1.Mechanism of Linggui Zhugantang in Promoting Astrocyte Endocytosis and Degradation of Amyloid β
Min GAO ; Xiaojing CHENG ; Qingrong TIAN ; Yun LING ; Xibin ZHOU ; Chunxiang ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):1-8
ObjectiveTo investigate the effects of Linggui Zhugantang (LGZGT)-containing serum on primary astrocytes (AS) induced by β amyloid 1-42 (Aβ1-42) in a rat model of Alzheimer's disease (AD) and explore the phagocytic and degradative effects of LGZGT on Aβ. MethodAn AD model was established by inducing AS with Aβ1-42. The cells were divided into normal group, model group, LGZGT low-, medium-, and high-dose (LGZGT-L, LGZGT-M, and LGZGT-H) groups, and donepezil hydrochloride group. The model group was treated with Aβ1-42 at a final concentration of 10 μmol∙L-1. The LGZGT-L, LGZGT-M, and LGZGT-H groups were treated with 10% serum containing LGZGT on the basis of the model group. Cell viability was assessed using a cell counting kit-8 (CCK-8), lactate dehydrogenase (LDH) activity was measured using an LDH assay kit, and cell morphology was observed using an inverted microscope. The expression of Aβ-related degradation enzymes insulin-degrading enzyme (IDE) and cathepsin D (CTSD) was detected using Western blot, and the fluorescence intensity of cathepsin B (CTSB) was measured using immunofluorescence. The content of Aβ1-42 in cells was determined using an enzyme-linked immunosorbent assay (ELISA). ResultCompared with the normal group, the viability of AS in all groups decreased, and Aβ1-42 at different concentrations had inhibitory effects on AS proliferation. After administration, compared with the normal group, the cell survival rate of the model group decreased significantly (P<0.05). Compared with the model group, the cell survival rates of the LGZGT-H group and donepezil hydrochloride group increased significantly (P<0.05). The LDH activity of cells in the model group was significantly increased compared with that in the normal group (P<0.05), and cell bodies were swollen and enlarged with increased protrusions and elongation, suggesting more obvious cell damage. Compared with the model group, the LDH activity of cells in the donepezil hydrochloride, LGZGT-L, LGZGT-M, and LGZGT-H groups decreased significantly (P<0.05). After administration, the cell swelling in the LGZGT-M, LGZGT-H, and donepezil hydrochloride groups improved, cell protrusions shortened, and cell clustering decreased. Compared with the normal group, the expression of IDE and CTSD in the model group decreased significantly (P<0.05). Compared with the model group, the expression of IDE increased significantly in the LGZGT-M and LGZGT-H groups (P<0.05). Compared with the model group, the expression of CTSD increased significantly in the LGZGT-L, LGZGT-M, LGZGT-H, and donepezil hydrochloride groups (P<0.05). The average fluorescence intensity of CTSB in the model group was significantly lower than that in the normal group (P<0.05). Compared with the model group, the average fluorescence intensity of CTSD in the LGZGT-L, LGZGT-M, LGZGT-H, and donepezil hydrochloride groups increased significantly (P<0.05). The intracellular content of Aβ1-42 in cells in the model group was significantly higher than that in the normal group (P<0.05). After administration, compared with the model group, the intracellular content of Aβ1-42 in cells in the LGZGT-L, LGZGT-M, LGZGT-H, and donepezil hydrochloride groups decreased significantly (P<0.05), and LGZGT-containing serum reduced Aβ1-42 in a dose-dependent manner (P<0.05). ConclusionLGZGT has a protective effect on Aβ1-42-induced AS and can promote the degradation of Aβ. Its mechanism may be related to reducing Aβ toxicity, enhancing cell viability, promoting the expression of IDE, CTSD, and CTSB, and restoring lysosomal function.
