To investigate the effect of propofol on the release of glutamate and gamma-aminobutyric acid (GABA) from rat hippocampal synatosomes, synaptosomes was made from hippocampus and incubated with artificial cerebrospinal fluid (aCSF). With the experiment of Ca(2+)-dependent release of glutamate and GABA, dihydrokainic acid (DHK) and nipectic acid were added into aCSF. For the observation of Ca(2+)-independent release of glutamate and GABA, no DHK, nipectic acid and Ca2+ were added from aCSF. The release of glutamate and GABA were evoked by 20 micromol/L veratridine or 30 mmol/L KCI. The concentration of glutamate and GABA in aCSF was measured by using high-performance liquid chromatography (HPLC). 30, 100 and 300 micromol/L propofol significantly inhibited veratridine-evoked Ca(2+)-dependent release of glutamate and GABA (P < 0.01 or P < 0. 05). However, propofol showed no effect on elevated KCl-evoked Ca(2+)-dependent release of glutamate and GABA (P > 0.05). Veratridine or elevated KCI evoked Ca(2+)-independent release of glutamate and GABA was not affected significantly by propofol (P > 0.05). Propofol could inhibit Ca(2+)-dependent release of glutamate and GABA. However, it has no effect on the Ca(2+)-independent release of glutamate and GABA.
Anesthetics, Intravenous/pharmacology ; Calcium/metabolism ; Glutamic Acid/*biosynthesis ; Hippocampus/*metabolism ; Propofol/*pharmacology ; Rats, Sprague-Dawley ; Synaptosomes/*metabolism ; gamma-Aminobutyric Acid/*biosynthesis

Objective Allergic rhinitis (AR) is studied extensively while nonallergic rhinitis (NAR) insufficiently in the recent years .The aim of this study is to describe the inflammation characteristics of different types of NAR . Methods Using the skin prick test , we investigated the characteristics , nasal cytokine levels , serum cytokine levels , and the proportion of peripheral blood Treg cells in 12 cases of AR, 10 cases of NAR with eosinophilia (EOS) syndrome (NARES), 12 cases of NAR without ES (NAR), and 11 control adults . Results The NARES patients had a signifi-cantly higher level of IFN-γ(28.89 [10.97-127.07] pg/mL) than the control (8.98 [7.88-14.90] pg/mL) and the NAR patients (7.92 [7.67-45.85] pg/mL) ( P<0.05) but a lower level of nasal IL-10 than the control ([3.97±0.68] vs [4.80±1.32] pg/mL, P<0.05) .The contents of nasal IL-4, serum IL-4, nasal IL-17 and ser-um IL-17 were all markedly higher in the AR and NARES groups than in the control (P<0.05).The proportion of CD4+CD25+FOXP3+Treg cells in the CD4+T cells in the peripheral blood was (4.5±1.3)%in the AR group and (4.0±1.8) %in the NARES group, both significantly lower than (6.5±1.0) %in the control group (P<0.05) and (6.5±1.0) %in the NAR group (P<0.05). Conclusion NAR was classified according to the EOS level into NARES and NAR without EOS, which had different mechanisms and manifestations of inflammation and similar inflammatory manifestations of Th 2 and Th17.The classification of rhinitis by the level of EOS has more practical significance .

A 54-year-old man diagnosed with chronic lymphocytic leukemia (CLL) was admitted in our department in June 2014. After one cycle of FC chemotherapy, a bone marrow examination revealed normalized lymphocyte count and another acute myeloid leuke-mia (AML)-M5 clone. The patient refused sequential treatment and only received follow-up examination. He had continuous hemato-logically stable disease and died of pulmonary infection on July 2015. After a multidisciplinary team discussion, we confirmed the si-multaneous diagnosis of CLL and AML-M5. Through this discussion,tumor second hit model,tumor evolution model,andtumor heterogeneitywere further defined.

Objective:Ciliary neurotrophic factor (CNTF) plays important roles in the maintenance and survival of motor neurons. This study attempted to explore the expression and distribution of CNTF mRNA and its protein in the ambiguous nucleus(Amb) motoneuron in order to clarify its functional state after long term laryngeal denervation. Methods: The recurrent laryngeal nerves were obtained from dogs. Brain stems were removed and sectioned for histochemistry, immunohistochemistry and in situ hybridization of CNTF. Amb motoneurons were identified by Nissl staining. The count and intensity of positive reactive motoneurons were measured by computer image processing system. Results: Transection of the laryngeal nerve led to a very marked reduction in the count and intensity of CNTF mRNA positive reactive motoneurons, and reached minimal levels at week 3. CNTF immunoreactivity increased rapidly and reached maximal levels also at week 3. At week 4, a significant increase in CNTF mRNA expression and decrease in CNTF immunoreactivity were observed. At week 6, both CNTF mRNA and its protein expression were significantly less than those of unlesioned contraletaral sides. Although a difference between week 6 and 12 was observed, the motoneurons were generally stable in the expression level of CNTF mRNA and its protein, and in the size and count after 12 weeks, with 78%, 84.4%, 80.9% and 83.7% respectively as compared with the unlesioned contralateral Amb. Conclusion: The results indicate that although degenerating changes occurre in the Amb motoneurons after long term laryngeal denervation, the ciliary neurotrophic factors activity of the lesioned motoneurons is still maintained at a certain level. [

