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.Research progress in hydrogels in tissue engineering trachea
Wenxuan CHEN ; Yibo SHAN ; Fei SUN ; Zhiming SHEN ; Yi LU ; Jianwei ZHU ; Lei YUAN ; Hongcan SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1195-1199
In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.
4.Study on the improvement effects and mechanism of proanthocyanidins on steroid-induced osteonecrosis of the femoral head in rabbits
Chunli WU ; Liting LIU ; Xuting ZHAO ; Ruifen SUN ; Wenxuan WANG
China Pharmacy 2025;36(20):2519-2524
OBJECTIVE To study the improvement effects and mechanism of proanthocyanidins (PACs) on steroid-induced osteonecrosis of the femoral head (SONFH) in rabbits based on the receptor-interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling pathway. METHODS SONFH model in rabbits was induced by injecting Escherichia coli endotoxin+methylprednisolone. The successfully modeled rabbits were randomly divided into Model group (normal saline), low-dose PACs group (PACs-L group, 11 mg/kg), high-dose PACs group (PACs-H group, 22 mg/kg), high-dose PACs+ RIPK1 activator (rRIPK1) group (PACs-H+rRIPK1 group, 22 mg/kg PACs+4 μg/kg rRIPK1), along with a control group (normal saline), with 6 rabbits in each group. Each administration group was given relevant medicine once a day intragastrically/via injection, for 4 consecutive weeks. After the last administration, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rabbit serum were measured. The changes in the microstructure of rabbit femurs, including bone mineral density (BMD), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb. Sp) were examined. The histopathological features of rabbit femoral tissues were observed, and the apoptotic status of cells within the rabbit femoral tissues was detected. The mRNA expressions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) in rabbit femoral tissues were determined. The expressions of RIPK1/RIPK3/MLKL signaling pathway-related proteins in femoral tissues were detected. RESULTS Compared with the Control group, serum contents of TNF-α and IL-6, Tb.Sp, empty bone cavity rate, cell apoptosis rate, phosphorylation levels of RIPK1, RIPK3 and MLKL in femoral tissue were significantly increased in the Model group (P<0.05). BMD, Tb.Th, Tb.N, as well as the mRNA expression of VEGF and BMP2, along with protein expression of caspase-8, in the femoral tissues were all decreased (P<0.05). The bone cells in the femoral tissue were unevenly distributed, and the trabeculae were arranged sparsely. Compared with the Model group, the aforementioned quantitative indicators (P<0.05) and pathological changes in all dosage groups of PACs showed significant improvements. Compared with the PACs-H group, the aforementioned quantitative indicators (P<0.05) and pathological changes in the PACs-H+rRIPK1 group showed significant reversal. CONCLUSIONS PACs can ameliorate SONFH in rabbits, and its mechanism of action may be related to the inhibition of the activation of the RIPK1/RIPK3/MLKL signaling pathway, suppression of apoptosis in femoral tissue cells, and promotion of angiogenesis.
5.A preliminary investigation study of islet function assessment
Wenxuan BIAN ; Yunqiang HE ; Qi FU ; Shuang CHEN ; Min SUN ; Tao YANG
Chinese Journal of Diabetes 2024;32(3):161-168
Objective To investigate doctors'knowledge and differences in islet function assessment methods in China.Methods This is a cross-sectional study that conducted by online questionnaire survey.Demographic data,examination items,blood collection point of OGTT,detection method,kit type and follow-up frequency were collected and compared among doctors in different regions,different levels of hospitals,different specialties and different titles.Results 79.2%and 85.1%of physicians believed that the levels of insulin and C-peptide should be measured at the same time to assess islet function in patients with newly diagnosed and follow-up diabetes mellitus patients.Endocrinologists preferred to access insulin and C-peptide at the same time(P<0.05).56.0%of physicians chose bread meal test for T1DM patients and 54.7%for T2DM patients.Compared with non-specialists,endocrinologists preferred to commit bread meal test to T1DM patients(61.4%vs 41.0%,P<0.05).In addition,for the islet function assessment of new-onset diabetes patients,7.6%of physicians chose the six-point method(0,30,60,90,120,180 min),27.3%selected the five-point method I(0,30,60,120,180 min),8.5%selected the five-point method II(0,30,60,90,120 min),9.8%selected the four-point method I(0,30,60,120 min),10.3%selected the four-point method II(0,60,120,180 min),13.8%chose the three-point method(0,60,120 min)and 13.4%chose the two-point method(0,120 min).At the time of follow-up assessment,the above selection rates were 5.3%,20.4%,6.4%,6.6%,9.4%,15.8%and 24.1%,respectively.In terms of the frequency of assessment,39.2%of doctors assessed islet function once a year and 24.7%once every six months.Specialists preferred to assess islet function once a year,and physicians with senior titles chose to assess islet function more variably.Conclusion At present,there are still great differences in assessment methods of islet function in China.It is of great significance for the clinical diagnosis and treatment of diabetes to understand the differences in the selection of islet function assessment methods among doctors in different regions,specialties and job titles.
