1.Toxicokinetics of MDMA and Its Metabolite MDA in Rats
Wei-Guang YU ; Qiang HE ; Zheng-Di WANG ; Cheng-Jun TIAN ; Jin-Kai WANG ; Qian ZHENG ; Fei REN ; Chao ZHANG ; You-Mei WANG ; Peng XU ; Zhi-Wen WEI ; Ke-Ming YUN
Journal of Forensic Medicine 2024;40(1):37-42
Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.
2.Effect of safflower yellow on SCOP-induced cognitive impairment in mice based on BDNF/TrkB/CREB pathway
Yan-Qiang QI ; Hong-Xia YE ; Yan-You WANG ; Xia LI ; Ying-Xi HE ; Hui TIAN ; Le LI ; Yan-Li HU
Chinese Pharmacological Bulletin 2024;40(10):1858-1865
Aim To investigate the effect of safflower yellow on the learning and memory of scopolamine hydrobromide-induced memory impairment model mice.Methods 6-month-old C57BL/6J mice were randomly divided into the control group,model group,SY high-dose group,SY medium-dose group,SY low-dose group,and Huperzine-A group(12 mice in each group).SCOP was used to establish a memory impair-ment model,the spatial learning,memory and cognitive ability of mice with memory impairment were evaluated by behavioral experiments,the function of the choliner-gic nervous system in the cortex of mice was measured by ELISA kit,the pathological changes of brain tissue were observed by Nissl staining,and the expression of synaptic plasticity and BDNF/TrkB/CREB pathway re-lated proteins in the cortical and hippocampus of mice in each group was detected by Western blot.Results Compared with the model group,the learning and mem-ory ability of the mice in each administration group was improved.The neurons in the hippocampus and corti-cal were neatly arranged,the cell morphology tended to be complete,and the number of normal neurons in-creased.The function of the cortical cholinergic nerv-ous system was significantly improved,the expression of synaptic plasticity-related proteins in brain tissue was increased,and the BDNF/TrkB/CREB signaling path-way was activated.Conclusions SY can significantly improve the learning and memory ability of mice with SCOP-induced memory impairment,and its mechanism may play a neuroprotective role by improving choliner-gic nervous system function,activating BDNF/TrkB/CREB signaling pathway,regulating synaptic plasticity,and reduces neuronal damage.
3. Resveratrol promotes autophagy through zinc ion and induces cardiomyocyte protection
Pei WANG ; Jin-Kun XI ; Hu MA ; Ying YANG ; You-Cheng HU ; Tian-Yu LIU ; Jia-Bao GUO ; Yong-Gui HE
Chinese Pharmacological Bulletin 2023;39(6):1048-1054
Aim To investigate whether resveratrol (Resveratrol, Res) induces cardiomyocyte protection by increasing intracellular zinc ion and its possible signal mechanism. Methods H9c2 cells were routinely cultured and 2-deoxyglucose (2-DG) was used to establish an endoplasmic reticulum stress (ERS) model. The experiment was randomly divided into control group, 2-DG group, Res +2-DG group, TPEN + Res + 2-DG group and 3-MA + Res +2-DG group. Cell viability was detected by MTT and CCK-8; the expression levels of ERS molecular chaperone proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94) and autophagy proteins LC3 II / I, p62 and p-AMPK were detected by Western blot; the expression of LC3 protein was measured by cellular immunofluorescence; the mitochondrial membrane potential (Aijjm) and the intracellular zinc ion level were measured by laser scanning confocal microscope. Results Compared with the control group, 2-DG reduced cell activity and resveratrol inhibited the changes caused by 2-DG, which was reversed by zinc chelator TPEN. 2-DG increased GRP78 and GRP94 expression and resveratrol inhibited the protein changes caused by 2-DG, which was reversed by TPEN. 2-DG increased the expression of LC3 II / I, p-AMPK and decreased the expression of p62, and resveratrol promoted the effect of 2-DG. 2-DG increased the fluorescence intensity of LC3, and resveratrol enhanced the effect of 2-DG, which was reversed by TPEN and 3-MA. 2-DG reduced the red fluorescence intensity of mitochondrial TMRE and green fluorescence intensity of intracellular zinc ions, and resveratrol inhibited these changes caused by 2-DG, which was also reversed by TPEN and 3-MA. The above differences were all statistically significant (P < 0. 05). Conclusion Resveratrol increases intracellular zinc to promote ERS-induced autophagy and prevent the mPTP opening in H9c2 cardiac cells.
