Objective To evaluate the effects of hearing disorder factors on analgesic efficacy of propofol. Methods Ninety?five patients with hearing disorders, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 18-60 yr, with body mass index of 20-30 kg∕m2, scheduled for elective ear surgery, served as test group(group T). Ninety?five patients with normal hearing function, of Ameri?can Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 18-60 yr, with body mass index of 20-30 kg∕m2, scheduled for elective non?ear surgery, served as control group(group C). Propofol was given at the initial target plasma concentration of 1.2 μg∕ml. When the target plasma concentration was achieved, 1 min later the concentration was increased in increments of 0.3 μg∕ml. When the patients lost eyelash reflex and had no responses to clapping on the shoulder, bispectral index value and target plasma and effect?site concentrations of propofol, consumption of propofol and time for loss of consciousness were recorded. Re?sults Compared with group C, no significant change was found in bispectral index value at baseline or at loss of consciousness(P>0.05), the target plasma and effect?site concentrations and consumption of propofol were significantly decreased, and the time for loss of consciousness was shortened in group T(P<0.05). The consumption of propofol required at loss of consciousness was gradually reduced with the aggra?vated severity of hearing disorders in group T(P<0.05). Conclusion The analgesic efficacy of propofol is enhanced in the patients with hearing disorders.

Objective To evaluate the efficacy of airway topical anesthesia with combination of su-perior laryngeal nerve block ( SLNB) and thyrocricoid membrane puncture for tracheal intubation in the ped-iatric patients with Pierre Robin Sequence. Methods Thirty-two American Society of Anesthesiologist physical statusⅠorⅡpediatric patients with Pierre Robin Sequence, aged 5-12 months, weighing 5-13 kg, scheduled for elective cleft palate repair under general anesthesia, were divided into 2 groups ( n=16 each) using a random number table method: control group ( group C) and airway topical anesthesia with SLNB-thyrocricoid membrane puncture group ( group ST) . After anesthesia was induced by inhaling sevoflu-rane by mask on admission to the operating room, 2％ lidocaine 0. 5 ml was injected around the bilateral su-perior laryngeal nerve under ultrasound guidance, and then 2％ lidocaine 1 ml was injected via the thyrocri-coid membrane in group ST, and the root of tongue, pharynx and larynx were sprayed with 2％ lidocaine by using a laryngotracheal mucosal atomization device in group C. The pediatric patients were tracheally intuba-ted guided by a video laryngoscope 3 min later. The development of cardiovascular responses, vocal cord activity and body movement was recorded during intubation. The intubation time, success rate of intubationat first attempt and patient′s tolerance to tube were recorded. The occurrence of postoperative hoarseness was also recorded. Results Compared with group C, the incidence of cardiovascular responses, vocal cord activity and body movement was significantly decreased, the intubation time was shortened, the suc-cess rate of intubation at first attempt was increased, and the patient′s tolerance to tube score was decreased in group ST ( P<0. 05) . Conclusion Airway topical anesthesia with combination of SLNB and thyrocricoid membrane puncture can provide better intubation conditions when used for the pediatric patients with Pierre Robin Sequence.

17α hydroxylase is a key enzyme for the conversion of progesterone to prepare various progestational drug intermediates. To improve the specific hydroxylation capability of this enzyme in steroid biocatalysis, the CYP260A1 derived from cellulose-mucilaginous bacteria Sorangium cellulosum Soce56 and the Fpr and bovine adrenal-derived Adx_4-108 derived from Escherichia coli str. K-12 were used to construct a new electron transfer system for the conversion of progesterone. Selective mutation of CYP260A1 resulted in a mutant S276I with significantly enhanced 17α hydroxylase activity, and the yield of 17α-OH progesterone reached 58% after optimization of the catalytic system in vitro. In addition, the effect of phosphorylation of the ferredoxin Adx_4-108 on 17α hydroxyl activity was evaluated using a targeted mutation technique, and the results showed that the mutation Adx_4-108T69E transferred electrons to S276I more efficiently, which further enhanced the catalytic specificity in the C17 position of progesterone, and the yield of 17α-OH progesterone was eventually increased to 74%. This study provides a new option for the production of 17α-OH progesterone by specific transformation of bacterial-derived 17α hydroxylase, and lays a theoretical foundation for the industrial production of progesterone analogs using biotransformation method.
Animals ; Cattle ; Progesterone/metabolism* ; Hydroxylation ; Biocatalysis ; Electron Transport ; Mixed Function Oxygenases/metabolism*

Objective:This study aimed to explore the application of interaction-dependent fucosyl-biotinylation (FucoID), a chemical biology-based proximity labeling technique, in capturing tumor antigen-specific T cells and its clinical value in chronic myelogenous leukemia (CML) .Methods:Flow cytometry and fluorescence microscopy were employed to evaluate the experimental parameters for FucoID in CML. Peripheral blood samples were obtained from 14 newly diagnosed CML patients in the chronic phase. These samples underwent flow cytometry-based sorting and were subsequently labeled with FucoID to facilitate the isolation of tumor cells and T cells, followed by the immunophenotypic identification of tumor antigen-specific T cells. Finally, the diagnostic and therapeutic potential of FucoID in CML was assessed.Results:Initially, the experimental parameters for FucoID in CML were established. The proportion of CD3 + T cells in patients was (8.96±6.47) %, exhibiting a marked decrease compared with that in healthy individuals at (38.89±22.62) %. The proportion of tumor-specific antigen-reactive T cells was (3.34±4.49) %, which demonstrated interpatient variability. In addition, the proportion of tumor-specific antigen-active T cells in CD4 + T cells was (3.95±1.72) %, which was generally lower than the proportion in CD8 + T cells at (5.68±2.18) %. Compared with those in tumor-specific antigen-nonreactive T cells, CCR7 -CD45RA - effector memory T cells and CCR7 -CD45RA + effector T cells were highly enriched in tumor-specific antigen-reactive T cells. Moreover, the intensity of tumor immune reactivity in patients exhibited a significant correlation with white blood cell count (WBC) and hemoglobin (HGB) levels in peripheral blood, while no such correlation was observed with other clinical baseline characteristics. Conclusion:The combination of FucoID and flow cytometry enables the rapid identification and isolation of tumor antigen-specific T cells in CML. The successful application of this method in CML and the implications of our findings suggest its potential clinical value in the field of hematologic malignancies.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.