Objective To observe the intervention effect of acupuncture at"Zusanli"(ST36)or"Neiguan"(PC6)on the ulcerative colitis(UC)model mice.And to analyze the similarities and differences of gene transcription expression between the diseased colon and the non-diseased heart after acupuncture intervention by using transcriptomics,to explore whether there are efficacy differences between the two acupoints.Methods The UC mouse model was established by inducing dextran sulfate sodium salt(DSS).After successful modeling,the mice were randomly divided into model group,Zusanli group,and Neiguan group,with 9 mice in each group.Zusanli group and Neiguan group intervened with acupuncture at"Zusanli"and"Neiguan",respectively,30 min each time,once a day,for 5 consecutive days.The control and model groups were only bound without acupuncture.Observe the general situation of mice in each group,calculate the disease activity index(DAI),observe the morphological changes of colon tissue by HE staining.Use transcriptome sequencing technology to sequence and biologically analyze the colon tissue of mice in each group,and compare and study whether the two acupoints have differences in acupoint efficacy from the perspective of diseased tissue.At the same time,take the heart tissues of each group for comparative analysis,and discuss whether the effects of the two acupoints are different from the perspective of non-diseased tissue.Results Compared with control group,the DAI score of the model group increased significantly(P<0.001),and HE staining results showed significant pathological damage;after acupuncture at Zusanli or Neiguan,the DAI scores of UC mice were reduced considerably(P<0.05),and the pathological damage was significantly improved.The results of transcriptome sequencing and bioinformatics analysis showed that the effects of acupuncture at Zusanli or Neiguan on the colon of diseased tissue involved multiple genes,and 825 differential genes with similar changes(co-DEGs)were mainly enriched in white blood cells and chemokine pathways;there were 168 differentially expressed genes(ST36 only-DEGs)affected only by Zusanli,which were enriched to gastric acid secretion and other pathways;there were 325 differentially expressed genes(PC6 only-DEGs)only affected by Neiguan,which were enriched in cytokine-cytokine receptor interaction and other pathways.There were 95 co-DEGs in the heart of non-diseased tissue,which were mainly enriched in positive regulation of defense response and response to interleukin-1;there were 28 ST36 only-DEGs;there were114 PC6 only-DEGs,which were enriched in cardiovascular diseases and other pathways.Conclusion Acupuncture of"Zusanli"and"Neiguan"could improve UC mice's symptoms and pathological colon changes.However,through transcriptomic analysis,it was found that the two acupoints had differences in gene transcription effects on the colon of diseased tissue and the heart of non-diseased tissue,suggesting that acupoints with different distribution positions had some similarities in macro efficacy.Still,there were some differences at a micro level.

OBJECTIVE To study the sedative and hypnotic effects of zolpidem and the content of amino acid neurotransmitters in the thalamus and hypothalamus after treatment with zolpidem.METHODS Experiments on the loss of righting reflex(LORR)induced by the upper-threshold dose pentobarbital sodium(50 mg·kg-1,ip)were conducted to establish a hypoxic insomnia model in mice by simulating an altitude of 5500 m.Based on this model,the synergistic effect of zolpidem(0.33,1,3,9 and 27 mg·kg-1,ip)and the subthreshold(20 mg·kg-1,ip)and upper-threshold pentobarbital sodium,as well as the sedative hypnotic effect of zolpidem(10,13,17,20,23,30 and 40 mg·kg-1,ip)were evaluated via the LORR in normoxic and hypoxic environments.One hour after ip given zolpidem,the levels of glutamic acid(Glu)and γ-aminobutyric acid(GABA)in the thalamus and hypothalamus of mice in either environment were determined by the high-performance liquid chromatography(HPLC)with fluorescence detection.RESULTS One-day treatment with hypoxia significantly shortened the duration of LORR induced by the upper-threshold dose pentobarbital sodium.Compared with normoxia vehicle and hypoxia induced insomnia vehicle groups,zolpidem 9 and 27 mg·kg-1 significantly shortened the latency to LORR(P<0.01,P<0.05)and prolonged duration of LORR induced by subthreshold and upper-threshold pentobarbital sodi-um(P<0.01,P<0.05).The median effective dose(ED50)of LORR induced by zolpidem was 16.21 and 20.55 mg·kg-1 in normoxic and hypoxic environments,respectively.The results of neurotransmitter level detection showed that Glu contents in the thalamus and hypothalamus and the ratio of Glu/GABA in the hypothalamus were decreased after treatment with zolpidem 40 mg·kg-1 in a normoxic environment(P<0.01,P<0.05).Compared with the normoxia control group,Glu content and the ratio of Glu/GABA in the hypothalamus were significantly increased after treatment with hypoxia(P<0.01,P<0.05),and zolpidem 40 mg·kg-1 could reverse their elevation.CONCLUSION The sedative-hypnotic effect of zolpidem is weakened in a hypoxic environment,and the effect of zolpidem on the levels of Glu and GABA in the hypothalamus may play an important role in the sedative-hypnotic effect of zolpidem.