2.Establishment of a noninvasive predictive model for antiviral therapy in patients with chronic hepatitis B virus infection and an age of≤30 years
Changxiang LAI ; Qingrong TANG ; Xiulian ZHANG ; Qiyuan TANG ; Zhiyu LI ; Xuan ZHOU ; Wenjie XIAN ; Ruikun CHEN ; Xiaojuan WU ; Fang WANG
Journal of Clinical Hepatology 2024;40(7):1328-1333
Objective To predict whether antiviral therapy is required in patients with chronic hepatitis B virus(HBV)infection and an age of≤30 years by establishing a noninvasive model,and to investigate the diagnostic value of this model.Methods A retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People's Hospital from January 2017 to January 2023 and met the inclusion criteria,and according to the results of liver biopsy,they were divided into treatment group with 41 patients(with indications for antiviral therapy)and observation group with 134 patients(without indications for antiviral therapy).The two groups were analyzed in terms of the indicators including clinical data,imaging examinations,and serum biochemical parameters.The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy,and different models for predicting the need for antiviral therapy were constructed based on related parameters.The receiver operating characteristic(ROC)curve was used to compare the diagnostic value of different models.The independent-samples t test was used for comparison of normally distributed continuous variables between groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results There were significant differences between the treatment group and the observation group in alanine aminotransferase,ferritin,total cholesterol(CHOL),triglyceride,platelet count,liver stiffness measured by sound touch elastography(STE),and procollagen Ⅲ N-terminal propeptide(PIIIP)(all P<0.05).The multivariate Logistic regression analysis showed that CHOL(odds ratio[OR]=0.4,95%confidence interval[CI]:0.2—1.0),STE(OR=1.5,95%CI:1.0—2.1),and PIIIP(OR=1.1,95%CI:1.0—1.1)were independent predictive factors for the indications for antiviral therapy.Model 1(STE+PIIIP+CHOL),model 2(STE+PIIIP),model 3(STE+CHOL),model 4(PIIIP+CHOL)had an area under the ROC curve of 0.908,0.848,0.725,and 0.725,respectively,while STE,PIIIP,and CHOL used alone had an AUC of 0.836,0.725,and 0.634,respectively,suggesting that model 1 had the largest AUC,with a specificity of 77.34%and a sensitivity of 96.36%,and had a significant difference compared with STE,PIIIP,CHOL,and the models 2,3,and 4(Z=0.21,3.08,3.06,3.23,0.89,and 0.88,all P<0.05).Conclusion The noninvasive model established based on CHOL,STE,and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of≤30 years.
3.The First Application of Domestically Produced Self-expanding Transcatheter Aortic Valve Controllable Bending Delivery System in China
Yang CHEN ; Guoliang CHEN ; Di SONG ; Hongliang ZHANG ; Moyang WANG ; Guannan NIU ; Zheng ZHOU ; Qian ZHANG ; Qingrong LIU ; Zhenyan ZHAO ; Jie ZHAO ; Bin ZHANG ; Dejing FENG ; Wence SHI ; Jicheng XI ; Yongjian WU
Chinese Circulation Journal 2024;39(3):285-289
A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.
4.Progress of community intervention in ankylosing spondylitis patients
Xueling ZHANG ; Qing XUE ; Yi ZHOU ; Tao CHEN ; Qingrong LI ; Bin LIU
Chinese Journal of General Practitioners 2021;20(1):115-118
Ankylosing spondylitis (AS) is a chronic inflammatory disease with early onset of reduced bone mineral density,which can lead to spinal deformity and even fracture,affecting patients′ quality of life seriously. To improve the compliance and long-term quality of life for AS patients, it is neccessary to enhance the awareness and knowledge of this disease among community primary health care providers.
5.Effects of repetitive transcranial magnetic stimulation on depressive behavior and hippocampal lipid in rats with chronic unpredictable stress
Cuihong ZHOU ; Shanshan XUE ; Huan YU ; Jianshuai ZHAO ; Zhengwu PENG ; Qingrong TAN ; Huaning WANG
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(1):2-8
Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the hippocampal lipidome in a rat model of chronic unpredictable stress(CUS).Methods:Twenty-four SD rats were randomly assigned to the following 3 groups ( n=8 for each group): sham group, CUS group and CUS+ rTMS group. The sham group received only sham stimulation and rats in the CUS and CUS+ rTMS group were subjected to CUS stimulation. Then, rats received 5 Hz rTMS (5 Hz, 1.26 Tesla) or sham rTMS for 7 days. After the last stimulation, all rats underwent sucrose preference test, open filed test and forced swimming test so as to observe the effect of rTMS on depressive behavior. Then, rats were sacrificed, and the levels of lipid composition in hippocampus were determined by high performance liquid chromatography mass