1.Pharmacokinetics and tissue distribution of deferiprone in rats
Quanquan GONG ; Ping LIU ; Yanan ZHANG ; Hualei XU ; Yucai LI ; Xiaojing JIA
Chinese Journal of Pharmacology and Toxicology 2010;24(1):59-63
OBJECTIVE To study the pharmacokinetics and tissue distribution of deferiprone (DFP) in rats. METHODS Plasma and tissues were collected after male Wistar rats were ig given DFP 35, 70 and 140 mg·kg~(-1) at different time points. The DFP in plasma and tissues was determined by high performance liquid chromatography. The compartment model was fitted and pharmacokinetic parameters were calculated by DAS 2.0. RESULTS The results showed that the pharmacokinetic process of DFP in rats was two-compartment model after rats were ig given DFP 35, 70 and 140 mg·kg~(-1). The t_(1/2α) were 23.3, 22.2 and 20.9 min, respectively. The t_(1/2β) were 53.3, 50.9 and 46.3 min, respectively. The Cl were 0.017, 0.021 and 0.016 L·min~(-1)·kg~(-1), respectively. The content of DFP was high in stomach and liver tissues after rats were ig given DFP 70 mg·kg~(-1), and it was lower in the other tissues. The content of DFP in liver tissues was (359.22±31.16)μg·g~(-1), at 60 min after rats were ig given DFP 70 mg·kg~(-1). CONCLUSION The absorption and elimination of DFP are quick and the tissue distribution of DFP is wide in vivo.
2.Paeoniflorin ameliorates neuropathic pain-induced depression-like behaviors in mice by inhibiting hippocampal neuroinflammation activated via TLR4/NF-kB pathway
Hualei BAI ; Shize CHEN ; Tiezheng YUAN ; Dongyuan XU ; Songbiao CUI ; Xiangdan LI
The Korean Journal of Physiology and Pharmacology 2021;25(3):217-225
Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-kB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-kB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-kB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.
3.Paeoniflorin ameliorates neuropathic pain-induced depression-like behaviors in mice by inhibiting hippocampal neuroinflammation activated via TLR4/NF-kB pathway
Hualei BAI ; Shize CHEN ; Tiezheng YUAN ; Dongyuan XU ; Songbiao CUI ; Xiangdan LI
The Korean Journal of Physiology and Pharmacology 2021;25(3):217-225
Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-kB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-kB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-kB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.
4.Effect of zinc-fingers and homeoboxes 2 in the dorsal root ganglion on peripheral nerve injury-induced pain hypersensitivity
Hualei GONG ; Huali XU ; Kai MO
Chinese Journal of Neuromedicine 2018;17(9):918-924
Objective To explore the roles of zinc-fingers and homeoboxes (ZHX) in the dorsal root ganglia (DRG) in peripheral nerve injury-induced pain hypersensitivity,and provide a new idea for molecular mechanism ofneuropathic pain (NP).Methods (1) Twenty-four 8-week-old male C57BL6 mice were randomly divided into sham-operated group and chronic constriction injury (CCI) of the sciatic nerve model group (n=12).One d before modeling and 7 d after modeling,the changes of paw withdrawal frequency (PWF) to mechanical stimuli and paw withdrawal latency (PWL) to thermal stimulation were detected.Seven d after modeling,reverse transcription real-time quantitative PCR (RT-qPCR) was used to detect the ZHX1,ZHX2,and ZHX3 mRNA expressions,and Westem blotting was employed to detect the ZHX2 protein expression.(2) Thirty-six 8-week-old male C57BL6 mice were randomly divided into equivalent dose solvent CCI group,nonsense negative control sequence [siNC]CCI group and ZHX2 siRNA CCI group,and equivalent dose solvent sham-operated group,siNC sham-operated group and ZHX2 siRNA sham-operated group (n=6);each treatment was given to the DRG.One d before drug injection and 7 d after drug injection,the changes of PWF to mechanical stimuli and PWL to thermal stimulation were detected;RT-qPCR was used to detect the ZHX2 mRNA expression.Results (1) Seven d after modeling,PWF was significantly increased and PWL was statistically shorten in the hind-paw of the ipsilateral side in the CCI group as compared with those in the sham-operated group (P<0.05);DRG ZHX2 mRNA expression in the CCI group increased for 1.71 times as compared with that in the sham-operated group,with significant difference (P<0.05);DRG ZHX2 protein expression in the CCI group increased for 2.15 times as compared with that in the sham-operated group,with significant difference (P<0.05).(2) As compared with the equivalent dose solvent sham-operated group,siNC sham-operated group and ZHX2 siRNA sham-operated group,equivalent dose solvent CCI group and siNC CCI group had significantly increased PWF and DRG ZHX2 mRNA expression,and statistically shorten PWL (P<0.05);and ZHX2 siRNA CCI group had significantly decreased PWF of the ipsilateral side and DRG ZHX2 mRNA expression,and statistically longer PWL of the ipsilateral side as compared with equivalent dose solvent CCI group and siNC CCI group (P<0.05).Conclusion Knockdown periphery nerve injury-induced DRG ZHX2 up-regulation attenuates pain hypersensitivity following periphery nerve injury,and ZHX2 may be a new potential target to treat NP.
