OBJECTIVE To study the effects of Ro 64-6198,a selective nociceptin/orphanin FQ receptor(NOPR)agonist,on heroin self-administration and drug-seeking behavior in rats.METHODS Rats were trained to self-administer heroin intravenously at a dose of 0.05 mg·kg-1 under a fixed ratio 1(FR1)reinforcement schedule.Heroin motivation was assessed using a progressive ratio(PR)schedule.Firstly,a stable heroin self-administered rat model was established before the effects of Ro 64-6198 on heroin rewarding under the FR1 schedule were observed.After three days of self-administration recovery training,the effects of Ro 64-6198 on heroin reward motivation were observed under the PR3-4 schedule.Following extinction,the reinstatement of heroin seeking induced by either conditioned cues or heroin priming was evaluated in rats withdrawn from self-administration.The expressions of cAMP response element-binding protein(CREB)and brain-derived neurotrophic factor(BDNF)in the ventral tegmental area(VTA)were analyzed using Western blotting,while the expression of the NOPR in neurons in the VTA was examined through immunofluorescence staining.RESULTS Pretreatment with 3 mg·kg-1 Ro 64-6198 significantly reduced active responses and heroin infusions during FR1 testing,as well as decreased breakpoints,indicating reduced motivation under the PR schedule.At a dose of 1 mg·kg-1,Ro 64-6198 markedly attenuated the reinstatement of heroin-seeking behavior induced by conditioned cues or heroin priming.Furthermore,the administration of SB-612111,an NOPR antagonist,blocked the inhibitory effects of Ro 64-6198 on cue-induced heroin-seeking,although SB-612111 alone had no effect on heroin-seeking behavior.Ro 64-6198 treatment also suppressed the reduction of both phos-phorylated CREB(p-CREB)and BDNF levels in the VTA and the decreased expression of NOPR and p-CREB in dopaminergic neurons of the VTA.CONCLUSION These results demonstrate that Ro 64-6198 can mitigate heroin-seeking behavior through NOPR activation and CREB/BDNF pathway in the VTA.This study is expected to offer evidence for its potential as a clinical treatment for heroin addiction and relapse.

OBJECTIVE To study the effects of Ro 64-6198,a selective nociceptin/orphanin FQ receptor(NOPR)agonist,on heroin self-administration and drug-seeking behavior in rats.METHODS Rats were trained to self-administer heroin intravenously at a dose of 0.05 mg·kg-1 under a fixed ratio 1(FR1)reinforcement schedule.Heroin motivation was assessed using a progressive ratio(PR)schedule.Firstly,a stable heroin self-administered rat model was established before the effects of Ro 64-6198 on heroin rewarding under the FR1 schedule were observed.After three days of self-administration recovery training,the effects of Ro 64-6198 on heroin reward motivation were observed under the PR3-4 schedule.Following extinction,the reinstatement of heroin seeking induced by either conditioned cues or heroin priming was evaluated in rats withdrawn from self-administration.The expressions of cAMP response element-binding protein(CREB)and brain-derived neurotrophic factor(BDNF)in the ventral tegmental area(VTA)were analyzed using Western blotting,while the expression of the NOPR in neurons in the VTA was examined through immunofluorescence staining.RESULTS Pretreatment with 3 mg·kg-1 Ro 64-6198 significantly reduced active responses and heroin infusions during FR1 testing,as well as decreased breakpoints,indicating reduced motivation under the PR schedule.At a dose of 1 mg·kg-1,Ro 64-6198 markedly attenuated the reinstatement of heroin-seeking behavior induced by conditioned cues or heroin priming.Furthermore,the administration of SB-612111,an NOPR antagonist,blocked the inhibitory effects of Ro 64-6198 on cue-induced heroin-seeking,although SB-612111 alone had no effect on heroin-seeking behavior.Ro 64-6198 treatment also suppressed the reduction of both phos-phorylated CREB(p-CREB)and BDNF levels in the VTA and the decreased expression of NOPR and p-CREB in dopaminergic neurons of the VTA.CONCLUSION These results demonstrate that Ro 64-6198 can mitigate heroin-seeking behavior through NOPR activation and CREB/BDNF pathway in the VTA.This study is expected to offer evidence for its potential as a clinical treatment for heroin addiction and relapse.

