1.Effects of quercetin on inflammatory response in allergic rhinitis rats through TLR4/IRAK4/NF-κB signaling pathway
Xixi LEI ; Kebin DENG ; Rui JIANG
China Pharmacy 2025;36(7):832-836
OBJECTIVE To investigate the effects and mechanism of quercetin (QUE) on inflammatory response in allergic rhinitis (AR) model rats based on Toll-like receptor 4/interleukin 1 (IL-1) receptor-associated kinase/nuclear factor κB (TLR4/ IRAK4/NF-κB) signaling pathway. METHODS AR model rats were constructed by ovalbumin sensitization method. A total of 48 successfully constructed rats were randomly divided into AR group, QUE-L and QUE-H groups (i.g administration, 17.5, 35 mg/kg) and QUE-H+TLR4 activator lipopolysaccharide (LPS) group (i.g administration of 35 mg/kg QUE+intravenous administration of 0.4 mg/kg LPS via tail vein), with 12 rats in each group. Another 12 normal healthy rats were selected as control group, once a day, for 21 consecutive days. After the last medication, rhinitis symptoms of rats in each group were scored. The serum levels of immunoglobulin E (IgE), histamine (HIS), and inflammatory factors were all detected. The proportions of regulatory T cells (Treg) and helper T cells 17 (Th17) cells in blood were detected, the Th17/Treg ratio was calculated, and the pathological condition of nasal mucosal tissue was observed. The expressions of TLR4/IRAK4/NF-κB pathway related protein in nasal mucosal tissue were determined. RESULTS Compared with control group, nasal mucosal tissue damage in the AR group was more severe, with partial shedding of epithelial cells, the proliferation of goblet cells, and obvious inflammatory cell infiltration. The rhinitis symptom score, the levels of IgE, HIS and IL-17, Th17 proportion, Th17/Treg ratio,p-IRAK4/IRAK4 and p-NF-κB p65/NF-κB p65 ratios as well as relative expression of TLR4 protein were increased significantly (P<0.05), while IL-10 level and Treg proportion were decreased significantly (P<0.05). Compared with AR group, the pathological injuries of nasal mucosa and the above indexes in QUE-L and QUE-H groups were all improved significantly (P<0.05). LPS treatment could reverse the improvement effects of high-dose QUE on histopathological damage to nasal mucosa tissue and the aforementioned indicators (P< 0.05). CONCLUSIONS QUE can inhibit the inflammatory response in AR rats by inhibiting TLR4/IRAK4/NF- κB signaling pathway.
2.Evaluation of surgical efficacy in patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023
Xixi CHENG ; Yu FENG ; Xu WANG ; Zhiyi WANG ; Jiaxi LEI ; Mingzhe JIANG ; Guobing YANG ; Xiaojuan ZHANG ; Shijie YANG ; Liying WANG
Chinese Journal of Schistosomiasis Control 2025;37(3):247-254
Objective To evaluate the therapeutic efficacy for surgical treatments among patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023, so as to provide insights into optimization of the diagnosis and treatment strategies against hepatic cystic echinococcosis. Methods The demographic and clinical data of all echinococcosis cases included in central government fiscal transfer payment program for echinococcosis control and undergoing surgical treatments in Gansu Province from 2006 to 2023 were captured. Hepatic cystic echinococcosis patients with complete medical records and follow-up data were included in the study, and patients’ characteristics, including hospital where patients received diagnosis and treatment, methods of case identification, year of surgery, classification of lesions, number of lesions, size of lesions, course of disease, surgical methods, and post-surgical follow-up data. The cure and recurrence of hepatic cystic echinococcosis were evaluated according to the Guidelines for Management of Echinococcosis Patients in the Central Government Fiscal Transfer Payment Program, and the cure and recurrent rates were calculated. Results Data were collected from 1 686 surgical patients with hepatic cystic echinococcosis. According to the inclusion and exclusion criteria, 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments were included during the period from 2006 to 2022, including 1 166 cured patients (95.42%) and 88 patients with postsurgical recurrence (7.20%), and the cure rate of surgical treatments appeared a tendency towards a rise among patients with hepatic cystic echinococcosis from 2008 to 2022 (χ2trend = 19.39, P < 0.05). The cure rates of hepatic cystic echinococcosis were 100% (177/177), 94.81% (128/135) and 