5.Recent advance in clinical manifestations and differential diagnoses of Kikuchi-Fujimoto disease involving nervous system
Jialei YANG ; Lei WANG ; Hualei CHEN ; Fang XU ; Shimin YIN
Chinese Journal of Neuromedicine 2020;19(1):79-83
Histiocytic necrotic lymphadenitis is known as Kikuchi-Fujimoto disease (KFD).KFD is a systemic disease,which is characterized by fever,necrotizing lymphadenopathy and leukopenia.However,involvement of the central and peripheral nervous system is rare.It can present as aseptic meningitis,encephalomyelitis,peripheral neuropathy,cerebellar ataxia and tremor,which makes it difficult to be differentiated with other nervous system diseases.Our review summarizes the clinical manifestations and differential diagnoses of KFD involving nervous system in order to reduce misdiagnoses and mistreatments.
6.Diagnostic value of 18 F-FDG PET/CT for hepatic epithelioid hemangioendothelioma
Jiqin YANG ; Hongcheng SHI ; Yanmei LI ; Weimin WANG ; Zhen YE ; Hualei XU ; Qian ZHAO ; Juan LI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2017;37(11):700-704
Objective To explore the imaging characteristics and diagnostic value of 18 F-FDG PET/CT in patients with hepatic epithelioid hemangioendothelioma ( HEH) . Methods From January 2014 to December 2015, 5 HEH patients (2 males, 3 females; average age (49.2±13.7) years) confirmed by pathology and underwent 18 F-FDG PET/CT imaging were enrolled in this retrospective study. The character-istics of PET/CT images were analyzed. Two-sample t test and Pearson linear correlation analysis were used for data analysis. Results A total of 26 lesions were detected in 4 patients with multiple lesions, of which 88.5%( 23/26) distributed at the liver edge, and 42. 3%( 11/26) had hepatic capsule retraction sign. SUVmax of the 26 lesions was 5.1±2.6 and it was not correlated with tumor size (r=0.054, P>0.05). Lesion FDG uptake in patients with distant metastases was higher than that in patients without distant metastases (6.08±1.80 vs 3.84±1.14;t=4.15, P<0.05). Two patients underwent the delayed imaging, and FDG up-take in 11/14 lesions was higher compared with that of early imaging, and 3/14 lesions were newly detected by the delayed imaging. One patient had diffuse low-density lesions with diameters between 6.1 and 35.5 mm and SUVmax between 2.6 and 8.1. Conclusion Liver lesions of HEH patients show some features on 18F-FDG PET/CT images which can find distant metastases, and the delayed imaging can improve the detection rate of lesions.
