Objective:To investigate the motor and non-motor symptoms and polysomnographic features in patients with rapid eye movement sleep behavior disorder (RBD), early Parkinson's disease (PD) with and without RBD.Methods:Patients with idiopathic RBD (IRBD) and early PD were collected from the clinics in West China Hospital of Sichuan University from August 2020 to May 2021.All the patients were divided into 3 groups including IRBD group (67 cases), PD with RBD (PD+ RBD) group (19 cases), and PD without RBD (PD-RBD) group (22 cases). Unified Parkinson's disease rating scale part 3 (UPDRS-Ⅲ), Hoehn-Yahr(H-Y) stage, Epworth sleepiness scale (ESS), REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK), 17-item Hamilton depression scale(HAMD-17), mini-mental state examination(MMSE), Sniffin’Sticks olfactory function test, visual analogue scale (VAS), and scale for outcomes in Parkinson's disease-AUT(SCOPA-AUT) were used to assess the motor and non-motor symptoms including sleepiness, RBD, depression, cognitive function, olfactory function, pain and autonomic function respectively.All patients were performed to the polysomnography (PSG) examination.One-way ANOVA, Krukal-Wallis test, χ2 test and Fisher accurate test were used to analyze the data of motor and non-motor symptoms and sleep parameters among the 3 groups accordingly. Results:There were statistically significant differences in motor symptoms among the three groups ( F=57.009, P<0.05), and the scores of UPDRS Ⅲ and H-Y stage were higher in the PD+ /- RBD group than those in the IRBD group(both P<0.05). However, there was no significant difference in motor symptoms between PD+ RBD group and PD-RBD group ( P>0.05). There were no significant differences in the scores of ESS, MMSE, olfactory function test and VAS (all P>0.05). But the HAMD-17 score was significantly higher in the PD+ RBD group(2(1, 9)) than that in the IRBD group (0(0, 3)( P<0.05). The SCOPA-AUT scores of autonomic function were significant differences in the three groups, mainly in the digestive system, urinary system, and sexual function ( P<0.05). Notably, the IRBD group (8(4, 14)) and PD+ RBD group (11(7, 14)) had higher scores of SCOPA-AUT compared with PD-RBD group (4(4, 5.75)(all P<0.05), especially in the digestive dysfunction(all P<0.05). The PD+ RBD group(3.47±1.17) had higher scores of sexual function compared with IRBP group(1.78±0.60)( P<0.05), and the urinary system scores also higher than PD-RBD group( P<0.05). The PD-RBD group(21.30 (6.10, 34.00)/h) had a significantly higher oxygen desaturation index in REM sleep compared with that of IRBD group(5.90(2.70, 16.73)/h) ( P<0.05). Conclusions:Early PD with RBD has more severe non-motor symptoms, especially depression and autonomic dysfunction.RBD can be related with the earlier and more widely autonomic dysfunction.

The degree of hemodynamic support by vasoactive drugs in critically ill patients is often considered one of the markers of disease severity. The sequential organ failure assessment (SOFA), European system for cardiac operative risk evaluation Ⅱ (EuroScoreⅡ), and other scores only roughly quantify the drug support of cardiovascular system. When patients need large doses of vasoactive drugs, the mortality increases accordingly. The vasoactive-inotropic score (VIS) objectively quantifies the degree of cardiovascular support using a simple formula that standardizes the dose of different agents, and it is recommended as a simple, effective, and accurate prognostic indicator. In recent years, there are more and more clinical applications and related studies at home and abroad. This paper reviews the application and progress of VIS score in critically ill patients, providing help for doctors to judge the condition and prognosis of patients and guiding the decision-making of diagnosis and treatment.

