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.Mediating role of health education competency in the relationship between supportive communication and general self-efficacy among medical undergraduates
Hui YIN ; Wenxuan LI ; Ying ZHANG ; Yuchun TAO ; Zehui LI ; Wei LIU ; Zuoming ZHANG ; Limin WANG ; Depin CAO
Chinese Journal of Medical Education Research 2024;23(3):347-352
Objective:To explore the factors influencing the supportive communication ability of medical undergraduates, and to propose strategies to improve supportive communication.Methods:By cluster sampling, we selected 388 medical undergraduates of grades 2017 and 2018 from Harbin Medical University for a questionnaire survey on supportive communication, general self-efficacy, and health education abilities. SPSS 22.0 was used for descriptive statistical analysis. AMOS 22.0 was used to construct a structural equation model to verify the relationship between the three variables. Mediating effects were also tested.Results:The students showed good supportive communication ability, with a total score of (74.28±10.84) points. The general self-efficacy score was (27.81±5.58) points, and the total score of health education ability was (25.50±4.76) points. General self-efficacy had direct positive effects on supportive communication and health education abilities ( β=0.75, 0.31, both P<0.001). Health education ability had a direct positive effect on supportive communication ability ( β=0.14, P<0.001). Health education ability played a significant mediating role in the influence of general self-efficacy on supportive communication ability (standardized mediating effect value=0.042, P<0.01), with the mediating effect accounting for 5.1%. Conclusions:The health education competency of medical undergraduates can mediate the effect of general self-efficacy on supportive communication ability. By strengthening medical humanities education to increase general self-efficacy and also emphasizing the cultivation of health education competency, the supportive communication ability of students can be improved.
4.Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021
Ni CHEN ; He JIANG ; Huanhuan CHEN ; Qiuying ZHU ; Xiuling WU ; Jianjun LI ; Nengxiu LIANG ; Qin MENG ; Xuanhua LIU ; Jinghua HUANG ; Wenxuan HOU ; Zhaoquan WANG ; Guanghua LAN
Chinese Journal of Epidemiology 2024;45(4):529-535
Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.
5.Analysis on disease burden of digestive system cancers in population in China
Zhangyan LYU ; Wenxuan LI ; Guojin SI ; Yacong ZHANG ; Mengbo XING ; Yubei HUANG ; Ben LIU ; Fangfang SONG ; Fengju SONG ; Kexin CHEN
Chinese Journal of Epidemiology 2024;45(5):633-639
Objective:To explore the incidence and mortality of digestive system cancers, and the trend of the disease burden attributed to different risk factors in population in China.Methods:Data were obtained from the GLOBOCAN 2020 and the Global Burden of Disease Study in 2019 databases and only the data from the Chinese population were included. Using Excel 2019 and R 4.2.1 software, indicators including age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life year (DALY) rate and its rate of change were used to illustrate the disease burden of digestive system cancers attributed to different factors and their trends.Results:In 2020, the ASIR of digestive system cancers in China was 83.00/100 000, and the ASMR was 63.80/100 000. The numbers of digestive system cancer cases and deaths increased with age, and more cases and deaths occurred in men than in women in all age groups. The age-standardized DALY rate of esophageal cancer, gastric cancer and liver cancers showed decreasing trends in China from 1990 to 2019 (rate of change: -45.26%, -46.87%, and -65.63%, respectively), whereas the age-standardized DALY rate of pancreatic cancer, colorectal cancer and gallbladder and biliary tract cancer showed increasing trends (rate of change: 67.61%, 30.52%, and 7.21%, respectively). The trend of the mortality rate was consistent with the DALY rate. Compared with the age-standardized DALY rate attributed to behavioral factors, the annual proportion of the age-standardized DALY rate attributed to metabolic factors to the total age-standardized DALY rate of esophageal cancer, liver cancer, pancreatic cancer, and colorectal cancer increased from 1990 to 2019. There was no significant change in the rank of age-standardized DALY rate of gastric cancer, liver cancer, pancreatic cancer, and gallbladder and biliary tract cancer attributed to different risk factors in China from 1990 to 2019, but the rank of certain attributed risk factors for the age-standardized DALY rate of esophageal cancer and colorectal cancer moved ahead (esophageal cancer: high BMI; colorectal cancer: low milk intake, and low whole-grain intake).Conclusions:The incidence and mortality of digestive system cancers was serious in China in 2020, and the annual proportion of the disease burden of digestive system cancers attributed to metabolic factors increased from 1990 to 2019. The rank of attributed risk factors for several digestive system cancers changed significantly.