spectrometry and analyzed by lipid search software version 4.1 and SIMCA-P 14.1.The software of SPSS 19.0 was used for statistical analysis. Univariate analysis of variance was used for comparison among groups, and Tukey test was used for multiple comparison. Results:(1)There were significant differences in open field test, sugar preference test and forced swimming test among the three groups( F=6.853-7.466, all P<0.05). In the open field experiment, the exploring time and percentage of movement distance in central area of rats in CUS group((50.72±6.38)s, (11.41±1.55)%) was significantly less than that of sham group ((86.06±7.31)s, (18.60±1.21)%) and CUS+ rTMS group((79.87±7.87)s, (16.74±1.27)%)(all P<0.05). The results of sucrose preference test showed that the percentage of sucrose intake of rats in CUS group ((37.63±6.06)%) was significantly lower than that in sham group ((68.30±6.39)%) and CUS+ rTMS group ((62.68±5.50)%)(both P<0.05) . In forced swimming test, the immobility time of rats in CUS group ((137.60±13.36)s) was significantly longer than that of sham group ((80.57±10.36)s)) and CUS+ rTMS group ((86.14±11.49)s) (both P<0.05). (2)The levels of lipid composition in hippocampus were significantly different in the three groups( F=3.826-15.440, all P<0.05). The contents of phosphatidylethanolamine (PE) ((20 850±956.56)×10 7, (24 133.33±1 242.04)×10 7), phosphatidylinositol (PI) ((788.78±136.11)×10 7, (953.65±131.26)×10 7), lysophosphatidylcholine (LPC) ((340.29±35.66)×10 7, (275.32±35.78)×10 7), creatine phosphate (CerP) ((239.65±18.14)×10 7, (293.82±38.28)×10 7), sphingosine (So) ((22.96±4.04)×10 7, (15.36±3.87)×10 7), diglyceride (DG) ((3.35±0.85)×10 7, (4.57±1.02)×10 7) and monoglyceride (MG) ((6.71±0.82)×10 7, (7.94±0.91)×10 7)in hippocampus of rats in CUS group were significantly higher than those of sham group(all P<0.05), while the phosphatidic acid(PA) ((424.52±33.38)×10 7, (509.22±42.09)×10 7) and acyl carnitine(AcCa) ((2.68±0.33)×10 7, (3.39±0.33)×10 7) decreased(both P<0.05). Compared with CUS group, the contents of PE(21 816.67±928.26)×10 7, PI(83.16±91.52)×10 7, LPC(323.59±33.91)×10 7, CerP(236.39±32.02)×10 7, So(23.35±4.46)×10 7, DG(3.16±0.85)×10 7 and MG(7.03±0.26)×10 7 in the hippocampus of CuS+ rTMS group decreased, while the contents of PA(421.55±44.28)×10 7 and ACCA(2.56±0.32)×10 7 in the hippocampus of CUS+ rTMS group increased (all P<0.05). Conclusion:The levels of glycerophospholipids, glyceroglycerides, sphingolipids, fatty acids and other lipids in the hippocampus of CUS model rats are abnormal. And the 5 Hz rTMS intervention can ameliorate the depression like behavior and the disturbances of lipid in hippocampus of CUS model rats.
6.Dehydroepiandrosterone attenuates microglial activation and exerts neuroprotective effect after subarachnoid hemorrhage
Tao TAO ; Guangjie LIU ; Yan ZHOU ; Han WANG ; Wei LI ; Qingrong ZHANG ; Chunhua HANG
International Journal of Cerebrovascular Diseases 2020;28(2):105-112
Objective:To investigate the regulatory effect of dehydroepiandrosterone (DHEA) on the microglial activation after subarachnoid hemorrhage (SAH) in vivo and in vitro.Methods:C57BL/6 mice were used for in vivo experiments. A SAH model was induced by intravascular puncture. They were randomly divided into solvent group, model group, and DHEA pretreatment group. TUNEL staining was used to detect neuronal apoptosis level at 24 h after modeling. Iba-1/CD86 fluorescence double staining was used to detect the activation of microglia. Quantitative fluorescent polymerase chain reaction and Western blot analysis were used to detect the expression of inflammatory factors, including interleukin (IL) -1β, IL-6, tumor necrosis factor (TNF) -α, and inducible nitric oxide synthase (iNOS). The primary cultured microglia was used for in vitro experiments and it was simulated SAH by hemoglobin stimulation. They were randomly divided into control group, model group, and DHEA pretreatment group. Iba-1/CD86 fluorescence double staining was used to detect the microglial activation, and fluorescence quantitative polymerase chain reaction and Western blot analysis were used to detect the expression of inflammatory factors.Results:In vivo model experiments showed that DHEA significantly reduced neuronal apoptosis ( P<0.01) and microglial activation ( P<0.01) after SAH modeling, and IL-6 expression level significantly decreased ( P<0.01), while IL-1β, TNF-α and iNOS showed a downward trend, but there were no statistical differences. In vitro model experiments showed that DHEA could significantly inhibit microglial activation ( P<0.001) and the expression levels of various inflammatory factors ( P<0.001). Conclusions:DHEA pretreatment can reduce neuronal apoptosis and microglia activation after SAH, and it has neuroprotective effect.