4.Efficacy of thunder-fire moxibustion plus glucosamine sulfate potassium capsule in treating knee osteoarthritis: a clinical trial
Shuxiang SONG ; Wei TIAN ; Wei YOU ; Xin WANG ; Hong HE ; Xiaolu PEI
International Journal of Traditional Chinese Medicine 2023;45(12):1508-1511
Objective:To evaluate the clinical efficacy of thunder-fire moxibustion plus glucosamine sulfate potassium capsule in treating knee osteoarthritis (KOA).Methods:This study was a randomized controlled trial. A total of 90 participants with KOA in the Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from February 2020 to December 2021 were randomized and assigned into 3 groups, with 30 cases in each group according to the random number table method. The thunder-fire moxibustion group was only treated with thunder-fire moxibustion on Neixiyan and Dubi acupoints, while the medication group was only treated with oral glucosamine sulfate potassium capsule, and the thunder-fire moxibustion plus medication group was treated with thunder-fire moxibustion on Neixiyan and Dubi acupoints combined with oral glucosamine sulfate potassium capsule. All the three groups were treated for 4 weeks. The degree of joint pain and stiffness was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC); the amount of knee joint cavity effusion was detected by ultrasound; the knee circumference was measured to assess the degree of knee swelling.Results:After treatment, the amount of knee joint cavity effusion [(3.21±2.44) mm, (3.73±2.53) mm vs. (4.80±3.07) mm, F=6.82], the WOMAC score [(65.88±30.25), (77.74±28.27) vs. (86.58±31.50), F=7.92], knee circumference [(36.74±2.74) cm, (37.59±2.63) cm vs. (38.51±3.09) cm, F=8.94] in the thunder-fire moxibustion plus medication group and the thunder-fire moxibustion group were lower than those in the medication group ( P<0.01). Conclusion:Thunder-fire moxibustion plus oral glucosamine sulfate potassium capsule can reduce the amount of knee joint cavity effusion, WOMAC score and the degree of knee swelling, and the efficacy is better than thunder -fire moxibustion and oral glucosamine sulfate potassium capsule.
5.Evaluation of the effect of internet-based dietary self-management on blood pressure in high-risk population of hypertension in Haikou City community.
Li Min HE ; You Xuan YAN ; Chan Juan ZHAO ; Xue Li ZHU ; Bi Feng LIANG ; Guo Tian LIN ; Jun Cai CHEN ; Fan ZHANG
Chinese Journal of Preventive Medicine 2023;57(10):1581-1589
To explore the effect of Internet+diet self-management intervention technology on the blood pressure control of hypertension high-risk population through the intervention of hypertension high-risk population in Haikou City community, so as to provide scientific evidence for the prevention and treatment of cardiovascular diseases (CVD). The multi-stage cluster sampling method was used, and 295 hypertension high-risk participants were recruited from 15 communities in Haikou City from July to December 2021. The 15 communities were randomly divided into three groups: blank group, traditional group and Internet plus group by random number table method. The blank group referred to the group (99 participants) that did not take special intervention measures but the routine interventions in accordance with the "National Basic Public Health Service Standards (the Third Edition) Health Education Service Standards". On the basis of the blank group, the traditional group (95 participants) was intervened by giving additional traditional methods such as holding lectures and distributing popular science books. The Internet plus group (101 participants) was given additional Internet measures on the basis of the intervention of the traditional group. After 6 months, questionnaires, laboratory biochemical tests, and physical measurements were conducted. SPSS 25.0 software was applied for data analysis. Measurement data that followed normal distribution