1.Neuroprotective Effect of Sinomenine on Parkinson's Disease Mice by Regulating GSK3β/Nrf2/HO-1 and NF-κB Signaling Pathways
Lingyu ZHANG ; Changhong HE ; Zhongzheng ZHAO ; Haojie NI ; Lang YI ; Yan DONG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):607-614
Objective To investigate the intervention effect and mechanism of sinomenine(SIN)on Parkinson's disease(PD)mice based on GSK3 β/Nrf2/HO-1 and NF-κ B signaling pathways.Methods C57BL/6 mice were randomly divided into 6 groups:normal group,model group,positive drug group(Levodopa,75 mg?kg-1)and SIN low-,medium-and high-dose groups(20,40,80 mg?kg-1),with 8 mice in each group.Mice were intraperitoneally injected with 20 mg?kg-1 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once a day for 5 days.Intragastric administration was performed 1 hour after injection of MPTP,once a day for 12 days.On the day 11 of administration,the mice were subjected to a pole-climbing experiment,and on the day 12,a rotating rod experiment was performed to test the behavioral changes of the mice.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were detected by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in brain tissue were detected by RT-qPCR.The protein expression levels of TH,Nrf2,HO-1,p-GSK3β,GSK3β,p-IκB,IκB,p-NF-κB and NF-κB in brain tissue were detected by Western Blot.Results Compared with the normal group,the automatic turning latency(T-turn)of the model group was significantly prolonged(P<0.05),and the number of falls was significantly increased(P<0.001).The expression level of TH protein in brain tissue was significantly decreased(P<0.01),and the mRNA expression levels of IL-1β,TNF-α and IL-6 were significantly increased(P<0.001).The serum levels of TNF-α,IL-1β and IL-6 were significantly increased(P<0.05,P<0.01).The protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly decreased(P<0.05,P<0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly increased(P<0.001).Compared with the model group,the T-turn in the Sin medium-and high-dose groups was significantly shortened(P<0.05,P<0.001),the falling latency was significantly prolonged(P<0.05,P<0.01),the times of falls was significantly reduced(P<0.001),the expression level of TH protein in brain tissue was significantly increased(P<0.01,P<0.001),and the level of serum TNF-α was significantly decreased(P<0.05).The mRNA expression levels of IL-1β,TNF-α and IL-6 in brain tissue of mice in each administration group were significantly decreased(P<0.001),the serum levels of IL-1β and IL-6 were significantly decreased(P<0.01,P<0.001),the protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly increased(P<0.05,P<0.01,P<0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly decreased(P<0.001).Conclusion SIN can enhance anti-oxidative stress and inhibit neuroinflammation by regulating GSK3β/Nrf2/HO-1 and NF-κB pathways in the brain of Parkinson's disease mice,thereby exerting neuroprotective effects.
2.Construction and application of Zhejiang provincial rare blood group information sharing system based on data modeling
Junna QIU ; Changhong KONG ; Xianguo XU ; Yebiao XU ; Cuie WANG ; Kaili WU ; Risheng HE
Chinese Journal of Blood Transfusion 2024;37(9):1068-1072
【Objective】 To establish an information management platform for provincial rare blood group bank to achieve the interconnection and sharing of data such as rare blood group types, donor information and blood inventory, so as to enhance the supply security of rare blood group blood. 【Methods】 The information barriers of rare blood group management in each business link and among blood stations in Zhejiang province were analyzed using fishbone diagram. Data modeling technology was introduced based on the unified blood collection and supply business system and blood cloud platform of Zhejiang, the database view of rare blood group donors and rare blood group was constructed through demand analysis and model design, and a unified query platform was developed to achieve the sharing of rare blood group information. 【Results】 The system integrated, retrievaled and displayed rare blood type information, achieving the interconnection of information among various business links and blood stations within blood banks. Up to now, in addition to RhD negative blood group, there were 8 types of rare red blood cells in the bank, covering 7 blood group systems, 289 rare blood group donors and 216 units of frozen red blood cells of rare blood group. 【Conclusion】 The information system based on data modeling can improve the overall efficiency and collaboration of the system, and reduce the workload of system development and operation. It can provide reference for standardized data management and application, and also provide a model for establishing and improving of a national rare blood group information network.