6.A bibliometric analysis of nanoparticles in the treatment of non-small cell lung cancer
Xiangyu XU ; Lei YUAN ; Fei SUN ; Zhiming SHEN ; Yibo SHAN ; Yi LU ; Jianwei ZHU ; Wenxuan CHEN ; Hongcan SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(08):1139-1147
Objective To analyze the current research application status and hotspots of nanoparticles in the treatment of non-small cell lung cancer (NSCLC) and predict the future development trend. Methods The Web of Science database was searched for literatures on nanoparticles use in the treatment of NSCLC from inception to November 2022. CiteSpace, VOSviewer and literature measurement analysis online platform (https://bibliometric.com/) were used for the visual analysis of the number of documents, source journals, authors, organizations, countries and keywords. Results A total of 742 English literatures were included. The results showed that the number of published literatures increased year by year from 2011 and reached the peak in 2020. Researches on nanoparticles and NSCLC treatment were mainly concentrated in China, the United States, India and Japan. China is a major research country in this field, but it lacked cooperation with other countries and related institutions. Among numerous research institutions, the Chinese Academy of Sciences was the authoritative and backbone force in this research field, with the number of published literatures ranking first and the research achievements outstanding. The keyword analysis found that "poly lactic-co-glycolic acid nanoparticles (PLGA NPs)" and "photothermal therapy" had become the latest breakout words since 2018. Moreover, the occurrence frequency of related keywords such as "drug delivery" increased significantly, indicating that the application of PLGA NPs in photothermal therapy might be the current research hotspot and future development trend of NSCLC treatment. Conclusion Currently, the domestic research on the treatment of nanoparticles and NSCLC is in a leading position in the world. The organic combination of nanoparticles with different materials and other NSCLC therapies is expected to improve the prognosis of NSCLC patients. In the future, attempts to develop nanoparticles with different sources and structures and combined with photothermal therapy for the treatment of NSCLC may become a research hotspot of nanoparticles in the treatment of NSCLC.
7.Meta-analysis of rehabilitation effect of Otago exercise in patients with limb dysfunction
Wenxuan SUN ; Li GAO ; Cuilian YANG ; Shuqin XIAO
Chinese Journal of Modern Nursing 2023;29(16):2197-2201
Objective:To systematically evaluate the rehabilitation effect of Otago exercise in patients with limb dysfunction.Methods:Randomized controlled trials and quasi trials on the rehabilitation effect of Otago exercise in patients with limb dysfunction were searched through computer on PubMed, Cochrane Library, Medline, Embase, Ovid, Scopus, China National Knowledge Infrastructure, VIP, and Wanfang Data. The search period was from the establishment of the database to July 31, 2022. Two researchers independently screened article, evaluated article quality, and extracted data. Meta-analysis was conducted using RevMan 5.3 software.Results:A total of 12 articles were included, including 682 patients with limb dysfunction. Meta-analysis results showed that compared with conventional physical therapy, Otago exercise could improve fall efficacy ( MD=8.64, 95% CI: 7.08-10.20, P<0.01) and balance ability ( MD=2.90, 95% CI: 0.72 -5.08, P<0.01) of patients with limb dysfunction. Conclusions:Otago exercise can improve fall efficiency and balance ability of patients with limb dysfunction, and has a positive impact on patients' limb function rehabilitation.