7.Early Efficacies of Drainage in Arthroscopic Reconstruction with Anterior Cruciate Ligament Reconstruction
Yuping DUAN ; Hualei ZHAO ; Xueliang FEI ; Yongxin TANG ; Yongsheng XU
Journal of Kunming Medical University 2024;45(1):122-126
Objective To investigate the impact of not using drainage on clinical outcomes after arthroscopic autologous semitendinosus tendon reconstruction with anterior cruciate ligament reconstruction.Methods From March 2022 to June 2023,59 patients undergoing arthroscopic autologous semitendinosus tendon reconstruction with anterior cruciate ligament reconstruction in Lincang People's Hospital were collected and randomly divided into the non-drainage group consisting of 29 cases(observation group)and the 24-hour drainage group consisting of 30 cases(control group).The pain levels of the two groups of patients were recorded on the 1st,3rd,7th,14th,and 30th day after the surgery by using a visual analog scale.Additionally,the knee joint range of motion,length of hospital stay,and occurrence of postoperative complications were monitored.The circumference of the thigh was measured before and after the surgery,and the difference was calculated.Results Repeated measures analysis of variance revealed that there were statistically significant within-subject differences in pain ratings,thigh circumference,and knee joint range of motion(P<0.05),but no statistically significant between-subject differences(P>0.05).Independent samples t-tests showed that on the first day after the surgery,the observation group had lower pain ratings(P<0.001),and higher thigh circumference and knee joint range of motion compared to the control group(P<0.05).There were no statistically significant differences in pain ratings,knee joint range of motion,and thigh circumference between the two groups at the remaining follow-up times(P>0.05);The observation group had a shorter hospital stay than the control group(P<0.001);Both groups of patients had no complications such as lower limb nerve damage,deep vein thrombosis,knee joint infection,or hematomas requiring puncture and aspiration.Conclusion In the early postoperative period following arthroscopic autologous hamstring tendon reconstruction of the anterior cruciate ligament,the omission of drainage does not affect the clinical outcomes in terms of pain,knee joint mobility,and thigh circumference.Moreover,omitting drainage reduces the level of pain experienced by patients on the first day after the surgery,improves the knee joint mobility,and decreases the length of hospital stay.Therefore,in arthroscopic autologous hamstring tendon reconstruction of the anterior cruciate ligament,it is not recommended to routinely use drainage for preventive purposes.
8.Effects of Coptis detoxification powder on transcription of PBMC TLRs mRNA and its mediated expression of inflammatory factors in Bama pigs under heat stress
Lin DONG ; Yanping WANG ; Qianqian XU ; Jishan LIU ; Jinliang WANG ; Hualei WANG ; Zhiqiang SHEN
Chinese Journal of Veterinary Science 2024;44(8):1813-1820
In order to explore the effects of Coptis detoxification powder on immune suppression and inflammatory response caused by heat stress in animals,Bama pigs were used as experimental animals to establish an animal model of heat stress,and the effects of Coptis detoxification powder on transcriptional activation of TLRs mRNA in PBMC induced by heat stress and its mediated ex-pression of inflammatory factors were studied in vivo.The animal model of heat stress was estab-lished by artificial climate greenhouse,Chinese medicine"Coptis detoxification powder"was pre-pared,and its inhibitory effect on heat stress and inflammation was studied by preventive and therapeutic administration.Real-time fluorescence quantitative PCR was used to determine the transcriptional changes of HSP70,TLRs and IL-17 mRNA,and ELISA was used to determine the dynamic changes of serum IL-2,IL-6 and TNF-α.Western blot and indirect immunofluorescence(IFA)were used to determine the nuclear translocation and protein expression of p65 phosphoryl-ated protein in NF-κβ inflammatory factor pathway.The transcription of PBMC TLRs mRNA and its mediated inflammatory factor expression and function in Bama pigs under heat stress were sys-tematically analyzed.The results showed that the experimental animal model of Bama pigs under heat stress was successfully established,and heat stress significantly up-regulated the mRNA tran-scription levels of HSP70,TLR2,TLR4 and inflammatory factor IL-17,resulting in significantly enhanced expressions of serum inflammatory factors IL-2,IL-6 and TNF-α.The NF-κβ pathway significantly promoted the level of p65 nuclear phosphorylation and the expression of cytoplasmic protein.The Chinese medicine"Coptis detoxification powder"could significantly reduce the upreg-ulation effect of heat stress conditions on the transcription levels of HSP70 and TLRs mRNA,thus inhibiting the mRNA transcription of inflammatory factor IL-17 and the expression of IL-2,IL-6 and TNF-α in serum,and significantly antagonizing the transcriptional activity of NF-κβ caused by heat stress.It showed good anti-heat stress effect.The anti-inflammatory effects of Chinese veteri-nary medicine prescription"Coptis detoxification powder",its pathway of action and its effectors were investigated,the expression and secretion levels of the regulatory factors related to the path-way associated with TLRs mRNA inhibition were analyzed,and the functional effects and mecha-nism of its clinical anti-heat stress and anti-inflammatory effects were clarified,which laid a data foundation for the promotion and application of this prescription and related mechanism research.