7.Proximal versus distal tibial bone transport in the treatment of chronic tibial osteomyelitis
Guoyun CHENG ; Qingrong LIN ; Chunhao ZHOU ; Xiangqing MENG ; Hongan ZHANG ; Jia FANG ; Chenghe QIN
Chinese Journal of Orthopaedic Trauma 2020;22(5):379-383
Objective:To compare the clinical effects on new bone formation and foot-ankle function between proximal tibial bone transport and distal tibial bone transport in the treatment of massive bone defects after tibial osteomyelitis debridement.Methods:From July 2012 to July 2017, 42 patients with chronic tibial osteomyelitis received bone transport surgery at Department of Orthopaedics, Nanfang Hospital.According to the Cierny-Mader classification for chronic osteomyelitis, all of them belonged to diffusive tibial osteomyelitis (type IV).Of them, 32 were treated by proximal tibial bone transport after tibial osteomyelitis debridement.In the proximal group, there were 27 males and 5 females, aged from 17 to 65 years and involving 20 left and 12 right sides. The other 10 cases received distal tibial bone transport. In the distal group, all of them were male, aged from 25 to 63 years and involving 6 left and 4 right sides. The 2 groups were compared in terms of external fixation index (EFI) and American Orthopaedic Foot & Ankle Society(AOFAS) Ankle and Hindfoot Scale.Results:There were no significant differences between the 2 groups in the preoperative general data such as gender, age or osteomyelitis site, indicating the 2 groups were comparable ( P>0.05). Both groups obtained complete follow-up. The proximal group was followed up for 590.1 d ± 287.3 d and the distal group for 615.6 d ± 130.6 d, showing no significant difference between groups ( P>0.05). In the proximal group 2 cases developed talipes equinovalgus after bone transport while in the distal group 3 cases did, and surgical intervention was needed for them. Surgical intervention was also carried out for16 cases of non-union at the docking site in the proximal group and for 2 ones in the distal group. The EFI was 76.2 d/cm±50.0 d/cm for the proximal group and 84.3 d/cm ± 59.9 d/cm for the distal group, showing no significant difference between groups ( P>0.05). The AOFAS scores were 81.4±10.1 for the proximal group and 60.0±5.9 for the distal group, showing a significant difference ( P<0.05). Conclusion:In the treatment of massive bone defects after tibial osteomyelitis debridement, no significant difference has been observed in the effect on bone formation between proximal tibial bone transport and distal tibial bone transport, but the former transport may have a less adverse effect on foot-ankle function.
8.Initial research on the brain functional magnetic resonance imaging induced by olfactory stimulations in multiple sclerosis
Qingrong OUYANG ; Si FAN ; Qiaojun PENG ; Yufeng WANG ; Chao WU ; Changyue HOU ; Xiaoyan ZHOU ; Xiaoming WANG
Chinese Journal of Neurology 2019;52(2):98-103
Objective To observe the characteristics of brain activation of multiple sclerosis (MS) patients and healthy controls at functional magnetic resonance imaging (fMRI) with olfactory stimulation,determine the locations of activation in areas of olfactory center and explore the MS olfactory related network.Methods Eighteen MS patients from the Affiliated Hospital of North Sichuan Medical College from February 2017 to March 2018 were enrolled as MS group,and 20 matched healthy adults during the same period served as controls.The Visual Analogue Scale was used to evaluate olfactory function in all subjects,the rest structure MRI was performed first,and volatile gases of lavender and rose solution were used to alternately stimulate olfactory during fMRI scanning.The brain activation was obtained by using matlab2013a and SPM8 softwares.The distribution and quantity of demyelination lesions were counted on T2 weighted image,and Spearman correlation analysis was done with SPSS 17.0 software package.Results The activated brain areas in the healthy control group included bilateral middle frontal gyrus,bilateral insula,bilateral supramarginal gyrus,bilateral orbitofrontal gyrus,right thalamus,right central anterior gyrus,bilateral cingulated gyrus,bilateral hippocampus,bilateral amygdala and bilateral superior frontal gyrus (t =2.11,P<0.05).The activated brain areas in the MS group included right cerebellum,left insula,left superior temporal gyrus,right inferior frontal gyrus (t=2.19,P<0.05).Compared with the control group,the MS group showed statistically significant decrease in activated values in right insula,right amygdala,right inferior frontal gyrus,right frontal middle gyrus,and the left supramarginal gyrus (t=2.04,P<0.05).The distribution and number of demyelination lesions and major activation of brain regions with olfactory in the MS group demonstrated no significant correlation (r=-0.524,P=0.054).Conclusions Multiple brain areas involved in the olfactory processing and olfactory-related brain network existed.The activation of olfactory center had dominance in the right brain.The activation of the brain area in the MS group was significantly reduced,and the activation voxel and activation intensity were weakened.The olfactory-related brain network changed in MS patients.The distribution and number of demyelination lesions had no significant effect on the major activation of brain regions with olfactory stimulation.
