical characteristics of the sensitized area. The control area was set up, 0.5 cm away from the sensitized area, and with the same nerve segment innervation. Disease activity index (DAI) score of rats was compared between the normal group and the model group, and the morphological changes in the colon tissue were investigated with HE method. Using infrared thermal imaging technology and laser speckle flow imaging technology, skin temperature and blood infusion were determined in the sensitized area and the control area of the rats in the model group. Immunofluorescence technique was adopted to observe the expression levels of the positive nerve fibers of substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), and the correlation with blood vessels; as well as the expression levels of SP positive nerve fibers/tryptase+ mast cells, and tryptase+ mast cells/5-hydroxytryptamine (5-HT) in skin tissue in the sensitized area and the control area of the rats in the model group. MSD multi-level factorial method and ELISA were applied to determine the contents of pro-inflammatory and anti-inflammatory cytokines (e.g. TNF-α, IL-1ß, IL-6, IL-4 and IL-10) and anti-inflammatory substance corticosterone (CORT). RESULTS: Sensitization occurred at the T12-S1 segments of the colitis model rats, especially at L2-L5 segments. Compared with the normal group, DAI score was increased in the rats of the model group (P<0.05), and the colonic mucosal damage was obvious, with the epithelial cells disordered, even disappeared, crypt destructed, submucosal edema and a large number of inflammatory cells infiltrated. In comparison with the control area, the skin temperature and blood infusion were increased in the sensitized area of the model group (P<0.05, P<0.01); as well as the expression levels of the positive nerve fibers of SP, CGRP and TH of skin tissue (P<0.05), which was specially distributed in peripheral vessels, the expression levels of SP positive nerve fibers/tryptase+ mast cells, and tryptase+ mast cells/5-HT of the skin tissue were all expanded (P<0.05) in the sensitized area of the model group. Compared with the model group, the number of sensitized areas was reduced in the guanethidine group (P<0.05). In comparison with the control area of the model group, in the sensitized area, the contents of pro-inflammatory cytokines, e.g. TNF-α, IL-1ß and IL-6, and the anti-inflammatory substance CORT of skin tissue were all increased (P<0.05); and the contents of IL-6 and TNF-α were negatively correlated with CORT (P<0.05). CONCLUSION: The sensitized areas on the body surface of colitis rats are mainly distributed in the L2-L5 segments. Sensory and sympathetic nerves are involved in the acupoint sensitization, and the sensitized areas may have the dynamic changes in pro-inflammatory and anti-inflammatory substances.

Integrating Chronic Obstructive Pulmonary Disease Treatment With 8-Week Tai Chi Chuan Practice: An Exploration of Mind-Body Intervention and Neural Mechanism.

Objective: This study aims to explore the effect of integrating routine treatment with Tai Chi Chuan (TCC) intervention on the clinical symptom of patients with Chronic Obstructive Pulmonary Disease (COPD) from clinical and neurological perspectives. Methods: Twenty patients with COPD were recruited for regular treatment combined with 8-week TCC rehabilitative practice. Clinical symptoms were evaluated by Chronic Obstructive Pulmonary Symptom Assessment Scale (CAT) and Modified Dyspnea Scale (mMRC) at baseline and after treatment. Resting-state MRI scan was also performed with multiline T2-weighted echo-planar imaging (EPI) to acquire their functional images before and after the treatment. TCC rehabilitation involved a total of 8 weeks of practice with 90 min per session, three times a week. Results: After an 8-week integration routine treatment with TCC practice, the patient's clinical symptoms improved significantly. Imaging analysis showed that COPD patients exhibited decreased Degree of Centrality (DC) in the right inferior frontal gyrus (IFG), right middle frontal gyrus, bilateral cingulate cortex, bilateral precuneus, and right precentral gyrus. Moreover, correlation analysis found that the decreased DC in the right IFG was positively correlated with the CAT improvements. Conclusion: The routine treatment involving TCC rehabilitation practice could improve the clinical symptoms of patients with COPD. The right IFG might be a key brain region to contribute to the neural mechanism underlying integrative intervention on the clinical symptoms in COPD. These findings provide neurological evidence for treating COPD rehabilitation practice with mind-body practice based on Chinese culture to some extent, which also advances the understanding of the efficacy of TCC as the adjuvant technology from a neuroscience perspective. Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx?proj=45189], identifier [ChiCTR1900028335].

