Peripheral neural mechanism of visceral pain and acupoint sensitization in 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis model mice. / ç»“è‚ ç‚Žæ¨¡åž‹å°é¼ å† è„ç—›åŠç©´ä½æ•åŒ–çš„å¤–å‘¨ç¥žç»æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To explore the neural mechanism of visceral pain and related somatic (acupoints) sensitization by using in vivo calcium imaging of dorsal root ganglia (DRG) neurons. METHODS: Eight BALB/c mice were randomly divided into control and model groups, with 4 mice in each group. The colitis model was induced by colorectal perfusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) once daily for 7 days. Mice of the control group received colorectal perfusion of normal saline once daily for 7 days. The location and area of the somatic neurogenic inflammation (cutaneous exudation of Evans blue ï¼»EBï¼½) of the 2 groups of mice were observed after intravenous injection of EB. For pain behavioral tests, sixteen C57BL/6J mice were randomly divided into control and model groups, with 8 mice in each group, and a Von Frey filament was used to stimulate the referred somatic reactive regions in colitis mice, and the number of avoidance and paw withdraw reaction within 10 tests was recorded. For in vivo DRG calcium imaging tests, 24 Pirt-GCaMP6s transgenic mice were randomly and equally divided into control group and colitis model group. The responses of the neurons in L6 or L4 DRG to colorectal distension (CRD), lower back brushing, or mechanical stimulation at the hindpaw were observed using confocal fluorescence microscope. RESULTS: Compared with the control group, the area of EB exudation spot in the hindpaw and lower back regions was increased in the colitis model group (P<0.05), and the avoidance or paw withdraw numbers induced by Von Frey stimulation at the lower back and hindpaw were increased (P<0.01, P<0.05), indicating that colitis induced regional skin (acupoints) sensitization in the lower back and hindpaw regions. Compared with the control group, the percentage of L6 DRG neurons activated by 60 mm Hg CRD in the colitis model mice were apparently increased (P<0.01), the activated neurons mainly involved the medium-sized DRG neurons (P<0.01). In Pirt-GCaMP6s transgenic mice, following brushing the skin of the receptive field (lower back) of L6 DRG neurons, the fluorescence intensity of the brushing-activated DRG neurons and small, medium and large-sized neurons were significantly higher in the colitis model group than those in the control group (P<0.001, P<0.01, P<0.05). After brushing and clamping the skin of the right hindpaw (receptive field of L4 DRG neurons), the percentages of the activated L4 DRG neurons were obviously higher in the colitis model group than those in the control group (P<0.01, P<0.05), while there were no significant changes in the proportion of small, medium and large-sized neurons between the control and colitis model groups. CONCLUSIONS: Colitis may lead to body surface sensitization at the same and adjacent neuro-segments as well as to an increase of the number and activity of the responsive lumbar DRG neurons, among which the L6 DRG neurons at the same neuro-segment as the rectum colon showed an increase in the number of responders and intensity of calcium fluorescence signal while L4 DRG neurons at the level adjacent to the rectum colon showed an increase in the number of responders, suggesting that there may be different mechanisms of peripheral neural sensitization.

[Comparison of effects of routine electroacupuncture and pre-electroacupuncture in improving lung function in acute lung injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) and pre-EA at"Taiyuan"(LU9) on histopathological changes, pulmonary ventilation function, pneodynamics, and contents of TNF-α, IL-1ß and IL-10 in the bronchoalveolar lavage fluid in rats with acute lung injury (ALI), in order to explore their differences of therapeutic effects. METHODS: A total of 92 male SD rats were randomly divided into control, model, routine EA and pre-EA groups, with 23 rats in each group. The ALI rat model was established by instillation of 0.5% lipopolysaccharide solution (5 mg/kg) intratracheally. EA (3 mA, 10 Hz) was applied to bilateral LU9 for 20 min, once 5 h after modeling for rats of the routine EA group, and once on the 1st, 3rd and 5th day respectively before modeling for rats of the pre-EA group. The pulmonary ventilation functions, including dynamic lung compliance (Cdyn), tidal volume (TV)，minute ventilation volume (MV), lung resistance, peak inspiratory flow (PIF), peak expiratory flow (PEF), were measured by using a small animal lung function detection system. The electromyogram (EMG) of the diaphragm muscle was recorded for observing changes of the total integral electromyogram(iEMG), single iEMG and respiration rate. Pathological changes of the lung tissue were scored after H.E. staining. The contents of TNF-α, IL-1ß and IL-10 in the bronchoalveolar lavage fluid were determined by enzyme linked immunosorbent assay. RESULTS: Compared with the control group, the Cdyn, TV, MV and PIF consi-derably decreased (P<0.000 1), and the lung resistance, total iEMG of diaphragm muscle, lung injury score, and contents of TNF-α and IL-1ß were significantly increased (P<0.05, P<0.001, P<0.01) in the model group. In comparison with the model group, the TV, MV and PIF in both routine EA and pre-EA groups,and the Cdyn, total iEMG and single iEMG in the routine EA group, as well as the IL-10 content in the pre-EA group were significantly increased (P<0.01, P<0.001, P<0.05), whereas the lung injury score, and contents of TNF-α and IL-1ß were significantly decreased in the pre-EA group (P<0.05). CONCLUSION: Both pre-EA and routine EA at LU9 can improve the lung function of ALI model rats. Pre-electroacupuncture is related to local immunoregulation, while electroacupuncture is mainly related to the improvement of pulmonary ventilation function and respiratory motility.