9.Study on relationship between the level LP-PLA2 in serum and type H-hypertension ischemic stroke
Xiaohong CHEN ; Tao ZHOU ; Run MA ; Meiling LI ; Mei YIN ; Qingrong LI
International Journal of Laboratory Medicine 2018;39(13):1615-1618,1621
Objective To observe the change of results of lipoprotein-associated phospholipase A2 (Lp-PLA2) ,homocysteine (Hcy ) ,high-sensitivity C-reactive protein (hs-CRP ) ,lipids and other indicators in the patients with normal group ,primary hypertension group ,type H hypertension group and type H hypertension ischemic stroke group ,and search the relationship between LP-PLA2 and type H-hypertension ischemic stroke .Methods From January 2015 to June 2017 ,continuous selected 103 patients with type H hypertension ischemic stroke group ,124 patients with type H hypertension group ,80 patients with primary hypertension group and 50 patients with healthy controls as normal group .Analyzed level of Lp-PLA2 ,Hcy ,hs-CRP and lipids in serum ,compared the difference with each group .A binary Logistic regression analysis was used to an-alyze its correlation with ischemic stroke .Results The serum concentration of total cholesterol(TC) ,low-den-sity lipoproteincholesterol(LDL-C) ,LP-PLA2 in type H hypertension group and type H hypertension ischemic stroke group was higher than primary hypertension group and normal group ,the difference was statistically significant(P<0 .05) .The serum concentration of triglyceride (TG) in type H hypertension ischemic stroke group was higher than primary hypertension group and normal group ,the difference was statistically signifi- cant(P<0 .05) .The serum concentration of Hcy in primary hypertension group ,type H hypertension group and type H hypertension ischemic stroke group was higher than normal group ,the difference was statistically significant(P<0 .05) ;The serum concentration of Hcy in type H hypertension group and type H hypertension ischemic stroke group was higher than primary hypertension group ,the difference was statistically significant (P< 0 .05) ;The serum concentration of Hcy ,LP-PLA2 in type H hypertension ischemic stroke group was higher than type H hypertension group ,the difference was statistically significant (P<0 .05) .The serum con-centration of hs-CRP in type H hypertension group was higher than primary hypertension group and normal group ,the difference was statistically significant (P<0 .05) ;The serum concentration of hs-CRP in type H hy-pertension ischemic stroke group was higher than type H hypertension group ,primary hypertension group and normal group ,the difference was statistically significant (P<0 .05) .Two element Logistic regression analysis , Lp-PLA2 were significantly related to type H hypertension ischemic stroke ( SE = 0 .013 ,P < 0 .05 ) . Conclusion LP-PLA2 is an inflammatory biomarker and it is closely related to the occurrence and develop-ment of type H hypertension ischemic stroke .
10.Integration of spatial epidemiology and molecular epidemiology used for study on tuberculosis
Wenming CHEN ; Qingrong ZHOU ; Xiaomeng WANG ; Huishu MAO ; Ping WANG ; Lin ZHOU ; Weibing WANG
Chinese Journal of Epidemiology 2016;37(12):1683-1686
Spatial epidemiology and molecular epidemiology have been widely used in the studies of tuberculosis (TB),but each with limitations.Integration of the two methods provides new ideas and methods in TB research.All referenced articles are from CNKI,Wan Fang database,PubMed database and Web of Science database.Method of combining spatial epidemiology and molecular epidemiology has been widely used in determining the local epidemic strains of TB genotype,the transmission mechanism,risk factors of TB,drug-resistant TB,as well as evaluating the effectiveness of TB prevention and control measures.Application of the combined methods is of important significance in the studies of TB,thus worthy to be further introduced to researchers and disease prevention and control workers in this country.

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