8.A preliminary experience of retroperitoneal approach by partial resection of the tenth rib for repairing Crawford type Ⅳ thoracoabdominal aortic aneurysm and complex abdominal aortic aneurysm
Wenxuan XIANG ; Xiaoning SUN ; Fangda LI ; Hui ZHANG ; Lei WANG ; Rong ZENG ; Xiao DI ; Xiaolong LIU ; Zijian WANG ; Yuehong ZHENG
Chinese Journal of General Surgery 2023;38(7):496-499
Objective:To evaluate a surgical approach for partial resection of the tenth rib through a retroperitoneal approach for the exposure of Crawford type IV thoracoabdominal aortic aneurysm and complex abdominal aortic aneurysm from 2014 to 2019.Methods:A retrospective analysis was conducted on clinical data and follow-up results of 7 patients who underwent treatment for Crawford type IV thoracoabdominal aortic aneurysm and complex abdominal aortic aneurysm through partial resection of the tenth rib via a retroperitoneal approach.Results:One case (14.3%) had associated Marfan syndrome, and 5 cases (71.4%) underwent left renal artery reconstruction. None of the patients experienced severe complications such as cardiopulmonary complications or renal failure postoperatively, and there was no statistically significant difference in serum creatinine levels between preoperative and postoperative stages during hospitalization ( P=0.205). Follow-up examinations showed no long-term vascular stenosis. Conclusions:Partial resection of the tenth rib through a retroperitoneal approach can avoid incisions of the pleura and diaphragm. It allows for the exposure of the aorta below the diaphragm and has the ability to treat aortic diseases below the diaphragm with smaller incisions and lower complication risks.
9.Impact of Roux-en-Y reconstruction with isolated pancreatic drainage on delayed gastric emptying after pancreaticoduodenectomy
Shaohong WANG ; Wenxuan ZHANG ; Shigang GUO ; Chunmin NING ; Aolei LI ; Xinliang KONG ; Xiangtao WANG ; Shangsheng LI ; Shan KE ; Jun GAO ; Jian KONG ; Qiang LI ; Wenbing SUN
Chinese Journal of Hepatobiliary Surgery 2021;27(6):415-420
Objective:To study the impact of Roux-en-Y reconstruction with isolated pancreatic drainage (RYR) on delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD).Methods:The data of 203 patients who underwent PD at 5 clinical centers from January 2014 to June 2020 were collected. According to the method of reconstruction of the digestive tract, the patients were divided into the RYR group ( n=88) and the conventional loop reconstruction (CLR) group ( n=115). The incidence and severity of DGE were compared between groups. The risk factors of clinically relevant DGE (CR-DGE) after PD were analysed by univariate and multivariate analyses. Results:Of 203 patients, there were 124 males and 79 females, aged (61.6±10.2) years. The overall incidence of DEG was 27.6% (56/203). The incidence of CR-DGE in the RYR group was significantly lower than that in the CLR group [13.6%(12/88) vs 26.1%(30/115), P=0.030]. Patient age of more than 65 years ( OR=2.966, 95% CI: 1.162-8.842, P=0.024), clinically relevant pancreatic fistula ( OR=3.041, 95% CI: 1.122-8.238, P=0.029), ascites and abdominal infection ( OR=10.000, 95% CI: 2.552-39.184, P=0.001), and CLR ( OR=3.206, 95% CI: 1.162-8.842, P=0.024) were identified as independent risk factors for CR-DGE. The duration of hospitalization and hospital expenditure of patients were significantly increased in the CR-DGE group ( P<0.05). Conclusions:Patients over 65 years with clinically relevant pancreatic fistula, with ascites or abdominal infection after operation, had a higher evidence of CR-DGE. Roux-en-Y reconstruction with isolated pancreatic could helped to decrease the incidence of CR-DGE after PD.
10. Research Status of Exosomes and Pathogenesis of Inflammatory Bowel Disease
Xiangdian BU ; Baoyue LI ; Wenxuan CHEN ; Dandan WANG ; Yaxing SUN ; Baisui FENG
Chinese Journal of Gastroenterology 2020;25(12):749-753
Exosomes are extracellular vesicles with a diameter of 30-150 nm, which exist in multi-vesicular bodies in the form of intraluminal vesicles. Exosomes can be secreted by a variety of immune cells. Studies have shown that exosomes might play an important role in IBD through their components, such as annexin-A1 (ANXA1), the miRNAs and lipids. As a carrier of antigen presentation, it can affect the signaling pathways related to IBD, regulate the immune response and intestinal homeostasis. This article reviewed the relationship between exosomes and IBD.

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