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The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, Calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals Calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.
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Objective:To compare the patient-centered doctor-patient communication skills in anesthesiologists with different working experience and genders.Methods:The second and third year residents who had been trained as residents in the Department of Anesthesiology in our hospital from September 2017 and September 2018 and senior physicians who had worked for 10-15 yr in our hospital, were recruited to perform a preoperative interview in a standardized patient counter.Consultation and Relational Empathy (CARE) measure was used to assess the communication skills among senior physicians, residents, and anesthesiologists of different genders.The residents also took the objective structured clinical examination (OSCE) and theory examination.Results:Thirty-six residents and 20 senior physicians were included.There was no significant difference in the CARE measure score between residents and senior physicians and in the total CARE measure score between residents who received doctor-patient communication training at the stage of medical students and those who did not ( P>0.05). Compared with the residents in the second year, the listening ability score and decision-making ability score were significantly decreased ( P<0.05), and no significant change was found in the scores for the other items in the residents in the third year ( P>0.05). Compared with residents, the listening ability scores were significantly increased, and the caring ability scores were decreased ( P<0.05), and no significant change was found in the scores for the other items in senior physicians ( P>0.05). There was no difference in CARE measure scores between the male and female anesthesiologists.The resident′s CARE measure score was positively correlated with the annual OSCE score ( r=0.486, P<0.05), and there was no correlation between the resident′s CARE measure score and annual theoretical examination grade ( r=0.308, P>0.05). Conclusion:Senior anesthesiologists with more clinical experience are not superior to the junior residents in patient-centered communication skills, and the doctor-patient communication skills of residents are not related to their medical theoretical grade.Moreover, there is no significant difference between male and female anesthesiologists in terms of doctor-patient communication skills before surgery.Therefore, training of patient-centered doctor-patient communication skills should be strengthened at all levels of anesthesiologists.
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Objective Intra-operative coagulopathy has a close relationship with blood loss and the prognosis of patients. Rapid-thrombelastography (r-TEG) is a comprehensive assessment of coagulation abnormalities and also an effective way for constructing blood transfusion. This study attempts to investigate the correlation of r-TEG indices with intra-operative hemorrhage.Methods Patients who underwent transphenoidal hypophysectomy and craniotomy from January 15 to April 30, 2013 in Peking Union Medical College hospital were recruited. All patients had pre- and post-operative r-TEG and conventional coagulation tests (CCTs). Patients' information and intra-operative blood loss as a percentage of estimated blood volume were recorded. Spearman's correlation analyses were used for discovering the relationship between indices in r-TEG or CCTs and the intra-operative blood loss. The significant correlated index of r-TEG was further investigated using linear regression analysis. Results A total of 181 patients participated in this study. Intra-operative change of α-angle, which reflects the fibrinogen level and function, was the only r-TEG index that correlated with blood loss significantly (P=0.013, r= -0.184), thus challenging the current empirical cognition of the effects of intra-operative hemorrhage on coagulation. As intra-operative blood loss increased, α-angle decreased, and every 1% loss of estimated blood volume (EBV) led to 0.60 degree decrease of α-angle. As for CCT results, changes of fibrinogen and platelet count were also significantly correlated with blood loss (P=0.015 and P=0.001, respectively).Conclusions Peri-operative change of α-angle, as an index of r-TEG, exhibited a significant negative correlation with intra-operative blood loss. The impact of hemorrhage on fibrinogen, instead of clotting factors, should be scrutinized.
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Coagulação Sanguínea , Perda Sanguínea Cirúrgica , Fibrinogênio , Procedimentos Neurocirúrgicos , Contagem de Plaquetas , TromboelastografiaRESUMO
Objective To investigate the anesthesia and perioperative blood management of patients with Marfan syndrome (MS) undergoing scoliosis surgery.Methods The clinical data of MS patients underwent scoliosis surgery from January 2013 to December 2015 in Peking Union Medical College Hospital were collected and compared with patients received the same surgery but without MS.Perioperative information and data on anesthesia and blood management were analyzed.Results Compared with control group,MS patients were found with more preoperative comorbidities with statistical significance,including eye disease,echocardiographic abnormalities,and ventilatory defects.MS patients had significantly more blood loss,more intraoperative and postoperative allogeneic and autologous blood transfusion.The operation time,anesthesia time,and length of postoperative hospital stay were all significantly longer in MS patients.Conclusions MS patients are common with multi-system involvement and comorbidities.Considering the high risk of perioperative bleeding,the anesthesia and blood management for MS patients undergoing scoliosis surgery should be with extra caution.Blood management should be applied and appropriate invasive monitoring methods should be considered when necessary.
