Targeted local anesthesia: a novel slow-release Fe3O4-lidocaine-PLGA microsphere endowed with a magnetic targeting function.

PURPOSE: Lidocaine microspheres can prolong the analgesic time to 24-48 h, which still cannot meet the need of postoperative analgesia lasting more than 3 days. Therefore, we added Fe3O4 to the lidocaine microspheres and used an applied magnetic field to attract Fe3O4 to fix the microspheres around the target nerves, reducing the diffusion of magnetic lidocaine microspheres to the surrounding tissues and prolonging the analgesic time. METHODS: Fe3O4-lidocaine-PLGA microspheres were prepared by the complex-emulsion volatilization method to characterize and study the release properties in vitro. The neural anchoring properties and in vivo morphology of the drug were obtained by magnetic resonance imaging. The nerve blocking effect and analgesic effect of magnetic lidocaine microspheres were evaluated by animal experiments. RESULTS: The mean diameter of magnetically responsive lidocaine microspheres: 9.04 ± 3.23 µm. The encapsulation and drug loading of the microspheres were 46.18 ± 3.26% and 6.02 ± 1.87%, respectively. Magnetic resonance imaging showed good imaging of Fe3O4-Lidocain-PLGA microspheres, a drug-carrying model that slowed down the diffusion of the microspheres in the presence of an applied magnetic field. Animal experiments demonstrated that this preparation had a significantly prolonged nerve block, analgesic effect, and a nerve anchoring function. CONCLUSION: Magnetically responsive lidocaine microspheres can prolong analgesia by slowly releasing lidocaine, which can be immobilized around the nerve by a magnetic field on the body surface, avoiding premature diffusion of the microspheres to surrounding tissues and improving drug targeting.

Recent advances in small molecule inhibitors of interleukin‑1 receptor-associated kinase / 药学学报

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

Anesthetic Management of Patients After Scoliosis Surgery: A Single-Center Retrospective Study.

PURPOSE: To evaluate the effect of anesthetic management on scoliosis surgery and review the incidence rate of perioperative adverse events. METHODS: This was a retrospective study and approved by the ethics committee. Patients who underwent scoliosis surgery from April 2011 to March 2018 in the Third Hospital of ChengDu were enrolled in this study. Characteristics of patients were obtained from the hospital's electronic records. The following information on patients was collected: preoperative assessment details, premedication, type of anesthesia and operation, the main postoperative outcome, and complications. Data were presented as the mean ± standard deviations (SD) for normally distributed continuous variables and numbers for categorical variables. Statistical analyses were performed using SPSS version 22.0. RESULTS: In total, 513 patients were enrolled in the present study. The main preoperative complication was cardiopulmonary dysfunction (386 cases, 75.24%). Anesthesia induction was performed with conscious tracheal intubation after oral surface anesthesia. In total, the common postoperative complications involved anesthesia (24 cases, 4.68%), surgery (23 cases, 4.48%), the respiratory system (138 cases, 26.90%), and the gastrointestinal tract (nine cases, 1.75%). The majority of postoperative complications were postoperative hypoxemia and hypercapnia, caused by poor cardiopulmonary function. Rare and serious complications still occurred. Three patients died in hospital. CONCLUSION: Our study demonstrated a high incidence of complications in scoliosis surgery, especially postoperative complications. Extreme postoperative vigilance is required and high-level monitoring of conditions is highly recommended.

[Identification of the IgE-binding epitopes in main dust mite allergen Der p 1].

OBJECTIVE: To identify the IgE-binding epitopes in the allergen Der p 1 of main house dust mites, which can be recognized by the specific IgE in the sera from allergic individuals, and obtain a hypoallergen derived from the T-B epitope fused peptide for potential use in specific immunotherapy (SIT). METHODS: Thirty-one peptides containing 15 amino acids each, which covered the full 222 amino acids of Der p 1 protein sequence, were synthesized on the cellulous membrane by solid-phase peptide (SPOTs) synthesis, with 8 overlapping amino acids between every two neighboring peptides. The membrane bearing the spots of the synthesized peptides were incubated with the allergic serum pools consisting of the sera from 5 allergic individuals. The membrane was then probed with HRP-conjugated anti-human IgE, followed by enhanced chemiluminescence (ECL) for visualization and gray scale analysis of the positive peptide spots. RESULTS: Three strong IgE-binding epitopes were identified in the amino acid sequence of Der p 1 molecule, namely Ep1 (amino acids 85-99), Ep2 (amino acids 106-120) and Ep3 (amino acids 190-204). CONCLUSION: The 3 IgE-binding epitopes (B cell epitopes) identified in Der p 1 confirm the presence of linear epitopes in Der p 1, suggesting the possibility of constructing T/B epitope-fused hypoallergens.

