1.Effects of vitamin D mediated MEK/ERK pathway on myocardial damage in rats with gestational diabetes mellitus
Er-Xia JIA ; Na XU ; Shuai LI ; Qiu-Fang SHU
The Chinese Journal of Clinical Pharmacology 2024;40(7):1014-1018
Objective To investigate the effects of vitamin D mediated mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK)pathway on myocardial injury in rats with gestational diabetes mellitus.Methods Fifty SD rats were divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,and the gestational diabetes rat model was established.After successful modeling,experimental-L,experimental-M,experimental-H groups were given intragastric administration of 0.05,0.10 and 0.15 μg·kg-1 concentration of vitamin D,while control group and model group were given intragastric administration of 0.9%NaCl at the same dose once a day for 2 weeks.Fasting blood glucose concentration and insulin level were detected before intervention,1 week and 2 weeks after intervention.Echocardiography was used to detect cardiac function[left ventricular ejection fraction(LVEF),maximum rate of rise(+dp/dtmax)and maximum rate of decline(-dp/dtmax)of left ventricular pressure].Myocardial enzyme indexes[troponin Ⅰ(cTn Ⅰ)kit,creatine kinase isoenzyme(CK-MB)]and inflammatory factors[tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)]in serum and myocardial tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA),and MEK/ERK pathway protein expression was detected by western blot.Results The levels of cTn Ⅰ in cardiac tissue of control group,model group,experimental-L group,experimental-M group,experimental-H group were(10.50±1.08),(42.26±4.30),(31.85±2.44),(23.31±2.15)and(14.85±1.19)ng·mL-1;serum cTn Ⅰ levels were(23.79±3.46),(63.59±5.52),(51.02±4.27),(42.75±3.19)and(29.20±2.11)ng·mL-1;myocardial tissue levels of CK-MB were(8.52±0.90),(17.65±1.75),(15.62±1.27),(13.11±1.24)and(9.85±0.87)ng·mL-1;serum levels of CK-MB were(11.32±0.98),(21.24±1.45),(18.75±1.32),(15.11±1.02)and(12.27±1.11)ng·mL-1;phosphorylated-MEK protein expression were 0.24±0.03,0.85±0.09,0.72±0.06,0.57±0.07 and 0.35±0.04;phosphorylated-ERK1/2 protein expression were 0.18±0.02,0.66±0.07,0.52±0.06,0.40±0.07 and 0.24±0.05,respectively.There were statistically significant differences of above indexes between control group and model group(all P<0.05);the difference between model group and experimental-L,experimental-M,experimental-H groups were all statistically significant(all P<0.05).Conclusion Vitamin D may reduce myocardial injury in rats with gestational diabetes by inhibiting the activation of MEK/ERK pathway.
2.Pharmacological research of Licraside in activating FXR to relieve cholestasis
Guo-Xu WANG ; ZEBANUER·Yue-mai-er-jiang ; Hui-Yu ZHANG ; Li-Li XI ; Fan ZHANG ; Yu-Hui WEI
The Chinese Journal of Clinical Pharmacology 2024;40(12):1759-1763
Objective To investigate the molecular mechanism of action of isoglycoside-4'-O-apigenin(1 → 2)glucoside(licraside)intervention in alleviating cholestasis.Methods Farnesol X receptor(FXR)was silenced in human HepG2 cells using lentivirus,and bilirubin and α-isothiocyanate(ANIT)were used to induce HepG2 cells to construct a hypercholate-hyperbilirubin model.The effects of licraside on cell viability,biochemical indices contents and the expression level of FXR and its downstream related proteins in the model were investigated.HepG2 cells and FXR-silenced HepG2 cells were divided into normal,model and experimental groups.Bilirubin and probenecid were added to all groups except the normal group,and 80 μmol·L-1 licraside was added to the experimental group.After 24 h of culture,cell viability and the levels of total bile acids(TBA),bilirubin and other biochemical indices were examined in each group;the protein expression levels of FXR and bile salt efflux pump(BSEP)were examined in each group by Western blot assay.Results The cell viability in HepG2 cells normal group,HepG2 cells model group,HepG2 cells experimental group,siFXR-HepG2 cells normal group,siFXR-HepG2 cells model group and siFXR-HepG2 cells experimental group were(100.00±17.15)%,(39.41±2.91)%,(70.79±3.74)%,(81.41±5.12)%,(33.49±2.69)%and(44.08±4.82)%;the levels of TBA were(7.98±5.87),(46.18±10.93),(9.25±7.20),(11.18±3.36),(38.28±5.12)and(34.79±5.39)μmol·L-1;the levels of total bilirubin were(5.21±3.27),(40.29±24.88),(5.21±2.64),(12.00±4.64),(56.36±14.85)and(15.39±5.56)μmol·L-1;the relative expression levels of FXR protein were 1.00±0.10,0.81±0.07,1.11±0.09,0.10±0.02,0.12±0.02 and 0.10±0.04;the relative expression levels of BSEP protein were 1.00±0.17,0.81±0.02,0.88±0.03,0.70±0.09,0.49±0.07 and 0.60±0.10.The differences of the above indexes in the HepG2 cells experimental group compared with the model group were statistically significant(P<0.001,P<0.01);except for TBA,the differences of the above indexes in siFXR-HepG2 cells experimental group compared with the model group were statistically significant(P<0.001,P<0.01).Conclusion Licraside can effectively reduce the biochemical indices level of hypercholate-hyperbilirubin cell model.This effect is achieved by agonizing of FXR protein expression,increase the efflux of bile acid salt and then reduce the synthesis of bile acids,and eventually achieve the effect of alleviating the cholestasis.