were statistically described by using mean±standard deviation, analysis of variance was used for inter group comparisons before intervention, analysis of covariance was used for inter group comparisons after intervention, and Bonferroni adjustment was used for pairwise comparisons between groups. Measurement data that did not follow the Normal distribution were represented by M (Q1, Q3). The rank sum test was used for inter group comparison. The k sample Kruskal Wallis single factor ANOVA was used to compare the distribution between different groups. Counting data were described by composition ratio or rate. Under the premise of balanced comparison between groups before intervention, Chi-squared test was used for inter group comparison after intervention, and Bonferroni adjustment method was used for pairwise comparison between groups. The results showed that a total of 295 participants were included, with males accounting for 35.6% (105) and females accounting for 64.4% (190). The age ranged from 55 to 74 years old, with an average age of (64.69±5.73) years. The number of married accounted for 95.6% (282 participants). There were no statistically significant differences in gender, age, family history, education level, occupation, marital status, drinking habits, regular exercise, dietary status, SBP (systolic blood pressure), DBP (diastolic blood pressure), pulse pressure difference, BMI (body mass index), folic acid, and 24-hour urine sodium among the three groups upon enrollment (P values>0.05). After the intervention, the drinking rate was as follows: Internet plus group (29, 28.7%)
Male
;
Female
;
Humans
;
Middle Aged
;
Aged
;
Blood Pressure
;
Self-Management
;
Hypertension/prevention & control*
;
Cardiovascular Diseases/prevention & control*
;
Diet
;
Sodium
;
Internet
;
Folic Acid
6.O-arm real-time guidance in cervical pedicle screw fixation.
Chao ZHANG ; Yue LIU ; You LYU ; Tian-Yong WEN ; Chao LI ; Qing HE ; Di-Ke RUAN
China Journal of Orthopaedics and Traumatology 2023;36(5):487-489
OBJECTIVE:
To explore the technical aspects of the accuracy of cervical pedicle screw placement with O-arm guidance.
METHODS:
The clinical data of 21 patients who underwent cervical pedicle screw fixation by O-arm real-time guidance from December 2015 to January 2020 were analyzed retrospectively. There were 15 males and 6 females, aged from 29 to 76 years old with an average of (45.3±11.5) years. The postoperative CT scan was utilized to evaluate the placement of the pedicle screw and classified according to the Gertzbein and Robbins classification.
RESULTS:
A total of 132 pedicle screws were implanted in 21 patients, 116 at C3-C6 and 16 at C1 and C2. According to Gertzbein & Robbins classification, the overall breach rates were found to be 11.36% (15/132) with 73.33% (11 screws) Grade B, 26.67% (4 screws) Grade C, and no Grade D or E screw breaches. There were no pedicle screw placement related complications at final follow-up.
CONCLUSION
The application of O-arm real-time guidance technology can make cervical pedicle screw placement reliable. High accuracy and better intra-operative control can increase surgeon's confidence in using cervical pedicle instrumentation. Considering the high-risk nature of anatomical area around cervical pedicle and the possibility of catastrophic complications, the spine surgeon should have sufficient surgical skills, experience, ensures stringent verification of the system, and never relies solely on the navigation system.
Male
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Female
;
Humans
;
Adult
;
Middle Aged
;
Aged
;
Retrospective Studies
;
Imaging, Three-Dimensional
;
Surgery, Computer-Assisted
;
Tomography, X-Ray Computed
;
Pedicle Screws
;
Spinal Fusion
7.Evaluation of the effect of internet-based dietary self-management on blood pressure in high-risk population of hypertension in Haikou City community.
