Objective: Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established. Methods: SD rats were exposed to propofol on postnatal day 7 (PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus (DG). The expression of p-Akt and p27 were measured by western blotting. The Morris water maze, novel object recognition test, and object location test were used to evaluate neurocognitive function 2-month-old rats. Results: Phosphorylation of Akt was inhibited, while p27 expression was enhanced after neonatal exposure to propofol. Propofol also inhibited proliferation of neural stem cells (NSCs) and decreased differentiation to neurons and astroglia. Moreover, the neurocognitive function in 2-month-old rats was weakened. Of significance, intra-hippocampal injection of the Akt activator, SC79, attenuated the inhibition of p-AKT and increase of p27 expression. SC79 also rescued the propofol-induced inhibition of NSC proliferation and differentiation. The propofol-induced neurocognition deficit was also partially reversed by SC79. Conclusion Taken together, these results suggest that neurogenesis is hindered by neonatal propofol exposure. Specifically, neonatal propofol exposure was shown to suppress the proliferation and differentiation of NSCs by inhibiting Akt/p27 signaling pathway.
Animals ; Cell Proliferation ; Hippocampus/metabolism* ; Neural Stem Cells ; Propofol/toxicity* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

OBJECTIVE: To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). METHODS: Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. RESULTS: The ratio of CD4 CONCLUSION The ITI regimen can raise the ratio of CD4
CD8-Positive T-Lymphocytes ; Humans ; Interferon-alpha ; Interleukin-2 ; Leukemia, Myeloid, Acute/drug therapy* ; Perforin ; Thalidomide

Objective:To evaluate the clinical efficacy of Bupi Qingfei decoction in the treatment of bronchiectasis colonized by Pseudomonas aeruginosa （PA） （lung-spleen Qi deficiency syndrome and phlegm heat accumulating in lung syndrome）. Method:A total of 72 bronchiectasis patients colonized with PA （ lung-spleen Qi deficiency syndrome and phlegm heat accumulating in lung syndrome ） were randomly divided into the observation group （36 cases， two cases were lost to follow-up and three dropped out） and control group （36 cases， three cases were lost to follow-up and four dropped out）. There were 31 cases in the observation group and 29 cases in the control group completing the trial. Patients in the observation group were treated with Bupi Qingfei decoction orally，once in the morning and again in the evening， one bag every other day， and simulated azithromycin tablet at the dose of 0.5 g，once every other day， while those in the control group with azithromycin tablet at 0.5 g，once every other day， and simulated Bupi Qingfei decoction， once in the morning and again in the evening， one bag every other day. Patients in both groups received health education and postural expectoration. The treatment lasted for 24 weeks，followed by a 24-week follow-up. The frequency of acute exacerbation，quality of life （St. George's Respiratory Questionnaire） score，traditional Chinese medicine （TCM） syndrome score，lung function ［forced expiratory volume in one second percentage of predicted（FEV₁%pred） and FEV₁/forced vital capacity（FVC）］， and serum immunoglobulin （Ig）A，IgE，IgG，and IgM levels of the two groups were evaluated after treatment. Result:The frequencies of acute exacerbation after 24 weeks of treatment and during the 24-week follow-up in the observation group were lower than those in the control group （P<0.05）. The total quality of life （St. George's Respiratory Questionnaire） score and symptom scores in the observation group after 24 weeks of treatment were significantly decreased as compared with those before treatment （P<0.05）. There was no significant improvement in the quality of life in the control group either after 24 weeks of treatment or during the 24-week follow-up. The effective rate against TCM syndrome in the observation group was 64.52%（20/31） after 12 weeks of treatment，which was obviously higher than 31.03%（9/29） in the control group （χ²=6.726，P<0.05）. After 24 weeks of treatment，the effective rate in the observation group was 83.87%， slightly higher than 68.97% in the control group. After 12 and 24 weeks of treatment，the scores of cough，expectoration，fatigue，anorexia，spontaneous sweating，abdominal distension， and loose stool in the observation group were better than those in the control group （P<0.05）. There were no significant changes in lung function and serum immunoglobulin classes in the two groups. Conclusion:Bupi Qingfei decoction is effective in reducing the frequency of acute exacerbation， alleviating the symptoms， and improving the quality of life of bronchiectasis patients colonized by PA （lung-spleen Qi deficiency syndrome and phlegm heat accumulating in lung syndrome）.

Objective:To investigate the pharmacodynamics effects of antiobesity, lipid-lowering and the regulations of serum bile acid profiles of Lidan Ruanjian prescription (LDRJ) in obesity rats induced by high-fat diet. Method:The 42 rats were fed high-fat diet for 9 weeks to establish model of obese rats，24 rats were randomly divided into model group, high and low-dose LDRJ group (30,15 g·kg^-1). Another 8 normal rats were selected as the normal group.The model group and normal group were given normal saline, and drug group was given the corresponding dose of drug for 4 weeks. Body weight, liver weight, white adipose tissue (WAT) weight were determined after administration medicine for 4 weeks. The bile flow of the rats was measured by bile duct intubation and fasting serum lipid levels of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were detected by automatic biochemical analyzer. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was used to test serum bile acid profile of each group rats. Result:Compared with the control group, the average body weight, liver weight, WAT weight of the model group were significantly increased (P<0.01), while the fasting serum TC, TG and LDL-C levels were elevated (P<0.05，P<0.01). The total bile secretion and bile flow at each test point within 2 h were decreased and the proportion of primary bile acids was decreased (P<0.05).The serum total bile acid content decreased significantly（P<0.01），levels of cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), taurochenodeoxycholic acid (TCDCA), taurohyodeoxycholic acid (THDCA) and glycodeoxycholic acid (GDCA) were significantly reduced (P<0.05，P<0.01). Compare with model group, body weight, liver weight in high and low-dose LDRJ groups reduced significantly(P<0.05，P<0.01). Fasting serum TC, TG and LDL-C levels were decreased in high-dose group(P<0.05，P<0.01), so did as TG levels in low-dose group(P<0.05). The bile flow rate increased significantly in high-dose group 1~1.5 h after administration (P<0.05). All dose treatment groups increased the proportion of primary bile acids (P<0.05) and changed the bile acid profile, especially elevated the bile acid levels of TCA, DCA, glycocholic acid (GCA), GDCA in high-dose LDRJ group (P<0.05，P<0.01), while TCA and TCDCA in low-dose group (P<0.05). Conclusion:LDRJ has significant lipid-lowering and antiobesity effects and the mechanism might involve the increase of bile secretion, the stimulation of primary bile acid synthesis and the regulation of bile acid profile.