OBJECTIVE To evaluate the psychological dependence of the extrasynaptic GABAA receptor(GABAAR)agonist gaboxadol and compare it with the synaptic GABAAR modulator midazolam in the two-bottle free-choice model of mice.METHODS ① Male C57BL/6J mice were ig administered with vehicle,midazolam(59.0,73.7,92.2,115.2,144.0 and 180.0 mg·kg-1)or gaboxadol(8.4,10.5,13.1,16.4,20.5,25.6 and 32.0 mg·kg-1),and the loss of righting reflex was observed.The median effective dose(ED50)was obtained from the dose-response curve.② A two-bottle free-choice model was used to find out whether gaboxadol and midazolam induced preference behavior in mice.The mice were divided into normal control,gaboxadol or midazolam groups.During the habituation stage(the first day to the third day,D1-D3),both test and vehicle bottles contained water.During the trail stage(D4-D5),4%sucrose solution was provided in both bottles.During the test stage(D6-D15),test bottles contained vehicle,gaboxadol(3.9×10-6 mol·L-1)or midazolam(1.4×10-5 mol·L-1)in sucrose solu-tions,while other bottles contained the corresponding vehicle in sucrose solutions.Bottles were placed on the two sides of the home cage,to which mice had free access,and their consumption from each bottle was recorded daily.Total consumption,accumulated daily consumption,relative consumption,and accumulated relative consumption during the test stage were calculated.The weight of the mice was also recorded.RESULTS ① Midazolam and gaboxadol dose-dependently increased the rate of loss of right reflex in mice,with ED50 of 105.3 mg·kg-1(95%CI:96.4-115.2 mg·kg-1,R2=0.9796),13.7 mg·kg-1(95%CI:12.6-15.0 mg·kg-1,R2=0.9773),respectively.② Compared with the normal control group,there was no significant difference in the total consumption in the gaboxadol and midazolam groups.Compared to the vehicle bottles,the daily consumption from test bottles in the midazolam group increased significantly on D11-D15 of the test stage(P<0.05),while daily consumption from gaboxadol test bottles was significantly higher than that of vehicle bottles(P<0.01).Compared with the normal control group,the daily relative consumption in the gaboxadol group was significantly increased on D9(P<0.05),and the accumulative relative consumption was significantly higher than in the normal control group(P<0.01).There was no significant change in body weight across the groups over the test stage.CONCLU-SION Like midazolam,gaboxadol exhibits psychological dependence potential in a two-bottle free-choice model.

Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.