[Effect of electroacupuncture on mood and estrogen receptor α expression in mice with polycystic ovary syndrome induced by bisphenol A exposure].

OBJECTIVE: To compare the effect of electroacupuncture (EA) on "Guanyuan" (CV4) or sensitization points in mice with polycystic ovary syndrome (PCOS), so as to explore its mechanisms underlying improvement of PCOS. METHODS: In the first part of this study, 26 female ICR mice were randomized into control group (8 mice) and model group (18 mice). The PCOS model was established by gavage of bisphenol A (BPA) at a dose of 100 mg/kg, and the control group were gavage of equal volume of corn oil, once daily, 5 days a week for 4 conse-cutive weeks. Evans blue (EB) dye (0.1 mL/10 g) was injected into the caudal vein after modeling. The size, number and distribution of EB exudation points at the skin were observed. In the second part of this study, 32 mice were randomized into control, model, EA-CV4 and EA-sensitization points groups (8 mice in each group). EA (2 Hz, 2 mA) was applied to the sensitization points or CV4 for 20 min, once daily, 5 days a week for 4 conse-cutive weeks. The body weight was measured once a week for 8 consecutive weeks. The behavior changes were evaluated by open field test and elevated plus maze test. H.E. staining was used to observe the histopathologic changes of the ovary tissue. Serum level of estradiol (E2) was measured by ELISA. The expressions of estrogen receptor α (ER-α) in ovarian and uterine tissues were detected by Western blot and immunofluorescence. RESULTS: (1) In PCOS mice, the EB exudation points were found to overlap the lower abdomen, lumbosacral, chest, back and lower limbs regions, and the number of EB points was significantly more than that of the control group (P<0.01). (2) After the intervention and compared with the control group, the ovaries showed polycystic changes and an increase of atresia follicles with a larger diameter, the activity time in the central area, the total distance of movement, the times of open-arm entries, the duration in open-arm, the serum E2 content and the expression of ER-α in ovarian tissue were significantly decreased (P<0.01, P<0.05), while the mice's body weight and the expression of ER-α in uterine tissue were increased (P<0.05) in the model group. After the intervention and compared with the model group, a small number of normal follicles and corpus luteum were observed under microscope, the activity time in the central area, the total distance of movement, the times of open-arm entries, the duration in open-arm, the serum E2 content and the expression of ER-α in ovarian tissue were significantly increased (P<0.05, P<0.01), while the mice's body weight and the expression of ER-α in uterine tissue was decreased (P<0.05) in both EA-CV4 and EA-sensitization points groups. CONCLUSION: EA at sensitization points and CV4 can regulate the expression of estrogen and ER-α in PCOS mice, and improve the anxiety like behavior. EB exudation points on the body surface can not only reflect the functional changes of organs, but also treat diseases through body surface stimulation, suggesting a dual role in diagnosis and treatment.

Paclitaxel, 5-fluorouracil, and leucovorin combination chemotherapy as first-line treatment in patients with advanced gastric cancer.

The aim of this retrospective analysis was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, 5-fluorouracil, and leucovorin (TFL) as first-line treatment in patients with advanced gastric cancer (AGC). One hundred and thirteen patients were enrolled in the study who were confirmed to have AGC by histopathology. These patients were treated with TFL: paclitaxel at a dose of 135 mg/m as a 3-h intravenous infusion on day 1, LV 400 mg/m as an intravenous infusion over 2 h on day 1, followed by 5-fluorouracil 2400 mg/m as an infusion over a 46-h period on 3 consecutive days. Cycles were repeated every 2 weeks. A total of 113 patients were assessed for their response to therapy. A total of three patients achieved complete responses and 46 patients achieved partial responses, yielding an overall objective response rate of 43.4% [95% confidence interval (CI): 34.3-52.5%]. Fifty-four cases of stable disease and 10 cases of progressive disease were observed in the remaining patients. The median time to progression and overall survival were 5.2 months (95% CI: 4.7-5.8 months) and 14.1 months (95% CI: 12.5-15.8 months), respectively. Toxicities were tolerable and moderate. The most common grade 3-4 toxicities included leukopenia (16.8%), neutropenia (17.7%), anemia (8.0%), thrombocytopenia (5.3%), and fatigue (6.2%). Combination chemotherapy with TFL offers an active and safe therapeutic approach for patients with AGC.

