Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Objective:To evaluate the effect of gender on neuromuscular blockade of rocuronium in epileptics.Methods:Forty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 18-59 yr, with body mass index of 18.5-24.0 kg/m 2, scheduled for elective surgery for treatment of epilepsy under general anesthesia, were divided into 2 groups ( n=20 each) according to gender: male group (group M) and female group (group F). Neuromuscular conduction function was monitored with a muscle relaxation monitor.Ulnar nerve was stimulated in TOF mode (frequency 2 Hz, wave width 0.2 ms, stimulation current 70 mA and interval 12 s). Rocuronium 0.8 mg/kg was injected intravenously during anesthesia induction, and endotracheal intubation was performed when T l reached maximum inhibition.The conditions of endotracheal intubation were evaluated by the modified method.When T 1 recovered to 25% during operation, rocuronium 0.15 mg/kg was intravenously injected.Sugammadex sodium 2 mg/kg was injected intravenously when T 1 recovered to 50% after surgery.The onset time (T onset), peak time (T peak), 10% recovery time (T 10%), 10%-25% recovery time (T 10%-25%), 25%-50% recovery time (T 25%-50%), 50%-75% recovery time (T 50%-75%) and 75%-90% recovery time (T 75%-90%) of rocuronium were recorded.Peripheral venous blood samples (3 ml) were collected when T 1 recovered to 25% and 75%, and the concentration of rocuronium was detected by liquid chromatography-tandem mass spectrum.The consumption of rocuronium per unit of weight per minute was calculated. Results:There was no significant difference between the two groups in terms of T onset, T peak, T 10%, T 10%-25%, T 25%-50%, T 50%-75%, T 75%-90%, endotracheal intubation conditions, blood concentration of rocuronium at varied time points, or consumption of rocuronium per unit of weight per minute ( P>0.05). Conclusion:Gender exerts no effect on the neuromuscular blockade of rocuronium in epileptics.

Objective To compare the effects of different anesthetics on the recovery of neurologi-cal function after intracranial aneurysm embolization. Methods One hundred patients of both sexes with aneurysmal subarachnoid hemorrhage, aged more than 18 yr, with body mass index of 18. 5-24. 0 kg∕m2 , of American Society of Anesthesiologists physical status Ⅱ or Ⅲ and WFNS grade Ⅰ-Ⅳ, with the thick-ness of subarachnoid hemorrhage more than 4 cm, were divided into 2 groups (n= 50 each) using a random number table: propofol group (group P) and sevoflurane group (group S). After anesthesia induction, group P received intravenous infusion of propofol 100-300 μg·kg-1 ·min-1 , while the end-tidal sevoflu-rane concentration was maintained at 1. 4％-3. 5％ in group S. Immediately before induction (T0 ), imme-diately after the end of induction (T1 ), immediately after successful embolization of aneurysm (T2 ) and at 1, 2, 3 and 5 days after surgery (T3-6 ), central venous blood samples were collected for determination of plasma neuron-specific enolase and S100β protein concentrations by enzyme-linked immunosorbent assay. The development of postoperative cerebral vasospasm and delayed ischemic neurological deficit was recorded. The patients were followed up, and the Glasgow outcome score and occurrence of newly developed cerebral infarction were recorded within 6 months after surgery. Results There was no significant difference in the concentrations of plasma neuron-specific enolase and S100β protein at each time point, incidence of postop-erative cerebral vasospasm and delayed ischemic neurological deficit, or Glasgow outcome score and inci-dence of newly developed cerebral infarction within 6 months after surgery between two groups (P>0. 05). Conclusion Propofol and sevoflurane exert no effect on the recovery of neurological function after intracra-nial aneurysm embolization.

Objective To evaluate the efficacy and safety of oxycodone in patients undergoing microvascular decompression in treating trigeminal neuralgia and oxycodone versus sufentanil on early recovery after microvascular decompression in treating trigeminal neuralgia.Methods Eighty-six patients (38 males, 48 females, aged 18-65 years, BMI 18-30 kg/m2, ASA physical status Ⅰ or Ⅱ) scheduled for microvascular decompression in treating trigeminal neuralgia, were randomly divided into either oxycodone group (group O) and sufentanil group (group S) using a random number table, n=43 in each group.All patients received combined intravenous-inhalational anesthesia, as well as oxycodone 0.3 mg/kg injected intravenously in group O, sufentanil 0.4 μg/kg injected intravenously in group S for anesthesia induced analgesia.When the epidural was closed, oxycodone 0.07 mg/kg was injected intravenously in group O, sufentanil 0.1 μg/kg was injected intravenously in group S.On preoperative day 1 and 4, 24, 48 hours after surgery, numeric rating scale (NRS) was used to assess the incision pain and facial pain.When NRS scores≥4, oxycodone 3 mg in group O and sufentanil 5 μg in group S was injected intravenously as rescue analgesic.On preoperative day 1 and 3 days after surgery, the global QoR-40 aggregating score was used to assess the quality of patients recovery.The requirement for rescue analgesics was recorded.The occurrences of nausea and vomiting were recorded.Extubation time and discharge were recorded.The other adverse events (bradycardia, dysuria, dizziness and pruritus) were recorded.Results Compared with group S, the physical comfort score, the emotional state score, the psychological support score, the pain score and the global QoR-40 scores were higher in group O 3 days after surgery (P<0.05).Compared with group S, the incidence of nausea and vomiting was significantly lower in group O (20.9% vs 37.2%) (P<0.05).Conclusion In surgery less than 5 hours of microvascular decompression on treating trigeminal neuralgia, oxycodone 0.3 mg/kg can be safely and effectively used for anesthesia induction, oxycodone 0.07 mg/kg and 3 mg can be respectively used for postoperative prophylactic analgesia and remedial analgesia.Compared with sufentanil, oxycodone can improve the quality of recovery during the early period after microvascular decompression on treating trigeminal neuralgia, and decrease the incidence of nausea and vomiting.