9.Effect of NEP1-40/PLGA on facial nerve repair in rats
XUE Bing ; XI Hualei ; YAO Lihong ; XU Wanqiu ; XU Xiaohang ; LIN Song ; PIAO Guiyan ; WANG Xiumei
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(2):110-119
Objective:
To investigate the effect of neurite outgrowth inhibitor extracellular peptide residues 1-40 (NEP1-40) combined with poly (lactic-co-glycolic acid) (PLGA) and gelatin electrospun fiber membrane on facial nerve repair in rats.
Methods:
According to the principle of random grouping, 108 male SD rats were divided into four groups (n = 27 in each group, approved by the ethics committee), namely, the sham group, control group, PLGA group, and NEP1-40 + PLGA group. A facial nerve fracture model was established for all of the groups except for the sham group. The control group received no further treatment, the PLGA group and the NEP1-40+PLGA group were supported by PLGA membrane, and the NEP1-40+PLGA group received one immediate local injection of NEP1-40 (5 μg/μL) at a dose of 10 μL. Facial nerve function analysis, electrophysiological examination, transmission electron microscope observation, HE staining, and immunohistochemical staining of myelin marker S100β and axonal marker β3-tubulin were used to evaluate the recovery of injured facial nerves of rats at 2, 4 and 8 weeks.
Results :
At 8 weeks, the facial nerve function score of the NEP1-40+PLGA group was better than that of the control group and PLGA group (P < 0.001), and facial nerve function was significantly restored. Electrophysiological examination of nerve action potentials at the injured facial nerve showed that the amplitude in the NEP1-40+PLGA group was higher than that of the control group and PLGA group (P < 0.001), but there was no significant difference in latency and conduction velocity results between the groups (P > 0.05). At 2, 4, and 8 weeks, transmission electron microscopy showed that the number of myelinated nerve fibers and myelin sheath thickness in the cross-section of the injured facial nerve in the NEP1-40+PLGA group were greater than those in the other groups (P < 0.05). At 8 weeks, HE staining showed that the facial nerves in the control group had partially recovered, but the overall cell distribution was uneven and the boundary with surrounding tissues was slightly blurred. In contrast, the NEP1-40+PLGA group had a relatively uniform cell distribution and a clearer boundary with surrounding tissues. At 2, 4, and 8 weeks, the immunohistochemical results showed that in the cross-section of the injuried facial nerve, NEP1-40 increased the expression of neural markers S100 β and β3-tubulin, especially β3-tubulin, which was close to normal levels (P > 0.05)
Conclusion
NEP1-40 is beneficial for the generation of new myelin sheaths and axons at the site of injury, and it can promote the repair and regeneration of injured facial nerves to a certain extent, thus accelerating the recovery of injured nerve function.
10. Evaluation on occupational exposure to whole body vibration in workers of a hydroelectric power station
Tao CHEN ; Huafei ZHANG ; Chuanbao YI ; Hongyan LI ; Hualei XU ; Lijun ZHAO ; Chengxun SUN ; Hansheng LIN ; Bin XIAO ; Maosheng YAN
China Occupational Medicine 2018;45(02):210-213
OBJECTIVE: To examine the level of occupational exposure to whole body vibration( WBV) in a hydroelectric power station,and evaluate its effects on workers' health. METHODS: A hydroelectric power station in Hangzhou City was chosen as study subject by using judgment sampling method. The level of WBV exposure to workers and high vibration level areas were measured,and the vibration frequency was analyzed. The comfort and allowing duration of occupational exposure in WBV exposed workers was evaluated. RESULTS: The median root-mean-square of accelerometer acceleration of WBV exposure in generator floor,turbines-floor,middle-floor,hydraulic floor of the hydroelectric power station were 0. 894,0. 995,1. 095 and 0. 904 m/s~2,respectively. The central frequency of WBV in this station was 1. 25 Hz. Among the 105 monitoring spots,8. 6% of WBV exposed workers of the spots did not perceive or feel uncomfortable,but 91. 4%of them felt uncomfortable or very uncomfortable. Only 12. 4% of the WBV exposed workers tolerated more than 8 hours of WBV occupational exposure. CONCLUSION: There is an occupational hazard of WBV in this hydroelectric power station.The low frequency vibration with central frequency below 1. 25 Hz is the key control point of the WBV of this hydroelectric power station.