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Objective To evaluate the effect of gabapentin for treatment of neuropathic pain induced by bilateral sciatic nerve chronic constriction injury (bCCI) of rats.Methods Forty-eight female SPF Sprague-Dawley rats,weighing 180-200 g,aged 7-9 weeks,were randomly divided into 4 groups (n =12 each) using a random number table:control group (C group),sham operation group (S group),bCCI group,and bCCI + gabapentin group (G group).Gabapentin 100 mg/kg was intraperitoneally injected once at 15 min before operation and twice a day during 7-13 days after operation for 7 consecutive days.The bilateral mechanical paw withdrawal threshold (MWT),thermal paw withdrawal latency (TWL) and number of cold-stimulated paw withdrawal were measured before operation (baseline) and at 1,3,6,8,10,14 days after operation.Results Compared with C group,the bilateral MWT was significantly decreased,and the bilateral TWL was shortened in bCCI and G groups,and no significant change was found in MWT and TWL in S group.Compared with bCCI group,the bilateral MWT was significantly increased,the bilateral TWL was prolonged,and no significant change was found in the number of cold-stimulated paw withdrawal in G group.Conclusion Gabapentin can relieve thermal and mechanical hyperalgesia induced by bCCI,however,it exerts no effect on cold allodynia in rats.
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Objective To evaluate the effects of vitamin C combined with low dose of gabapentin on neuropathic pain (NP) in rats.Methods Fifty male Sprague-Dawley rats,weighing 225-275 g,aged 6-7 weeks,were randomly assigned into 5 groups (n =10 each):sham operation group (group Sham),NP group,vitamin C group (group VitC),gabapentin group (group Gap),and vitamin C combined with gabapentin group (VitC + Gap group).NP was induced by chronic constrictive injury in the rats anesthetized with pentobarbital sodium.The sciatic nerve was exposed and 4 silk ligatures were placed on the sciatic nerve at 1 mm intervals.In VitC,Gap and VitC+ Gap groups,vitamin C 500 mg/kg,gabapentin 30 mg/kg,and vitamin C 500 mg/kg + gabapentin 30 mg/kg diluted in normal saline 1 ml were injected intraperitoneally,respectively,twice a day for 7 consecutive days starting from 7 days after NP.Normal saline 1 ml was given in Sham and NP groups.Before NP and at 3,7,and 14 days after NP,the paw withdrawal threshold to mechanical stimuli (PWMT) and paw withdrawal latency to thermal stimuli (PWTL) were measured.At 14 days after NP,the blood samples were drawn from the carotid arteries.The rats were then sacrificed and the spinal cord was removed for determination of concentrations of malondialdehyde (MDA) in serum (by using Thiobarbituric acid method) and Slc23a2 mRNA expression (by RTPCR).Results Compared with Sham group,PWMT and PWTL in left paws were significantly decreased in NP,VitC,Gap ard VitC + Gap groups,the concentrations of MDA in serum were increased and Slc23a2 mRNA expression was down-regulated in NP group,Slc23a2 mRNA expression was down-regulated in VitC and Gap groups,and no significant change in Slc23a2 mRNA expression was found in VitC + Gap group.Compared with NP group,PWMT and PWTL in left paws were significantly increased,the concentrations of MDA in serum were decreased,and Slc23a2 mRNA expression was up-regulated in VitC + Gap group,the concentrations of MDA in serum were decreased in VitC group,and no significant changes were found in PWMT and PWTL in left paws in VitC and Gap groups.There were no significant differences in PWMT and PWTL in fight paws at each time point between the five groups.Conclusion Vitamin C combined with low dose of gabapentin can relieve NP effectively,and up-regulation of Slc23a2 mRNA expression,increased trafficking of vitamin C to neurons and inhibition of oxidative stress may be involved in the mechanism.