Sensitive silica-alumina modified capacitive non-Faradaic glucose sensor for gestational diabetes.

A highly sensitive silica-alumina (Si-Al)-modified capacitive non-Faradaic glucose biosensor was introduced to monitor gestational diabetes. Glucose oxidase (GOx) was attached to the Si-Al electrode surface as the probe through amine-modification followed by glutaraldehyde premixed GOx as aldehyde-amine chemistry. This Si-Al (∼50 nm) modified electrode surface has increased the current flow upon binding of GOx with glucose. Capacitance values were increased by increasing the glucose concentrations. A mean capacitance value was plotted and the detection limit was found as 0.03 mg/mL with the regression coefficient value, R² = 0.9782 [y = 0.8391x + 1.338] on the linear range between 0.03 and 1 mg/mL. Further, a biofouling experiment with fructose and galactose did not increase the capacitance, indicating the specific glucose detection. This Si-Al-modified capacitance sensor detects a lower level of glucose presence and helps in monitoring gestational diabetes.

Electroacupuncture and Moxibustion-Like Stimulation Relieves Inflammatory Muscle Pain by Activating Local Distinct Layer Somatosensory Afferent Fibers.

Recent studies have shown that both superficial and deep acupuncture produced clinically relevant and persistent effect on chronic pain, and several subtypes of somatic primary afferents played critical roles in acupuncture and moxibustion analgesia. However, which kind of primary afferents in the superficial and deep tissue of the acupoint is activated by acupuncture or moxibustion to relieve pain persistently remains unclear. The aim of this study is to investigate the roles of distinct peripheral afferents in different layers of the tissue (muscle or skin) in the acupoint for pain relief. Muscular A-fibers activated by deep electroacupuncture (dEA) with lower intensity (approximately 1 mA) persistently alleviated inflammatory muscle pain. Meanwhile, cutaneous C-nociceptors excited by noxious moxibustion-like stimulation (MS) and topical application of capsaicin (CAP) on local acupoint area produced durable analgesic effect. Additionally, spontaneous activity of C-fibers caused by muscular inflammation was also inhibited by dEA and CAP. Furthermore, decreases in pain behavior induced by dEA disappeared after deep A-fibers were demyelinated by cobra venom, whereas CAP failed to relieve pain following cutaneous denervation. Collectively, these results indicate that dEA and MS ameliorate inflammatory muscle pain through distinct primary afferents in different layers of somatic tissue; the former is achieved by activating muscular A-fibers, while the latter is mediated by activating cutaneous C-fibers.

[Effect of acupuncture on the cognitive function of migraine patients with depression/anxiety disorder].

OBJECTIVE: To observe the effect of five-element acupuncture on the cognitive function repair of migraine patients with depression/anxiety disorder. METHODS: The migraine patients with depression/anxiety disorder (19 cases, 5 cases dropped off) were taken as the observation group, and received five-element acupuncture twice a week for 8 weeks. Healthy subjects (19 cases) were selected by demographic data matching as the control group. The cognitive function was evaluated with the event related potential (ERP) technique, and the latency and amplitude of visual evoked potential P300 were adopted as the observation indexes. The headache days (every 4 weeks), headache intensity [visual analogue scale(VAS) score], and headache impact test-6 (HIT-6) score, Hamilton depression scale (HAMD) score and Hamilton anxiety scale (HAMA) score were used as the observation indexes for curative effect. RESULTS: Before the treatment, latency of target stimulus at Fz [ (417.5±34.3) ms] in the observation group was extended compared with the healthy subjects of the control group [(388.6±42.1) ms, P<0.05]. In the observation group, the latency of each point target stimulus [Fz: (376.1±36.2) ms, F3: (374.8±37.6) ms, F4: (372.0±37.6) ms] after treatment were shorter than those [Fz: (417.5±34.3) ms, F3: (417.4±33.8) ms, F4: (416.0±36.6) ms] before treatment (P<0.05). Before and after treatment, there was no significant difference in the amplitude of each point between the observation group and the control group (P>0.05). In the observation group, the headache days was shorter than that before treatment (P<0.01), and the VAS score, HIT-6 score, HAMD score and HAMA score were all lower than before treatment (P<0.01). CONCLUSION: There are some cognitive impairments in migraine patients with depression/anxiety disorder. Five-element acupuncture not only relieves headache, anxiety and depression effectively, but also improves the activation level of the frontal lobe. It significantly repairs the impaired cognitive function.

