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Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. Despite much advances, the pathophysiological mechanism is still poorly understood comparing with its somatic counterpart and, as a result, the therapeutic efficacy is usually unsatisfactory. Acupuncture has long been used for the management of numerous disorders in particular pain and visceral pain, characterized by the high therapeutic benefits and low adverse effects. Previous findings suggest that acupuncture depresses pain via activation of a number of neurotransmitters or modulators including opioid peptides, serotonin, norepinephrine, and adenosine centrally and peripherally. It endows us, by advancing the understanding of the role of ion channels and gut microbiota in pain process, with novel perspectives to probe the mechanisms underlying acupuncture analgesia. In this review, after describing the visceral innervation and the relevant afferent pathways, in particular the ion channels in visceral nociception, we propose three principal mechanisms responsible for acupuncture induced benefits on visceral pain. Finally, potential topics are highlighted regarding the future studies in this field.

Increasing evidence has been accumulated for the effectiveness of acupuncture therapy in relieving pain. However, there are limited data on regulation of protein expression after electroacupuncture (EA) intervention. Thus, the present study is designed to determine changes in protein expression following EA stimulation in rats with sciatic nerve chronic constrictive injury (CCI) induced neuropathic pain. Sixty Wistar rats were equally randomized into normal control group, CCI group, and CCI with EA stimulation (EA) group. The CCI model was established by ligature of the left sciatic nerve. EA stimulation was applied at Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed hypothalamic proteins in the three groups were identified by 2-D gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering and pathway of the identified proteins were analyzed by Mascot software. Results showed that, after CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of EA treatment. Following EA intervention, there were 17 hypothalamic proteins identified with significant changes in the expression (>twofold). Three gene-ontologies (oxidoreductase activity, oxidation reduction, and protein binding) were enriched, while there was a significant regulation of glycolysis/gluconeogenesis/hexose metabolism pathway. These data demonstrate that EA intervention can attenuate pain via regulation of expression of multiple proteins in the hypothalamus. Further, hypothalamic glucose metabolism may be important in supporting energy and neurotransmitter homeostasis in the effects of EA intervention.

Postoperative cognitive dysfunction (POCD) is a clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery, especially in geriatric surgical patients. Although it has been documented that isoflurane exposure impaired cognitive function in several aged animal models, there are few clinical interventions and treatments available to prevent this disorder. Minocycline has been well established to exert neuroprotective effects in various experimental animal models and neurodegenerative diseases. Therefore, we hypothesized that pretreatment with minocycline attenuates isoflurane-induced cognitive decline in aged rats. In the present study, twenty-month-old rats were administered minocycline or an equal volume of saline by intraperitoneal injection 12 h before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Two weeks later, spatial learning and memory of the rats were examined using the Morris Water Maze. We found that pretreatment with minocycline mitigated isoflurane-induced cognitive deficits and suppressed the isoflurane-induced excessive release of IL-1β and caspase-3 in the hippocampal CA1 region at 4 h after isoflurane exposure, as well as the number of TUNEL-positive nuclei. In addition, minocycline treatment also prevented the changes of synaptic ultrastructure in the hippocampal CA1 region induced by isoflurane. In conclusion, pretreatment with minocycline attenuated isoflurane-induced cognitive impairment in aged rats.

In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic effect of repeated electroacupuncture stimulation at bilateral Zusanli (ST36) and Yanglingquan (GB34). In addition, associated synaptic changes in neurons in the paraventricular nucleus of the hypothalamus were examined. Results indicate that the thermal pain threshold (paw withdrawal latency) was significantly increased in rats subjected to 2-week electroacupuncture intervention compared with 2-day electroacupuncture, but the analgesic effect was weakened remarkably in ovariectomized rats with chronic constrictive injury. 2-week electroacupuncture intervention substantially reversed the chronic constrictive injury-induced increase in the synaptic cleft width and thinning of the postsynaptic density. These findings indicate that repeated electroacupuncture at bilateral Zusanli and Yanglingquan has a cumulative analgesic effect and can effectively relieve chronic neuropathic pain by remodeling the synaptic structure of the hypothalamic paraventricular nucleus.

In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanli (ST36) and Yanglingquan (GB34) once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold (paw withdrawal latency) was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptic cleft width and thinning of the postsynaptic density, and it significantly suppressed the down-regulation of intracellular calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region.