3.Study on the Analgesic Material Basis of Zhejiang Vinegar Corydalis Rhizoma Based on Chemometrics
LI Yafei ; ZHAO Mingling ; TANG Rui ; FANG Ke' ; er ; ZHANG Hair ; GE Weihong ; DU Weifeng
Chinese Journal of Modern Applied Pharmacy 2024;41(14):1892-1899
ABSTRACT
OBJECTIVE To explore the correlation between HPLC fingerprint and analgesic efficacy of Zhejiang vinegar Corydalis Rhizoma, and to screen out the material basis of analgesic effect of Zhejiang vinegar Corydalis Rhizoma.METHODS Established HPLC fingerprint of Zhejiang vinegar Corydalis Rhizoma and dysmenorrhea model in rats. The weight loss rate, writhing response, serum malondialdehyde(MDA), estradiol(E2), prostaglandin E2(PGE2) and prostaglandin F2α(PGF2α) levels were used as the evaluation indexes of analgesic efficacy. Combined with chemometrics, the main active components of analgesic effect of Zhejiang vinegar Corydalis Rhizoma and the important components with great contribution to the content were screened.RESULTS The fingerprints of different batches of Zhejiang vinegar Corydalis Rhizoma were established, and nine components were identified; compared with the blank group, the weight loss rate, writhing reaction, MDA, E2 and PGF2α levels in the model group were significantly increased. Compared with the model group, the above indexs in the administration group was decreased. Compared with the blank group, the PGE2 level in the model group was significantly decreased. Compared with the model group, the PGE2 level in the administration group was significantly increased. The vinegar Corydalis Rhizoma produced in Zhejiang had a good analgesic effect, and the main active components of its analgesic effect were protopine, palmatine hydrochloride, and dehydrocorydaline. The important components with greater contribution to the content were tetrahydropalmatine, protopine, palmatine hydrochloride and stylopine.CONCLUSION The efficacy of Zhejiang vinegar Corydalis Rhizoma is the result of the combined action of multiple components, and each component has a strong correlation with the pharmacodynamic indexes. This study provides a reference for the screening of analgesic material basis of Zhejiang vinegar Corydalis Rhizoma.
4.Application and Biological Evaluation of Magnetic Cell Sorting Technology
Tian HONG ; Jing-Wen LI ; Ren-Ai LI ; Er-Ning CHEN ; Lu-Lu ZHAO ; Mei-Hong DU
Progress in Biochemistry and Biophysics 2024;51(1):123-135
Magnetic cell sorting technology is a highly specific and rapid cell sorting technology using superparamagnetic nanocomposites for cell sorting, which is widely used in immunology, stem cytology, oncology, clinical medicine and other fields. Magnetic cell sorting technology is divided into positive isolation, negative isolation/untouched cell isolation, depletion, multi-step isolation and automated cell separation systems. In this review, we firstly give a brief introduction to the classification and application of magnetic cell sorting technology, then discuss several new techniques and challenges based on magnetic cell sorting in recent years, such as improving the sorting efficiency by improving the structure of magnetic materials and magnetic field structure. The necessity of biological evaluation of magnetic cell sorting products was emphatically analyzed. Through the biological evaluation, the advantages and disadvantages of magnetic cell sorting products can be understood, and the research and development ability could be improved. Therefore, 10 biological evaluation technical parameters related to magnetic cell sorting products were proposed: yield, purity, sterility, cytotoxicity, cell morphology, viability, light scattering characteristics of cells, fluorescent antibody labeling ability of cells, cell activation and cell proliferation. The 10 biological evaluation technical parameters play an important role in promoting the standardized application of magnetic cell sorting.