3.Influence of functional ankle instability on balance and lower limb explosive power
Changhong ZHUANG ; Yufeng WANG ; Sijie HE ; Tao JIANG ; Jintao YE ; Tianfeng ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(9):1107-1116
Objective To observe the influence of functional ankle instability(FAI)on balance and lower limb explosive power. Methods A total of 26 male FAI participants,13 bilateral(bilateral group)and 13 left(left group),who regularly en-gaged in high-intensity exercise,were recruited at Harbin Sport University in May,2024.Meanwhile,13 unin-jured male participants who engaged in high-intensity exercise were recruited as control group.They were mea-sured the moving area of the left foot,right foot and body center of gravity standing on feet with the eyes opened and closed;as well as the sway angle,confidence ellipse diameter(maximum and minimum)to circle area ratio,sway ratio and confidence ellipse standing on single foot,with Gaitview plantar pressure analysis system.They were also tested with Y-balance test(YBT),and were measured flight time and center of gravity height during jumps single leg left/right drift,stiffness and counter movement jump using Opto-jump Optical Measurement of Motor Quality. Results There were significant differences among the groups in swing angle,confidence ellipse diameter(maximum and minimum)to circle area ratio,swing ratio and confidence ellipse as left-leg stance with eyes closed(F>3.300,P<0.05),which was the least in the control group(P<0.05).Swing angle,swing ratio and confidence ellipse were also different among the groups as right-leg stance with eyes closed(F>4.404,P<0.05),and they were less in the control group than in the bilateral group(P<0.05),and less in the left group than in the bilateral group(P<0.05),except swing angle.There was a significant difference in YBT results(F>3.649,P<0.05),which was the least in the bilateral group(P<0.05).There were significant differences in the flight time and center of gravity height during counter movement jump(F>7.458,P<0.01),which was the least in the bilateral group(P<0.05). Conclusion FAI may impair the static balance as single-leg stance with eyes closed,dynamic balance and lower limb ex-plosive power.
4.Research progress of brain imaging in cognitive behavioral therapy for depression
Manyu HE ; Huiying WANG ; Yan LI ; Xinyu WANG ; Chen QIU ; Zihan YU ; Yifang FU ; Jinyu ZHANG ; Yali WANG ; Changhong WANG
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(12):1148-1152
The prevalence and recurrence rate of depressive disorder are high, while the recognition and cure rate are low. Early intervention can improve the quality of life of patients with depression. In clinical practice, it has been found that psychological treatments can effectively improve the symptoms and prognosis of depression.Cognitive behavior therapy(CBT) has been widely used in the treatment of depression, however, its mechanisms are still unclear. In this paper, the neuroimaging studies of patients with depression before and after CBT were summarized, and the structural or functional changes of different brain regions in patients with depression before and after CBT were described. The findings suggest that CBT improved depressive symptoms by increasing gray matter volume, activation level, and functional connectivity strength in the dorsolateral prefrontal cortex, reducing activation levels in the amygdala and parahippocampal gyrus, and restoring abnormal brain network activity or functional connectivity. Larger gray matter volume in anterior cingulate gyrus and higher activation levels in hippocampus and amygdala before treatment can effectively predict the effect of CBT in depressed patients. In the future, machine learning could be combined with brain imaging data to more accurately predict the effectiveness of CBT in treating depression.
