1.Jujuboside A Improves Cognitive Function in Rat Model of VCI via PI3K/Akt Signaling Pathway
Zixuan HUANG ; Shuo YANG ; Jiaqi ZHOU ; Gengchao ZHANG ; Qiuyun YOU ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):107-114
ObjectiveTo investigate the effects of jujuboside A (JuA) on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment (VCI) and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group (n=10), a blank control group (n=10), and a modeling group (n=30). The rats in the modeling group underwent bilateral carotid artery ligation (2-VO) for the modeling of VCI. After stabilization, the VCI rats were randomized into model, JuA (20 mg·kg-¹), and donepezil (0.45 mg·kg-¹) groups. After 4 weeks of gavage, the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β (GSK-3β), cAMP response element-binding protein (CREB), B cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β, p-GSK-3β, p-CREB, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group, the model group exhibited declines in the learning and memory abilities (P<0.01), neuronal damage and decreased neurons in the hippocampal CA1 region (P<0.01), up-regulation in the mRNA level of GSK-3β (P<0.01), and down-regulation in the mRNA levels of PI3K, Akt, CREB, and Bcl-2, as well as the protein levels of p-PI3K, p-Akt, p-GSK-3β, p-CREB, and Bcl-2 (P<0.01). In comparison to the model group, both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities (P<0.05, P<0.01), with reduced neuronal damage and increased neurons (P<0.05, P<0.01). In addition, the two groups showed down-regulation in the mRNA level of GSK-3β (P<0.01) and up-regulation in the mRNA levels of PI3K, Akt, CREB, and Bcl-2 and the protein levels of p-PI3K, p-Akt, p-GSK-3β, p-CREB, and Bcl-2 (P<0.05, P<0.01). There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities, neuron count, and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway, reducing the apoptosis of hippocampal neurons, and alleviating the hippocampal neuronal damage.
2.Jieduan Niwan Formula regulates AMPK to alleviate mitochondrial damage in HepG2 cells
Ruimin MA ; Hanjing WANG ; Wenxin ZHANG ; Chongyang MA ; Qiuyun ZHANG ; Yuqiong DU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):193-204
Objective:
To investigate the regulatory effect of Jieduan Niwan Formula (JDNWF) drug-containing serum on AMPK-mediated mitochondrial quality control in D-GalN-induced HepG2 cells.
Methods:
Twenty male Wistar rats were randomly divided into blank control and JDNWF-containing serum groups, 10 rats per group. The JDNWF-containing serum group was gavaged with JDNWF (21.7 g/kg), whereas the blank control group was gavaged with saline. Blood was collected to prepare JDNWF-containing and blank control serum. Cell viability, mitochondrial damage indicators, and MQC pathway protein expression levels were evaluated to determine the optimal volume fraction of JDNWF. HepG2 cells were divided into control, D-GalN, DMSO, AMPK inhibitor, JDNWF drug-containing serum, and JDNWF drug-containing serum plus AMPK inhibitor groups, and corresponding drug interventions were administered to each group. Cells were collected after the interventions, and the CCK-8 assay was used to measure cell viability, the 2′-7′-dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) levels, JC-1 was used to detect mitochondrial membrane potential, thiobarbituric acid was used to measure malondialdehyde (MDA) levels, WST-8 was used to measure superoxide dismutase (SOD) activity, and western blotting was used to detect the expression levels of mitochondrial quality control-related proteins, including p-AMPK, AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1.
Results:
5% JDNWF drug-containing serum most significantly restored cell viability, mitochondrial damage markers, and MQC pathway protein expression in the model group. Therefore, it was chosen for intervention in subsequent experiments. Compared to the control group, the cell viability of the D-GalN, DMSO, and AMPK inhibitor groups was significantly reduced (P<0.01). In contrast, the heterogeneity of mitochondrial membrane potential, ROS, and MDA levels was significantly increased (P<0.01), and SOD activity was significantly decreased (P<0.01). The p-AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1 protein expression levels were significantly decreased (P<0.01). After JDNWF drug-containing serum intervention, compared to the DMSO group, cell viability significantly increased (P<0.01), mitochondrial membrane potential heterogeneity, ROS, and MDA levels significantly decreased (P<0.01), SOD activity significantly increased (P<0.01), and p-AMPK, PGC-1α, NRF1, TFAM, and MFN2 protein expression levels significantly increased (P<0.01), whereas DRP1 protein expression significantly decreased (P<0.01). Compared to the JDNWF drug-containing serum group, the cell viability in the JDNWF plus AMPK inhibitor group significantly decreased (P<0.01), mitochondrial membrane potential heterogeneity and ROS levels significantly increased (P<0.01), MDA levels significantly increased (P<0.05), SOD activity significantly decreased (P<0.05), p-AMPK, PGC-1α, NRF1, and TFAM protein expression levels significantly decreased (P<0.01), MFN2 protein expression significantly decreased (P<0.05), and DRP1 protein expression significantly increased (P<0.01).