Objective To explore the difference of the left ventricular global longitudinal strain (GLS) and the segment strains between cardiac amyloidosis (CA) and non-obstructive hypertrophic cardiomyopathy (HCM). Methods Twenty patients with immunoglobulin light chain cardiac amyloidosis (AL-CA) as CA group and 20 patients with non-obstructive HCM selected as controls (HCM group) were enrolled from January 2016 to April 2022 in Zhongshan Hospital, Fudan University. All patients underwent two-dimensional speckle tracking echocardiography (2D-STE). The left ventricle GLS and the segmental strains were calculated. The values of these strains to distinguish AL-CA from HCM were analyzed by receiver operating characteristic (ROC) curves and logistic regression analysis. Results In the CA group, the GLS parameters (3P, 4Ch, 2Ch, 3Ch), as well as the left ventricle segmental strains (MID-ANT/LAT, MID-INF/SEPT, BASAL-ANT/LAT, BASAL-INF/SEPT, MID-ANT, MID-INF, BASAL-ANT, BASAL-INF, MID-INF/LAT, BASAL-ANT/SEPT, and BASAL-INF/LAT) were all lower than those in the HCM group (P＜0.01). ROC results showed that GLS(4Ch), GLS(2Ch), GLS(3Ch), GLS(3P), BASAL-ANT/LAT, BASAL-INF/SEPT, BASAL-ANT, BASAL-INF, BASAL-ANT/SEPT and BASAL-INF/LAT had good efficacy in distinguishing AL-CA from HCM. Logistic regression analysis showed that BASAL-ANT/LAT was an independent factor in distinguishing AL-CA from HCM (P＜0.01). The consistency of test results was good. Conclusions The left ventricular segmental myocardial strains show good efficacy in distinguishing AL-CA from HCM, and BASAL-ANT/LAT has highest application value.

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

Objective:To design a large-scale mobile emergency resuscitation unit based on 5G communication technology to improve the efficiency of prehospital transportation and treatment.Methods:The study was conducted in Hangzhou from November 2022 to September 2023. It's sorted out the application scenario requirements for prehospital first aid, transfer, and prehospital-intrahospital emergency linkage in carrying out the program design, single technology testing, onboard debugging, and integration debugging phases sequentially.Results:In September 2023, a large-scale 5G mobile emergency resuscitation unit was completed and delivered. The unit was converted from an electric bus and consists of five parts: (1) Vehicle appearance: the vehicle is 12.9 meters long, 2.3 meters wide and 2.6 meters high, with a single mileage of 200 kilometers; (2) The overall internal structure: the vehicle has one resuscitation bed and two stretcher positions. Additionally, there is a comprehensive operating table located at the front of the vehicle. The middle of the vehicle is equipped with a central digital control screen. (3) First aid materials and instruments: the vehicle's materials are modularly configured in accordance with the resuscitation, guardianship, surgery, inspection and testing, Communication modular configuration, equipped with a defibrillation monitor, transfer ventilator, extracorporeal membrane lung oxygenation and other critical care first aid and electrocardiogram, digital radiography, blood gas analyzer, chest pain 5 monitors and other inspection and testing equipment; (4) Vehicle communication and information systems: equipped with high-definition remote video interactive system, telemedicine terminal DP300 integrated system, a real-time panoramic experience system and centralized guardianship system; (5) Vehicle disinfection: a plasma disinfector installed on the top of the car can meet the hospital disinfection hygiene standardsⅡ class environmental management requirements.Conclusions:Incorporating 5G communication technology, the large-scale mobile emergency resuscitation unit is equipped with various advanced treatment equipment and remote consultation systems. It can accommodate the resuscitation needs of the most critically ill patients, offering substantial support for public emergency rescues. Further exploration of its potential is merited.

