1.Establishment of a Rat Model of Alzheimer's Disease by Introducing Human Triple Mutant APP Gene into Hippocampus via Brain Stereotactic Technology
Linlin XIAO ; Yixuan YANG ; Shanshan LI ; Lanshiyu LUO ; Siwei YIN ; Juming SUN ; Wei SHI ; Yiqiang OUYANG ; Xiyi LI
Laboratory Animal and Comparative Medicine 2025;45(3):269-278
Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.
2.Establishment of a Rat Model of Alzheimer's Disease by Introducing Human Triple Mutant APP Gene into Hippocampus via Brain Stereotactic Technology
Linlin XIAO ; Yixuan YANG ; Shanshan LI ; Lanshiyu LUO ; Siwei YIN ; Juming SUN ; Wei SHI ; Yiqiang OUYANG ; Xiyi LI
Laboratory Animal and Comparative Medicine 2025;45(3):269-278
Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.
3.Mechanism of Huazhuo Jiedu Prescription in Alleviating Renal Fibrosis in 5/6 Nephrectomy Rats Based on AMPK/mTOR Pathway
Wanqing WANG ; Yashi WANG ; Hui GAO ; Linlin ZHENG ; Dong BIAN ; Cun FENG ; Xiaona WEI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):90-97
ObjectiveBased on the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway, this study aimed to observe the effect of the Huazhuo Jiedu prescription on renal fibrosis in 5/6 nephrectomy rats and explore its underlying mechanism. MethodsA total of 67 SPF-grade male SD rats were used, of which 11 were randomly selected as the normal group. A chronic renal failure (CRF) model was established using 5/6 nephrectomy. The successfully modeled rats were randomly assigned to the model group, losartan potassium group (4.5 mg·kg-1), and low- (1.175 g·kg-1), medium- (2.35 g·kg-1) and high-dose (4.7 g·kg-1) Huazhuo Jiedu prescription groups, with 9 rats per group. Each group received an equivalent volume of saline or the corresponding concentration of Huazhuo Jiedu prescription by gavage once daily for 8 weeks. Hematoxylin-eosin (HE) and Masson staining were used to observe renal tissue pathological changes. Transmission electron microscopy examined renal ultrastructure. Immunohistochemistry (IHC) detected expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1). Western blot analyzed expression levels of microtubule-associated protein Ⅰ light chain 3Ⅱ (LC3Ⅱ), Beclin1, p62, AMPK, phosphorylated AMPK (p-AMPK), mTOR, and phosphorylated mTOR (p-mTOR). ResultsCompared with the normal group, the model group exhibited glomerular shrinkage, mesangial and interstitial thickening, and tubular vacuolar degeneration, with no evident autophagosomes or autophagolysosome structures. Expression levels of α-SMA and TGF-β1 were significantly increased (P0.01), while p-AMPK/AMPK, Beclin1, and LC3Ⅱ were significantly decreased (P0.01), and p-mTOR/mTOR and p62 were significantly increased (P0.01). Compared with the model group, the medium- and high-dose Huazhuo Jiedu prescription groups and the losartan potassium group showed varying degrees of pathological improvement. Autophagosomes with double- or multiple-layer membranes and autophagolysosomes with monolayer membranes containing undegraded organelles were observed. Renal α-SMA and TGF-β1 protein expression levels were markedly reduced (P0.05, P0.01), p-mTOR/mTOR and p62 were significantly decreased (P0.05, P0.01), and p-AMPK/AMPK, Beclin1, and LC3Ⅱ expression levels were significantly increased (P0.05, P0.01). ConclusionHuazhuo Jiedu prescription may improve renal fibrosis in 5/6 nephrectomy rats by regulating the AMPK/mTOR signaling pathway and enhancing autophagy.
4.Association of takeaway consumption and sedentary behavior with emotional symptoms among freshman students
YAO Zhiyuan, WEI Ruihong, WANG Xinyue, JIANG Linlin, WAN Yuhui
Chinese Journal of School Health 2025;46(10):1474-1477
Objective:
To investigate the assocation of sedentary behavior among college students on psychological health issues, such as depressive, anxiety, and stress symptoms, and to analyze the moderating role of takeaway consumption behavior in the context, in order to provide a scientific basis for reducing emotional symptoms among college students.
Methods:
A stratified cluster sampling method was employed to conduct a questionnaire on 3 427 first year students of a higher education institution in Hefei of Anhui Province from May to June 2021. The study variables included demographic characteristics, sedentary time, takeaway consumption behavior, and emotional (symptoms depressive, anxiety, and stress symptoms). The Spearman correlation analysis was used to analyze the association between variables, and linear regression analysis was used to analyze the association between takeaway consumption behavior and depressive, anxiety and stress symptoms among college students with sedentary time.