Objective This study aims to compare the accuracy of self-developed universal implant guide(SDG),3D printed digital guide(DG),and free hand(FH)simulated implantation in the posterior tooth area of dental models.Methods Ten junior dentists were selected to place three implants in the 35,37,and 46 tooth sites of the mandibular models(35,36,37,and 46 missing teeth)by using SDG,DG,and FH,and the process was repeated again to take the av-erage value.Cone beam computed tomography(CBCT)was used to evaluate the global coronal deviation,global apical deviation,depth deviation,and angular deviation between the actual position and preoperative planned position.Re-sults The coronal deviation and apical deviation of the three implant sites in the SDG group were not significantly dif-ferent from those in the two other groups(P>0.05).The depth deviation and angular deviation in the SDG group were smaller than those in the DG group(P<0.05)and FH group(P<0.05),respectively.All deviations at site 37 in the SDG group were not different from those at site 35(P>0.05),while the depth and angular deviation at site 37 in the DG group were higher than those at site 35(P<0.05).Conclusion The precision of the self-developed universal dental im-plant guide can meet the requirements of clinical posteri-or implantation.

Neuropsychiatric disorders such as Parkinson disease,Alzheimer disease,and schizo-phrenia may induce hallucinations,delusions,and other psychiatric symptoms during the course of disease development.These symptoms are highly prevalent and difficult to cure,and have a impact on the lives of patients.Classical antipsychotic drugs such as chlorpromazine,sulpiride and perphenazine can con-trol related symptoms,but they can also cause uncontrollable extrapyramidal system reactions and side effects such as hyperprolactinemia.In recent years,it has been found that non-classical antipsy-chotics such as olanzapine,clozapine,risperidone and pimovanserin can treat hallucinatory symptoms in neuropsychiatric disorders by antagonising the 5-hydroxytryptamine 2A(5-HT2A)receptor,or by antago-nising both the 5-HT2A receptor(strong)and the dopamine 2(D2)receptor(weak).In preclinical studies,non-classical antipsychotic drugs have shown great therapeutic effects against hallucination induced by multiple factors.Clinical studies have confirmed that these drugs improve psychotic symptoms(mainly hallucinations and delusions)significantly.In patients who are insensitive or tolerant to clozapine and risperidone,pimavanserin still shows therapeutic effects.At the same time,the incidence and severity of adverse reactions to non-classical antipsychotic drugs are reduced,and they are well tolerated.This article reviews the research progress in the role of 5-HT2A receptor antagonists in attenuating hallucino-genic symptoms so as to provide reference for the design and development of new therapeutic drugs.

Objective To discover 5-HT2A receptor antagonist molecules with novel structures and explore their structure-activity relationship through structure-and mechanism-based drug design,synthesis and activity evaluation.Methods The way in which pimovanserin interacted with 5-HT2A receptor was analyzed via molecular docking,molecular dynamics simulation and binding free energy calculations.Based on the results of this study,the 5-HT2A receptor antagonist target compounds with novel structures were designed using pimovanserin as the lead molecule.According to the structures of target compounds,corresponding synthetic routes were designed.The heterocyclic methylamine intermediates were obtained by reductive amination or reduction reaction from heterocyclic formaldehyde or heterocyclic methanonitrile before being reacted with 4-(4-fluorobenzylamino)-1-methylpiperidine to obtain the target compounds using CDI urea synthesis method.The inhibitory activity of the target compounds against 5-HT2A receptor was tested at the cellular level,and the anti-hallucinogenic effects of the target compounds were tested in the mouse head twitch response model.Results Twelvenovel compounds were synthesized and their structures were confirmed by HR-MS,1H-NMR and 13C-NMR.The results of the activity assay showed that compounds 6a,6c and 6d exhibited better 5-HT2Areceptor inhibitoryactivity with IC50 values of 120,152 and 285 nmol/L,respectively while compounds 6c and 6d exhibited better anti-hallucinogenic activity in mice with inhibition rates of 97.0％and 82.9％(10 mg/kg),respectively.Conclusion The novel compound 6c and 6d have shown strong 5-HT2A receptor inhibitoryactivity and anti-hallucinogenic activity and deserve more research.Structure-activity relationship analyses of target compounds indicate that the repulsion of the heterocyclic ring with basic N atoms and the accommodation of the heterocyclic ring without basic N atoms by the side extended pocket of the 5-HT2A receptor could significantly affect the ex vivo and in vivo effects of antagonists.