Objective To detect the role of PAR2-PKA/PKCε signaling pathway in periphery neurons in the tran-sition from acute to chronic pain,and investigate the possible approach to prevent both acute and chronic pain simultane-ously. Methods SD rats were randomly divided into control group,sham model group,model group,iPAR2-1 group and iPAR2-2 group. The hyperalgesia priming model was established by injection of carrageenan and PGE2 into the left hind-paw except control and sham model group. PGE2 was administrated at 7 days after carrageenan injection. The PAR2 inhibi-tor was administrated before and after PGE2 injection separately in the iPAR2-1 group and iPAR2-2 group. The paw with-drawal thresholds(PWTs)of rats in each group was detected before and at 5 h,3 d,6 d,7 d 0.5 h,7 d 4 h,7 d 24 h after carrageenan injection. The expression level of PAR2, PKA and PKCε proteins in the dorsal root ganglion(DRG) were detected at 24 h after carrageenan injection. Results The hyperalgesia priming model was successfully generated. When PGE2 was administrated at 7 days after carrageenan injection, the hyperalgesia induced by PGE2 was significantly prolonged. The PWTs of rats in the model group were significantly lower than that of the control and sham model groups(P<0.01),though the PWTs of sham model group had no significant difference with the control on 7 d 24 h after carrageenan injection(P>0.05). The expression level of PAR2 and PKCε in the ipsilateral DRG neurons were significantly increased on 7 d 24 h after carrageenan injection,when compared with the control and sham model groups(P<0.05). PAR2 inhibi-tor prevented the prolonged hyperalgesia induced by PGE2(P<0.05)and decreased the PKCε expression in DRG neurons whenever it was given(P<0.05). However,PAR2 inhibitor did not regulate the acute inflammatory pain of PGE2 and the expression of PKA in DRG neurons(P>0.05). Conclusions Inhibition of the expression of PAR2 can prevent the tran-sition from acute to chronic pain. This effect may be related with the inhibitory effect on the activation of PAR2-PKCε sig-naling pathway in DRG neurons. However,inhibition of PAR2 can not regulate the acute pain. These may because of that the PAR2-PKA signaling pathway does not play a role in acute pain.

Objective: To study the effect of lentivirus-mediated microRNA (miR) -1246 RNA interference (RNAi) on biological characteristics and behaviors in cervical cancer cells as well as to identify the downstream signaling pathways affected. Methods: MiR-1246 specific cDNA was synthesized and cloned into the recombinant lentiviral vector (LV-miR-1246-inhibitor) . The SiHa cells were devided into three groups: no viral infection (negative control, NC) , infection with control virus (LV-NC) , and infection with miR-1246-inhibitor virus (LV-miR-1246-inhibitor) . The expression of the miR-1246 was detected by reverse transcription (RT) -PCR. Cell growth was analyzed by cell counting kit 8 (CCK-8) assay. The invasion was dectected by transwell matrige gel. Cell apoptosis was detected by flow cytometer. The growth of xenograft tumors was also investigated. Expression of thrombospondin-2 (THBS2) , matrix metalloproteinase (MMP) 2, 9 were also evaluated in the cells. Results: (1) The expression level of miR-1246 in SiHa cells (0.11±0.13) was significantly lower in group LV-miR-1246-inhibitor than those in the group LV-NC and the group NC (1.14±0.86 and 1.30±0.73, respectively; P<0.01) . (2) The proliferation of SiHa was also markedly suppressed in CCK-8 at 96 hours (P<0.01) . (3) The number of group LV-miR-1246-inhibitor was significantly less than those in the LV-NC and NC groups in transwell invasion assay (71±4, 162±5 and 188±5, respectively; P<0.01) . (4) The apoptosis rate of SiHa cells in the group LV-miR-1246-inhibitor [ (16.10±3.37) %] was significantly lower than those of group LV-NC and group NC [ (5.67±0.89) % and (1.78±0.08) %,P<0.01]. (5) The tumor volume in the nude mice group LV-miR-1246-inhibitor [ (287±59) mm³] was significantly lower than those in the LV-NC and NC groups [ (571±137) and (657±144) mm³, respectively; P<0.01]. (6) Compared with the LV-NC group and the NC group, THBS2 protein expression in the tumor tissue of the nude mice in the group LV-miR-1246-inhibitor was significantly increased (P<0.05) , while the expression levels of MMP-2 and MMP-9 protein were significantly decreased (P<0.01) . Conclusion These results suggest that miR-1246 functions during cervical cancer pathogenesis and tumor formation via the THBS2, MMP signaling pathway.

OBJECTIVETo observe the intervention effect of electroacupuncture (EA) on small intestinal motility in the rats of postoperative ileus (POI) at perioperative stage and explore the mechanism on the regulation of interstitial cells of Cajal (ICC) in the treatment of POI.

METHODSSixty heathy male SD rats were randomized into a sham-operation group, a model group, an EA group and a sham-EA group, 15 rats in each one. Except the sham-operation group, POI modeling was done in the rest groups. In the EA group, separately, 48 h, 24 h and 0.5 h before modeling, during modeling and 6 h, 12 h and 24 h after modeling, EA was given bilaterally to "Zusanli" (ST 36), 5 Hz, 1-2 mA, for 30 min. The sham-EA stimulation was given in the sham-EA group at the same time points. The same fixation was the only intervention in the model group. No intervention was applied in the sham-operation group. Five rats were selected randomly from each group 6 h, 12 h and 24 h after modeling for the determination of small intestine motility and they were sacrificed. Afterwards, the small intestinal muscular layer was collected for the determination of c-kit and P2X7 mRNA. In 24 h of modeling, the immunofluorescence test was done for c-kit determination.