Antitumor Effects of Baicalein and Its Mechanism via TGFß Pathway in Cervical Cancer HeLa Cells.

BACKGROUND: Due to dual-regulating carcinogenesis, the TGFß pathway is an ideal and alternative tumor target. Natural flavonoids possess the similar structures to estrogen and could exert an important benefit to cervical cancer. The present study aimed to screen the inhibitor of TGFß pathway from natural flavonoids and evaluate the function and mechanism of the TGFß pathway inhibitor on cervical cancer. MATERIALS AND METHODS: The cervical cancer HeLa cells were firstly treated with different flavonoids and probed by western blot for screening the inhibitor of TGFß pathway. And then, the effect of the identified inhibitor on cell proliferation was studied by CCK-8 and clone formation assay. Then, RT-PCR and western blot assay were performed to evaluate the effect of identified inhibitor on mTOR/p70S6K pathway, and the cell migration and EMT pathway were also examined using scratching analysis and western blot assay. Finally, the role of TGFß was assessed via the classic inhibitor of TGFß/SMAD pathway. RESULTS: Screening data by western blot assay showed that baicalein displayed the best inhibitor effect on TGFß expression. CCK-8 and clone formation assay showed that baicalein inhibited the cell proliferation and clone cell number. RT-PCR and western bolt for probing mTOR, p70S6K, and 4EBP1 revealed that baicalein could suppress their expression and phosphorylation. The scratching analysis and western blot assay displayed that baicalein inhibited the cell migration and EMT progression in HeLa. The use of SB431542, a TGFß inhibitor, revealed that TGFß was crucial to baicalein-regulating cell proliferation and migration in HeLa cells. CONCLUSION: Baicalein, a medicine agent screened from natural flavonoids targeting TGFß pathway, could suppress mTOR/p70S6K pathway-mediated cell proliferation and EMT pathway-related migration via TGFß pathway in cervical cancer HeLa cells.

Brain Functional Specialization Is Enhanced Among Tai Chi Chuan Practitioners.

OBJECTIVE: To investigate the effect of long-term Tai Chi Chuan (TCC) practice on practitioners' brain functional specialization compare with the TCC novices. DESIGN: A cross-sectional study. SETTING: A psychology Institute. PARTICIPANTS: TCC practitioners (N=22) (52.4±6.8y; 7 men; educated years: 12.18±3.03y) and 18 healthy adults (54.8±6.8y; 8 men; education years: 11.78±2.90y) matched by age, sex, and education were enrolled. MAIN OUTCOME MEASURES: Participants underwent functional magnetic resonance imaging scanning and cognitive test to measure the differences in functional specialization and cognitive function. Functional specialization was evaluated by voxel-mirrored homotopic connectivity (VMHC) method. RESULTS: Lower middle frontal gyrus VMHC in TCC practitioners compared to controls. For TCC practitioners, the longer they practice, the lower their VMHC in precentral and precuneus. TCC practitioners showed better cognition performance. CONCLUSIONS: Changed VMHC indicated that TCC practice could enhance functional specialization in the middle frontal cortex of practitioners, which may be associated with higher-order cognitive ability.

The Effect of Tai Chi Chuan on Negative Emotions in Non-Clinical Populations: A Meta-Analysis and Systematic Review.

Tai Chi Chuan (TCC) as a typical mind-body practice has been investigated for its preventive role on negative emotions and has demonstrated its efficacy in healthy populations. However, the results are not consistent. We performed a meta-analysis and systematically evaluated the effect of TCC on selected negative emotions (i.e., anxiety and depression). Fourteen experimental studies from three English-and two Chinese-language databases were evaluated. The results showed that the positive effects of TCC on negative emotions were moderately to largely significant. In addition, although TCC significantly improved negative emotions in both the young adults and the older adults, old adults benefited more from TCC than young adults. These findings suggest that TCC is a worthy complementary non-pharmacological resource towards depression and anxiety and, thus, has great implications for the public health domain.

[Moxibustion promoted wound healing in rats with full-thickness cutaneous wounds].

