1.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
2.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
3.Yinqiao Powder affects macrophage polarization-mediated herpes simplex keratitis through the cGAS-STING-IRF3 molecular pathway
Ning YAO ; Rongli ZHAO ; Xuemei YANG ; Yuhuan LIU ; Yaqin DING ; Yan DAI
International Eye Science 2025;25(8):1227-1233
AIM: To investigate the specific molecular mechanism of Yinqiao Powder in affecting macrophage polarization in herpes simplex keratitis(HSK)through the cyclic GMP-AMP synthetase(cGAS)-stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)molecular pathway.METHODS:Human corneal epithelial cells(HCE-T)were divided into control, HSK, and HSK + Yinqiao Powder groups. M0 macrophages were grouped as Ctrl, HSV-1, HSV-1+oe-cGAS, HSV-1+Yinqiao Powder, and HSV-1+oe-cGAS+Yinqiao Powder. Conditional medium(CM)from each group of M0 macrophages was collected to intervene in HCE-T cells and divided into Ctrl-CM, HSV-1-CM, HSV-1+oe-cGAS-CM, and HSV-1+Yinqiao Powder-CM groups. Cell viability was detected by MTT assay, and apoptosis was detected by TUNEL assay. ELISA was used to detect the concentrations of Arg-1 and iNOS in cell supernatants, and Western blotting was used to detect the relative protein expressions of cGAS, STING, and IRF3. Balb/c mice were divided into control, model, and drug groups. The model and drug groups were inoculated with HSV-1 on the cornea of Balb/c mice using the corneal scratch method to construct an HSK mouse model, and the drug group was treated with Yinqiao Powder. The incidence and mortality of the three groups were compared on days 1, 3, 5, 7, and 14 after modeling.RESULTS:Compared with the control group, the HCE-T cell viability in the HSK group was decreased but apoptosis was increased, which was reversed by Yinqiao Powder intervention. Compared with the Ctrl group, the Arg-1 concentration in the cell supernatant of the HSV-1 group was decreased, the iNOS concentration was increased, and the protein expressions of cGAS, STING, and IRF3 were decreased. Compared with the HSV-1 group, the Arg-1 concentration was increased, the iNOS concentration was decreased, and the protein expressions of cGAS, STING, and IRF3 were enhanced in the HSV-1+oe-cGAS group and the HSV-1+Yinqiao Powder group, and the same results were obtained in the HSV-1+oe-cGAS+Yinqiao Powder group. Compared with the Ctrl-CM group, the HCE-T cell viability was decreased and apoptosis was increased in the HSV-1-CM group, which was reversed by overexpressing cGAS in macrophages or intervening with Yinqiao Powder. In vivo experiments found that Yinqiao Powder intervention could improve the pathological progression of keratitis.CONCLUSION:Yinqiao Powder inhibits M1 polarization of macrophages through the cGAS-STING-IRF3 molecular pathway, thereby delaying the progression of HSK.
4.Clinical characteristics and prognostic analysis of asparaginase-associated pancreatitis in pediatric acute lymphoblastic leukemia
Dun JIANXIN ; Zhang AI ; Wang YAQIN ; Wang YAO ; Liu AIGUO ; Hu QUN
Chinese Journal of Clinical Oncology 2024;51(11):547-551
Objective:To analyze the clinical characteristics and risk factors of asparaginase-associated pancreatitis(AAP)in children with acute lymphoblastic leukemia(ALL),and to investigate the impact of AAP on their prognosis following re-exposure to asparaginase(ASP).Methods:Clinical children data with ALL at Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology between January 2015 and June 2020 were collected to analyze the clinical features of AAP.Logistic regression was used to identify risk factors for AAP.Prognostic analysis was performed using the Log-rank test and Kaplan-Meier survival curves.Results:Overall,252 children with ALL were included,among whom 23(9.1%)developed AAP.Most AAP cases(82.6%)occurred during remission induction,with a medi-an time from the last ASP to AAP of 12 d.Elevated total cholesterol(≥3.5 mmol/L)at initial diagnosis was identified as an independent risk factor.Six children(26.1%)were re-exposed to ASP,leading to recurrent pancreatitis in 3 cases.The 5-year overall survival(OS)was signific-antly lower in the AAP group(78.3%±8.6%)compared to the non-AAP group(90.3%±2.2%)(P<0.05).Similarly,children who discontinued ASP due to AAP had a 5-year OS of 77.8%±9.8%,significantly lower than the control group(90.1%±2.1%).Conclusions:AAP typically oc-curred within 12 d of the last ASP administration and was associated with poorer 5-year OS.Re-exposure to ASP posed a risk of recurrent AAP;however,completing the ASP chemotherapy regimen may be crucial for improving prognosis.