94.62% (861/910) among patients detected through regular physical examinations, screened by the central government fiscal transfer payment program for echinococcosis control, and those who passively sought healthcare services, respectively (χ2 = 9.95, P < 0.05). The cure rates of hepatic cystic echinococcosis were 95.96% (1 046/1 090) among patients with a disease course of 2 years and less and 90.90% (120/132) among patients with a disease course of over 2 years (χ2 = 6.87, P < 0.05), and there were significant differences in the cure rates among patients with hepatic cystic echinococcosis in terms of number of lesions (χ2 = 24.44, P < 0.05) and surgical methods (P < 0.05). The cure rate of hepatic cystic echinococcosis patients was significantly higher following initiation of the central government fiscal transfer payment program for echinococcosis control (96.06%, 1 096/1 141) than before the program (86.42%, 70/81) (χ2 = 16.06, P < 0.05), and the cure rate of hepatic cystic echinococcosis patients was significantly higher in designated hospitals (96.48%, 741/768) than in non-designated hospitals (93.37%, 366/392) (χ2 = 5.78, P < 0.05). The median follow-up period was 4 (interquartile range, 7) years among 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments. The recurrent rate of hepatic cystic echinococcosis appeared a tendency towards a decline from 2008 to 2022 (χ2trend = 36.86, P < 0.05), with a reduction from 23.08% (9/39) in 2008 to 1.85% (1/54) in 2021, and the post-surgical recurrence rate of hepatic cystic echinococcosis was lower following initiation of the central government fiscal transfer payment program for echinococcosis control (5.87%, 67 / 1 141) than before the program (25.93%, 21/81) (χ2 = 45.51, P < 0.05). In addition, the post-surgical recurrence rate of hepatic cystic echinococcosis was higher in non-designated hospitals (10.46%, 41/392) than in designated hospitals (5.60%, 43/768) (χ2 = 9.12, P < 0.05), and there was a significant difference in the post-surgical recurrence rate among patients with hepatic cystic echinococcosis in terms of surgical methods (P < 0.05), with the highest recurrence rate (11.54%) seen among patients undergoing percutaneous fine-needle aspiration of cyst fluids-based surgical procedures (P < 0.05). Conclusion Since the initiation of the central government fiscal transfer payment program for echinococcosis control in Gansu Province in 2006, an increase in the surgical cure rate and a reduction in the recurrence of hepatic cystic echinococcosis had been found among patients with hepatic cystic echinococcosis, indicating a high overall therapeutic efficacy.
3.Analysis of microstructure and blood perfusion in thalamus and basal ganglia in patients with untreated depressive disorder
Lei ZHANG ; Lianping ZHAO ; Sirun LIU ; Yanbin JIA ; Shuming ZHONG ; Yao SUN ; Xixi WANG ; Li HUANG ; Ying WANG
Chinese Journal of Medical Imaging Technology 2018;34(2):176-180
Objective To investigate the changes of microstructure and blood perfusion of thalamus and basal ganglia in patients with untreated depressive disorder using diffusion kurtosis imaging (DKI) and three-dimensional arterial spin labeling (3D ASL) perfusion imaging.Methods Totally 21 untreated patients with depressive disorder (disease group) and 32 healthy volunteers (control group) underwent DKI,3D ASL and routine MR scanning were enrolled.DKI parameters (mean kurtosis [MK],axial kurtosis [Ka],radial kurtosis [Kr],fractional anisotropy [FA],mean diffusivity [MD],axial diffusivity [Da] and radial diffusivity [Dr]) and 3D ASL parameters (cerebral blood flow [CBF]) of bilateral heads of caudate nucleus,thalamus and putamens were measured and compared between the 2 groups.Results Compared with control group,Ka of left caudate head in disease group was significantly higher,while Kr was significantly lower (both P< 0.05).Ka of right putamens in disease group was significantly higher than that in control group (P<0.05).Compared with control group,CBF of left caudate head and bilateral putamens decreased significantly in disease group (all P<0.05).Conclusion Untreated depressed patients show abnormal DKI parameters and blood perfusion in basal ganglia,which indicating that microstructure integrity is impaired and blood perfusion decreases.The abnormalities in basal ganglia microstructure and blood perfusion may serve as one of the neuroimaging features of depressive disorders.