6.A cortical thickness study of insomnia disorder patients based on MRI
Wei CHEN ; Hui WANG ; Ziyi LIU ; Yu SHANG ; Haining LI ; Wenxuan HAN ; Qiange ZHU ; Ming ZHANG
Journal of Practical Radiology 2024;40(11):1766-1769
Objective To investigate the changes of cortical thickness in patients with insomnia disorder(ID).Methods High-resolution MRI data were collected from 32 ID patients(ID group)and 30 healthy controls(HC)(HC group).The cortical thickness of both groups were analyzed using statistical parametric mapping 12(SPM12)software,while considering age,gender,and educational level as covariates.The cortical thickness in brain regions showed statistically significant differences was extracted for Pearson's correla-tion analyses with sleep and mood-related scales.Results Compared with the HC group,the ID group exhibited significantly decreased cortical thickness in brain regions such as the left insula,fusiform gyrus,orbitofrontal lobe,superior temporal gyrus,middle temporal gyrus,lateral occipital lobe and right caudal anterior cingulate gyrus[P<0.05,family-wise error(FWE)correction].Furthermore,reduced cortical thickness of the cingulate gyrus was negatively correlated with the Pittsburgh sleep quality index(PSQI)score(r=-0.437,P=0.012).Conclusion The cortical thickness of several brain regions associated with sleep and mood are significantly reduced in patients with ID,providing potential neuroimaging evidence for understanding the pathophysiological mechanism of ID.
7.The current state of sunscreen development and analysis of its scientific application and safety
Shaomin ZHONG ; Yuchen TANG ; Wenxuan ZHANG ; Yan WU ; Hang LI
Chinese Journal of Preventive Medicine 2024;58(11):1771-1776
Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.
8.Investigation on psychological status of nursing staff in the hemodialysis units and analysis of influential factors
Yinghua LI ; Wenxuan ZHANG ; Suiqin WEN ; Xiaoqing YE ; Raoping WANG
Chinese Journal of Nephrology 2024;40(11):858-867
Objective:To investigate the psychological status of HD nursing staff in hospitals in Guangdong province and its influential factors.Methods:1 630 nursing staff in HD rooms of 71 hospitals or units in Guangdong Province in February and March 2020 were evaluated by using the 10-item Kessler psychological distress scale (Kessler 10), General self-efficacy scale (GSES) and Connor-Davidson resilience scale (CD-RISC) to conduct a questionnaire survey on their psychological status. Insomnia severity index (ISI) and Fatigue scale-14 (FS-14) were used to investigate their degree of insomnia and fatigue. General information on gender, age, educational level, marital status, economic income, professional title, HD working hours, average weekly overtime times and hours, total number of HD patients per day, and whether holding other positions were collected.Results:A total of 1 630 questionnaires were collected, among which 1 629 were valid, with an effective recovery rate of 99.9%. The scores of the three scales were (20.16±7.47), (27.03±4.45) and (58.37±15.75), respectively. According to the Kessler 10, 835 people (51.2%) had mental disorders. Univariate analysis showed that age, educational level, economic income, type of work unit, total number of HD patients per day and living status in recent one week were related with Kessler 10 score (all P<0.05). Economic income, type of work unit, whether holding other positions, total number of HD patients per day and living status in recent one week were related with GSES scores (all P<0.05). Age, marital status, economic income, professional title, type of work unit, whether holding other positions and living status in recent one week were related to CD-RISC score (all P<0.05). Spearman rank correlation analysis showed that the number of HD machines ( r=0.100, P<0.001), the number of nurses ( r=0.082, P=0.001), average weekly overtime times ( r=0.142, P<0.001) and overtime hours ( r=0.136, P<0.001), ISI score ( r=0.572, P<0.001) and FS-14 score ( r=0.635, P<0.001) were correlated with Kessler 10 score. ISI score ( r=-0.311, P<0.001) and FS-14 score ( r=-0.335, P<0.001) were correlated with GSES score. Working years of HD service ( r=0.112, P<0.001), ISI score ( r=-0.289, P<0.001) and FS-14 score ( r=-0.314, P<0.001) were correlated with CD-RISC score. Multiple linear regression analysis showed that the economic income in 5 001-10 000 yuan (with<3 000 yuan as reference, B=-1.603, 