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BACKGROUND: N-methyl-D-aspartate receptor antagonists and nonsteroidal anti-inflammatory drugs are believed to prevent opioid-induced hyperalgesia and/or acute opioid tolerance, which could cause an increase in postoperative opioid requirement. In this randomized, double-blind, placebo-controlled study, we investigated whether co-administration of ketamine or lornoxicam and fentanyl could prevent the increase of postoperative morphine requirement induced by fentanyl alone. METHODS: Ninety females undergoing total abdominal hysterectomy with spinal anesthesia were randomly assigned to six groups consisting of placebo (normal saline, C), fentanyl (three bolus of 1 microg x kg(-1), F), ketamine (infusion of 15 microg x kg(-1) x min(-1), K), ketamine and fentanyl (infusion of 15 microg x kg(-1) x min(-1) ketamine plus three bolus of 1 microg x kg(-1) fentanyl, FK), lornoxicam (one bolus of 8 mg, L), and lornoxicam and fentanyl (one bolus of 8 mg lornoxicam plus three bolus of 1 microg x kg(-1) fentanyl, FL). Cumulative morphine consumption, pain score, and adverse effects were recorded at 1, 3, 6, 12, 24, and 48 h postoperatively. RESULTS: Cumulative morphine consumption in Group F was significantly more than that in Group C at 3, 6, and 12 h postoperatively (P < 0.05). Postoperative cumulative morphine consumption was similar in Groups C, K, FK, L, and FL. No differences in postoperative pain scores were observed among groups. More patients in Groups K and FK had hallucinations during and/or after surgery than those in Group C (P < 0.05). CONCLUSIONS: Our data suggest that the increase of postoperative morphine requirements induced by intraoperative administration of fentanyl could be prevented by ketamine or lornoxicam.
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Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Fentanila/administração & dosagem , Ketamina/administração & dosagem , Morfina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Piroxicam/análogos & derivados , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Adulto , Raquianestesia , Método Duplo-Cego , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Piroxicam/administração & dosagemRESUMO
NMDA(N-Methyl-D-Aspartate)receptor is a kind of ionotropic receptors, which have been widely localized in peripheral somatic tissues and visceral pain pathways. The activation or expression changes of peripheral NMDA receptor may play an important role in pain occurrence. Peripheral administration of NMDA receptor antagonist can alleviate or prevent pain and enhance the analgesic effect of opiate. This method of administration can reduce the side effect of central action induced by the drug. It will be an important research direction of pain management.
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AIM: To observe the effects of ketamine on preventing the increase of postoperative morphine requirement induced by fentanyl.METHODS: Sixty women undergoing total abdominal hysterectomy by spinal anaesthesia were assigned to 4 groups consisting of placebo(normal saline,C),fentanyl(3 bolus of 1 ?g/kg,at 15 min intervals,F),ketamine(infusion of 15 ?g?kg-1?min-1 ketamine from the skin incision until 20 min before the end of the surgery,K),ketamine and fentanyl(infusion of 15 ?g?kg-1?min-1 ketamine from the skin incision until 20 min before the end of the surgery plus 3 bolus of 1 ?g/kg fentanyl,at 15-min intervals,FK).The cumulative morphine consumption,pain score,and adverse effects(nausea, vomiting,hallucination,dizziness and itching) were recorded at 1,3,6,12,24,48 h postoperatively.RESULTS: There were no significant differences in age,weight,duration of surgery and the post-operative sensory block time.The cumulative morphine consumption in group F was significantly higher than those in group C at 3,6,12 h postoperatively(P
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60yr, weighting 50-80kg undergoing general thoracic surgery (lung resection and esophagus cancer resection) were enrolled in this study. Their preoperative hepatic and renal function were normal (blood creatinine