OBJECTIVE: To explore the effects of moxibustion intervention on wound healing in rats with full-thickness cutaneous wounds. METHODS: A total of 28 adult SD male rats were randomly assigned to model group and moxibustion group (n＝14 in each one). The skin wound model was established by removal of a piece of full-thickness skin from the median line of the rats' back (about 2 cm below the shoulder blade). Moxibustion intervention was applied to the surrounding area of the focus for 25 min, once daily for 6 days. The wound healing was observed and photographed after each moxibustion intervention. The wound tissues were harvested after transcardiac perfusion with 4% paraformaldehyde solution on the 2nd and 7thday after modeling, and stained with H．E. and Masson methods for displaying histopathological changes and collagen fiber growth status, respectively. RESULTS: After modeling, the cutaneous wound was healed gradually in both groups, and the wound area was significantly smaller from the 2nd day to the 5th day in the moxibustion group than in the model group (P<0.01, P<0.05). Correspondingly, the wound closure area was significantly bigger from the 2nd to the 5th day in the moxibustion group than in the model group (P<0.01). H．E. and Masson staining showed that the number of the inflammatory cells (monocytes, macrophages, neutrophile, etc.) and the collagen fiber area in the local wound tissue of the moxibustion group were significantly bigger than those of the model group on the 2nd day after intervention (P<0.01). After 6 sessions of moxibustion intervention, the number of fibroblasts and collagen fibers in the moxibustion group were obviously increased than that in the model group, characterized by closer arrangement of fibroblasts and collagen fibers, more and larger of the new-born blood vessels, and thicker of the scab in the wound area. CONCLUSION: Moxibustion can promote the wound healing by enhancing the growth of collagen fibers and cell proliferation in the traumatic cutaneous area in full-thickness cutaneous wound rats.

[From molecular pharmacy to electroceuticals: SPARC program and acupuncture research].

The NIH-funded "Stimulating Peripheral Activity to Relieve Conditions (SPARC)" program has been initiated in Octomber 2016, aiming at developing high resolution neural circuit maps and next generation neural modulation devices. This program has brought great stimulus to acupuncturists and acupuncture researchers both at home and abroad. Is the SPARC program a driving force or a challenge of acupuncture research? In the present study, we introduced the SPARC program and compared it with current acupuncture research. The first step of SPARC is to better map neural circuits associated with disease on the anatomical level so as to identify the best points for intervention, and to decode the neural language at these intervention points for developing a dictionary of patterns associated with health and disease states on the signaling level. Similarly, our acupuncture research also focuses on revealing the neural encoding of acupuncture stimulation and its effect on visceral function, seeking suitable stimulation parameters to regulate the abnormal visceral activity precisely. Therefore, the common point of SPARC program and acupuncture research is the scientific basis of peripheral somatic neuronal regulation, and their difference is that acupuncture regulates the visceral function through multiple neural circuits and neural feedbacks by stimulating the sensitized points or acupoints, achieving homeostasis at last. Acupuncture-induced regulation effect is limited and the therapy is safe. Whereas, "stimulating periphe-ral activity (SPA)" can regulate the visceral organs precisely but without neural feedback. Inevitably, SPA will produce tolerance or side effects. Therefore, there is still much work to be done in terms of the initiation of trigger stimulation and the feedback inhibition of target organ effects. The SPARC program is definitely a powerful force in revealing the mechanisms by which acupuncture works.

Electroacupuncture Alleviated Referral Hindpaw Hyperalgesia via Suppressing Spinal Long-Term Potentiation (LTP) in TNBS-Induced Colitis Rats.

Although referred pain or hypersensitivity has been repeatedly reported in irritable bowel syndrome (IBS) patients and experimental colitis rodents, little is known about the neural mechanisms. Spinal long-term potentiation (LTP) of nociceptive synaptic transmission plays a critical role in the development of somatic hyperalgesia in chronic pain conditions. Herein, we sought to determine whether spinal LTP contributes to the referral hyperalgesia in colitis rats and particularly whether electroacupuncture (EA) is effective to alleviate somatic hyperalgesia via suppressing spinal LTP. Rats in the colitis group (induced by colonic infusion of 2,4,6-trinitrobenzenesulfonic acid, TNBS), instead of the control and vehicle groups, displayed evident focal inflammatory destruction of the distal colon accompanied not only with the sensitized visceromotor response (VMR) to noxious colorectal distension (CRD) but also with referral hindpaw hyperalgesia indicated by reduced mechanical and thermal withdrawal latencies. EA at Zusanli (ST36) and Shangjuxu (ST37) attenuated the severity of colonic inflammation, as well as the visceral hypersensitivity and referral hindpaw hyperalgesia in colitis rats. Intriguingly, the threshold of C-fiber-evoked field potentials (CFEFP) was significantly reduced and the spinal LTP was exaggerated in the colitis group, both of which were restored by EA treatment. Taken together, visceral hypersensitivity and referral hindpaw hyperalgesia coexist in TNBS-induced colitis rats, which might be attributed to the enhanced LTP of nociceptive synaptic transmission in the spinal dorsal horn. EA at ST36 and ST37 could relieve visceral hypersensitivity and, in particular, attenuate referral hindpaw hyperalgesia by suppressing the enhanced spinal LTP.