Results:
Both sedentary time and takeaway consumption behavior were positively correlated with depressive, anxiety and stress symptoms among college students ( r =0.10, 0.10, 0.10; 0.10, 0.11, 0.11, all P <0.05). The results of linear regression analysis showed that the interaction term between takeaway consumption behavior and sedentary time was positively correlated with symptoms of depressive, anxiety, and stress symptoms among college students (depression: β =0.04, anxiety: β =0.04, stress: β =0.04, all P <0.05). The results of the simple slope test demonstrated that regardless of the level of takeaway consumption behavior, sedentary time was positively correlated with the depressive symptoms of college students; compared with low takeaway consumption behavior, high takeaway consumption behavior ( β=0.77, P <0.01) enhanced the association between sedentary time and depressive symptoms among college students. In addition, under the condition of high takeaway consumption behavior, sedentary time was positively correlated with the anxiety and stress symptoms of college students (anxiety: β =0.64; stress: β =0.71, both P <0.01); while under the condition of low takeaway consumption behavior, sedentary time was not related to the anxiety and stress symptoms of college students ( β =0.17, 0.22, both P >0.05).
Conclusions
Sedentary behavior is related to a the emotional symptoms of depressive, anxiety, and stress among college students. Takeaway consumption behavior may exacerbate this impact.
5.Study on the correlation between the growth and eruption of the mandibular third molar and the crowding of the mandibular dentition
Yuting WANG ; Min HU ; Wei FAN ; Qihui GU ; Zhendong WANG ; Linlin ZHU
STOMATOLOGY 2025;45(11):808-812,818
Objective To explore the association between the growth condition of mandibular third molars(M3)and the parameters of mandibular dental arch through a retrospective cross-sectional study on M3 in adults,and to provide a basis for the selection of clini-cal treatment of M3.Methods A total of 221 adult patients were randomly selected for our study.Dolphin software was used to analyze the CBCT of all the patients.Parameters of the mandibular dentition including the entire dental crowding(EDC)were recorded.Then the association between M3 growth condition and these parameters was analyzed.Results The mesio-impacted angle of M3 was posi-tively correlated with EDC(P<0.05),and negatively correlated with the retromolar space(RMS,P<0.0 1).It was worth noting that me-dian mesio-impacted M3 significantly increased EDC(P<0.01),and the erupting M3 in the vertical orthotopic position significantly in-creased RMS(P<0.01).Conclusion For patients with median mesio-impacted M3 or insufficient RMS,preventive removal of M3 may be considered clinically,which may help to reduce crowding and prevent relapse after orthodontic treatment.
6.Relationships between color Doppler ultrasound parameters and insulin sensitivity index and clinical efficacy in rats with polycystic ovary syndrome complicated with hyperinsulinemia
Xizhen SUN ; Linlin GENG ; Juan CHEN ; Wei ZHANG ; Deming SUN ; Nan LI
Chinese Journal of Comparative Medicine 2025;35(3):82-89
Objective To analyze the relationships between color Doppler ultrasound parameters and insulin sensitivity index(ISI)and clinical efficacy in rats with polycystic ovary syndrome(PCOS)combined with hyperinsulinemia(HI).Methods A total of 140 3-week-old female SD SPF-grade rats were divided randomly into a PCOS without HI model(control group,n=70)and a PCOS combined with HI model(study group,n=70).After successful modeling,we used color Doppler ultrasound to detect the physical indicators,hemodynamic indicators,and ultrasound features of rat ovaries,and draw venous blood to evaluate ISI.Rats in the study group were treated with metformin by intragastric administration.The color Doppler ultrasound parameters of the good-effect and the poor-effect group were compared and a receiver operating characteristic curve(ROC)was drawn to analyze the value of the color Doppler ultrasound parameters for evaluating the curative effect of metformin in rats with PCOS combined with HI.Results The total ovarian area(TA),ovarian volume(OV),ovarian interstitial area(SA),vascularization index(VI),blood flow index(FI),fasting insulin(FINS),and fasting blood glucose(BFG)of the research group were all greater than those of the control group,while the resistance index,pulsatility index and ISI were observed significantly lower compared with contrast,there were obvious difference(P<0.05).The color Doppler ultrasound parameters TA and SA were negatively correlated with ISI(r=-0.501,r=-0.492,respectively,P<0.05),and ovarian RI and PI were positively correlated with ISI(r=0.504,r=0.485,respectively,P<0.05).TA,OV,SA,VI,FI,VFI,PSV,PDV,low-density lipoprotein cholesterol,FPG,FINS,LH,and FSH were all significantly lower while RI and PI were significantly higher in the good-curative-effect group compared with the poor-curative-effect group(all P<0.05).According to ROC curve analysis,the sensitivity and specificity of color Doppler ultrasound parameters combined with clinical efficacy were 90.9%and 90.2%,respectively,and the area under the curve(AUC)was 0.901.Conclusions Color Doppler ultrasound parameters are closely related to ISI and therapeutic efficacy in rats with PCOS combined with HI,and may thus predict clinical efficacy in patients with these conditions.