5.A comparative study on SaTScan and FleXScan software for spatial clustering analysis regarding the incidence of pulmonary tuberculosis
Ting LI ; Jin'ge HE ; Changhong YANG ; Jing LI ; Yue XIAO ; Yunkui LI ; Chuang CHEN ; Jianlin WU
Chinese Journal of Epidemiology 2020;41(2):207-212
Objective To detect the spatial clustering and high risk areas of pulmonary tuberculosis (PTB) in Sichuan province in 2018 and,to compare the effects of application on both SaTScan 9.4.1 software and FleXScan 3.1.2 software to detect the PTB spatial clusters.Methods Geographic information database was established by using the incidence data of PTB and demographic data reported in the'China disease prevention of infectious disease reporting information management system'in Sichuan province in 2018.Spatial clustering analysis was conducted using the Poisson model in software SaTScan 9.4.1 and FleXScan 3.1.2 to detect the high risk areas of PTB by software ArcGIS 10.5.Differences of clusters locations and scopes in the two scanning methods were compared.Results The reported incidence rate of PTB was 57.34/100 000 (47 601 cases) in Sichuan province in 2018,presenting an obvious clustering distribution.SaTScan and FleXScan scanned 8 and 10 clusters showed statistically significant differences (P<0.05),with log-likelihood ratio (LLR) as 24.62-2 416.05 and 1.48-2 618.96,respectively.Results from scanning of the two methods showed that the most likely clusters appeared in the Daliangshan and Xiaoliangshan of Liangshan Yi ethnic aggregation areas.The other clustering areas would include some minority areas in the western Sichuan plateau,detected by both two methods differences in the shape and scope of the clustering were detected by both methods.The clustering scopes detected by SaTScan covered some counties,in which the actual incidence was not high.FleXScan could distinguish the clusters and detect more irregular shaped clusters.Conclusions Obvious spatial clusters of PTB distribution were found in Sichuan in 2018.Areas of Daliangshan,Xiaoliangshan and the minority areas in Western Sichuan plateau appeared at high risk,suggesting these were the key areas for prevention and control.FleXScan seemed more conducive in accurately distinguishing the "cold spot" areas in the highly aggregated areas,and more suitable for the application of spatial clustering detection for TB,in Sichuan province.
6.Preliminary application of 3D printing navigation template in the screw insertion of the suprapubic fracture
Fei WANG ; Shenshen HAO ; Zhibin LIU ; Xiaona JI ; Changhong LI ; Yongjin HE ; Yanxiong LIU ; Jun LIU
Clinical Medicine of China 2019;35(2):107-110
Objective To introduce the method of using hollow pull screw insertion for the suprapubic fracture with 3D printing navigation template and to evaluate its clinical effect.Methods From March 2016 to August 2017,eighteen cases of suprapubic ramus fractures treated with hollow lag screw fixation in the Department of Orthopedics of Yanan University Affiliated Hospital were retrospectively collected was collected.Before operation,the thin slice CT scan of pelvis was used to get raw data,and the mimics17.0 software was used to reconstruction the model,to design and make the personalized navigation template assisting the suprapubic fractures surgery.The navigation template was printed out pre-operatively,and the nail was inserted via the assisted by the template intra-operatively.After the operation,the fracture reduction was evaluated by Matta imaging scores and the pelvis function was evaluated by Majeed scores.Results All the operations were successfully completed.The Matta scores were excellent in 11 cases,good in 6 cases,and fair in 1 case.The Majeed scores were excellent in 13 cases,good in 3 cases,and fair in 2 cases.Conclusion 3D Printing navigation template assisted the placement of the hollow screw on the suprapubic fracture could provide personalized treatment,reduce the difficulty of operation and satisfy the clinical effect.
7.Thoraco-laparscopic surgery for synchronous esophageal squamous cell carcinoma and adenocarcinonm at esophagogastric junction
Qiang ZHAO ; Changhong LIAN ; Yuan HE ; Yingming SONG ; Chao HAN ; Huiqing ZHANG ; Shuzhe XIE ; Liang WANG ; Qingfu LU
Chinese Journal of General Surgery 2019;34(4):298-301
Objective To evaluate endoscopic surgical treatment of synchronous esophageal squamous cell carcinoma and adenocarcinonm at the esophagogastric junction.Methods The clinical data of 17 patients with synchronous esophageal squamous cell carcinoma associated with adenocarcinoma of esophagogatric junction between Jan 2010 and Jan 2017 were analyzed retrospectively.Results Among these 17 patients,9 patients underwent thoracoscopy and laparoscopy with partial resection of esophagus and proximal stomach,and gastroesophageal and neck anastomosis.3 patients underwent thoracoscopy and laparoscopy with partial resection of esophagus and proximal stomach,gastroesophageal intrathoracic anastomosis.Laparoscopic radical total gastrectomy combined with radiotherapy for esophageal cancer was performed in 5 cases.There was not perioperative death or serious complications.The cumulative survival rates of 1,3 and 5 years after surgery were 100%,42% and 24%,respectively.Conclusion Thoracolaparscopic surgery combined with local radiation therapy is a safe and effective treatment for patients with synchronous esophageal squamous cell carcinoma and adenocarcinoma at esophagogastric junction.