Objective To investigate the effect of ultrasound-guided subcostal transverses ab-dominis plane block with dexmedetomidine mixed ropivacaine in related-living kidney transplantation donor.Methods Forty related living kidney transplantation donors (male 1 5 cases,female 25 cases, aged 20-60 years,ASA grade Ⅰ or Ⅱ)were randomized into dexmedetomidine group (group D,n =20)and control group (group C,n =20).All the patients received ultrasound-guided subcostal TAP block after operation,group D with dexmedetomidine 1 μg/kg and 0.375% ropivacaine to 20 ml,and group C with 0.375% ropivacaine 20 ml.All the patients were assessed with both Ramsay scores and Visual Analogue Scale (VAS)at rest or on moving at 2,4,8,24 and 48 hours after operation.The duration of sensory blockade,the first time and the times of pressing the analgesia pump in the first 24 hours after operation,the requirements of flurbiprofen axetil and midazolam were recorded.The u-rine on the first and the second day after operation and the first flatus time were compared.The plas-ma concentrations of urea nitrogen (BUN)and creatinine(Cr)before surgery and on the second and fifth day after operation were determined.Results Compared with group C,the scores of VAS were de-creased at 4 and 8 hours after operation in group D (P <0.05).There were no differences in Ramsay scores between the two groups.Compared with group C,less frequency of use of flurbiprofen axetil (15% vs 0%) and midazolam (10% vs 0%)in group D,longer time of sensory blockade,postponed time to firstly press the analgesia pump and the less frequency of pressing the analgesia pump in group D (P <0.05),the urine on the first day was increased and the first flatus time was earlier,the plasma concentrations of BUN and Cr were significantly lower on the second day after operation in group D (P < 0.05 ). Conclusion Dexmedetomidine mixed ropivacaine can promote the anaesthesia of ultrasound-guided subcostal TAP block with ropivacaine,prolong the time of sensory blockade and improve the recovery after nephrecto-my in living-related kidney donor.

Objective To investigate the role of inducible nitric oxide synthase (iNOS) in reduction of myocardial ischemia-reperfusion (I/R) injury by sufentanil preconditioning in rats. Methods Thirty adult male SD rats, weighing 250-330 g, were randomly divided into 5 groups ( n =6 each): sham operation group (group S),I/R group, sufentanil preconditioning group (group SF), sufentanil preconditioning + a specific inhibitor of iNOS S-methyl thiourea (SMT) group (group SF+ SMT) and S-methyl thiourea group (group SMT). In I/R,SF,SF+SMT and SMT groups, myocardial I/R was produced by occlusion of left anterior descending coronary artery for 30 min followed by 120 min reperfusion. Group SF received 30 min infusion of sufentanil 120 μg/kg via caudal vein 24 h before ischemia. Group SF + SMT received infusion of sufentanil 120 μg/kg via caudal vein 24 h before ischemia and then SMT 10 mg/kg was injected 10 min before ischemia. In group SMT, SMT 10 mg/kg was injected 10min before ischemia. MAP and HR were recorded at 30 min before ischemia, at 30 min of ischemia and at the end of reperfusion. The rate-pressure product (RPP) was calculated. Arterial blood samples were obtained immediately at the end of reperfusion to determine the plasma concentration of NO. Then the animals were sacrificed and myo cardial tissues were obtained to determine the area at risk (AAR), infarct size (IS) and iNOS expression. IS/AAR was calculated. Results Compared with group S, MAP and RPP were significantly decreased, while IS/AAR was significantly increased at 120 min of reperfusion in the other four groups, and MAP and RPP were significantly decreased at 30 min of ischemia in I/R and SMT groups ( P ＜ 0.05). Compared with group I/R, no significant change was found in HR, MAP and RPP in SF, SF + SMT and SMT groups, and in IS/AAR and plasma NO concentrations in SF + SMT and SMT groups ( P ＞ 0.05), but IS/AAR was significantly decreased, and the plasma NO concentration and iNOS expression were significantly increased in group SF ( P ＜ 0. 05). Conclusion iNOS is involved in reduction of myocardial I/R injury by sufentanil preconditioning in rats.