Combination chemotherapy with paclitaxel and oxaliplatin as first-line treatment in patients with advanced gastric cancer.

PURPOSE: This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with Paclitaxel (PTX) and Oxaliplatin (OXA) as first-line treatment for patients with advanced gastric cancer (AGC). METHODS: One hundred and seven patients with locally advanced or metastatic gastric adenocarcinoma received intravenous infusions of PTX at 135 mg/m2 and OXA at 85 mg/m2 on day 1 every 14 days. RESULTS: Among 107 patients enrolled, 9 patients could not be evaluated for a response because of the absence of any measurable lesions. Assessment of the response of 98 patients was made. The overall objective response rate was 42.9% (95% CI 32.9-52.8%), with two complete responses and 40 partial responses. The disease control was 79.6% (95% CI 71.5-87.7%). With 29 months of the median time of follow-up, the median progression-free survival was 5.8 months (95% CI 4.30-7.30 months) and the median overall survival was 11.5 months (95% CI 9.08-13.9 months). The 1-year survival rate was 48.0%. The most common grades 3 and 4 toxicities included neutropenia (32.7%), leucopenia (17.8%), fatigue (5.61%), and anemia (4.67%). Peripheral neuropathy occurred in 23.4% patients and grade 2 or higher peripheral neuropathy occurred in 12.1% of the patients. CONCLUSIONS: Combination chemotherapy with PTX and OXA offers a new, effective and safe regimen for patients with advanced gastric cancer.

[Possible Living Factors Influencing the Efficacy of Acupuncture Analgesia Between Chinese and Western Populations:Caffeine].

It has been known for thousands of years that acupuncture can relieve pain. However, the efficacy of acupuncture analgesia (AA) now has to be reconsidered due to negative reports from western countries. In the present study, the possible correlation between caffeine and the difference in AA in China and western countries was determined using the following factors:1) caffeine and pain; 2) adenosine, adenosine receptor and caffeine; 3) AA and caffeine. As a non-selective antagonist of the adenosine receptor, caffeine at low doses can be used as an adjuvant analgesic, and can augment antinociception combined with other analgesics. Caffeine can act as an important neural modulator, and adenosine can produce antinociception when combined with the A1 receptor located in spinal, supraspinal and peripheral tissue. A preclinical study demonstrated that caffeine at moderate doses could inhibit AA efficacy following plantar incision surgery in a mouse model. Caffeine is present in various foods, especially coffee, and approximately 85% of adults in western countries consume coffee regularly. Therefore, by reconsidering the correlation between caffeine, adenosine receptor and AA, and by determining the possible relationship between caffeine intake habits and AA efficacy, these findings will demonstrate the differences in AA between Chinese and western populations.

Application of the chronic constriction injury of the partial sciatic nerve model to assess acupuncture analgesia.

PURPOSE: To validate and explore the application of a rat model of chronic constriction injury to the partial sciatic nerve in investigation of acupuncture analgesia. METHODS: Chronic constriction injury of the sciatic nerve (CCI) and chronic constriction injury of the partial sciatic nerve (CCIp) models were generated by ligating either the sciatic nerve trunk or its branches in rats. Both models were evaluated via paw mechanical withdrawal latency (PMWL), paw mechanical withdrawal threshold (PMWT), nociceptive reflex-induced electromyogram (C-fiber reflex EMG), and dorsal root ganglion immunohistochemistry. Electroacupuncture (EA) was performed at GB30 to study the analgesic effects on neuropathic pain and the underlying mechanisms. RESULTS: Following ligation of the common peroneal and tibial nerves, CCIp rats exhibited hindlimb dysfunction, hind paw shrinkage and lameness, mirroring those of CCI rats (generated by ligating the sciatic nerve trunk). Compared to presurgery measurements, CCIp and CCI modeling significantly decreased the PMWL and PMWT. EA at GB30 increased the PMWL and PMWT in both CCI and CCIp rats. Calcitonin gene-related polypeptide and substance P expressions were apparently increased in both CCI and CCIp groups, but were not different from each other. The C-fiber reflex EMG of the biceps femoris was preserved in CCIp rats, but it could not be recorded in CCI rats on the 5th day after nerve ligation. The C-fiber reflex EMG was reduced at 0, 1, and 2 minutes after EA in CCIp rats, but only at 0 and 1 minute after EA in normal rats. CONCLUSION: The CCIp model is better than the CCI model for studying acupuncture analgesia on chronic neuropathic pain and the underlying mechanisms.