Objective:To explore the feasibility and effectiveness of the construction of urban unmanned aerial vehicle (UAV) blood distribution system, and to provide a novel way for the distribution of emergency blood.Methods:The study was completed in Hangzhou from April 2019 to January 2021, and the main participants were from the Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang Province Blood Center and Hangzhou Fast Ant Network Technology Co., Ltd. Firstly, an unmanned aircraft delivery system was built for urban emergency blood and a special blood storage box for drones were developed. The drone was used to deliver blood products from Zhejiang Province Blood Center to Binjiang Campus, the Second Affiliated Hospital of Zhejiang University School of Medicine, and the following indicators were obtained: (1) flight time of the drone blood delivery; (2) real-time temperature of blood products during transportation; (3) Baidu map software was used to measure the blood delivery time of road traffic, which was compared with the flight time of the drone.Results:The urban drone blood delivery system consists of intelligent logistics drones, cryogenic blood storage tanks, unmanned logistics hub stations, and cloud-based operation control platforms. The drone route distance from Zhejiang Provincial Blood Center to Binjiang Campus, the Second Affiliated Hospital of Zhejiang University School of Medicine was 2.36±0.06 km, and the ground distance was 5.8 km, with 27 flights from April 12, 2019 to January 29, 2021, and the drone flight time was, shorter than the road travel time for a round trip [(6.37±0.35) min vs. (17.00±1.94) min]. At different time points of the day, UAV blood delivery could save 15.98-4.28 min, with an average saving of 10.62±1.87 min. Conclusions:Urban UAV blood delivery systems have the advantages of being fast, unaffected by ground traffic conditions, and can ensure the safety of blood products during transportation, and are worthy of further exploration.

Objective To investigate the training expectations and training strategies of orthopedic clinical specialist nurses (OCSN).Methods Totally 5 020 orthopedic nurses from 342 hospitals from 30 provinces and cities were selected bv convenience sampling.Participants were investigated hy WeChat platform with self-designed questionnaire.Results A total of 4 982 effective questionnaires were collected.Among investigated nurses,13.7％ of them received orthopedic specialist nurses training;91.4％ believed that training should be carried out.Qualifications should be:college degree and above,senior nurse and above,at least 3 ～5 years of nursing experience,1～3 years of nursing experience in orthopedic department.For curriculum,public courses expected to be arranged were communieation skills,nursing teaching,nursing management,and nursing research;expected professional courses were functional exercises,pain management,extremity injury nursing,common treatment techniques in orthopedic department,traction nursing,and position nursing.It was suggested that training was divided into subspecialties and off-duty;classroom teaching,teaching rounds,case discussion and experience exchange were expected training methods;"theory-practice-theory-practice" was most preferable traiuing mode.The preferred teachers were orthopedic doctors,orthopedic head nurses,orthopedic specialist nurses,and senior orthopedic nurses.The length of training was expected to be three months,time for clinical practice should be greater than or equal to theoretical teaching,and the practice bases should be tertiary hospitals.Evaluation should be performed before completion,recertification could be later than completion,and the interval time of recertification should be within 5 years.Conclusion Training needs of orthopedic nurses for OCSN are strong.Training expectations(contents,length,modes and teachers) of orthopedic nurses should be considered when designing systematic training program on OCSN.

Objective To explore the experience in critical nursing intervention for patients with postpartum hemorrhoids. Methods 100 primiparas with hemorrhoids who had normal delivery in our hospital were assigned, by odd or even number of the delivery date, into the control group including 53 patients or the observation group including 47 patients. Patients in the control group received normative vital signs monitoring, hemorrhoid swelling observation, bowel movement observation, medication observation, dietary nursing, psychological support, treatment for complications, health education, and discharge instruction, etc. Patients in the observation group received critical analysis and nursing in addition to the care received in the control group. The hemorrhoid pain intensity and patient-perceived comfort were observed for both groups at 2 h, 24 h and 48 h postpartum. Results The hemorrhoid pain intensity score at 2 h postpartum was (1.30 ± 0.46) points and (1.32 ± 0.47) points , respectively, in the observation group and control group;the comfort score at 2h postpartum was (5.04 ± 0.83) points and (5.11 ± 0.82) points , respectively, in the observation group and control group, without statistically significant difference (t=0.245, 0.426, P>0.05);the hemorrhoid pain intensity score at 24h postpartum was (2.85 ± 0.62) points and (3.53 ± 0.58) points , respectively, in the observation group and control group;the comfort score at 24 h postpartum was (5.85 ± 1.02) points and (4.17 ± 0.89) points , respectively, in the observation group and control group, with statistically significant difference (t=5.643, 8.784, P < 0.01) ;the hemorrhoid pain intensity score at 48 h postpartum was (2.55 ±0.50) points and (3.42 ± 0.50) points , respectively, in the observation group and control group;the comfort score at 48h postpartum was (7.47 ± 1.10) points and (6.47 ± 0.89) points , respectively, in the observation group and control group, with statistically significant difference (t=8.606, 5.001, P<0.01). Conclusions Critical nursing intervention for postpartum patients with hemorrhoids could significantly alleviate hemorrhoid pain, improve patient comfort, and facilitate postpartum recovery.