The present study observed the effects of repeated electroacupuncture of Zusanli (ST36) and Yanglingquan (GB34) on expression of hippocampal acetylcholinesterase, vesicular acetylcholine transporter, and muscarinic M1 receptor mRNA in chronic constrictive injury (neuropathic pain) and/or ovariotomy rats. Results demonstrated increased expression of hippocampal acetylcholinesterase, vesicular acetylcholine transporter, and muscarinic M1 receptor mRNA, as well as decreased pain threshold, in a rat model of chronic neuropathic pain after electroacupuncture. The effects of electroacupuncture increased with prolonged time, but the above-mentioned effects decreased in memory-deficient animals. Results indicated that repeated electroacupuncture has a cumulative analgesic effect, which is closely associated with upregulation of acetylcholinesterase and vesicular acetylcholine transporter activity, as well as M1 receptor mRNA expression and memory.

Objective: To explore the effect of trichostatin A (TSA) alone and combination with imatinib on the proliferation and apoptosis of K562R cells., Methods: 3-(4,5-dimethylthiazol-2-yl) -5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay was used to observe the proliferation of K562R cells and apoptosis was analyzed by annexin-V/propidium iodide(PI) staining., Results: After exposure to TSA, the proliferation of K562R cells was inhibited, and the effect was in both time- and dose-dependent manner. The apoptosis was induced. Combined with imatinib, the effect of proliferation inhibition was better., Conclusion: TSA combined with imatinib can inhibit the proliferation of K562R cells and induce its apopotosis. TSA may become a new drug for imatinib-resistant patients.

Objective: To evaluate the curative effect and adverse effect of low dose cytarabine and aclarubin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on patients with the intermediate and high-risk myelodysplastic syndrome., Methods: A: total of 46 patients with intermediate and high-risk myelodysplastic syndrome was retrospectively analyzed. Twenty-eight patients received CAG regimen and 18 received conventional chemotherapy. CAG regimen: aclarubicin 10 mg/(m2.d)intravenously daily, Day 1~8; cytarabine 10 mg/ m2 subcutaneously once every 12 hours, Day 1~14; and subcutaneously use of granulocyte colony-stimulating factor 200 mug/(m2.d) until 12 hours before the last use of cytarabine. The initial outcome was evaluated after the first course of treatment. The responders received the second course. The ultimate therapeutic effect was evaluated after the 2 courses., Results: The overall response rate in the CAG regimen group was 78.6% (22/28). Thirteen patients (46.4%) responded, 5 (17.9%) showed partial response, and 4 (14.3%) hematologic improvement. The overall response rate in the conventional chemotherapy group was 50%(9/18). Six patients (33.3%) achieved complete response, 2 (11.1%) partial response, and 1(5.6%) hematologic improvement. The overall response rate of the CAG group was significantly higher than that in the control group (P<0.05). The adverse effects of CAG regimen were bearable., Conclusion: With acceptable adverse effect, CAG regimen is effective for the intermediate and high-risk myelodysplastic syndrome. Long-time outcome needs further observation.

Objective: To observe the effects of electroacupuncture (EA) at different acupoints on abnormal changes of uterine myoelectric activities in pregnant rats so as to analyze the specificity of regulative effects of the acupoint., Methods: Forty-eight pregnant (18-20 days) Wistar rats were randomly divided into control group (n=10), "Sanyinjiao" (SP 6) group (n=9), "Neiguan" (PC 6) group (n=10), "Hegu" (LI 4) group (n=8), and "Sanyinjiao plus Hegu" group (n= 11). These rats were anesthetized by intraperitoneal injection of a mixture solution of 1.5% chloralose (50mg/kg) and 25% urethane (420mg/kg). Electrohysterogram (EHG) was recorded by using a pair of stainless steel electrodes inserted into the subserous layer of the left mid part of the uterus. The reference electrode was placed in the adjoining subcutaneous tissue of the incision. Oxytocin and progesterone were given to the local uterus nearby the recording electrode to induce excitement and suppression of myoelectric activities of the uterus respectively. EA (2mA, 5/15Hz) was carried out at the above-mentioned acupoints separately for 20 min, and the influence of EA on changes (amplitude and frequency) of fast waves and slow waves of the uterine myoelectric activity was analyzed., Results: As compared with control group, EA at SP6 plus LI4 and at SP6 alone had a significantly inhibitory effect on oxytocin-induced increase in the frequency and amplitude of both fast and slow waves (P<0.05); and EA at LI4 had a markedly inhibitory effect on the amplitude of fast waves (P<0.05). EA at PC6 had no any marked effect on both frequency and amplitude of fast and slow waves of EHG (P>0.05). Compared with control group, EA at SP6 plus LI4 and at SP6 alone could relieve or significantly relieve progesterone-induced suppression of the frequency and amplitude of both fast and slow waves (P<0.05); and the effects of EA at SP6 plus LI4 appeared earlier and lasted longer than those of EA at SP6; while EA at LI4 and PC6 had no obvious effect on progesterone-induced changes of the frequency and amplitude of both fast and slow waves (P>0.05)., Conclusion: EA at SP6 plus LI4 and at SP6 alone has a dual-directional regulative effect on abnormal EHG, the effect of EA at SP6 plus LI4 is the strongest, EA at SP6 the secondary, EA at LI4 the weakest, and EA at PC6 shows no effect. In short, EA at different acupoints have their own relative specificity in regulating abnormal uterine myoelectric activities.