5.Influencing factors for depression and anxiety symptoms among the elderly
YANG Hongying ; LI Lian ; PAN Kaijie ; CHEN Xiang ; TANG Jianyan ; HUA Er ; ZHOU Ying ; BIAN Guolin
Journal of Preventive Medicine 2024;36(11):926-930
Objective:
To investigate the factors affecting depression and anxiety symptoms among the elderly, so as to provide the basis for promoting mental health among the elderly.
Methods:
The elderly aged 60 years and above in Ningbo City, Zhejiang Province were recruited using the multistage stratified random sampling method from June to August 2022, and demographic information, lifestyle and self-rated health status were collected by questionnaires. The symptoms of depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. The presence of depressive and anxiety symptoms was determined when both the PHQ-9 score and the GAD-7 score were 10 points and higher. Factors affecting depressive and anxiety symptoms were identified using a multivariable logistic regression model.
Results:
A total of 7 771 individuals were surveyed, including 3 490 males (44.91%) and 4 281 females (55.09%), and had a mean age of (72.11±6.79) years. The prevalence of depression and anxiety symptoms was 2.05%. Multivariable logistic regression analysis identified residence (urban area, OR=0.316, 95%CI: 0.201-0.498), sedentary duration (<3 h/d, OR=0.349, 95%CI: 0.232-0.525; 3-5 h/d, OR=0.458, 95%CI: 0.313-0.671), physical activity (≥3 times/week, OR=0.551, 95%CI: 0.373-0.815), sleep quality (poor, OR=2.491, 95%CI: 1.738-3.571), social isolation (OR=1.688, 95%CI: 1.148-2.481) and self-rated health (poor, OR=5.857, 95%CI: 3.547-9.671; normal, OR=1.903, 95%CI: 1.234-2.937) as the influencing factors for depression and anxiety symptoms among the elderly.
Conclusion
The prevalence of depression and anxiety symptoms among the elderly is associated with residence, sedentary duration, sleep quality, physical activity, social interactions and self-rated health status.
6.Study on The Toxicity of Strychnos nux-vomica L. in vivo in Rats:Application of Bagging Algorithm and 16S rRNA Gene Sequencing Technology in Toxicology Research
Xi-Ye WANG ; Le-Er BAO ; Ming-Yang JIANG ; Dan LI ; Mei-Rong BAI
Progress in Biochemistry and Biophysics 2024;51(2):404-422
ObjectiveThe traditional Chinese medicine Strychnos nux-vomica L. (SN) has the clinical effect of reducing swelling and relieving pain; however, SN is toxic due to its alkaloid components. Little is known about the endogenous metabolic changes induced by SN toxicity in rats and their potential effects on the metabolic dysregulation of intestinal microbiota. Therefore, toxicological investigation of SN is of great significance to its safety assessment. In this study, the toxic mechanisms of SN were explored using a combination of metabonomics and 16S rRNA gene sequencing. MethodsThe toxic dose, intensity, and target organ of SN were determined in rats using acute, cumulative, and subacute toxicity tests. UHPLC-MS was used to analyze the serum, liver, and renal samples of rats after intragastric SN administration. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16S rRNA V3-V4 region of bacteria. ResultsThe bagging algorithm improved the accuracy of sample classification. Twelve biomarkers were identified, where their metabolic dysregulation may be responsible for SN toxicity in vivo. Several types of bacteria such as Bacteroidetes, Anaerostipes, Oscillospira and Bilophila, were demonstrated to be closely related to physiological indices of renal and liver function, indicating that SN-induced liver and kidney damage may be related to the disturbance of these intestinal bacteria. ConclusionThe toxicity mechanism of SN was revealed in vivo, which provides a scientific basis for the safe and rational clinical use of SN.