Conclusion
JDNWF drug-containing serum may restore mitochondrial function and improve D-GalN-induced HepG2 cell injury by regulating AMPK-mediated mitochondrial quality control.
3.Analysis on the Medication Law of Qian Ying in Treatment of Primary Liver Cancer Based on Data Mining
Haitian ZHANG ; Chongyang MA ; Weixin HOU ; Bo DOU ; Xian FANG ; Xuejiao JIANG ; Peng FANG ; Jiajun LIANG ; Xiaoyi WEI ; Wenhan HU ; Qiuyun ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(8):52-57
Objective To study the medication law of Professor Qian Ying in the treatment of primary liver cancer based on data mining technology;To provide ideas for the clinical treatment of primary liver cancer.Methods Outpatient TCM prescriptions of Professor Qian Ying for the treatment of liver cancer from November 2008 to August 2020 were collected,and a data table was established after sorting.The drug frequency,property and taste and tropism were analyzed using Excel 2019.The medical case analysis module of the Great Physician Inheritance Platform was used to analyze the core drugs,the symbiosis analysis between drug pairs,the drug association analysis,and the drug clustering analysis of the screened TCM prescriptions.Results Totally 108 prescriptions were included,involving 188 kinds of Chinese materia medica,with a total frequency of 1 322 times.High-frequency drugs included Hedyotis Sinensis,Angelicae Sinensis Radix,Visci Herba,Curcumae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.The medicinal properties were mainly cold,mild and warm,and the tastes were mainly bitter,sweet and pungent,and the main meridians were liver meridians,spleen meridians,kidney meridians and stomach meridians.There were 9 pairs of high frequency drug combinations in drug association,such as Curcumae Radix-Polygoni Orientalis Fructus,Visci Herba-Curcumae Rhizoma.In the correlation analysis of drug disease,the ones with higher correlations include"stomachache-Salviae Miltiorrhizae Radix et Rhizoma""abdominal mass-Paeoniae Radix Rubra and Citri Reticulatae Pericarpium""tinnitus-Adenophorae Radix,Lycii Fructus,Visci Herba""prolonged sublingual collaterals-Curcumae Rhizoma,Polygoni Orientalis Fructus,Salviae Miltiorrhizae Radix et Rhizoma"and so on.Drug clustering could be divided into three potential drug clusters.Conclusion Professor Qian Ying often uses heat-clearing drugs,tonifying drugs,and promoting qi and blood circulation drugs to treat liver cancer,with Huqi Powder as the main formula and modified according to the syndromes.Clearing heat and detoxifying,soothing liver and relieving depression,removing blood stasis and regulating collatrals are used to treat its symptoms,and tonifying qi and invigorating spleen,regulating liver and nourishing liver and kidney are used to treat its essence.
4.Study on Medication Law of Qian Ying for the Treatment of Chronic Hepatitis B Based on Data Mining
Wenhan HU ; Chongyang MA ; Xuejiao JIANG ; Jiajun LIANG ; Qiuyun ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):59-64
Objective To analyze the medication law and academic thoughts of national TCM master Qian Ying in the treatment of chronic hepatitis B through data mining.Methods Totally 168 cases of chronic hepatitis B treated by Professor Qian Ying from Mar.2000 to Dec.2020 were retrospectively collected,and the properties,tastes and tropism meridians,core prescriptions and drug groups of the prescription drugs were analyzed by using the famous doctor inheritance platform.Results Totolly 168 medical cases involved 168 patients and 227 kinds of Chinese materia medica,with a total frequency of 2 158 times.The characteristics of properties,tastes and tropism meridians showed that the main property was cold,and the main taste was bitter,and the main meridian was liver meridian.34 kinds of high-frequency Chinese materia medica(mainly were tonics,heat-clearing medicines,and medicines for activating blood circulation and reducing stasis),28 kinds of core Chinese materia medica,10 pairs of highly co-occurring drugs,and 10 potential drug groups were mined.Conclusion Professor Qian Ying believes that the pathogenesis of chronic hepatitis B is deficiency in nature and excess in superficiality,and the treatment focuses on tonifying deficiency.It is often treated from the liver and emphasizes the harmonization of liver,spleen and kidney.Tonifying deficiency,clearing heat,promoting blood circulation and removing blood stasis are the main treatment methods,followed by dispelling dampness,promoting qi,eliminating phlegm,opening stagnation and relieving the exterior,etc.He pays attention to the harmonization of body and use,is good at using multiple methods.