[Expression, purification and identification of Abeta fusion protein with enhanced solubility].

OBJECTIVE: To economically obtain the Abeta peptide for Alzheimer's disease (AD) research by expressing the Abeta peptide fused with the maltose binding protein (MBP) possessing high solubility in E.coli. METHODS: The cDNA-coding sequence of Abeta peptide was modified by the addition of a BamH I site at the 5' end and a Hind III site at the 3' end using PCR. The modified sequence was ligated into the maltose-binding protein (MBP) fusion expression vector pMAL-c2 containing an thrombin cleavage site, which was transformed into competent E.coli DH5alpha cells. After identification of the single clones by PCR and DNA sequencing, the recombinant plasmid was transformed into E.coli TB1 and induced to express MBP-Abeta fusion protein. The expressed fusion protein was purified using amylose resin column and identified by SDS-PAGE and Western blotting. RESULTS: The result of DNA sequencing verified the consistency between the inserted sequence and Abeta (1-42) sequence. SDS-PAGE electrophoresis showed that MBP-Abeta fusion protein was highly expressed in E.coli TB1, and Western blotting demonstrated that the purified fusion protein and the separated Abeta peptide could be recognized by specific anti-Abeta (22-35) antibody. CONCLUSION: MBP-Abeta fusion protein highly expressed in E. coli TB1 cells with enhanced solubility and the separated Abeta peptide with good immunogenicity obtained may lend support to AD research.

Cardioprotection of Shenfu Injection against myocardial ischemia/reperfusion injury in open heart surgery.

OBJECTIVE: To investigate the protective effect of Shenfu Injection (SFI) against myocardium ischemia/reperfusion injury (IRI) in mitral valve replacement (MVR) with cardiopulmonary bypass (CPB). METHODS: Forty patients undergoing selective MVR were randomly assigned to the control group and trial Groups I, II, III, and IV according to the different administrations of SFI, 8 patients in each group. The changes of systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) in each group were monitored, respectively. The recovering percentage of spontaneous heart beat, the heart rate (HR) and cardiac rhythm as well as the abnormal duration of ECG-ST segment were recorded after the restoration of heart beat. The serum concentration of cardiac troponin I (cTnI), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were determined as well. RESULTS: (1) The SBP, MBP and DBP values, the recovering rate of spontaneous heart beat, HR, ECG-ST, atrioventricular block and ventricular arrhythmia were significantly improved in group IV compared with any other groups. (2) Compared with the control group, the postoperative serum contents of cTnI and MDA were significantly decreased, but the activity of SOD was significantly increased in group IV. CONCLUSIONS: SFI had a certain protective effect against myocardium IRI. Moreover, better efficacy was seen with the administration of 1.5 mL/kg SFI into CPB priming fluid and pumping 1.5 mL/kg SFI via CPB as soon as the clamped aorta was unclamped.

[Exploration on the effect and mechanism of shenfu injection on resuscitation from general anesthesia].

OBJECTIVE: To investigate the effect and the mechanism of Shenfu injection (SFI) on the resuscitation from general anesthesia. METHODS: Forty patients who received selective abdominal surgery with general anesthesia for 3-4 hrs and ASA grade I-II were divided into two groups, the trial group and the control group, 20 patients in each group. After being sent into the postanesthesia care unit (PACU), the trial group was treated with intravenous dripping of SFI 1.0 ml/kg and the control group was treated with intravenous dripping of equal volume of normal saline. All patients were observed in double blindly manner, the self ventilation recovery time, extubation time, the time of leaving PACU and their Glasgow coma scale (GCS) were recorded and compared. 2 ml of peripheral venous blood were taken to determine the plasma beta-endorphin (beta-EP) content at the time points of before (T1), 5 min (T2), 15 min (T3) and 30 min (T4) after dripping. RESULTS: The self ventilation recovery time, extubation time and time of leaving PACU in the trial group were all shorter than those in the control group (P < 0.01), the GCS in the trial group was better than that in the control group (P < 0.01). The plasma content of beta-EP raised gradually along the recovering of patients consciousness, as compared with the content before dripping (T1), it showed insignificant difference at time point T2 but significant difference at T3 and T4 comparison at the corresponding time point showed that the content at T1 and T2 were similar in the two groups (P > 0.05), but at T3 and T4, the content was higher in the trial group than that in the control group respectively (P < 0.01). CONCLUSION: SFI could accelerate the resuscitation after general anesthesia, the mechanism may be related with its action in raising plasma beta-EP level.