7. Finite element analysis of cervical intervertebral discs after removing different ranges of uncinate processes
Yang YANG ; Jun SHI ; Kun LI ; Shao-Jie ZHANG ; Er-Fei HOU ; Jie CHEN ; Xing WANG ; Zhi-Jun LI ; Kun LI ; Yuan MA ; Shao-Jie ZHANG ; Zhi-Jun LI ; Chao-Qun WANG
Acta Anatomica Sinica 2024;55(1):88-97
Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C
8.Comparison of application value of two risk prediction models for prediction of intolerance risk in critically ill patients with enteral nutrition
Li-Jing BU ; Fei-Er CHENG ; Ai-Qin ZHANG ; Min-Yan ZHAO ; Yi-Dan ZHANG
Parenteral & Enteral Nutrition 2024;31(2):101-106
Objective:To assess the predictive accuracy and practical utility of established risk prediction models for enteral nutrition intolerance in critically ill patients. Methods:A meta-analysis was conducted to identify existing risk prediction models for enteral nutrition intolerance in critically ill patients. Eligible patients admitted to the Department of Critical Care Medicine and various ICUs of General Hospital of Eastern Theater Command from March 2023 to August 2023, meeting natriuresis criteria, were included in the study. The discrimination and calibration of the two models were assessed using the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test (H-L test). Results:Two models were analyzed, encompassing a total of 395 patients, among whom 161 experienced intolerances, resulting in an incidence rate of 40.8%. Model 1 demonstrated an AUROC of 0.838 (95%CI:0.798 ~ 0.873), while model 2 yielded an AUROC of 0.744 (95%CI:0.698 ~ 0.786). The Delong method was utilized to compare the AUROC values of the two models, revealing a statistically significant difference (P=0.0043). Notably, the model 1 exhibited superior performance compered to model 2. The H-L test for model 1 indicated fair calibration (X2=61.116, P<0.001), whereas model 2 demonstrated better calibration (X2=3.659, P=0.887). Conclusion:Model 1 exhibits superior discriminatory ability compared tomodel 2, while the calibration of model 2 surpasses that of model 1. Model 1 is well-suited for dynamic prediction, accommodating changes in patient condition over time. Conversely, Model 2 is appropriated for initial prediction following enteral nutrition initiation. Healthcare professionals can integrate bothmodels based on the specific clinical conditions to enhance predictive accutacy. Additionally, they can undertake high-quality research to develop a novel risk prediction model.
9.Research status on the mechanism of action of Astragaloside Ⅳ on cardiovascular diseases
Er-Dan XIN ; Yu-Gui ZHANG ; Tian-Tian BIAN ; Ding-Cai MA ; Zhe WANG ; Mao-Mao WANG ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(17):2580-2585
Asragaloside Ⅳ(AS-Ⅳ)is one of the active ingredients of Astragalus membranaceus,and AS-Ⅳ can play a protective role in cardiovascular diseases by inhibiting inflammatory response,inhibiting cardiomyocyte apoptosis,improving myocardial ischemia reperfusion injury,regulating lipid metabolism,promoting cardiac vascular regeneration,inhibiting myocardial fibrosis,and improving myocardial hypertrophy.In this paper,we reviewed the relevant literature on the prevention and treatment of cardiovascular diseases of AS-Ⅳ,and summarized and analyzed its role and mechanism,in order to provide a reference for the in depth research on cardiovascular diseases and the development and application of drugs.
10.Analysis of nutritional status and influencing factors in esophageal cancer patients for home-based care after surgery
Fei-Er CHENG ; Li-Jing BU ; Yi-Dan ZHANG ; Ai-Qin ZHANG
Parenteral & Enteral Nutrition 2024;31(5):300-305,311
Objective:To evaluate the nutritional status and its influencing factors in esophageal cancer patients for home-based care after surgery.Methods:A total of 153 patients with esophageal cancer who underwent surgery between July 2022 and October 2023 in the General Hospital of Eastern Theater Command were enrolled in this study.The nutritional status of the patients at home in 1-month post-surgery was evaluated according to the patient-generated subjective global assessment(PG-SGA),and the possible influencing factors were analyzed.Results:Among the 153 patients,47 were well-nourished and 106 were malnourished,with an overall malnutrition rate of 69.3%.For the malnutritional patients,71 were suspected or moderately malnourished and 35 were severely malnourished.The hemoglobin levels,serum albumin levels,the route for nutrition support delivery,nutrition impact symptoms(NIS),oral nutritional supplements(ONS)and nutritional behavior were independent influencing factors of nutritional status(P<0.05),in which NIS≥2 was a risk factor for malnutrition in the patients.Normal hemoglobin and albumin levels,enteral tube feeding,oral nutritional supplement and achieving standard of nutritional behavior were protective factors for avoiding the presence of malnutrition.Conclusion:The esophageal cancer patients for home-based care after surgery have a high incidence of malnutrition.Many factors,including nutrient delivery route and nutritional behavior,were related to the occurrence of in the patients.Certain measures to the related factors should be taken early for preventing malnutrition in clinical practice.


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