Neuropeptide Initiated Mast Cell Activation by Transcutaneous Electrical Acupoint Stimulation of Acupoint LI4 in Rats.

Transcutaneous electrical acupoint stimulation (TEAS) has been consistently used clinically for its ease of operation, non-invasiveness and painlessness, in contrast to the characteristics of inserted needles. However, the mechanism remains unknown. The aim of this study was to investigate the local response of TEAS at Hegu acupoint (LI4). Immunohistochemistry was used to measure the expression of tryptase-positive mast cells, neuropeptides of the calcitonin gene-related peptide (CGRP) and substance P (SP) in LI4. Mast cells were also labelled with serotonin (5-HT), neurokinin-1 receptor (NK-1R) and toluidine blue. The results showed that cutaneous CGRP and SP immune-positive (CGRP-IP or SP-IP) nerve fibres in LI4 were more highly expressed. There were high degrees of mast cell aggregation and degranulation with release of 5-HT near the CGRP-IP or SP-IP nerve fibres and blood vessels after TEAS. The degranulation of mast cells (MCs) was accompanied by expression of NK-1R after TEAS. Either mast cell membrane stabilizer (Disodium cromoglycate) or NK-1R antagonist (RP 67580) diminished the accumulation and degranulation of MCs induced by TEAS. Taken together, the findings demonstrated that TEAS induced sensory nerve fibres to express CGRP and SP, which then bound to the NK-1R on MCs, after which MCs degranulated and released 5-HT, resulting in TEAS-initiated acupuncture-like signals.

[Clinical features analysis of Qingkailing injection for adolescent patients based on real world HIS].

To explore the clinical application features of Qingkailing injection for adolescent patients. This study was based on the information from the hospitalized patients in 1998-2011 in HIS (hospital information system) of 16 tertiary hospitals in China. 615 adolescent patients with Qingkailing injection were used to investigate the clinical characteristics of Qingkailing injection. Apriori algorithm was adopted to establish the model, and Clementine 12.0 was used for correlation analysis. The results showed that male patients (355 cases) were more than female patients (243 cases); the age of the most patients was under 14 years old, with an average age of 9.40 years old; the hospital stay was most of 4-7 d; the patients were mostly concentrated in pediatrics, mainly including upper respiratory tract infection; outpatient admission to the majority (451 cases, accounting for 75.54%). The traditional Chinese medicine (TCM) syndrome mainly included phlegm-dampness internal resistance (38.46%), Qi and Yin Deficiency (11.54%), Liver qi stagnation (15.38%), and Yang deficiency syndrome (11.54%); the highest admission rate was during Slight Cold (13.01%). In combined application, the most common western medicine pair was Cephalosporin injection+vitamin C (with supporting rate of 24.6%) and the most common TCM pair was Shuanghuanglian+Ganmao Qingre granules (with supporting rate of 4.065%). The most common 3 western medicines in combined use were Potassium chloride injection+Cephalosporin injection+vitamin C (supporting rate of 15.93%); while the most common three Chinese medicines were Shuanghuanglian+Yunnan Baiyao+Ganmao Qingre granules (supporting rate of 1.138%). Qingkailing injection was also widely used in adolescent patients; the diagnosis and use were basically in line with the instructions; men were slightly more than women; age of onset, solar terms and TCM syndromes were highly consistent. Qingkailing injection was mainly combined with western medicines in combined drug use, and Chinese medicines were also available. Combined drug use was more reasonable. Based on the results of the real world HIS, Qingkailing injection could provide the idea and reference for regulating the medication in adolescent patients.

Herbicide and insect resistant Bt cotton pollen assessment finds no detrimental effects on adult honey bees.