7.Relationships between color Doppler ultrasound parameters and insulin sensitivity index and clinical efficacy in rats with polycystic ovary syndrome complicated with hyperinsulinemia
Xizhen SUN ; Linlin GENG ; Juan CHEN ; Wei ZHANG ; Deming SUN ; Nan LI
Chinese Journal of Comparative Medicine 2025;35(3):82-89
Objective To analyze the relationships between color Doppler ultrasound parameters and insulin sensitivity index(ISI)and clinical efficacy in rats with polycystic ovary syndrome(PCOS)combined with hyperinsulinemia(HI).Methods A total of 140 3-week-old female SD SPF-grade rats were divided randomly into a PCOS without HI model(control group,n=70)and a PCOS combined with HI model(study group,n=70).After successful modeling,we used color Doppler ultrasound to detect the physical indicators,hemodynamic indicators,and ultrasound features of rat ovaries,and draw venous blood to evaluate ISI.Rats in the study group were treated with metformin by intragastric administration.The color Doppler ultrasound parameters of the good-effect and the poor-effect group were compared and a receiver operating characteristic curve(ROC)was drawn to analyze the value of the color Doppler ultrasound parameters for evaluating the curative effect of metformin in rats with PCOS combined with HI.Results The total ovarian area(TA),ovarian volume(OV),ovarian interstitial area(SA),vascularization index(VI),blood flow index(FI),fasting insulin(FINS),and fasting blood glucose(BFG)of the research group were all greater than those of the control group,while the resistance index,pulsatility index and ISI were observed significantly lower compared with contrast,there were obvious difference(P<0.05).The color Doppler ultrasound parameters TA and SA were negatively correlated with ISI(r=-0.501,r=-0.492,respectively,P<0.05),and ovarian RI and PI were positively correlated with ISI(r=0.504,r=0.485,respectively,P<0.05).TA,OV,SA,VI,FI,VFI,PSV,PDV,low-density lipoprotein cholesterol,FPG,FINS,LH,and FSH were all significantly lower while RI and PI were significantly higher in the good-curative-effect group compared with the poor-curative-effect group(all P<0.05).According to ROC curve analysis,the sensitivity and specificity of color Doppler ultrasound parameters combined with clinical efficacy were 90.9%and 90.2%,respectively,and the area under the curve(AUC)was 0.901.Conclusions Color Doppler ultrasound parameters are closely related to ISI and therapeutic efficacy in rats with PCOS combined with HI,and may thus predict clinical efficacy in patients with these conditions.
8.Application of patient navigation model in continuing care for elderly diabetic patients
Yanli LI ; Zaigang YANG ; Linlin QIN ; Xijuan NIU ; Lu WEI
Chinese Journal of Modern Nursing 2025;31(2):239-243
Objective:To analyze the application effect of the patient navigation model in the continuity of care for elderly diabetic patients.Methods:A convenience sampling method was used to select 163 elderly diabetic patients admitted to the First Affiliated Hospital of Zhengzhou University from June 2022 to December 2023. Patients were randomly divided into a control group ( n=81) and an observation group ( n=82) using a random number table. The control group received routine continuity of care, while the observation group received continuity of care based on the patient navigation model. The Diabetes Self-Management Behavior Scale (SDSCA) and the Chronic Disease Resources Survey were used to assess the patients. Self-management behaviors, chronic disease resource utilization, and blood glucose changes were compared between the two groups before and three months after the intervention. Results:After the intervention, the SDSCA dimension scores in the observation group were significantly higher than those in the control group ( P<0.01). Additionally, the chronic disease resource survey dimension scores in the observation group were significantly higher than those in the control group ( P<0.01). Moreover, the fasting blood glucose, 2-hour postprandial blood glucose, and HbA1c levels in the observation group were significantly lower than those in the control group ( P<0.01) . Conclusions:The application of the patient navigation model in the continuity of care for elderly diabetic patients helps patients fully access multi-dimensional social resources, improves self-management capabilities, and is beneficial for improving blood glucose control.
9.Study on the correlation between the growth and eruption of the mandibular third molar and the crowding of the mandibular dentition
Yuting WANG ; Min HU ; Wei FAN ; Qihui GU ; Zhendong WANG ; Linlin ZHU
STOMATOLOGY 2025;45(11):808-812,818
Objective To explore the association between the growth condition of mandibular third molars(M3)and the parameters of mandibular dental arch through a retrospective cross-sectional study on M3 in adults,and to provide a basis for the selection of clini-cal treatment of M3.Methods A total of 221 adult patients were randomly selected for our study.Dolphin software was used to analyze the CBCT of all the patients.Parameters of the mandibular dentition including the entire dental crowding(EDC)were recorded.Then the association between M3 growth condition and these parameters was analyzed.Results The mesio-impacted angle of M3 was posi-tively correlated with EDC(P<0.05),and negatively correlated with the retromolar space(RMS,P<0.0 1).It was worth noting that me-dian mesio-impacted M3 significantly increased EDC(P<0.01),and the erupting M3 in the vertical orthotopic position significantly in-creased RMS(P<0.01).Conclusion For patients with median mesio-impacted M3 or insufficient RMS,preventive removal of M3 may be considered clinically,which may help to reduce crowding and prevent relapse after orthodontic treatment.
10.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.


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