Objective To investigate the effect of ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament on postoperative analgesia and inflammation response in elderly patients undergoing robot-assisted laparoscopic radical prostatectomy.Methods A total of 60 elderly patients who had undergone robot-assisted laparoscopic radical prostatectomy from June 2022 to June 2023 were randomly divided into a group of ultra-sound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament combined with general anesthesia(observation group,n = 30)and a general anesthesia group(control group,n = 30).Both groups received patient-controlled intravenous analgesia after surgery.The first compression time of an analgesic pump and the numbers of effective compression and remedial analgesia were recorded.The VAS scores at postsurgical hours 2,12,24,and 48 during rest and coughing were recorded.Interleukin-6(IL-6)and systemic immunoinflammatory index(SII)at one day before surgery and two hours,one day and three days after surgery were recorded.Anal exhaust time,length of postoperative hospital stay and occurrence of adverse reactions were recorded.Results The observation group,as compared with the control group,had significantly longer first compression time of an analgesic pump and had fewer numbers of effective compressions and remedial analgesic administrations(P<0.05).The VAS scores during rest and coughing in the observation group were lower than those in the control group at postsurgical hours 2,12,24,and 48(P<0.05).As compared with one day before surgery,both IL-6 and SII in the two groups increased at 2 hours,1,and 3 days after surgery,but the changes in the observation group were lower than those in the control group(P<0.05).As compared with the control group,the observation group had shorter anal exhaust time and length of postoperative hospital stay,and a lower incidence of adverse reactions(P<0.05).Conclusions Ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament can provide better postoperative analgesia,reduce inflammatory response and accelerate postoperative recovery in elderly patients undergoing robot-assisted laparoscopic radical prostatectomy.

Objective:To evaluate the effect of anterior quadratus lumborum block at the lateral supra-arcuate ligament on the postoperative pulmonary function in patients undergoing robot-assisted laparoscopic radical prostatectomy under general anesthesia.Methods:Seventy-two American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged 50-80 yr, with body mass index of 18.5-27.9 kg/m 2, scheduled for elective robot-assisted laparoscopic radical prostatectomy under general anesthesia, were divided into 2 groups ( n=36 each) using a random number table method: control group and observation group. After induction of general anesthesia, observation group underwent anterior quadratus lumborum block at the lateral supra-arcuate ligament under ultrasound guidance, with 20 ml of 0.375% ropivacaine administered on each side. Control group only received total intravenous anesthesia. Postoperative analgesia was provided by patient-controlled intravenous analgesia until 48 h after operation, and intravenous dezocine was administered as rescue analgesic when the visual analogue scale score at rest≥4. Pulmonary function was assessed at 1 day before surgery and 1-7 days after surgery. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1), maximal mid-expiratory flow rate (FEF 25%-75%), and time to recovery of 80% predicted pulmonary function were recorded. Arterial blood gas analysis was performed at 1 day before surgery and 1-3 days after surgery, and SpO 2, PaO 2 and PaCO 2 were recorded. The consumption of intraoperative remifentanil, effective pressing times of patient-controlled analgesia, and the number of patients required rescue analgesia were recorded. Postoperative pulmonary complications within 7 days after operation and re-hospitalization within 30 days were recorded. The time to first flatus, postoperative length of hospital stay and occurrence of adverse reactions (dizziness, nausea, vomiting) within 3 days after surgery were also recorded. Results:Compared with control group, FVC, FEV 1 and FEF 25%-75% were significantly increased postoperatively, the time to recovery of 80% FVC, FEV 1 and FEF 25%-75% was shortened, postoperative SpO 2 and PaO 2 were increased, postoperative PaCO 2 was decreased, the consumption of intraoperative remifentanil, effective pressing times of patient-controlled analgesia, and the number of patients required rescue analgesia were reduced, the postoperative time to first flatus and length of hospital stay were shortened, and the incidence of adverse reactions and pulmonary complications was decreased ( P<0.05). Conclusions:Anterior quadratus lumborum block at the lateral supra-arcuate ligament can improve postoperative pulmonary function, reduce adverse reactions, and promote early recovery for the patients undergoing robot-assisted laparoscopic radical prostatectomy under general anesthesia.