One important concern regarding the use of transgenic cotton expressing insecticidal toxins from the bacterium Bacillus thuringiensis (Bt) is its potential detrimental effect on non-target organisms. The honey bee (Apis mellifera) is the most important pollinator species worldwide and it is directly exposed to transgenic crops by the consumption of genetically modified (GM) pollen. However, the potential effects of Bt cotton on A. mellifera remain unclear. In the present study, we assessed the effects of two Bt cotton varieties; ZMSJ expressing the Cry1Ac and Cry2Ab insecticidal proteins, and ZMKCKC producing Cry1Ac and EPSPS, on A. mellifera. Feeding on pollen from two Bt cotton varieties led to detection of low levels of Cry toxins (<10 ng/g fresh weight) in the midgut of A. mellifera adults, yet expression of detoxification genes did not change significantly compared to feeding on non-Bt cotton. Binding assays showed no Cry1Ac or Cry2Ab binding to midgut brush border membrane proteins from A. mellifera adults. Taken together, these results support minimal risk for potential negative effects on A. mellifera by exposure to Bt cotton.

[Distribution of algesia sensitized acupoints in the patients of intestinal cancer].

OBJECTIVE: To judge whether algesia sensitization of some acupoints is existed and whether the acupoint algesia sensitization area is expanded in the patients of intestinal cancer. METHODS: Totally, 30 patients of intestinal cancer and 30 healthy subjects were included. The electronic Von Fray was used to determine the pressure-pain thresholds at 13 acupoints relevant with gastrointestinal disorders and the reference points at the sites 1 cun and 2 cun lateral to those points as well as the sites at the corresponding nerve segments. Compared with the pressure-pain thresholds at the reference points of the different segments, the relative value was calculated. The changes were analyzed in the pressure-pain thresholds at the relevant acupoints on the body surface in the patients of intestinal cancer as compared with the relative pressure-pain thresholds in the healthy volunteers. RESULTS: The pressure-pain thresholds at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Quchi (LI 11) and Dachangshu (BL 25) in the patients of intestinal cancer were all significantly reduced as compared with those of the healthy subjects (P<0.05, P<0.01, P<0.001). At the non-acupoint sites 1 cun and 2 cun lateral to those acupoints as well as at the sites of the same segments, the pressure-pain thresholds were reduced significantly as compared with the control group (P<0.05, P<0.01, P<0.001). Particularly, the sensitization zone of Yinlingquan (SP 9) focused on the acupoint, the site 1 cun lateral to it as well as the non-acupoint sites of the same segments (P<0.01, P<0.001). CONCLUSION: The acupoint sensitization is displayed at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Quchi (LI 11), Dachangshu (BL 25) and Yinlingquan (SP 9) and the sensitization area is expended in the patients of intestinal cancer.

Astragaloside IV facilitates glucose transport in C2C12 myotubes through the IRS1/AKT pathway and suppresses the palmitate-induced activation of the IKK/IκBα pathway.

Astragaloside IV is a monomer isolated from Astragalus membranaceus (Fisch.) Bunge, which is one of the most widely used plant-derived drugs in traditional Chinese medicine for diabetes therapy. In the present study, we aimed to examine the effects of astragaloside IV on glucose in C2C12 myotubes and the underlying molecular mechanisms responsible for these effects. Four-day differentiated C2C12 myotubes were exposed to palmitate for 16 h in order to establish a model of insulin resistance and 3H glucose uptake, using 2-Deoxy­D­[1,2-3H(N)]-glucose (radiolabeled 2-DG), was detected. Astragaloside IV was added 2 h prior to palmitate exposure. The translocation of glucose transporter 4 (GLUT4) was evaluated by subcellular fractionation, and the expression of insulin signaling molecules such as insulin receptor ß (IRß), insulin receptor substrate (IRS)1/protein kinase B (AKT) and inhibitory κB kinase (IKK)/inhibitor-κBα (IκBα), which are associated with insulin signal transduction, were assessed in the basal or the insulin­stimulated state using western blot analysis or RT-PCR. We also examined the mRNA expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNFα) and Toll­like receptor 4 (TLR4). Taken together, these findings demonstrated that astragaloside IV facilitates glucose transport in C2C12 myotubes through a mechanism involving the IRS1/AKT pathway, and suppresses the palmitate-induced activation of the IKK/IκBα pathway.