Objective:To investigate the mechanism of programmed death 1(PD-1)/ programmed death ligand 1(PD-L1) signaling pathway and its feasibility as a potential therapeutic target and prognostic predictor by detecting the expressions, of PD-1 and PD-L1 in bone marrow mononuclear cells of children with acute lymphoblastic leukemia (ALL), and to provide new ideas for the diagnosis and treatment of ALL as well.Methods:Bone marrow samples were collected from 59 children with ALL in the First Affiliated Hospital of Zhengzhou University from September 2018 to July 2019.Flow cytometry was applied to detect the expression of PD-1 and PD-L1 in bone marrow mononuclear cells in 59 ALL patients, including 47 newly-diagnosed ALL patients and 12 relapsed ALL patients, respectively, at initial diagnosis, after induction therapy and early intensive treatment.Their relevant clinical data were collected and compared with the bone marrow specimens of 12 children suffering from non-malignant blood diseases as the control group of the same hospital during the same period.Results:There was no significant difference in the expression of PD-1 in the bone marrow mononuclear cells of the primary diagnosis group, recurrence group and control group ( H=2.402, P>0.05). The expression of PD-L1 in the relapsed and refractory group [(7.32±3.60)%] and the newly diagnosed group [(3.18±2.37)%] was higher than that in the control group [(0.84±0.39)%], and the differences were statistically significant ( H= 28.048, P<0.05). In the initial treatment group, the expression of PD-L1 in the bone marrow mononuclear cells was the strongest expression before treatment ( B=1.293), followed by after induction treatment ( B=0.036) and after early intensive treatment ( B=0.000), suggesting that there was a downward trend as the continued treatment.The expression of PD-L1 was the weakest expression in the low-risk group ( B=-3.912) than in the medium-risk group ( B=-3.595) and high-risk group ( B=0.000), revealing that the expression of PD-L1 is related to the risk grades of ALL.The higher the risk rating is, the higher the PD-L1 protein expression is. Conclusions:The high expression of PD-L1 may be involved in the pathogenesis and be used as an adverse predictor of ALL childhood and an evaluation index of chemotherapy efficacy.PD-1 / PD-L1 signaling pathway may be a potential therapeutic target of ALL childhood.

Objective:To explore the expression and distribution of ciliary neurotrophic factor (CNTF) in laryngeal nerve degeneration and regeneration. Methods:Transection of the recurrent laryngeal nerves in 8 dogs and suture following transection in 12 cases were performed. Both proximal and distal ends of transected or sutured region were sectioned at various survival times for CNTF immunohistochemistry and CNTF mRNA in situ hybridization. The area and intensity of reactive product were measured by computer image processing system. Results:After nerve transection, reactive product of CNTF mRNA and its protein reduced rapidly in distal stumps, after neurorrhaphy, they were observed in thin Schwann cell processes ensheathing axons and not found in the proliferating Schwann cells which didn′t ensheathe axons. CNTF immunoreactivity was also detected in the regenerated nerve axons. CNTF expression increased with survival time, but even at the longest survival time, it was still significantly less than that in intact nerve. The same change was observed in a short segment proximal to the transected or sutured region. Conclusion:CNTF expression is in the down regulation and is collected with Schwann cell axon in peripheral nerve degeneration and regeneration. The changed distribution of CNFT might provide a supportive environment for axonal regeneration.

To investigate the effect of propofol on the release of glutamate and γ-aminobutyric acid (GABA) from rat hippocampal synatosomes, synaptosomes was made from hippocampus and incubated with artificial cerebrospinal fluid (aCSF). With the experiment of Ca2+-dependent release of glutamate and GABA, dihydrokainic acid (DHK) and nipectic acid were added into aCSF. For the observation of Ca2+-independent release of glutamate and GABA, no DHK, nipectic acid and Ca2+were added from aCSF. The release of glutamate and GABA were evoked by 20μmol/L veratridine or 30 mmol/L KCl. The concentration of glutamate and GABA in aCSF was measured by using high-performance liquid chromatography (HPLC). 30, 100 and 300 μmol/L propofol significantly inhibited veratridine-evoked Ca2+-dependent release of glutamate and GABA (P＜0.01 or P＜0.05). However, propofol showed no effect on elevated KCl-evoked Ca2+-dependent release of glutamate and GABA (P＞0.05). Veratridine or elevated KCl evoked Ca2+ -independent release of glutamate and GABA was not affected significantly by propofol (P＞0.05). Propofol could inhibit Ca2+-dependent release of glutamate and GABA. However, it has no effect on the Ca2+-independent release ofglutamate and GABA.