Objective:To analyze the influence factors on the efficacy of immunosuppression therapy (IST) combined with eltrombopag and IST alone in the treatment of childhood severe aplastic anemia (SAA).Methods:A retrospective cohort study. A total of 124 children with SAA who were initially treated with IST at Beijing Children′s Hospital from March 2017 to May 2020 were enrolled. Clinical characteristics, laboratory examination and prognosis data were collected at the time of enrollment. According to the treatment plan, the children were divided into the eltrombopag combined with IST group (eltrombopag group) and the IST group. Binary Logistic regression model was used to analyze the factors affecting the efficacy of the two groups at 6 months of treatment, and the factors affecting the efficacy of the eltrombopag group at the end of follow-up.Results:There were 75 cases (45 males and 30 females) in the eltrombopag group. The age of diagnosis was 5.9 (3.5, 8.5) years. There were 49 patients in the IST group, including 23 males and 26 females, whose age at diagnosis was 6.2 (4.4, 8.8) years. The absolute lymphocyte count before treatment in the eltrombopag group was significantly lower than that in the IST group (1.1 (0.4, 1.6)×10 9vs. 2.1 (1.4, 2.8)×10 9/L). Absolute reticulocyte count in the eltrombopag group was significantly higher than that of IST group (26.9 (8.7, 54.2)×10 9vs. 9.5 (4.0, 19.0)×10 9/L) (both P<0.05). Influencing factors of 6-month response: a comparison between response and un-response groups in the eltrombopag treated patients showed that, before treatment, hemoglobin (69 (61, 78) vs. 64 (59, 68) g/L), platelet (10 (6, 16)×10 9vs. 6 (3, 8)×10 9/L), absolute reticulocyte count (ARC) (34.0 (15.8, 57.3)×10 9vs. 6.5 (4.6, 16.8)×10 9/L) and the response rate to granulocyte colony stimulating factor (G-CSF) after treatment (82.4% (47/57) vs. 9/18) were significantly different (all P<0.05). Logistic regression model analysis showed that ARC ( OR=1.09, 95% CI 1.02-1.18) and absolute neutrophil count were independent influencing factors of 6-month response rate in the eltrombopag group ( OR=0.00, 95% CI 0.00-0.89). ARC was also the independent influencing factors of the end of follow-up response rate in the eltrombopag group ( OR=1.04, 95% CI 1.01-1.07). Conclusions:Pre-treatment blood count and response to G-CSF were predictors of overall response to eltrombopag combined with IST. The higher the ARC before treatment, the higher the total response rate and complete response.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective To investigate effects of penehyclidine hydrochloride (PHC)protects a-gainst acute lung injury (ALI)in heart valve replacement patients with cardiopulmonary bypass (CPB).Methods Thirty rheumatic heart disease patients,eighteen males and twelve females with NYHA Ⅱ or Ⅲ,with cardiac valve replacement undergoing CPB were enrolled in the study.All pa-tients were randomly divided into group P and group C (fifteen in each group).Patients in group P re-ceived an intravenous injection of 0.03 mg/kg PHC before anesthesia induction and those in group C received the same volume of normal saline.Blood samples were collected to monitor the concentrations of IL-6,TNF-αand NF-κB at the following time points:before anesthesia induction (T0 ),the end of the operation (T1 ),6 hours (T2 ),12 hours (T3 )and 24 hours(T4 )postoperatively,arterial blood gas analyses were detected and oxygenation index (OI)was calculated at the time of T0 ,T1 and T4 , as well as lung dynamic compliance of patients adopt at the time of soon after anesthesia induction and the end of the operation.The outcomes included duration of intubation (DOI),length of intensive care unit stay (LOI)and length of hospital stay after the surgery (LOH).Results The DOI,LOI and LOH in group P were shorter than those in group C,but there was no statistical significance between groups.The plasma levels of IL-6,TNF-α and NF-κB were higher at T1-T4 than T0 in both groups (P <0.05),and those in group P were statistically lower than group C at T1-T4 (P <0.05).The val-ues of OI at T0 and T1 were obviously lower than T4 in both groups (P <0.05),and that in group P was slightly higher than group C at T4 but without statistical significance.The lung dynamic compli-ance of patients in group P at the end of operation was obviously higher than that in group C (P <0.05).Conclusion PHC inhibits systemic inflammatory response,improves lung compliance,amel-iorates tissue oxygen supply and encourages postoperative rehabilitation in valve heart replacement pa-tients with CPB,and its mechanisms is relevant to the regulation of NF-κB signal way on the produc-tion of such proinflammatory cytokines as IL-6 and TNF-α.