A full-length cDNA clone (pD212) of dengue virus type 2 isolated in China (DEN2-43) was constructed. Based on this, we constructed several mutants with deletions in capsid protein C using fusion PCR. These deletions removed part or almost all of the internal stretch of hydrophobic amino acid residues that is probably involved in virion assembly. We thus obtained viable mutant viruses. The propagation capacity of the mutant viruses in cell culture was impaired in parallel with the increasing size of the deletion, and the infectivity of mutant C(Delta42-59), from which all of helix III of capsid protein C was removed, was completely abolished. More importantly, the mutant viruses were highly attenuated in suckling mice but induced high levels of antibodies in adult mice. This study indicates that the structural and functional flexibility of capsid protein C make it a candidate target for the attenuation of dengue virus, which could open a promising new avenue for the development of live attenuated dengue vaccines.

Objective: To detect the expression and localization of human telomerase catalytic subunit (hTERT) and c-Myc oncogene protein product in human middle ear cholesteatoma, and to evaluate their roles in the proliferation of cholesteatoma epithelium., Method: The specimens from the middle ear cholesteatoma tissue of 32 cases and external ear skin of 14 cases were examined by immunohistochemical SP method and computer image analysis system for TERT and c-Myc oncogene protein product., Result: All 32 samples of cholesteatoma showed a stronger expression of TERT and c-Myc oncogene protein product than that of the external ear skin. The indexes, such as mean positive cell rate and mean obsorbency of cholesteatoma epithelium are much higher than that of the normal external ear shin remarkably( P < 0.05). Accompanied with numerous inflammatory cells(lymphocytes, plasmocytes, neutrophils and macrophages) subcutaneously, the high expression of TERT and c-Myc oncogene protein product were correlated with each other( P < 0. 05)., Conclusion: Excessive proliferation and keratinization of cholesteatoma are presented by the expression of TERT and c-Myc oncogene protein product in different ways, both of which play a cooperative role in the development of cholesteatoma. Subcutaneous inflammatory response may contribute to the excessive proliferation of keratose cells.

With the advent of the ski-skating technique, upper body power has increasingly been shown to be a major factor in cross-country skiing success. The purpose of this study was to evaluate 4 commonly used training methods (weight, circuit, rollerboard, and ski-specific training) for the development of upper body power (UBP) in junior cross-country skiers. Fifty-eight adolescent cross-country skiers (Boys: n = 29, age = 16.0 +/- 1.2 y and Girls: n = 29, age = 15.5 +/- 1.5 y) were assigned to one of the UBP training methods for a 10-week training program. Fourteen cross-country runners served as controls (boys: n = 7, age = 15.8 +/- 1.7 y; girls: n = 7, age = 14.9 +/- 1.3 y). Skiers were evaluated pre- and post-training for upper body strength (UBS) using a 10 repetition maximum (RM) rollerboard test, for UBP using a double-poling ergometer and for upper body endurance (UBE) with a 3-km, arms-only, rollerski endurance time trial. Competitive race results were collected during the winters before and after training as were all training data. Only the rollerboard training group improved significantly greater than the control group (p < 0.05) in UBP and UBS. Improvements in UBP, UPS, and UBE were significantly related (r = 0.545, 0.303, and 0.407, respectively) to improvements in competitive performance. These data suggest that training using a rollerboard with 5-12RM and explosive speed is more effective in developing UBP than other common training methods for adolescent cross-country skiers. The practical importance of these data was verified by the significant relationships between improvements in UBP, UBS, and UBE related to improvements in competitive race performance.