We report a critically ill pregnant woman in the third trimester with severe pneumonia due to COVID-19 who presented to Xiaolan People's Hospital of Zhongshan in February 2020. The 32-year-old patient was admitted at 35 +2 gestational weeks with a 4-day history of a sore throat and a fever for three hours. The patient had been to Xiaogan City, Hubei Province, and the symptoms occurred during a period of self-isolation after back home. The condition of the patient deteriorated rapidly, with left-sided chest and back pain, shortness of breath, dizziness, progressing to respiratory failure and septic shock 7 hours after her admission. In view of her critical condition and a history of two previous cesarean sections, an emergency cesarean section was performed. Blood gas analysis of the mother before the operation suggested respiratory failure, respiratory acidosis, and metabolic acidosis. During the operation, a baby boy was born. The Apgar score of the boy, birth weight of 2 700 g, was one at 1, 5 and 10 minutes despite the resuscitation efforts. The neonate died after withdrawing treatment. The patient was treated with tracheal intubation ventilator and other supportive treatments after the operation. The result of the new coronavirus nucleic acid test, taken on admission, but which was reported after delivery, was positive. The patient was transferred to the designated hospital for further treatment and was recovering with the withdrawal of extracorporeal membrane oxygenation and ventilation support at 26 and 36 days after surgery, respectively.

Objective To explore the characteristics of gait and surface electromyography (sEMG) of underwater treadmill training (UWTT). Methods From January to September, 2015, gait and sEMG parameters of ten healthy adults were synchronously collected using three-dimensional gait analysis system and sEMG systems on land and UWTT. Results When walking in self comfortable speed, compared with walk on land, there was significant increase in gait cycle (t=-11.411, P<0.001) and percentage of the swing phase (t=-5.252, P<0.05), significant reduction in walking speed (Z=-2.803, P<0.01) and step frequency (t=7.421, P<0.001). There was no significant difference in step strength (Z=-0.357, P>0.05). The integral electromyography of biceps femoris, gastrocnemius, tibialis anterior muscle were significant less than iEMG on land (t>3.984, P<0.01), but no significant difference of rectus femoris (t=0.054, P>0.05). Conclusion There are signifi-cant differences in gait and muscle contraction intensity between land walking and UWTT. The dynamic physiology and neural control of UWTT need further study.

Objective To explore the effects of self-efficacy theory on coping style and quality of life of patients with bladder cancer underwent the targeted therapy.Methods A total of 84 advanced bladder cancer patients in our hospital from May 2011 to May 2016 were selected in the study using convenience sampling method. All patients were randomly divided into control group and observation group,each 42 cases. Patients in both groups were given the combination of conventional chemotherapy and targeted therapy with trastuzumab intravenous injection. The therapy was observed for 4 cycles. Patients in the control group were given routine nursing during the treatment, while patients in the observation group received additional nursing intervention based on self-efficacy. The prognosis and curative effect, coping style and quality of life scores of patients were recorded in the two groups.Results The total curative effective rate of patients in the observation group was 52.38%, which was higher than that in the control group (28.57%). The difference was statistically significant between two groups (P<0.05). After the intervention, the positive coping scores of two groups significantly increased (P<0.05), while the negative coping scores significantly decreased (P<0.05). The changes in the observation group was significantly better than that in the control group (P<0.05). The average quality of life score of the observation group after the intervention was significantly higher than that of the control group (P<0.05).Conclusions The application of self-efficacy theory in the bladder cancer patients underwent the targeted therapy can promote the transformation of positive coping style and improve the quality of life of patients, which is beneficial to the improvement of the overall total effectiveness.