4.Effect of lidocaine infusion on the stress hormone level and the NK cell cytotoxicity in patients undergoing radical hysterectomy
Suling ZHANG ; Tingting LIU ; Xixi JIN ; Fei WEN ; Weifu LEI ; Huanliang WANG
The Journal of Clinical Anesthesiology 2017;33(11):1057-1060
Objective To discuss the effects of lidocaine infusion on perioperative immune function by evaluating the levels of stress hormone and natural killer (NK) cell cytotoxicity.Methods Thirty-five patients of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 35-65 yr,undergoing elective radical hysterectomy,were randomized into lidocaine group (group L)and control group (group C).Fifteen minutes before anesthesia induction,a bolus of 1.5 mg/kg of lidocaine was administered iv.to each patient in group L and followed by a continuous infusion at 1.5 mg·kg-1 ·h-1 lasting to the end of surgery.Meanwhile,the patients in group C received the same volume of saline.Venous blood samples were collected individually 24 h before the operation,the end of the operation and 48 h after the operation.Levels of prostaglandin,epinephrine and norepinephrine were assayed by ELISA kits.NK Cells were obtained by CD56 antibody magnetic isolation.The cytotoxicity of NK cell was detected by LDH releasing assay,and phosphor-protein kinase A (p-PKA)and protein kinase A (PKA) were detected by Western blotting.Results There were no significantly different in the plasm levels of PGF2,EP1 and NE.The plasm levels of prostaglandin (562.5±98.2 vs.663.2±119.0) pg/ml,epinephrine (24.9±4.8 vs.29.7±3.5) pg/ml and norepinephrine (408.3 ±47.2 vs.499.6±45.6) pg/ml in patients of group L were lower than those in group C (P<0.05)48 h after the surgery.The cytotoxicity of NK cell was higher in group L than that in group C (44.1 ±5.0 vs.37.1±5.5)% (P<0.05) 48 h after the surgery.The ratio of p-PKA/PKA was lower in group L than that in guoup C (0.060±0.008 vs.0.099±0.011) (P<0.05) at the end of the surgery.Conclusion Perioperative intravenous lidocaine infusion can reduce the level of plasma catecholamine and PGE2,and protect the cytotoxicity of NK cell,possibly via inhibiting of cAMP-PKA signaling pathway.
5. Sivelestat alleviates nonalcoholic steatohepatitis in mice through inhibiting activation of Kupffer cells
Shufei ZANG ; Xiaojie MA ; Lei WANG ; Geli ZHU ; Wenjun YANG ; Yinlan LIU ; Jian YAN ; Yan LUO ; Zhenjie ZHUANG ; Jianyu CHEN ; Yunhao XUN ; Junping SHI
Chinese Journal of Hepatology 2017;25(5):371-376
Objective:
To investigate the role of neutrophil elastase inhibitor, sivelestat, in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling mechanisms.
Methods:
A total of forty 4-week-old male C57BL/6J ApoE-/-mice were equally divided into the following four groups: standard chow (SC)+isotonic saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline; and HFHC+sivelestat. These mice were treated with above methods for 12 weeks. Blood and liver tissue samples were collected to measure biochemical parameters, hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score (inflammation) were evaluated by oil red O staining and HE staining, respectively. The mRNA and protein expression levels of hepatic inflammatory cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and immunohistochemistry, respectively. Comparison of means between the four groups was made by one-way analysis of variance, and comparison between any two groups was made by the LSD or SNK method (for data with homogeneity of variance) or the Tamhane or Dunnett method (for data with heterogeneity of variance).
Results:
Mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH compared with those fed with SC. Compared with mice fed with HFHC diet without sivelestat, those treated with HFHC and sivelestat exhibited the following features: (1) significantly reduced fast blood glucose, blood cholesterol, and hepatic biochemical parameters, as well as increased insulin sensitivity; (2) significantly reduced NAFLD activity score (5.71±1.11 vs 3.16±1.16,

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