RESULTSIn 6 h, 12 h and 24 h of modeling, in the model group, the EA groupand the sham-EA group, the small intestine motility was apparently lower than that in the sham-operation group at the same time points (all<0.01). In 6 h and 12 h of modeling, the small intestine motility in the EA group was not different significantly as compared with that in the model group (both>0.05). In 24 h of modeling, the small intestine motility in the EA group was better than that in the model group and the sham-EA group at the same time points (both<0.05). The difference was not significant between the sham-EA group and the model group (>0.05). In 6 h, 12 h and 24 h of modeling, c-kit mRNA expression of small intestine muscular layer was reduced apparently in the model group (all<0.01) and P2X7 mRNA expression did not change apparently (all>0.05). In 24 h of modeling, as compared with the model group and the sham-EA group, c-kit mRNA expression and positive cell area in the small intestine muscular layer were increased in the EA group (all<0.01).

CONCLUSIONSEA effectively increases the small intestinal motility in POI rats, shortens the recovery time, which is probably closely relevant with the increase of ICC count in small intestinal muscular layer.

Neuropathic pain is a chronic pain caused by primary nervous system damage and nerve dysfunction. Its pathogenesis is complex and diverse. It is difficult to treat clinically. In recent years, researchers used electroacupuncture to treat neuropathic pain and obtained a desirable effect. This article summarizes recent years’ studies on the main mechanisms of neuropathic pain and the intervention effect of electroacupuncture to provide reference for following studies on electroacupuncture treatment of neuropathic pain.

OBJECTIVETo observe the effects of electroacupuncture (EA) on pain behavior in rats with bone cancer pain and morphine tolerance, and to explore partial action mechanism.

METHODSForty-two SD healthy female rats were randomly divided into a sham operation group (7 rats), a bone cancer pain group (8 rats), a morphine tolerance group (9 rats), an EA group (9 rats) and a sham EA group (9 rats). The rats in the sham operation group were treated with injection of phosphate buffer saline at medullary cavity of left-side tibia, and the rats in the remaining groups were injected with MRMT-1 breast cancer cells. After operation, no treatment was given to rats in the sham operation group and bone cancer pain group. 11 days after operation, rats in the morphine tole-rance group, EA group and sham EA group were treated with intraperitoneal injection of morphine hydrochloride, once every 12 hours, for 11 days to establish the model of bone cancer pain and morphine tolerance. One day after the establishment of this bone cancer pain model, the rats in the morphine tolerance group were injected with morphine, once every 12 hours (9:00 a.m. and 9:00 p.m.) for 7 days; the rats in the EA group and sham EA group were injected with morphine at 9:00 a.m., and treated with EA (2 Hz/100 Hz) and sham EA (only injected into the subcutaneous tissue) at bilateral "Zusanli" (ST 36) and "Kunlun" (BL 60), 30 min per treatment, once a day for 7 days. One day before cancer cell injection, 6 days, 8 days, 10 days after operation, after 30 min on 1 days, 5 days, 9 days, 11 days of morphine injection, and after 30 min on 1 days, 3 days, 5 days, 7 days of EA treatment, the paw withdrawal threshold (PWT) was measured in each group. On 11 day of morphine injection, HE staining was applied to observe the morphology and structure change of tibia in the sham operation group, bone cancer pain group and morphine tolerance group, random 2 rats in each group. On 7 days of EA treatment, fluorescent immunohistochemical method was applied to observe the expression of μ-opioid receptor positive cells in nucleus ceruleus in each group, random 4 rats in each one.

RESULTSAfter 10 days of the cancer cells injection, the PWT of 28 rats of bone cancer pain model (8 rats in the bone cancer pain group, 8 rats in the morphine tolerance group, 6 rats in the EA group and 6 rats in the sham EA group) was significantly lower than that of 7 rats in the sham operation group (<0.01). After one day of morphine injection, the PWT of the morphine tolerance group, EA group and sham EA group was higher than that of the bone cancer pain group (all<0.01); on 11 d of morphine injection, the PWT of the morphine tolerance group, EA group and sham EA group was not significantly different from that of the bone cancer pain group (all>0.05). On 11 d of morphine injection, the tumor induced by cancer cells was observed in upper 1/3 tibia in the bone cancer pain group and morphine tolerance group, and the marrow cavity was filled with MRMT-1 cancer cells; no abnormal change was observed in the sham operation group. On 1 d, 3 d, 5 d and 7 d of EA treatment, the PWT of the cancer pain group, morphine tolerance group and sham EA group was lower than that of the EA group (all<0.01). On 7 d of EA treatment, the positive expression of MOR in nucleus ceruleus in the cancer pain group, morphine tolerance group, EA group and sham EA group was lower than that in the sham operation group (<0.01,<0.05), and that in the cancer pain group, morphine tolerance group and sham EA group was lower than that in the EA group (all<0.01).