5.Validity of questionnaires in screening chronic obstructive pulmonary disease in communities of Shanghai
Qundi YANG ; Danni LIU ; Qiuyun SU ; Xiaoxia LIU ; Xin ZHANG ; Cui WU ; Xuena LA ; Yang ZHENG ; Yan SHI
Shanghai Journal of Preventive Medicine 2024;36(12):1118-1123
ObjectiveTo evaluate the validity of four screening questionnaires on chronic obstructive pulmonary disease (COPD) among community residents in Shanghai, and to provide a scientific basis for selecting suitable screening questionnaires and plans for the community use. MethodsA multi-stage random sampling method was used to select community residents aged ≥40 for COPD questionnaire screening and spirometry. The screening questionnaires included the COPD Population Screener Questionnaire (COPD-PS), the COPD Screening Questionnaire (COPD-SQ), the COPD Diagnosis Questionnaire (CDQ), and the Lung Function Questionnaire (LFQ). The diagnostic gold standard for COPD was defined as a ratio of post-bronchodilator forced expiratory volume in one second to forced vital capacity (FEV1/FVC) less than 0.7. The receiver operating characteristic (ROC) curve was used to assess the validity of each questionnaire, and DeLong’s test was used to compare the area under the curve (AUC) of different questionnaires. ResultsAmong the 1 122 residents screened, 99 (8.8%) were diagnosed with COPD based on the gold standard criteria. The AUC values for the four questionnaires ranged from 0.643 to 0.682, with no statistically significant differences in screening accuracy among them (P>0.05). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each questionnaire at recommended cut-off points were as follows: COPD-PS (sensitivity: 33.3%, specificity: 84.9%, PPV: 17.6%, NPV: 92.9%), COPD-SQ (34.3%, 85.8%, 19.0%, 93.1%), CDQ (73.7%, 42.4%, 11.0%, 94.4%), and LFQ (48.5%, 74.8%, 15.7%, 93.8%). Optimal cut-off values for this population differed from the recommended values. When selecting the optimal cut-off value, the sensitivity of COPD-PS (58.6%), COPD-SQ (55.6%), and LFQ (64.7%) increased, while the specificity of CDQ (75.9%) increased. The AUC of sequential lung function testing for all four screening questionnaires increased to 0.7 or above. The optimal cut-off values for the four questionnaires in this population differed from the recommended values. When applying the optimal cut-off values, the sensitivity of three questionnaires increased: COPD-PS (58.6%), COPD-SQ (55.6%), and LFQ (64.7%), while the specificity of CDQ rose to 75.9%. The AUC of each questionnaire increased to above 0.7 when followed by sequential lung function testing. ConclusionThe COPD-PS, COPD-SQ, CDQ, and LFQ have limited value for COPD screening among Shanghai community residents, indicating that further refinement of these tools is needed.
6.Milk consumption behavior and its impact on bone mineral density among 696 pupils in Hainan Province
Chinese Journal of School Health 2023;44(11):1631-1635
Objective:
To investigate the milk drinking behavior and bone mineral density level of pupils in Hainan Province, and to explore the correlation between bone mineral density and milk drinking behavior, in order to provide scientific basis for promoting the healthy development of bones in children and adolescents.
Methods:
In November 2021, a cross sectional survey including demographic characteristics, milk intake, unhealthy eating behavior, physical activity and sleep was conducted among 696 students from grades 3 to 5 in Sanya and Baisha, Hainan by stratified cluster random sampling, and bone mineral density at the distal 1/3 of the right forearm was measured by dual energy X-ray absorptiometry. t-test was used to compare the differences in bone mineral density among different milk drinking behaviors of pupils, and multiple linear regression was used to analyze the correlation between milk consumption and bone mineral density.
Results:
About 25.3% students consumed milk daily and 13.9% consumed ≥ 300 g of milk daily. The mean bone mineral density at the distal 1/3 of the right forearm was (0.237±0.041)g/cm 2. The bone mineral density was greater in the group with daily milk intake than in the group without daily milk intake [(0.250± 0.037 )(0.204±0.034) g/cm 2 , t=15.00, P <0.01], and the bone mineral density was greater in the group with daily average milk intake ≥300 g than in the group with daily average milk intake <300 g [(0.284±0.036)(0.229±0.037)g/cm 2, t=13.48, P < 0.01 ]. Multiple linear regression analysis showed that daily average milk intake was positively correlated with bone mineral density, with a correlation coefficient ( β=0.020, t=21.46, P <0.01).
Conclusion
Milk consumption among pupils is inadequate, and milk drinking behavior has a positive impact on bone mineral density, so effective milk drinking intervention should be carried out to promote children s bone development.