Li Min HE ; You Xuan YAN ; Chan Juan ZHAO ; Xue Li ZHU ; Bi Feng LIANG ; Guo Tian LIN ; Jun Cai CHEN ; Fan ZHANG
Chinese Journal of Preventive Medicine 2023;57(10):1581-1589
To explore the effect of Internet+diet self-management intervention technology on the blood pressure control of hypertension high-risk population through the intervention of hypertension high-risk population in Haikou City community, so as to provide scientific evidence for the prevention and treatment of cardiovascular diseases (CVD). The multi-stage cluster sampling method was used, and 295 hypertension high-risk participants were recruited from 15 communities in Haikou City from July to December 2021. The 15 communities were randomly divided into three groups: blank group, traditional group and Internet plus group by random number table method. The blank group referred to the group (99 participants) that did not take special intervention measures but the routine interventions in accordance with the "National Basic Public Health Service Standards (the Third Edition) Health Education Service Standards". On the basis of the blank group, the traditional group (95 participants) was intervened by giving additional traditional methods such as holding lectures and distributing popular science books. The Internet plus group (101 participants) was given additional Internet measures on the basis of the intervention of the traditional group. After 6 months, questionnaires, laboratory biochemical tests, and physical measurements were conducted. SPSS 25.0 software was applied for data analysis. Measurement data that followed normal distribution were statistically described by using mean±standard deviation, analysis of variance was used for inter group comparisons before intervention, analysis of covariance was used for inter group comparisons after intervention, and Bonferroni adjustment was used for pairwise comparisons between groups. Measurement data that did not follow the Normal distribution were represented by M (Q1, Q3). The rank sum test was used for inter group comparison. The k sample Kruskal Wallis single factor ANOVA was used to compare the distribution between different groups. Counting data were described by composition ratio or rate. Under the premise of balanced comparison between groups before intervention, Chi-squared test was used for inter group comparison after intervention, and Bonferroni adjustment method was used for pairwise comparison between groups. The results showed that a total of 295 participants were included, with males accounting for 35.6% (105) and females accounting for 64.4% (190). The age ranged from 55 to 74 years old, with an average age of (64.69±5.73) years. The number of married accounted for 95.6% (282 participants). There were no statistically significant differences in gender, age, family history, education level, occupation, marital status, drinking habits, regular exercise, dietary status, SBP (systolic blood pressure), DBP (diastolic blood pressure), pulse pressure difference, BMI (body mass index), folic acid, and 24-hour urine sodium among the three groups upon enrollment (P values>0.05). After the intervention, the drinking rate was as follows: Internet plus group (29, 28.7%)
Male
;
Female
;
Humans
;
Middle Aged
;
Aged
;
Blood Pressure
;
Self-Management
;
Hypertension/prevention & control*
;
Cardiovascular Diseases/prevention & control*
;
Diet
;
Sodium
;
Internet
;
Folic Acid
8.Diagnostic value of MDM2 RNA in situ hybridization in atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma.
Chen CHEN ; Xin HE ; Wen Yi JING ; Yan QIU ; Min CHEN ; Tian You LUO ; Xiao Yu LIU ; Hui Juan CHEN ; Hong Ying ZHANG ; Hong BU
Chinese Journal of Pathology 2022;51(3):190-195
Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.