Objective To evaluate the effects of ulinastatin on hemorrhagic shock and resuscitation ( HS∕R)?induced acute lung injury in rats. Methods Fifteen SPF adult Sprague?Dawley rats, aged 2-3 months, weighing 300-400 g, were divided into 3 groups ( n=5 each) using a random number table:sham operation group ( group S ) , HS∕R group and ulinastatin group ( group U ) . Carotid arteries were cannulated for blood pressure monitoring and blood?letting. HS∕R was induced by blood?letting and maintained for 1 h, followed by resuscitation with autologous blood transfusion and infusion of normal saline. After cannulation of carotid arteries ( T0 ) , at 5 min after hemorrhagic shock ( T1 ) , before resuscitation ( T2 ) , at 5 min after the expected blood pressure was achieved following resuscitation ( T3 ) , and at 30 min, 1?5 h and 2?5 h after resuscitation ( T4?6 ) , arterial blood samples were collected for determination of interleukin?6 ( IL?6 ) and tumor necrosis factor?α ( TNF?α) concentrations ( by enzyme?linked immunosorbent assay) . Arterial blood samples were collected at T0 , T2 and T6 for blood gas analysis. The pH value, partial pressure of arterial carbon dioxide ( PaCO2 ) , HCO-3 and base excess ( BE) value were recorded, and oxygenation index ( PaO2∕FiO2 ) was calculated. Lungs were removed at T6 , and pulmonary specimens were obtained for examination of pathological changes which were scored, and nucleus was extracted for determination of nuclear factor?kappa B ( NF?κB ) p65 expression by enzyme?linked immunosorbent assay. Results Compared with group S, the pH values, HCO-3 , BE values and OI were significantly decreased, and PaCO2 , plasma IL?6 and TNF?α concentrations, expression of NF?κB p65 in lung tissues, and pathological scores were increased in U and HS∕R groups. Compared with group HS∕R, the plasma concentrations of IL?6 and TNF?α, expression of NF?κB p65 in lung tissues, and pathological scores were significantly decreased, and no significant changes were found in parameters of blood gas analysis in group U. Conclusion Although ulinastatin can alleviate HS∕R?induced acute lung injury, it is insufficient to improve lung oxygenation in rats.

Objective To observe the sedative effectiveness of dexmedetomidine (DEX) in digital subtraction angiography (DSA),and to investigate the optimal and safe administration dose.Methods Seventy-five patients undergoing DSA were divided into three groups by random digits table with 25 cases each group.Three groups were treated with constant infusion of DEX by micro-pump 10 min before surgery with the same dose of saline.Then group A,B,C respectively were given 0.3,0.5,0.7 μg/ (kg·h) of the maintenance infusion rate,and stop infusion 10 min before the end of the surgery.At administration (T0),10 (T1),20 (T2) and 30 (T3) min after administration,10 min after surgery (T4),the heart rate (HR),mean arterial pressure (MAP),peripheral oxygen saturation (SpO2),Ramsay score,number of cases that appeared body movement were recorded,and their forgotten degree of operating memory were compared.Results The HR,MAP in three groups at T1-T3 was significandy lower than that at T0 (P＜ 0.05),T4 levels returned to T0 (P＞ 0.05).The HR,MAP in group C at T2,T3 was significantly lower than that in group A and group B at the same time (P ＜ 0.05).The Ramsay score in three groups at T2,T3 was significantly higher than that at T0(P ＜0.05),group B and group C at T2,T3 was significantly higher than that in group A at the same time (P ＜0.05).The SpO2 in three groups at each time point compared within and among groups was no significant difference (P ＞ 0.05).Group B and group C intraoperative involuntary movement in response patients were significantly less than in group A (5,3 cases vs.10 cases).Group A and group C surgery requires intervention patients was significantly more than in group B (8,10 cases vs.3 cases).Group B and group C amnesia grade Ⅲ rate was significantly higher than that in group A [64％ (16/25),72％ (18/25) vs.40％(10/25),P ＜ 0.05].Conclusion Infusion with 0.5 μ g/(kg· h) DEX 10 min after intravenous injection with 0.5 μ g/kg can get a better sedative effect,stable vital signs and less intraoperative adverse memory,and it can also improve patients' comfortable degree,which is safe and appropriate sedative dosage in DSA.