7.Impacts of cadmium on mouse neural stem cells based on dose-response metabomics
Yixi LI ; Jiming ZHANG ; Qiuyun GU ; Zheng WANG ; Bing ZHANG ; Zhijun ZHOU ; Xiuli CHANG
Journal of Environmental and Occupational Medicine 2023;40(8):892-899
Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl2 at designed doses (0, 0.5, 1.0, and 1.5 μmol·L−1). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L−1 dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.
8.Comparison in Dosage of General Anesthetics in Patients from Different Regions of Xinjiang
Zhao ZHANG ; Mingcheng LI ; Qiuyun WANG
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2023;52(6):855-857
Objective To compare the difference in dose of general anesthesia between pastoral patients and urban pa-tients.Methods The patients who performed abdominal surgery under general anesthesia in Peoples hospital of Bortala Mongo-lian Autonomous Prefecture from January 1st to April 30th 2022 were included and divided into pastoral patient group and ur-ban patient group according to the residential place of patients.Anesthesia and surgery were carried out according to hospital regulations.The general characteristics of all patients were recorded and the dosages of general anesthesia drugs were compared between the two groups.Results There was no significant difference between the two groups in general and intraoperative con-ditions.Patients'performances were stable,and no severe adveres reaction was observed.The dosages of Propofol,Remifen and Rocuronium in pastoral patients were higher than that in urban patients(all P<0.05).Conclusion The dosage of general anes-thesia for patients in pastoral areas is higher,which ensures the stability of anesthesia depth and vital signs of patients,creates good conditions for surgery and promotes rapid recovery of patients.
9.A novel
Jinqin CHEN ; Xinhong LIU ; Shuo YU ; Jia LIU ; Rongfang CHEN ; Yunxiao ZHANG ; Ling JIANG ; Qiuyun DAI
Acta Pharmaceutica Sinica B 2021;11(9):2685-2693
10.Effects of different feeding patterns on mother-to-child transmission of HBV infections in pregnant women with high viral loads after antiviral medication during pregnancy: A prospective cohort study
Ruihua TIAN ; Xingming LI ; Gaofei LI ; Qiuyun LI ; Yuzhen ZHANG ; Jing LYU ; Biyun XU ; Yanxiang HUANG ; Junmei CHEN ; Yunxia ZHU ; Yihua ZHOU
Chinese Journal of Perinatal Medicine 2021;24(7):497-502
Objective:To study the influence of different feeding patterns on mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with high viral loads who received antiviral medication during pregnancy to the day of delivery.Methods:This prospective cohort study was conducted in Beijing You'an Hospital. From January 1, 2019, to March 31, 2020, and 574 pregnant women with positive hepatitis B surface antigen (HBsAg) and HBV DNA>2×10 5 IU/ml were enrolled. All participants received tenofovir, telbivudine, lamivudine, or propofol tenofovir from 24-28 weeks of gestation and discontinued on the day of delivery, and their neonates were postnatally given routine passive-active immunoprophylaxis. Based on the feeding patterns, the subjects were divided into three groups: breastfeeding ( n=257), bottle-feeding ( n=241) and mixed feeding groups ( n=76). The follow-up data were obtained from liver functions and HBV DNA level of the mothers at 6-8 weeks postpartum and HBV serological markers of infants at 7-12 months. One-way ANOVA, Student-Newman-Keuls, Chi-square test or Fisher exact test, and repeated measures ANOVA were used to analyze the data. Results:The average maternal HBV DNA levels before antiviral treatment did not differ significantly between the three groups [(7.90±0.67), (7.82±0.70), (7.83±0.70) log 10 IU/ml, F=0.912, P>0.05]. HBV DNA level before delivery in the mixed feeding group was slightly lower than that in the breastfeeding and bottle-feeding group [(3.87 ±1.08) vs (4.21±1.17) and (4.30±1.28) log 10 IU/ml, q= 3.052 and 3.831, both P<0.05], while the comparison between the latter two groups showed no significant differences ( P>0.05). After delivery, HBV DNA level in the bottle-feeding group was slightly lower than that in the breastfeeding group [(7.42±0.93) vs (7.69±0.90) log 10 IU/ml, q=4.583, P<0.05]. Among 580 infants (including six pairs of twins), only one bottle-fed infant (0.4%, 1/243) was infected with HBV through MTCT, and none in the breastfeeding or mixed feeding group ( P=0.553). Conclusions:For pregnant women with high viral loads of HBV who have received antiviral medication during pregnancy, although HBV DNA level will rebound after discontinuation upon delivery, breastfeeding is recommended considering it does not increase the risk of MTCT.


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