Biomarkers, Tumor/genetics*
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Gene Amplification
;
Humans
;
In Situ Hybridization, Fluorescence
;
Liposarcoma/genetics*
;
Proto-Oncogene Proteins c-mdm2/genetics*
;
RNA
9. Study of a-Asarone protecting BV2 cells damaged by OGD/R by regulating of NLRP3 pathway
Fei-Fei XU ; Kai GUI ; Li-You WANG ; Ya-Qi GUAN ; Ming LIU ; Qin-Qing LI ; Ya-Juan TIAN ; Wen-Bin HE ; Shi-Feng CHU
Chinese Pharmacological Bulletin 2022;38(8):1209-1218
Aim To evaluate the protective effect of α-asarone on microglials with cerebral ischemia/reperfusion injury by measuring the expression of polar transformation and related inflammatory proteins in BV2 cells in vitro and its mechanisms.Methods The cerebral ischemia/reperfusion injury BV2 cells were pretreated by α-asarone in vitro and simulated by OGD/R model.The effect of α-asarone on the viability of damaged cells in OGD/R model was determined by CCK-8; the morphological changes of cells were observed to analyze the general morphology of cells; the levels of proinflammatory factor IL-1β, IL-18 and anti-inflammatory factor IL-10, IL-4, and ROS activity secreted by BV2 cells were detected by ELISA; the protein expressions of TGF-β, TNF-α and inflammatory related protein NLRP3, caspase 1, p-NF-κB were detected by Western blot.Results The results of in vitro experiments were as follows: the activity of damaged cells in OGD/R model was significantly increased by α-asarone, with the increase of administration dose, the cells in the low, medium and high dose groups of α-asarone decreased, and the "amoeba-like" cells and the cell body were gradually became stereoscopic and full.From the results of cell morphology, it could be seen that α-asarone had a certain proliferative effect on normal cells; the release was significantly reduced of proinflammatory factor IL-1β, IL-18 and TNF-α in OGD/R injured BV2 cells pretreated with α-asarone, also increased the release of IL-10, IL-4 and TGF-β, with a dose-effect relationship, and the high dose(16 μmol·L-1)was the best; the expressions of inflammatory related protein NLRP3, caspase 1, NF-κB and ROS activity in injured cells of OGD/R model were significantly reduced after pretreatment with α-asarone.Conclusions α-asarone has a significant protective effect on cerebral ischemia/reperfusion injury, mainly by regulating ROS activity and inhibiting phosphorylation of NF-κB, in order to reduce the excessive activation of NLRP3 inflammatory corpuscles reducing the secretion of proinflammatory factor IL-1β and IL-18, promoting the secretion of anti-inflammatory factor IL-10 and IL-4, so as to protect cerebral ischemia/reperfusion injury by anti-inflammatory reaction.
10.Etiological analysis and epidemiological significance of plague in Qinghai, 1980-2011
Jian-guo YANG ; Juan JIN ; Pei-song YOU ; Hui XIE ; Cun-xiang LI ; Jian HE ; Lin-de MA ; Hao-ming XIONG ; qiang ZHANG ; Fu-zhang TIAN ; Rui-xia DAI
China Tropical Medicine 2022;22(12):1109-
Abstract: Objective To analyze the pathogenic characteristics and epidemiological significance of human plague related strains in Qinghai Province in recent 30 years, so as to provide scientific basis for on-the-spot disposal and prevention and control measures of plague outbreak in Qinghai Province. Methods A total of 35 strains of Yersinia pestis isolated from 29 typical human plague outbreaks in Qinghai Province from 1980 to 2011 were selected and studied by biochemical fermentation experiments. Virulence factors detection of Fraction 1 antigen (Fra1), virulence antigen (VW), pigmentation (Pgm) and Yersinia pestis Ⅰ (PstⅠ), determinants and genotyping of differential regions (DFRs) were used to study the pathogenic characteristics. At the same time, according to the epidemic situation of human and animal plague in Qinghai Province in recent years, the current situation of plague prevention and control and epidemic characteristics were analyzed. Results The biotypes of 35 strains of Yersinia pestis were classical, and the biotypes of 29 strains (82.86%) were of Qinghai-Tibet Plateau type, mainly distributed in southern Qinghai and around lake areas, 2 strains (5.71%) belonged to Qilian Mountains type, mainly distributed in Qilian mountains, and 6 genotypes were identified by DFR. Among them, 16 were type 5, 12 were type 8, 2 were type 10, 1 was type 36, 3 were type 30 and 1 was type 1b, the strains of type 5 and 1b were mainly distributed around the lake and the southern foot of Qilian Mountains, while the strains of type 8, 10, 36 and 30 were mainly distributed in the southern part of Qinghai. Conclusions The pathogen of Yersinia pestis in Qinghai Plateau has complex biochemical types, the epidemic situation among animals is continuous year after year, the situation of prevention and control is serious, the occurrence and prevalence of plague seriously endanger people's health and social development, so it is necessary to do a solid job in the prevention and control of plague to ensure the safety of people's lives.


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