ObjectiveTo observe the effect of nerve block combined with sequential analgesia in peri-operative knee arthroscopy.Methods Two hundred patients undergoing knee arthroscopy,were performed lumbar plexus and sciatic nerve block anesthesia by nerve stimulator with ultrasound guidance.Celecoxib was combined for sequential analgesia.The vital signs,the effect of anesthesia in the surgery,the duration of postoperative analgesia,and patient's satisfaction to analgesia were observed to evaluate the clinical effects.ResultsThe vital signs of the patients in the surgery were stable,the effect of anesthesia was good,180 cases of excellent,16 cases of good,4 cases of poor.The duration of postoperative analgesia was 6-10 (8.2 ± 0.5) h.Combined with sequential analgesia program,there was high patient's satisfaction [ excellent 75％ (150/200),good 10％ (20/200),general 10％ (20/200),poor 5％ ( 10/200 ) ].Conclusion The nerve block combined with sequential analgesia is safe and effective in knee arthroscopy,it achieves high patient's satisfaction,this maybe a routine in knee arthroscopy.

Objective To investigate the effects of cardiopulmonary bypass (CPB) with mild hypothermia on the pharmacodynamics of rocuronium in infants undergoing cardiac surgery.Methods Fifty ASA Ⅰ or Ⅱ and NYHA class Ⅰ or Ⅱ infants,aged 6 months-3 yr,weighing6-15 kg,undergoing repair ofventricular septal defect or atrial septal defect under CPB,were randomly divided into 2 groups ( n =25 each):profound hypothermia group and mild hypothermia group.The target temperature was controlled at 28-30 ℃ during CPB in profound hypothermia group,and at 32-34 ℃ during CPB in mild hypothermia group.Neuromuscular block was assessed by TOF-stimulation of ulnar nerve using with TOF-Watch accelerometer.Anesthesia was induced with midazolam O.1 mg/kg,propofol 2 mg/kg,fentanyl 6-8 μg/kg and rocuronium 600 μg/kg,and maintained with intermittent iv boluses of fentanyl and midazolam.The patients was tracheal intubated and mechanically venti1ated when the maximal depression of T1 was achieved.PETCO2 was maintained at 30-40 mm Hg.When T1 returned to 75％ of the control twitch,rocuronium 200 μg/kg was injected intravenously.The onset time,maximal N-M block time,clinical muscle relaxation time,and recovery index were recorded before CPB,during CPB and after CPB.Results Compared with profound hypothermia group,the onset time,maximal N-M block time and clinical muscle relaxation time were significantly shortened during CBP in mild hypothermia group ( P ＜ 0.05).Conclusion Compared with profound hypothermic CBP,mild hypothermic CBP can shorten the onset time and muscle relaxation time of rocuronium in infants undergoing cardiac surgery.

Objective To investigate the pharmacodynamics characteristics of continuously infused cisatracurium besylate during total intravenous anesthesia. Methods Sixty ASA Ⅰ - Ⅱ patients undergoing elective oromaxillo-facial region surgeon were randomly divided into 4 groups. 1.0, 2.0, 3.0 μg/ (kg · min ) of cisatracurium besylate was continuously infused differently in group Ⅰ, group Ⅱ and group Ⅲ, and 0.1 mg/kg of cisatracurinm besylate was injured interruptedly into group Ⅳ after anesthesia induction. Neuromuscular function was assessed using an accelerometer with train-of-four (TOF) stimulation, the maximum depression of T1and times to T1 recovered to 25%(the clinic time), 75%, 90%(the vivo time) were noted. The recovery index (time of T1 recovery from 25% to 75%) was also calculated. Results The drug consumptions of cisatracurium besylate in group Ⅰ and group Ⅱ were diminished than those in group Ⅲ and group Ⅳ [(59.1±9.6),(116.7±11.5)μg/kg vs (174.9±23.1), (177.2±20.4) μg/kg](P<0.01), and group Ⅲ and group Ⅳ were nearly (P>0.05 ). The maximum depression of T1, the clinic time and the vivo time in group Ⅰ, Ⅱ,Ⅲ were smaller than those in group Ⅳ [ ( 18.5±3.6)%, (6.4±2.7)%, 0 vs (25.0±0.0)% ] (P < 0.01 ), but there were. No significant differences in recovery index in 4 groups. The maximum depression was diminished (P< 0.01 ) and the clinic time and the vivo time were prolonged (P<0.05) with the inerease of the dosage of cisatracurium besylate in group Ⅰ, Ⅱ, Ⅲ. Conclusions With no cumulative effect, the duration of recovery of muscle relaxation is shortened and the recovery index of continuously infused eisatracurium besylate is prolonged. It indicates that the cisatracurium besylate is suitable for the continuously infusion for surgeon patients.