95% CI -3.036--0.169, P=0.028) and the total number of HD patients per day >200 (with ≤50 as reference, B=-1.153, 95% CI -2.242--0.065, P=0.038) were negatively correlated with Kessler 10 score, and average weekly overtime times ( B=0.221, 95% CI 0.069-0.374, P=0.004), ISI score ( B=0.518, 95% CI 0.454-0.582, P<0.001) and FS-14 score ( B=1.166, 95% CI 1.066-1.265, P<0.001) were positively correlated with Kessler 10 score. The economic income (with<3 000 yuan as reference) in 3 001-5 000 yuan ( B=1.930, 95% CI 0.847-3.013, P<0.001), 5 001-10 000 yuan ( B=1.949, 95% CI 0.887-3.012, P<0.001), 10 001-15 000 yuan ( B=1.482, 95% CI 0.318-2.647, P=0.013), >20 000 yuan ( B=4.300, 95% CI 2.463-6.136, P<0.001), secondary hospital (with primary hospitals as reference, B= 1.078, 95% CI 0.005-2.152, P=0.049) and holding other positions ( B=0.729, 95% CI 0.277-1.181, P=0.002) were positively correlated with GSES score, and ISI score ( B=-0.169, 95% CI -0.217--0.120, P<0.001) and FS-14 score ( B=-0.403, 95% CI -0.478--0.328, P<0.001) were negatively correlated with GSES score. The economic income (with<3 000 yuan as reference) in 3 001-5 000 yuan ( B=7.631, 95% CI 3.753-11.509, P<0.001), 5 001-10 000 yuan ( B=9.236, 95% CI 5.362-13.110, P<0.001), 10 001-15 000 yuan ( B=9.039, 95% CI 4.735-13.342, P<0.001), 15 001-20 000 yuan ( B=8.639, 95% CI 2.989-14.289, P=0.003), >20 000 yuan ( B=16.101, 95% CI 9.162-23.039, P<0.001) and holding other positions ( B=3.228, 95% CI 1.510-4.945, P<0.001) were positively correlated with CD-RISC score, and ISI score ( B=-0.593, 95% CI -0.765--0.420, P<0.001) and FS-14 score ( B=-1.258, 95% CI -1.525--0.992, P<0.001) were negatively correlated with CD-RISC score. Conclusion:The psychological status of nursing staff in HD rooms of hospitals in Guangdong Province needs to be improved. Effective preventive measures should be taken to provide timely psychological support, counseling and intervention to nursing staff with psychological abnormalities, and encourage them to take the initiative to seek psychological counseling when necessary, so as to promote their physical and mental health.
9.Research advances on the regulation of microglia polarization by autophagy in ischemic stroke
Fangming WANG ; Wenxuan SHANG ; Jingwen ZHANG ; Yingxiao JI ; Litao LI
The Journal of Practical Medicine 2024;40(9):1324-1330
Ischemic stroke is feature by high incidence,high disability and high mortality.Inflammation plays an important role in the occurrence and development of ischemic stroke.Activated microglia exhibit two different phenotypes of proinflammatory(M1)and anti-inflammatory(M2),and regulating the transformation of microglia from M1 to M2 is the key to clinical benefit.Recent studies have shown that autophagy plays a key role in regulating phenotypic transformation of microglia.How to exert the regulatory role of autophagy and promote the transformation of microglia into M2 type has become a hotspot of clinical research in reducing secondary brain injury after stroke.This paper reviews the research progress of autophagy regulation of microglia polarization in ischemic stroke,aim-ing to provide a reference for further clinical and basic research in this field.
10.Ceria nanoparticles:biomedical applications and toxicity
FU XIAOXUAN ; LI PENG ; CHEN XI ; MA YUANYUAN ; WANG RONG ; JI WENXUAN ; GU JIAKUO ; SHENG BOWEN ; WANG YIZHOU ; ZHANG ZHUHONG
Journal of Zhejiang University. Science. B 2024;25(5):361-388
Ceria nanoparticles(CeO2 NPs)have become popular materials in biomedical and industrial fields due to theirpotential applications in anti-oxidation,cancer therapy,photocatalytic degradation of pollutants,sensors,etc.Many methods,including gas phase,solid phase,liquid phase,and the newly proposed green synthesis method,have been reported for the synthesis of CeO2 NPs.Due to the wide application of CeO2 NPs,concerns about their adverse impacts on human health have been raised.This review covers recent studies on the biomedical applications of CeO2 NPs,including their use in the treatment of various diseases(e.g.,Alzheimer's disease,ischemic stroke,retinal damage,chronic inflammation,and cancer).CeO2 NP toxicity is discussed in terms of the different systems of the human body(e.g.,cytotoxicity,genotoxicity,respiratory toxicity,neurotoxicity,and hepatotoxicity).This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

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