5.Construction and application of a spinal cord injury rehabilitation care platform based on patient portrait
Yaqin DAI ; Ting SHAO ; Lifeng YAO ; Fei HU ; Qin JIA
Chinese Journal of Nursing 2024;59(22):2693-2699
Objective To construct a rehabilitation care platform for spinal cord injury patients,based on patient portrait technology and to validate its application effect.Methods Artificial intelligence technology was used to realize the fusion of data.We constructed a patient portrait rehabilitation nursing system that can provide systematic and personalized information support.By the convenience sampling method,53 perioperative patients with spinal cord injury from July 2023 to December 2023 were selected as the test group to implement the intelligent intervention based on patient portrait technology;53 perioperative patients with spinal cord injury who were hospitalized from January 2023 to June 2023 were selected as the control group to implement the conventional information support intervention.The self-efficacy,self-care ability,and quality of life were compared before the intervention,and 2 weeks,4 weeks,12 weeks after the intervention between the 2 groups.Results 45 cases in the experimental group and 43 cases in the control group reached the endpoint of the study after 12 weeks of intervention.The ANOVA of the 2 groups showed the test group having a greater advantage over the control group,with statistically significant differences in self-efficacy,ability to perform daily living tasks,and quality of life between groups,intergroup effect,and interaction effect(P<0.05).Conclusion The rehabilitation care platform based on patient portraits has a positive effect on improving self-efficacy,self-care ability and quality of life for spinal cord injury patients.
6.Effect of low frequency repetitive transcranial magnetic stimulation combined with bilateral isokinematic training on upper limb motor function of stroke patients
Fengbao SUN ; Yaqin ZENG ; Yao OUYANG ; Zhenhua JIN ; Xiaofeng ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2023;29(3):256-261
ObjectiveTo explore low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with bilateral isokinematic training (BIT) on upper limb motor function and activities of daily living of stroke patients. MethodsFrom September, 2021 to September, 2022, 60 stroke inpatients in Zhejiang Provincial People's Hospital were randomly divided into rTMS group (n = 20), BIT group (n = 20) and combination group (n = 20). All the patients accepted routine rehabilitation, moreover, rTMS group accepted 1 Hz rTMS on healthy side, BIT group accepted BIT, and the combination group accepted the combination of 1 Hz rTMS on healthy side and BIT, for four weeks. They were evaluated with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Wolf Motor Function Test (WMFT), Carroll Upper Extremities Function Test (UEFT) and modified Barthel Index (MBI) before and after treatment. ResultsThe scores of FMA-UE, WMFT, UEFT and MBI significantly improved in all the groups after treatment (|t| > 5.052, P < 0.001), and improved the most in the combination group (F > 9.834, P < 0.001). ConclusionBoth low-frequency rTMS and BIT can effectively improve upper limb motor function and activities of daily living of stroke patients, and the combination of them is more effective.
7.Lipoprotein glomerulopathy caused by mutation of apolipoprotein E gene in children: a report of two cases
Yaqin WEI ; Jun YAO ; Pei ZHANG ; Chunlin GAO ; Xu HE ; Lili JIA ; Xiaojie LI ; Zhengkun XIA
Chinese Journal of Nephrology 2023;39(3):215-219
The paper reports two cases of lipoprotein glomerulopathy (LPG) in children. The Sanger sequencing results in 2 cases indicated apolipoprotein E gene mutation[c.127 (exon3) C>T, p.R43C (p.Arg43Cys); c.494 (exon4) G>C, p.R165P (p.Arg165Pro),respectively]. Renal pathological presentation of two children showed that a large number of lipoprotein emboli were formed in the glomerular capillary loop, and the diagnosis of LPG was confirmed. The onset of LPG has no specific clinical manifestation, which is easy to be undiagnosed or misdiagnosed. Renal biopsy is a diagnostic means, glucocorticoid treatment is ineffective, and long-term lipid-lowering treatment may be required for LPG.