Treatment of Diabetic Gastroparesis by Complementary and Alternative Medicines.

Gastroparesis is a common gastrointestinal complication in diabetes, induced by hyperglycemia and characterized by delayed gastric emptying and upper abdominal symptoms, such asnausea, vomiting, early satiety, bloating and epigastric pain. Diabetic gastroparesis (DGP) affects life quality and glycemic control, and is a challenge to treat in both Western and Eastern medicine. Routine treatment in Western medicine includes gastric emptying promoted by prokinetic agents, gastric pacemaking, or surgery combined with lifetime hormono-therapy, all of which have unavoidable side effects and limitations, and are very expensive. Complementary and alternative medical treatments like acupuncture, moxibustion, and massage are becoming more and more attractive because of their effectiveness, fewer side effects, and reliable safety. This article aims to introduce representative methods of complementary and alternative medicine to treat DGP, which were searched in English through Pubmed and in Chinese through CNKI (China Knowledge Resource Integrated Database). Several lines of evidence demonstrated the effects of single or combined complementary alternative therapies on DGP outcomes; however, the mechanisms were rarely investigated. Randomized controlled trials are undoubtedly required in future studies.

Violet laser acupuncture--part 4: acute effects on human arterial stiffness and wave reflection.

We investigated the effects of violet laser acupuncture on arterial stiffness and other important parameters of the functional state of the heart such as augmentation index (AIx). This investigation ties together the medical perspectives of Eastern and Western medical practitioners; the Western medical perspective of the functional states of the human heart including systolic and diastolic blood pressures, and the Eastern medical perspective regarding taking patients' pulses for diagnosis and using acupuncture for subsequent treatments. Pulse wave velocity (PWV) is a direct marker of arterial stiffness; AIx indicates wave reflection. Both parameters can be measured by cuff applied to the brachial artery. The first results from a pilot study of 10 healthy volunteers (M/F, 3/7; mean age ± SD, 27.8 ± 6.8 years) regarding violet laser acupuncture (405 nm; 110 mW; 500 µm; 10 min) showed a marked but not statistically significant decrease in aortic PWV and an increase in brachial AIx during and after laser acupuncture at the acupoint Baihui. Further studies including control measurements are necessary.

[Effect of electroacupuncture of auricular concha on inflammatory reaction in endotoxaemia rats].

OBJECTIVE: To evaluate the effect of electroacupuncture (EA) of the auricular concha (EA-AC) on serum cytokines contents and pulmonary transcription factor nuclear factor-kappaB (NF-kappaB) expression in lipopolysaccharide (LPS) induced endotoxaemia rats so as to study its mechanism underlying cholinergic anti-inflammatory efficacy. METHODS: Male SD rats were randomized into normal control, model (LPS), simple EA-AC, EA-AC + LPS, vagal nerve stimulation (VNS) + LPS, and EA-Zusanli (ST 36) + LPS groups (n = 12/group). Endotoxaemia model was duplicated by intravenous (tail vein) injection of LPS (0.5 mL/kg). Two intradermal needles were inserted into the central sites of the cavity of concha and cymba of auricular concha respectively on each side and stimulated electrically by using an electrical stimulator (i.e, EA-AC). VNS was applied to the left cervical vagal nerve, and EA (1 mA, 10 Hz, pulse-width 1 ms) was also applied to bilateral "Zusanli" (ST 36). Serum cytokines (TNF-alpha IL-6) contents 2 h after modeling were determined by using enzyme linked immunosorbent assay (ELISA), and pulmonary NF-kappaB p 65 expression 2 h after modeling was detected by using western blotting. RESULTS: Compared with the normal control group, serum TNF-alpha and IL-6 contents, and pulmonary NF-kappaB p65 expression level in the model group were increased significantly (P < 0.01). In comparison with the model group, serum TNF-alpha contents in the simple EA-AC, EA-AC + LPS, VNS+ LPS and ST 36 + LPS groups, and serum IL-6 contents and pulmonary NF-kappaB p 65 expression levels in the simple EA-AC, EA-AC + LPS and VNS + LPS groups were down-regulated considerably (P < 0.05, P < 0.01). Compared with the VNS + LPS group, serum TNF-alpha -28) and IL-6 contents, and pulmonary NF-kappaB p 65 expression level in the ST 36 + LPS group were increased significantly (P < 0.05, P < 0.01). In comparison with the EA-AC + LPS group, pulmonary NF-kappaB p 65 expression level in the ST 36 + creased remarkably (P < 0.05). CONCLUSION: Both EA of auricular concha and vagus nerve stimulation can serum TNF-alpha and IL-6 contents, and down-regulate pulmonary NF-kappaB p 65 expression level in endotoxaemia similar cholinergic anti-inflammatory mechanism between them.