Objective:To explore the clinical efficacy and safety of Ruxolitinib, a Janus kinase inhibitor, in combination with Methylprednisolone as a bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for relapsed/refractory Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) in pediatric patients.Methods:The clinical data of 4 patients with relapsed/refractory EBV-AHS treated with Ruxolitinib in combination with Methylprednisolone as a bridge to allo-HSCT at the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from August 2018 to February 2020 were retrospectively analyzed, and the disease characteristics, diagnosis and treatment process, clinical experience and related research progress were analyzed and summarized.Results:Among 4 patients with relapsed/refractory EBV-AHS, 2 patients were treated with low-dose Ruxolitinb in combination with Methylprednisolone for 6-10 weeks after partial remission.The disease did not progress, and they survived after being bridged to allo-HSCT.One patient was treated with large-dose Ruxolitinib in combination with Methylprednisolone due to the intolerance to chemotherapy, with the biochemical indicators of hemophagocytic syndrome significantly improved, and then the bridging to allo-HSCT was performed 2 months ago and this patient survived.One patient with EBV-AHS relapsed was relieved by chemotherapy again, then was given maintenance therapy with Ruxolitinib and Methylprednisolone, but the condition still progressed and the treatment was ineffective.This patient underwent allo-HSCT for salvage treatment more than 1 year ago and survived.Except that 1 patient developed mild anemia, the other 3 patients had no significant Ruxolitinib-related toxicities.Conclusions:Ruxolitinib in combination with Methylprednisolone can be safely employed as a salvage treatment for pediatric patients with relapsed/refractory EBV-AHS and a bridge to allo-HSCT, which has favorable safety, efficacy and tolerance in clinical practice.

Objective:To investigate the clinical efficacy, safety and compliance of Voriconazole suspension formula on the prevention and treatment of invasive fungal infection (IFI) in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of 25 children treated Voriconazole suspension formula for the prevention and treatment of IFI during the period of allo-HSCT in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from August 1, 2020 to April 30, 2021 were retrospectively analyzed.The plasma trough concentration of Voriconazole was detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the genotype of CYP2C19 was detected by polymerase chain reaction-restriction fragment length polymorphism (RFLP). The effect of CYP2C19 genotype on Voriconazole trough concentration was analyzed by rank-sum test, and Fisher′ s accurate test was used to analyze the influence of severity of gastrointestinal mucositis on serum trough concentration of Voriconazole in children with allo-HSCT. Results:A total of 25 children, including 18 males and 7 females were recruited.The median age at allo-HSCT was 6 (2-13) years.After initial administration of conventional dose of Voriconazole suspension formula during transplantation, plasma trough concentration of Voriconazole was intermittently monitored.Only 13 cases (52.0%) reached the target plasma trough concentration, 11 cases(44.0%) reached the target plasma trough concentration after adjusting the dose according to the plasma concentration, and 1 cases(4.0%) failed to reach it after increasing the dose twice.Genotype detection of CYP2C19 was performed in 20 children, involving 4 cases of poor metabolizers (PM), 9 cases of intermediate metabolizers (IM), 6 cases of extensive metabolizers (EM), and 1 case of ultra extensive metabolizer (UEM). A significant difference in plasma trough concentration was detected among all groups ( F=24.012, P<0.01). During the transplantation, 12 cases developed mild to moderate gastrointestinal mucositis, and 7 cases had severe gastrointestinal mucositis.The stan-dard rate of plasma trough concentration in children with severe gastrointestinal mucositis (1/7 cases, 14.3%)was significantly lower than those with mild to moderate gastrointestinal mucositis (9/12 cases, 75.0%) ( P=0.02). Five children (71.4%) with severe gastrointestinal mucositis could reach the target trough concentration after increasing the drug dose, suggesting that severe gastrointestinal mucositis had a great influence on the plasma concentration of Vorico-nazole suspension.The incidence of IFI in 25 children with allo-HSCT was 0, and the compliance of children taking Voriconazole dry suspension was 100.0%.The incidence of adverse reactions was 24.0% and all adverse reactions were relieved after symptomatic treatment. Conclusions:The plasma concentration of Voriconazole varies greatly among children and in different states of the same patient.Therefore, it is necessary to monitor the trough concentration of the drug and adjust the drug dose.The use of Voriconazole suspension formula for the prevention and treatment of fungal infection during allo-HSCT in children is clinically safe and effective, with a good compliance in children.