8.Chemoterapeutic drug screening based on patient?derived pancreatic cancer xenograft(PDX)models
He ZHANG ; Xue CHEN ; Caiqin ZHANG ; Yong ZHAO ; Dengxu TAN ; Changhong SHI
Acta Laboratorium Animalis Scientia Sinica 2018;26(1):29-35
Objective To evaluate the therapeutic effect of chemotherapeutic drugs on pancreatic carcinoma based on patient-derived xenograft(PDX)models,and to screen an individualized treatment strategy. Methods Fresh human pancreatic carcinoma tissues were subcutaneously transplanted into nude mice to establish PDX models which could be stab-ly passaged. The traceability of PDX models was determined by STR analysis. The PDX models were treated with three dif-ferent clinical chemotherapeutic drugs oxaliplatin, gemcitabine and irinotecan, respectively, and the tumor volumes were measured at different times. The therapeutic effect of those drugs was assessed by TGD mathematical model and plasma CA19-9 test. Results The traceability of patient-derived xenograft samples was up to 99.99%. Compared with the con-trol group,the treatment with irinotecan and gemcitabine inhibited tumor growth significantly(P=0.001), and gemcit-abine had even better result. The minimum toxic effect in the mice was induced by irinotecan treatment,followed by gem-citabine treatment. Conclusions Pancreatic carcinoma PDX models are successfully established and can be stably pas-saged. Gemcitabine shows the most inhibitory effect on tumor growth based on TGD mathematical model assessment, and deserves to be recommended as the preferred drug for individual treatment of pancreatic carcinoma.
9.Establishment and characterization of a patient-derived orthotopic xenograft ( PDOX) model of pancreatic cancer
He ZHANG ; Caiqin ZHANG ; Yong ZHAO ; Dengxu TAN ; Changhong SHI
Acta Laboratorium Animalis Scientia Sinica 2018;26(3):296-301
Objective To establish and evaluate a patient-derived orthotopic xenograft ( PDOX ) model of pancreatic cancer. Methods Tissues of patient-derived pancreatic tumor were transplanted into nude mouse pancreas by surgery. The PDOX models were evaluated by the small animal near infrared fluorescence ( NIRF) optical imaging and PET/CT. The traceability of PDOX models was detected by STR technology, and the pathological changes were observed by H&E staining, immunohistochemistry, and serum level of CA19-9 was detected by ELISA. Results Apparent NIRF were observed to be accumulated in pancreatic site by optical imaging system. The location and size of the xenografts tumor were revealed by fluorescence intensity. The PET/CT images with 18F-FDG molecular probe confirmed the tumor's location and size. Ex vivo NIRF imaging of isolated organ further showed the tumor formation. The traceability of PDOX models was 99. 99% with human origin. H&E staining pathology and immunohistochemistry indicated the pancreatic cancer characteristics. The high serum level of ca19-9 confirmed the mice bearing tumor. Conclusions Pancreatic PDOX models are successfully established in this study, and it can be evaluated comprehensively by NIRF optical imaging and PET/CT, providing an appropriate platform for further research of pancreatic cancer.
10.Characteristics and research strategies of patient-derived orthotopic xenograft models
Xue CHEN ; He ZHANG ; Changhong SHI
Chinese Journal of Comparative Medicine 2018;28(1):118-122
The patient-derived orthotopic xenograft (PDOX) model better maintains the genetic characteristics of the primary tumor, and keep stable in histology, transcriptome, polymorphism and copy number variations. It also retains the interaction between the tumor mesenchyma, microvessels and stroma, and the tumor metastatic properties. Therefore, PDOX model can predict disease prognosis more accurately and can be used to screen appropriate individualized treatment strategies, thus, shows perfect prospect in clinical application. However, due to the differences between mouse and human microenvironment, morphological distinctions between orthotopic xenograft tumors and primary tumors still exist, and tumor metastasis can not be ensured by orthotopic xenograft. Thus, in order to construct the individualized PDOX model and to promote its clinical translation, it is necessary to analyze the histomorphology of orthotopic xenografts, to establish database of the transplantation model and share the information of the model. In this review, we will summarize the main features of PDOX models with its advantages and limitations, and looking forward to its application in the future.

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