8.Qualitative studies on the real experience of living related organ transplantation donors from relatives: a Meta-synthesis
Ke LI ; Qin JIA ; Yingying WANG ; Jiayun WU ; Yaqin DAI ; Lifeng YAO
Chinese Journal of Modern Nursing 2023;29(21):2824-2832
Objective:To systematically evaluate the real experience of living related organ transplantation donors from relatives and provide evidence-based basis for medical and nursing staff to develop personalized intervention measures.Methods:Qualitative study on the real experience of living related organ transplantation donors from relatives was searched on PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, WanFang Data, VIP, and Biology Medicine disc. The search period was from database establishment to August 31, 2022. The article was evaluated using the quality evaluation criteria for qualitative study of the Australian Joanna Briggs Institute (JBI) Evidence-Based Healthcare Center. We converged the results and performed Meta-synthesis.Results:A total of 15 articles were included, 32 research results were extracted, and summarized and integrated into 13 new categories. A total of 5 integration results were synthesized, including the motivation to donate, the pressure and challenges faced before transplantation, the physical and mental discomfort caused by donation, the positive impact of donation, and the desire for support and needs from various aspects.Conclusions:Donors of living related organ transplantation have multiple psychological experiences during the process of organ donation. Nurses should dynamically assess the pressure and challenges faced by donors, provide diverse support to meet their needs, help donors actively respond, and improve their quality of life.
9.Relationship between serum retinol binding protein, stromal cell derived factor-1 and renal function in patients with diabetic nephropathy
Liangyan LIN ; Yongjun JIN ; Xiaoyan YAO ; Yaqin TENG ; Tiantian ZHAO ; Qingsong JIN ; Dongdong ZHANG ; Hongxia SHANG
International Journal of Surgery 2021;48(3):184-189,F4
Objective:To investigate the relationship between serum retinol binding protein (RBP), stromal cell derived factor-1 (SDF-1) and renal function in patients with diabetic nephropathy (DKD).Methods:The patients with type 2 diabetes mellitus (T2DM) admitted to Yantai Affiliated Hospital of Binzhou Medical College from October 2017 to October 2020 were prospectively selected, 438 patients were divided into simple T2DM group ( n=276)and DKD group( n=162) according to the presence or absence of DKD, according to the ratio of urinary albinin/creatinine (UACR) were divided into normal( n=25), microalbuminuria ( n=75) and macroalbuminuria group ( n=62), according to the estimated glomerular filtration rate (eGFR) were divided into G1 stage ( n=28), G2 stage ( n=27), G3A + G3B stage ( n=35), G4 stage ( n=39)and G5 stages( n=33). The relationship between RBP, SDF-1 and renal function index UACR, serum uric acid (UA), blood urea nitrogen (BUN), β 2-microglobulin (β 2-MG) and serum creatinine (Scr) was analyzed. Measurement data of normal distribution were expressed as Mean± standard deviation ( Mean± SD). Independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups.Chi-square test was used to compare the enumeration data between groups. Receiver operating characteristic curve (ROC) was used to analyze the discriminant value of RBP and SDF-1 for DKD. Pearson was used for correlation analysis among indicators. Multivariate linear regression analysis was used to analyze the influencing factors of RBP. Results:In the DKD group, the duration of diabetes was longer, the levels of RBP, UACR, UA, BUN, β 2-MG, Scr were high, SDF-1 and eGFR were lower, with statistically significant differences compared with the simple T2DM group( P<0.05).The areas under the curve of RBP and SDF-1 to distinguish DKD were 0.903 and 0.868, and the optimal cut-off values was 70.71 mg/L and 5.69 ng/mL. With the increase of urinary albumin and clinical stage, the levels of RBP, UACR, UA, BUN, β 2-MG, Scr increased gradually, while SDF-1 and eGFR decreased gradually, and the differences were statistically significant ( P<0.05).RBP was positively correlated with UACR, UA, BUN, β 2-MG and Scr in DKD patients ( r=0.764, 0.787, 0.693, 0.577, 0.801, P<0.000 1), and negatively correlated with EGFR ( r=-0.782, P<0.000 1). SDF-1 was negatively correlated with UACR, UA, BUN, β 2-MG and Scr ( r=-0.744, -0.794, -0.666, -0.605, -0.820, P<0.000 1), and positively correlated with EGFR ( r=0.767, P<0.000 1). The multiple linear regression equation was RBP=29.852+ 0.007UACR+ 0.101UA+ 0.497BUN+ 0.034Scr-0.083eGFR ( P<0.001). Conclusion:RBP and SDF-1 have certain discriminant value for DKD patients in T2DM population, and the degree of DKD renal function injury is positively correlated with RBP and negatively correlated with SDF-1, the increase of UACR, UA, BUN, Scr and the decrease of eGFR are risk factors for the increase of RBP.
10.Correction to: Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg mice.
Yaqin DU ; Ting WANG ; Jun XU ; Chaoran ZHAO ; Haibo LI ; Yao FU ; Yaxing XU ; Liangfu XIE ; Jingru ZHAO ; Weifeng YANG ; Ming YIN ; Jinhua WEN ; Hongkui DENG
Protein & Cell 2019;10(2):154-155
In the original publication Fig. 1D and supplementary material is incorrect. The correct figure and supplementary material is provided in this correction.

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