CONCLUSIONSEA can improve mechanical pain threshold in rats with bone cancer pain-morphine tolerance, and improve the abnormal pain, which is likely to be involved with improvement of the MOR positive cells expression in nucleus ceruleus by EA.

Objective To observe the effect of ginkgobalide B (GB) on neurocyte apoptosis and protein kinase B expression in neonatal rats after hypoxic-ischemic brain damage (HIBD).Methods Ninety seven-day-old Sprague-Dawley rats were randomly divided into a sham group,an HIBD group and a GB group,each of 30.HIBD was induced in the HIBD and GB groups using the classical Rice method,while the sham group was given a sham operation.GB (10 mg/kg) was injected intraperitoneally to the rats in the GB group at 0 h and 24 h after the modeling.Then 6 rats were killed 6 h,12 h,24 h and 48 h after the modeling,and the expression of caspase-3 mRNA was detected using a real-time PCR to find the time point of maximum effectiveness.Then to further explore the role of the PI3K-AKT pathway in the anti-apoptosis effect of ginkgolide B,a a GB+LY294002 group of 6 rats,which was injected with PI3K-AKT pathway inhibitor LY294002 (1.8 mg/kg) intraperitoneally at 30 min before the modeling and with GB(10 mg/kg) at 0 h and 24 h after the modeling,was added to the experiment.Hematoxylin-eosin staining,terminal-deoxynucleotidyl transferase-mediated nick end labeling and immunohistochemical staining were then used to observe any morphological changes in the cortex,to detect neuronal apoptosis and to quantify the expression of P-AKT protein.Results The expression of caspase-3 in the HI and GB groups began to increase 6 hours after the HIBD and reached a peak after 24 hours,followed by a gradual decline.The expression of caspase-3 in the GB group was significantly lower than in the HI group throughout,while that of both of those groups was significantly higher than in the sham group.Apoptosis-positive cells and the expression of caspase-3increased had significantly in the HI,GB and GB+LY294002 groups 24 hours after the HIBD compared with the sham group,while the expression of P-AKT protein had decreased significantly.Moreover,the apoptosis-positive cells and the expression of caspase-3 of the HI and GB+LY294002 groups were significantly high-er than those of the GB group,while their expression of P-AKT protein was significantly lower after 24 hours.Conclusion Ginkgobalide B can decrease neurocyte apoptosis caused by hypoxic-ischemic brain damage,especially at 24 h after the damage.The PI3K-AKT signaling pathway plays an important role in this effect.

Objective To explore the effect of low-frequency electroacupuncture (EA) on neuropathic pain induced by spinal nerve injury and its underlying mechanism.Methods Thirty-two male Sprague-Dawley rats were randomly divided into a normal group,a sham spared nerve injury (SNI) group,an SNI group and an SNI+EA group,each of 8.The rats in the SNI and SNI+EA groups were given SNI surgery,while those of the sham-SNI group only had the sciatic nerve and its branches exposed without any lesion.EA at 2 Hz was applied over the ipsilateral Zusanli and Kunlun acupoints daily for 14 days after the surgery.The ipsilateral paw withdrawal threshold (PWT) was measured,along with protein kinase A (PKA) levels in the dorsal horn of the spinal cord,calcitonin gene-related peptide (CGRP) and substance P (SP) levels along with transient receptor potential V1 (TRPV1).Results Compared to the normal group,the SNI groups all showed significant decreases in their PWTs on the affected side and significant increases in PKA,TRPV1,CGRP and substance P on the affected side.Compared to SNI group,the average ipsilateral PWT in the SNI+EA group increased significantly after EA treatment,while PKA levels,TRPV1,CGRP levels and SP expression all decreased significantly.Conclusion Electroacupuncture at low frequency can effectively relieve neuropathic pain,perhaps through down-regulation of PKA in the spinal cord and by decreasing pain hypersensitivity related to CGRP and SP.

Postoperative ileus (POI) is a common abdominal postoperative complication of surgery as well as obstetrics and gynecology. There is a lack of an effective method of modern medicine due to its complex pathophysiological mechanism and the postoperative physiological disorder of patient. Acupuncture has remarkable regulatory effects on gastrointestinal function. Some clinical studies indicated that acupuncture was an effective method to treat POI, which could reduce the duration of POI and the treatment costs of patients in hospital. However, the mechanism and law of acupuncture on treating POI is still unclear. Some clinical studies indicated that the regulatory effect of acupuncture on the gastrointestinal motility was associated with its regulation of the autonomic nerve system and immune system. Based on its effect on regulating autonomic nerve system and immune system, acupuncture would be a potential and safe treatment for POI.