Objective To evaluate the effect of remffentanil postconditioning on myocardial ischemiareperfusion (I/R) injury in patients undergoing open heart surgery under CPB.Methods Thirty patients (ASA grade Ⅱ or Ⅲ, NYHA class Ⅰ or Ⅱ ) of both sexes aged 18-45 yr undergoing repair: of ventricular septal defect and/or atrial septal defect under CPB were randomly divided into 2 groups ( n = 15 each): control group (group C)and remifentanil postconditioning group (group R). Anesthesia was induced with midazolam, sufcntanil, propofol and rocuronium. The patients received 5 min infusion of remifentanil at 4 μg · kg- 1 · min - 1 8 min before aortic unclamping in group R, while the patients received equal volume of normal saline in group C. Blood samples were obtained from the right internal jugular vein for determination of plasma concentrations of cardiac troponin-I (cTnI)and MDA and activities of CK-MB and SOD before induction of anesthesia (baseline) and at4, 8, 24 and48 h after aortic unclamping. Results The plasma concentrations of cTnI and MDA and activity of CK-MB were significantly lower, while the plasma SOD activity was significantly higher at 4 and 8 h after aortic unclmping, and the plasma concentration of MDA was significantly lower at 24 h after aortic unclamping in group R than in group C ( P ＜ 0.05 ). Conclusion Remifentanil postconditioning can attenuate myocardial I/R injury in patients undergoing open heart surgery under CPB through inhibiting lipid peroxidation.

Objective To evaluate the effect of emulsified isoflurane preconditioning on myocardial iachemia-reperfusion (I/R) injury in rabbits.Methods Thixty-two male New Zealand white rabbits weighing 2.5-3.0 kg were randomly divided into 4 groups(n=8 each):group Ⅰ I/R;group Ⅱ isoflurane preconditioning (group Ⅰ);group Ⅲ emulsified isoflurane preconditioning (group EI) and group Ⅳ intralipid (group INT).Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 180 min of reperfusion.After 30 min of post-preparation equilibration.the animal inhaled 3%isoflurane for 30 min followed by 15 min washout in group Ⅰ(group Ⅱ);8% emulsified isoflurane 8-10 ml was injected iv at 1 ml/s followed by continuous infusion at 6-8 ml·kg-1·h-1,maintaining end-tidal isoflurane concentration at 1.28% for 30 min in group EI (groupⅢ);30% intralipid 9 ml was injected iv at 1 ml/s fullowed by continuous infusion at 7 ml·kg-1·h-1 for 30 min in group INT (group IV).HR and BP were monitored and recorded at 30 min of post-preparatory equilibration(T0),before ischemia(T1),at the beginning of ischemia(T2),at 30 min ofischemia(T3),60,120 and 180 min of reperfnsion(T4,5,6).HR-SP product (RPP) was calculated.Infarct size (IS) was determined by TIC staining.Blood samples were taken from carotid artery at T6 for determination of serum CK and LDH activities and IL-6 and IL-10 concentrations.Results HR,MAP and RPP were decreasing during T2-6, but there was no significant difference in HR, MAP and RPP among the 4 groups.The infarct size was signigicantly smaller, serum CK and LDH activities and IL-6 concentration were significantly lower while serum IL-10 concentration was significantly higher in group I and EI than in group I/R and INT.Conclusion Emulsified isoflurane preconditioning can attenuate myocardial I/R injury by inhibiting inflammatory response.

BACKGROUND: Anterior cervical discectomy and fusion has been considered the gold standard for treatment of symptomatic degenerative disc disease within the cervical spine.However,fusion may result in progressive degeneration of the adjacent segments.Artificial disc replacement seems to be promising,segmental motion and stability are preserved while the spinal canal has been enlarged,and the intervertebral disc biological mechanics has been preserved,but not leads to progressive degeneration of the adjacent segments.OBJECTIVE: To observe the functional outcome and kinematics after the Prodisc artificial neck intervertebral disc replacement.METHODS: A total of 55 cases (69 intervertebral discs),29 males and 26 females,aged 48 (31-76) years were selected,including14 with bi-segmental injury.There were 32 cases of cervical spondylotic myelopathy,9 of cervical spondylotic radiculopathy,and 14 of mixed type cervical spondylosis.Prodisc artificial neck intervertebral disc replacement was performed using anterior or oblique incision.Prospective data JOA score and kinematic measures were collected before surgery and at 3,6,12,and 24 months after surgery.Range of motion was determined by independent radiologic assessment of flexion-extension radiographs.RESULTS AND CONCLUSION: The 55 patients were followed-up,including 41 undergoing single segmental disc replacement and 14 undergoing bi-segmental disc replacement.They were followed up for 22(56-48)months postoperatively.JOA scores displayed improved cervical function by 56%.Range of motion of sagittal and coronal planes were similar to those prior to operation compared with preoperatively(P = 0.45,0.74),and the range of motion and stability were maintained as adjacent segments.Results showed that the artificial disc replacement maintained range of motion of original intervertebral disc,accelerated patient recovery,and slightly affected adjacent intervertebral disc.